Trial Outcomes & Findings for Safety and Effectiveness of HIV-1 DNA Plasmid Vaccine and HIV-1 Recombinant Adenoviral Vector Vaccine in HIV-Uninfected, Circumcised Men and Male-to-Female (MTF) Transgender Persons Who Have Sex With Men (NCT NCT00865566)

Last Updated: 2021-10-15

Results Overview

For participants remaining uninfected, dropout is assessed only for primary follow-up, i.e. clinic visits. Protocol versions 4 and earlier included 24 months of primary follow-up, and versions 5 and later included 48 months. Participants may terminate early after completing primary follow-up, and participants who were found to be HIV-1 infected are analyzed as non-dropouts, so the number of dropouts and number of early terminations need not match.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

2504 participants

Primary outcome timeframe

Enrollment through Month 48 visit

Results posted on

2021-10-15

Participant Flow

Participant milestones

Participant milestones
Measure	Vaccine Participants will receive a recombinant DNA plasmid vaccine injection at study entry and on Days 28 and 56, followed by a recombinant adenoviral serotype vector vaccine injection on Day 168. As of April 2013, all vaccinations in this study have been stopped. DNA plasmid vaccine: 4-mg injection administered as 1 mL intramuscularly (IM) via Biojector® in either deltoid Recombinant adenoviral serotype 5 (rAD5) vector vaccine: 1 x 10\^10 particle units (PU) administered as 1mL IM by needle and syringe in either deltoid	Placebo Participants will receive a recombinant DNA plasmid vaccine placebo injection at study entry and on Days 28 and 56, followed by a recombinant adenoviral serotype vector vaccine placebo injection on Day 168. As of April 2013, all vaccinations in this study have been stopped. DNA vaccine placebo: 1 mL IM via Biojector® in either deltoid HIV-1 recombinant adenovirus vaccine placebo: 1 mL administered IM by needle and syringe in either deltoid
Overall Study STARTED	1253	1251
Overall Study Modified Intent-to-Treat Population	1251	1245
Overall Study COMPLETED	629	564
Overall Study NOT COMPLETED	624	687

Reasons for withdrawal

Reasons for withdrawal
Measure	Vaccine Participants will receive a recombinant DNA plasmid vaccine injection at study entry and on Days 28 and 56, followed by a recombinant adenoviral serotype vector vaccine injection on Day 168. As of April 2013, all vaccinations in this study have been stopped. DNA plasmid vaccine: 4-mg injection administered as 1 mL intramuscularly (IM) via Biojector® in either deltoid Recombinant adenoviral serotype 5 (rAD5) vector vaccine: 1 x 10\^10 particle units (PU) administered as 1mL IM by needle and syringe in either deltoid	Placebo Participants will receive a recombinant DNA plasmid vaccine placebo injection at study entry and on Days 28 and 56, followed by a recombinant adenoviral serotype vector vaccine placebo injection on Day 168. As of April 2013, all vaccinations in this study have been stopped. DNA vaccine placebo: 1 mL IM via Biojector® in either deltoid HIV-1 recombinant adenovirus vaccine placebo: 1 mL administered IM by needle and syringe in either deltoid
Overall Study Death	1	11
Overall Study Lost to Follow-up	314	315
Overall Study Withdrawal by Subject	45	65
Overall Study Physician Decision	0	1
Overall Study Participant relocated	78	107
Overall Study Participant unable to adhere	27	42
Overall Study Other; N=245 due to early study closure	154	139
Overall Study HIV infection	5	7

Baseline Characteristics

Safety and Effectiveness of HIV-1 DNA Plasmid Vaccine and HIV-1 Recombinant Adenoviral Vector Vaccine in HIV-Uninfected, Circumcised Men and Male-to-Female (MTF) Transgender Persons Who Have Sex With Men

