Trial Outcomes & Findings for Safety of and Immune Response to an H1N1 Influenza Vaccine in HIV Infected Pregnant Women (NCT NCT00992017)

NCT ID: NCT00992017

Last Updated: 2021-11-05

Results Overview

Shows the number of participants who had at least one adverse event (AE) in each category. These include: abnormal laboratory values, signs and symptoms, or diagnoses; solicited local AEs; and solicited systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 130 participants
• Primary outcome timeframe: Measured up to 6 months after delivery
• Results posted on: 2021-11-05

Participant Flow

Pregnant women were enrolled from 31 sites between October 8, 2009 and November 13, 2009.

Two study participants were enrolled but left the clinic before receiving any vaccination and they were taken off study.

Participant milestones