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Vaccine n=1253 Participants Participants will receive a recombinant DNA plasmid vaccine injection at study entry and on Days 28 and 56, followed by a recombinant adenoviral serotype vector vaccine injection on Day 168. As of April 2013, all vaccinations in this study have been stopped. DNA plasmid vaccine: 4-mg injection administered as 1 mL intramuscularly (IM) via Biojector® in either deltoid Recombinant adenoviral serotype 5 (rAD5) vector vaccine: 1 x 10\^10 particle units (PU) administered as 1mL IM by needle and syringe in either deltoid	Placebo n=1251 Participants Participants will receive a recombinant DNA plasmid vaccine placebo injection at study entry and on Days 28 and 56, followed by a recombinant adenoviral serotype vector vaccine placebo injection on Day 168. As of April 2013, all vaccinations in this study have been stopped. DNA vaccine placebo: 1 mL IM via Biojector® in either deltoid HIV-1 recombinant adenovirus vaccine placebo: 1 mL administered IM by needle and syringe in either deltoid	Total n=2504 Participants Total of all reporting groups
Age, Continuous	29 years n=5 Participants	30 years n=7 Participants	29 years n=5 Participants
Age, Customized 18-20 years	105 Participants n=5 Participants	108 Participants n=7 Participants	213 Participants n=5 Participants
Age, Customized 21-30 years	585 Participants n=5 Participants	569 Participants n=7 Participants	1154 Participants n=5 Participants
Age, Customized 31-40 years	299 Participants n=5 Participants	299 Participants n=7 Participants	598 Participants n=5 Participants
Age, Customized 41-50 years	264 Participants n=5 Participants	275 Participants n=7 Participants	539 Participants n=5 Participants
Sex/Gender, Customized Male	1231 Participants n=5 Participants	1229 Participants n=7 Participants	2460 Participants n=5 Participants
Sex/Gender, Customized Female	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Sex/Gender, Customized Transgender Male	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Sex/Gender, Customized Transgender Female	13 Participants n=5 Participants	15 Participants n=7 Participants	28 Participants n=5 Participants
Sex/Gender, Customized Other	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	1253 Participants n=5 Participants	1251 Participants n=7 Participants	2504 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	125 Participants n=5 Participants	94 Participants n=7 Participants	219 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1128 Participants n=5 Participants	1157 Participants n=7 Participants	2285 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=5 Participants	10 Participants n=7 Participants	13 Participants n=5 Participants
Race (NIH/OMB) Asian	13 Participants n=5 Participants	20 Participants n=7 Participants	33 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) Black or African American	222 Participants n=5 Participants	204 Participants n=7 Participants	426 Participants n=5 Participants
Race (NIH/OMB) White	939 Participants n=5 Participants	944 Participants n=7 Participants	1883 Participants n=5 Participants
Race (NIH/OMB) More than one race	45 Participants n=5 Participants	46 Participants n=7 Participants	91 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	27 Participants n=5 Participants	21 Participants n=7 Participants	48 Participants n=5 Participants
Body Mass Index (BMI) <18.5 kg/m^2	22 Participants n=5 Participants	16 Participants n=7 Participants	38 Participants n=5 Participants
Body Mass Index (BMI) 18.5-24.9 kg/m^2	550 Participants n=5 Participants	586 Participants n=7 Participants	1136 Participants n=5 Participants
Body Mass Index (BMI) 25.0-29.9 kg/m^2	391 Participants n=5 Participants	381 Participants n=7 Participants	772 Participants n=5 Participants
Body Mass Index (BMI) 30.0-34.9 kg/m^2	189 Participants n=5 Participants	167 Participants n=7 Participants	356 Participants n=5 Participants
Body Mass Index (BMI) 35-39.9 kg/m^2	64 Participants n=5 Participants	59 Participants n=7 Participants	123 Participants n=5 Participants
Body Mass Index (BMI) >=40 kg/m^2	36 Participants n=5 Participants	41 Participants n=7 Participants	77 Participants n=5 Participants
Body Mass Index (BMI) Missing/Unknown	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Number of male sexual partners within 3 months prior to screening assessment 0	59 Participants n=5 Participants	64 Participants n=7 Participants	123 Participants n=5 Participants
Number of male sexual partners within 3 months prior to screening assessment 1	256 Participants n=5 Participants	243 Participants n=7 Participants	499 Participants n=5 Participants
Number of male sexual partners within 3 months prior to screening assessment 2	253 Participants n=5 Participants	242 Participants n=7 Participants	495 Participants n=5 Participants
Number of male sexual partners within 3 months prior to screening assessment 3-4	349 Participants n=5 Participants	367 Participants n=7 Participants	716 Participants n=5 Participants
Number of male sexual partners within 3 months prior to screening assessment 5 or more	330 Participants n=5 Participants	327 Participants n=7 Participants	657 Participants n=5 Participants
Number of male sexual partners within 3 months prior to screening assessment Unknown	6 Participants n=5 Participants	8 Participants n=7 Participants	14 Participants n=5 Participants
Number of male sexual partners within 3 months prior to screening assessment	3 partners n=5 Participants	3 partners n=7 Participants	3 partners n=5 Participants
Any unprotected receptive anal sex with a partner within 3 months prior to screening assessment	589 Participants n=5 Participants	573 Participants n=7 Participants	1162 Participants n=5 Participants

PRIMARY outcome

Timeframe: Enrollment through Month 48 visit

Population: MITT population

Outcome measures

Outcome measures
Measure	Vaccine n=1251 Participants Participants will receive a recombinant DNA plasmid vaccine injection at study entry and on Days 28 and 56, followed by a recombinant adenoviral serotype vector vaccine injection on Day 168. As of April 2013, all vaccinations in this study have been stopped. DNA plasmid vaccine: 4-mg injection administered as 1 mL intramuscularly (IM) via Biojector® in either deltoid Recombinant adenoviral serotype 5 (rAD5) vector vaccine: 1 x 10\^10 particle units (PU) administered as 1mL IM by needle and syringe in either deltoid	Placebo n=1245 Participants Participants will receive a recombinant DNA plasmid vaccine placebo injection at study entry and on Days 28 and 56, followed by a recombinant adenoviral serotype vector vaccine placebo injection on Day 168. As of April 2013, all vaccinations in this study have been stopped. DNA vaccine placebo: 1 mL IM via Biojector® in either deltoid HIV-1 recombinant adenovirus vaccine placebo: 1 mL administered IM by needle and syringe in either deltoid
Participant Dropout Through Month 48	340 Participants	436 Participants

PRIMARY outcome

Timeframe: Enrollment until the date of dropout, through April 22, 2013 (up to Month 24 visit)

Population: MITT population

The trial was unblinded on April 23, 2013, and the protocol was in version 4 at the time. For participants remaining uninfected, dropout is assessed only for primary follow-up, i.e. clinic visits. Protocol versions 4 and earlier included 24 months of primary follow-up, and versions 5 and later included 48 months. Participants may terminate early after completing primary follow-up, and participants who were found to be HIV-1 infected are analyzed as non-dropouts, so the number of dropouts and number of early terminations need not match.

Outcome measures

Outcome measures
Measure	Vaccine n=1251 Participants Participants will receive a recombinant DNA plasmid vaccine injection at study entry and on Days 28 and 56, followed by a recombinant adenoviral serotype vector vaccine injection on Day 168. As of April 2013, all vaccinations in this study have been stopped. DNA plasmid vaccine: 4-mg injection administered as 1 mL intramuscularly (IM) via Biojector® in either deltoid Recombinant adenoviral serotype 5 (rAD5) vector vaccine: 1 x 10\^10 particle units (PU) administered as 1mL IM by needle and syringe in either deltoid	Placebo n=1245 Participants Participants will receive a recombinant DNA plasmid vaccine placebo injection at study entry and on Days 28 and 56, followed by a recombinant adenoviral serotype vector vaccine placebo injection on Day 168. As of April 2013, all vaccinations in this study have been stopped. DNA vaccine placebo: 1 mL IM via Biojector® in either deltoid HIV-1 recombinant adenovirus vaccine placebo: 1 mL administered IM by needle and syringe in either deltoid
Participant Dropout Prior to Unblinding	99 Participants	127 Participants

PRIMARY outcome

Timeframe: April 23, 2013 through trial closure (up to Month 48 visit)

Population: MITT population participants who were HIV-uninfected and on-study as of April 23, 2013

Outcome measures

Outcome measures
Measure	Vaccine n=1036 Participants Participants will receive a recombinant DNA plasmid vaccine injection at study entry and on Days 28 and 56, followed by a recombinant adenoviral serotype vector vaccine injection on Day 168. As of April 2013, all vaccinations in this study have been stopped. DNA plasmid vaccine: 4-mg injection administered as 1 mL intramuscularly (IM) via Biojector® in either deltoid Recombinant adenoviral serotype 5 (rAD5) vector vaccine: 1 x 10\^10 particle units (PU) administered as 1mL IM by needle and syringe in either deltoid	Placebo n=999 Participants Participants will receive a recombinant DNA plasmid vaccine placebo injection at study entry and on Days 28 and 56, followed by a recombinant adenoviral serotype vector vaccine placebo injection on Day 168. As of April 2013, all vaccinations in this study have been stopped. DNA vaccine placebo: 1 mL IM via Biojector® in either deltoid HIV-1 recombinant adenovirus vaccine placebo: 1 mL administered IM by needle and syringe in either deltoid
Participant Dropout After Unblinding	241 Participants	309 Participants

PRIMARY outcome

Timeframe: Enrollment through Month 48 visit

Population: Modified Intent-to-Treat Cohort

For time-to-event analysis, an event is defined as HIV-1 infection and participants are censored if they dropped out early or completed the trial. HIV-1 diagnosis date is defined as the date of the earliest specimen collection yielding a positive HIV test. Participants remaining uninfected were censored at the latest specimen collection with a negative HIV-1 test.

Outcome measures

Outcome measures
Measure	Vaccine n=1251 Participants Participants will receive a recombinant DNA plasmid vaccine injection at study entry and on Days 28 and 56, followed by a recombinant adenoviral serotype vector vaccine injection on Day 168. As of April 2013, all vaccinations in this study have been stopped. DNA plasmid vaccine: 4-mg injection administered as 1 mL intramuscularly (IM) via Biojector® in either deltoid Recombinant adenoviral serotype 5 (rAD5) vector vaccine: 1 x 10\^10 particle units (PU) administered as 1mL IM by needle and syringe in either deltoid	Placebo n=1245 Participants Participants will receive a recombinant DNA plasmid vaccine placebo injection at study entry and on Days 28 and 56, followed by a recombinant adenoviral serotype vector vaccine placebo injection on Day 168. As of April 2013, all vaccinations in this study have been stopped. DNA vaccine placebo: 1 mL IM via Biojector® in either deltoid HIV-1 recombinant adenovirus vaccine placebo: 1 mL administered IM by needle and syringe in either deltoid
HIV-1 Infections Diagnosed After Day 0 Including All Available Follow-up Through the Maximum Month 48 Visit	75 participants	68 participants

PRIMARY outcome

Timeframe: Enrollment through Month 24 visit

Population: Modified Intent-to-Treat Cohort

For time-to-event analysis, an event is defined as HIV-1 infection and participants remaining uninfected through the month 24 visit were censored. HIV-1 diagnosis date is defined as the date of the earliest specimen collection at or prior to month 24 which yielded a positive HIV test. Participants remaining uninfected through the month 24 visit were censored at the latest specimen collection with a negative HIV-1 test at or prior to the month 24 visit.

Outcome measures

Outcome measures
Measure	Vaccine n=1251 Participants Participants will receive a recombinant DNA plasmid vaccine injection at study entry and on Days 28 and 56, followed by a recombinant adenoviral serotype vector vaccine injection on Day 168. As of April 2013, all vaccinations in this study have been stopped. DNA plasmid vaccine: 4-mg injection administered as 1 mL intramuscularly (IM) via Biojector® in either deltoid Recombinant adenoviral serotype 5 (rAD5) vector vaccine: 1 x 10\^10 particle units (PU) administered as 1mL IM by needle and syringe in either deltoid	Placebo n=1245 Participants Participants will receive a recombinant DNA plasmid vaccine placebo injection at study entry and on Days 28 and 56, followed by a recombinant adenoviral serotype vector vaccine placebo injection on Day 168. As of April 2013, all vaccinations in this study have been stopped. DNA vaccine placebo: 1 mL IM via Biojector® in either deltoid HIV-1 recombinant adenovirus vaccine placebo: 1 mL administered IM by needle and syringe in either deltoid
HIV-1 Infections Diagnosed After Day 0 Through the Month 24 Visit	49 participants	46 participants

PRIMARY outcome

Timeframe: Through 3 days post each study vaccination, and to resolution for events present at the third day post vaccination

Population: All Enrolled Participants

For each sign or symptom, we define the maximum observed grade for each participant over all vaccinations and post-vaccination assessments. Local and systemic signs and symptoms are assessed and graded based on The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December, 2004 (Clarification dated August 2009). Local reactogenicity parameters are pain, tenderness, erythema, and induration. We present the maximum grade for pain and/or tenderness, and erythema and/or induration.

Outcome measures

Outcome measures
Measure	Vaccine n=1253 Participants Participants will receive a recombinant DNA plasmid vaccine injection at study entry and on Days 28 and 56, followed by a recombinant adenoviral serotype vector vaccine injection on Day 168. As of April 2013, all vaccinations in this study have been stopped. DNA plasmid vaccine: 4-mg injection administered as 1 mL intramuscularly (IM) via Biojector® in either deltoid Recombinant adenoviral serotype 5 (rAD5) vector vaccine: 1 x 10\^10 particle units (PU) administered as 1mL IM by needle and syringe in either deltoid	Placebo n=1251 Participants Participants will receive a recombinant DNA plasmid vaccine placebo injection at study entry and on Days 28 and 56, followed by a recombinant adenoviral serotype vector vaccine placebo injection on Day 168. As of April 2013, all vaccinations in this study have been stopped. DNA vaccine placebo: 1 mL IM via Biojector® in either deltoid HIV-1 recombinant adenovirus vaccine placebo: 1 mL administered IM by needle and syringe in either deltoid
Number of Participants Experiencing Local Reactogenicity: Pain and/or Tenderness None	138 Participants	415 Participants
Number of Participants Experiencing Local Reactogenicity: Pain and/or Tenderness Mild	723 Participants	744 Participants
Number of Participants Experiencing Local Reactogenicity: Pain and/or Tenderness Moderate	370 Participants	90 Participants
Number of Participants Experiencing Local Reactogenicity: Pain and/or Tenderness Severe	22 Participants	2 Participants
Number of Participants Experiencing Local Reactogenicity: Pain and/or Tenderness Potentially life-threatening	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Through 3 days post each study vaccination, and to resolution for events present at the third day post vaccination

Population: All enrolled participants

Outcome measures

Outcome measures
Measure	Vaccine n=1253 Participants Participants will receive a recombinant DNA plasmid vaccine injection at study entry and on Days 28 and 56, followed by a recombinant adenoviral serotype vector vaccine injection on Day 168. As of April 2013, all vaccinations in this study have been stopped. DNA plasmid vaccine: 4-mg injection administered as 1 mL intramuscularly (IM) via Biojector® in either deltoid Recombinant adenoviral serotype 5 (rAD5) vector vaccine: 1 x 10\^10 particle units (PU) administered as 1mL IM by needle and syringe in either deltoid	Placebo n=1251 Participants Participants will receive a recombinant DNA plasmid vaccine placebo injection at study entry and on Days 28 and 56, followed by a recombinant adenoviral serotype vector vaccine placebo injection on Day 168. As of April 2013, all vaccinations in this study have been stopped. DNA vaccine placebo: 1 mL IM via Biojector® in either deltoid HIV-1 recombinant adenovirus vaccine placebo: 1 mL administered IM by needle and syringe in either deltoid
Number of Participants Experiencing Local Reactogenicity: Erythema and/or Induration >25 to 81 square cm (grade 1)	15 Participants	2 Participants
Number of Participants Experiencing Local Reactogenicity: Erythema and/or Induration >9 cm any diameter (grade 2)	6 Participants	0 Participants
Number of Participants Experiencing Local Reactogenicity: Erythema and/or Induration None	717 Participants	980 Participants
Number of Participants Experiencing Local Reactogenicity: Erythema and/or Induration >0 to 25 square cm	498 Participants	268 Participants
Number of Participants Experiencing Local Reactogenicity: Erythema and/or Induration >81 square cm (grade 2)	17 Participants	1 Participants

PRIMARY outcome

Timeframe: Through 3 days post each study vaccination, and to resolution for events present at the third day post vaccination

Population: All enrolled participants

For each sign or symptom, we define the maximum observed grade for each participant over all vaccinations and post-vaccination assessments. Local and systemic signs and symptoms are assessed and graded based on The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December, 2004 (Clarification dated August 2009). Systemic reactogenicity parameters are malaise/fatigue, myalgia, headache, nausea, vomiting, chills, and arthralgia. We present the maximum grade calculated over these parameters.

Outcome measures

Outcome measures
Measure	Vaccine n=1253 Participants Participants will receive a recombinant DNA plasmid vaccine injection at study entry and on Days 28 and 56, followed by a recombinant adenoviral serotype vector vaccine injection on Day 168. As of April 2013, all vaccinations in this study have been stopped. DNA plasmid vaccine: 4-mg injection administered as 1 mL intramuscularly (IM) via Biojector® in either deltoid Recombinant adenoviral serotype 5 (rAD5) vector vaccine: 1 x 10\^10 particle units (PU) administered as 1mL IM by needle and syringe in either deltoid	Placebo n=1251 Participants Participants will receive a recombinant DNA plasmid vaccine placebo injection at study entry and on Days 28 and 56, followed by a recombinant adenoviral serotype vector vaccine placebo injection on Day 168. As of April 2013, all vaccinations in this study have been stopped. DNA vaccine placebo: 1 mL IM via Biojector® in either deltoid HIV-1 recombinant adenovirus vaccine placebo: 1 mL administered IM by needle and syringe in either deltoid
Number of Participants Experiencing Systemic Reactogenicity Mild	408 Participants	406 Participants
Number of Participants Experiencing Systemic Reactogenicity None	563 Participants	667 Participants
Number of Participants Experiencing Systemic Reactogenicity Moderate	240 Participants	169 Participants
Number of Participants Experiencing Systemic Reactogenicity Severe	42 Participants	9 Participants
Number of Participants Experiencing Systemic Reactogenicity Potentially life-threatening	0 Participants	0 Participants

Adverse Events

Vaccine

Serious events: 77 serious events

Other events: 833 other events

Deaths: 1 deaths

Placebo

Serious events: 95 serious events

Other events: 828 other events

Deaths: 11 deaths

Serious adverse events

Other adverse events

Additional Information

Jessica Andriesen, PhD, Associate Director of HVTN SDMC Operations

Fred Hutchinson Cancer Research Center

Phone: 206-667-5812

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Vaccine n=1253 participants at risk Participants will receive a recombinant DNA plasmid vaccine injection at study entry and on Days 28 and 56, followed by a recombinant adenoviral serotype vector vaccine injection on Day 168. As of April 2013, all vaccinations in this study have been stopped. DNA plasmid vaccine: 4-mg injection administered as 1 mL intramuscularly (IM) via Biojector® in either deltoid Recombinant adenoviral serotype 5 (rAD5) vector vaccine: 1 x 10\^10 particle units (PU) administered as 1mL IM by needle and syringe in either deltoid	Placebo n=1251 participants at risk Participants will receive a recombinant DNA plasmid vaccine placebo injection at study entry and on Days 28 and 56, followed by a recombinant adenoviral serotype vector vaccine placebo injection on Day 168. As of April 2013, all vaccinations in this study have been stopped. DNA vaccine placebo: 1 mL IM via Biojector® in either deltoid HIV-1 recombinant adenovirus vaccine placebo: 1 mL administered IM by needle and syringe in either deltoid
Blood and lymphatic system disorders Any event in SOC	0.00% 0/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.08% 1/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Blood and lymphatic system disorders Anaemias NEC	0.00% 0/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.08% 1/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Cardiac disorders Any event in SOC	0.08% 1/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.48% 6/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Cardiac disorders Ischaemic coronary artery disorders	0.08% 1/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.16% 2/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Cardiac disorders Coronary artery disorders NEC	0.00% 0/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.08% 1/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Cardiac disorders Heart failures NEC	0.00% 0/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.08% 1/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Cardiac disorders Supraventricular arrhythmias	0.00% 0/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.08% 1/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Cardiac disorders Ventricular arrhythmias and cardiac arrest	0.00% 0/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.08% 1/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Congenital, familial and genetic disorders Any event in SOC	0.00% 0/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.08% 1/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Congenital, familial and genetic disorders Haemoglobinopathies congenital	0.00% 0/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.08% 1/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Gastrointestinal disorders Any event in SOC	0.16% 2/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	1.2% 15/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Gastrointestinal disorders Colitis (excl infective)	0.08% 1/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.24% 3/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Gastrointestinal disorders Acute and chronic pancreatitis	0.08% 1/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.08% 1/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Gastrointestinal disorders Duodenal ulcers and perforation	0.00% 0/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.16% 2/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Gastrointestinal disorders Intestinal ulcers and perforation NEC	0.00% 0/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.16% 2/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Gastrointestinal disorders Abdominal hernias NEC	0.00% 0/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.08% 1/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Gastrointestinal disorders Gastric ulcers and perforation	0.00% 0/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.08% 1/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Gastrointestinal disorders Gastrointestinal atonic and hypomotility disorders NEC	0.00% 0/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.08% 1/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Gastrointestinal disorders Gastrointestinal disorders NEC	0.00% 0/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.08% 1/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Gastrointestinal disorders Gastrointestinal stenosis and obstruction NEC	0.00% 0/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.08% 1/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Gastrointestinal disorders Non-site specific gastrointestinal haemorrhages	0.08% 1/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.00% 0/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Gastrointestinal disorders Oesophageal ulcers and perforation	0.00% 0/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.08% 1/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Gastrointestinal disorders Rectal inflammations NEC	0.00% 0/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.08% 1/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
General disorders Any event in SOC	0.16% 2/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.40% 5/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
General disorders Pain and discomfort NEC	0.08% 1/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.24% 3/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
General disorders Death and sudden death	0.00% 0/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.16% 2/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
General disorders Withdrawal and rebound effects	0.08% 1/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.00% 0/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Immune system disorders Any event in SOC	0.08% 1/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.08% 1/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Immune system disorders Acute and chronic sarcoidosis	0.00% 0/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.08% 1/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Immune system disorders Allergies to foods, food additives, drugs and other chemicals	0.08% 1/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.00% 0/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Infections and infestations Any event in SOC	2.0% 25/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	2.1% 26/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Infections and infestations Abdominal and gastrointestinal infections	0.64% 8/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.88% 11/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Infections and infestations Bacterial infections NEC	0.40% 5/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.32% 4/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Infections and infestations Infections NEC	0.16% 2/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.24% 3/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Infections and infestations Lower respiratory tract and lung infections	0.24% 3/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.08% 1/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Infections and infestations Upper respiratory tract infections	0.08% 1/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.16% 2/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Infections and infestations Clostridia infections	0.16% 2/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.00% 0/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Infections and infestations Sepsis, bacteraemia, viraemia and fungaemia NEC	0.08% 1/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.08% 1/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Infections and infestations Skin structures and soft tissue infections	0.08% 1/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.08% 1/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Infections and infestations Staphylococcal infections	0.16% 2/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.00% 0/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.

Other adverse events
Measure	Vaccine n=1253 participants at risk Participants will receive a recombinant DNA plasmid vaccine injection at study entry and on Days 28 and 56, followed by a recombinant adenoviral serotype vector vaccine injection on Day 168. As of April 2013, all vaccinations in this study have been stopped. DNA plasmid vaccine: 4-mg injection administered as 1 mL intramuscularly (IM) via Biojector® in either deltoid Recombinant adenoviral serotype 5 (rAD5) vector vaccine: 1 x 10\^10 particle units (PU) administered as 1mL IM by needle and syringe in either deltoid	Placebo n=1251 participants at risk Participants will receive a recombinant DNA plasmid vaccine placebo injection at study entry and on Days 28 and 56, followed by a recombinant adenoviral serotype vector vaccine placebo injection on Day 168. As of April 2013, all vaccinations in this study have been stopped. DNA vaccine placebo: 1 mL IM via Biojector® in either deltoid HIV-1 recombinant adenovirus vaccine placebo: 1 mL administered IM by needle and syringe in either deltoid
Endocrine disorders Male gonadal function disorders	0.08% 1/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.00% 0/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Blood and lymphatic system disorders Any event in SOC	1.8% 22/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	1.4% 17/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Blood and lymphatic system disorders Lymphatic system disorders NEC	1.6% 20/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	1.2% 15/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Blood and lymphatic system disorders Anaemias NEC	0.16% 2/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.00% 0/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Blood and lymphatic system disorders Leukocytoses NEC	0.00% 0/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.08% 1/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Blood and lymphatic system disorders Red blood cell abnormal findings NEC	0.00% 0/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.08% 1/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Blood and lymphatic system disorders Spleen disorders	0.08% 1/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.00% 0/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Cardiac disorders Any event in SOC	0.16% 2/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.40% 5/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Cardiac disorders Supraventricular arrhythmias	0.08% 1/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.16% 2/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Cardiac disorders Cardiac signs and symptoms NEC	0.00% 0/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.16% 2/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Cardiac disorders Rate and rhythm disorders NEC	0.08% 1/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.08% 1/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Congenital, familial and genetic disorders Any event in SOC	0.08% 1/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.08% 1/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Congenital, familial and genetic disorders Male reproductive tract disorders congenital	0.08% 1/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.08% 1/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Ear and labyrinth disorders Any event in SOC	0.80% 10/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.56% 7/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Ear and labyrinth disorders Ear disorders NEC	0.24% 3/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.40% 5/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Ear and labyrinth disorders Inner ear signs and symptoms	0.24% 3/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.08% 1/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Ear and labyrinth disorders External ear disorders NEC	0.08% 1/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.16% 2/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Ear and labyrinth disorders Middle ear disorders NEC	0.16% 2/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.00% 0/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Ear and labyrinth disorders Eustachian tube disorders	0.08% 1/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.00% 0/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Ear and labyrinth disorders Hearing losses	0.00% 0/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.08% 1/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Ear and labyrinth disorders Tympanic membrane disorders (excl infections)	0.08% 1/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.00% 0/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Endocrine disorders Any event in SOC	0.64% 8/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.16% 2/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Endocrine disorders Thyroid hypofunction disorders	0.32% 4/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.16% 2/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Endocrine disorders Endocrine abnormalities of gonadal function NEC	0.16% 2/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.00% 0/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Endocrine disorders Thyroid hyperfunction disorders	0.08% 1/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.00% 0/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Eye disorders Any event in SOC	1.4% 17/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.88% 11/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Eye disorders Lid, lash and lacrimal infections, irritations and inflammations	0.32% 4/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.08% 1/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Eye disorders Ocular disorders NEC	0.16% 2/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.16% 2/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Eye disorders Conjunctival and corneal bleeding and vascular disorders	0.16% 2/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.08% 1/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Eye disorders Ocular sensation disorders	0.00% 0/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.24% 3/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Eye disorders Visual disorders NEC	0.24% 3/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.00% 0/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Eye disorders Conjunctival infections, irritations and inflammations	0.08% 1/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.08% 1/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Eye disorders Eyelid movement disorders	0.08% 1/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.08% 1/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Eye disorders Lacrimation disorders	0.16% 2/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.00% 0/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Eye disorders Ocular infections, inflammations and associated manifestations	0.08% 1/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.08% 1/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Eye disorders Blindness (excl colour blindness)	0.00% 0/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.08% 1/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Eye disorders Glaucomas (excl congenital)	0.08% 1/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.00% 0/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Eye disorders Refractive and accommodative disorders	0.08% 1/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.00% 0/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Eye disorders Retinal, choroid and vitreous infections and inflammations	0.00% 0/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	0.08% 1/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.
Gastrointestinal disorders Any event in SOC	11.9% 149/1253 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.	11.7% 146/1251 • Reporting of all AEs occurred during 2 periods for each participant: 1) from enrollment through 28 days after the third vaccination, and 2) from the fourth vaccination through 28 days after the fourth vaccination. Between and after these time periods, only SAEs, new chronic conditions requiring medical intervention of more than 30 days, and newly diagnosed/treated STIs were reported. Events requiring expedited reporting (protocol section 12.3) were reported through the study, up to 60 months.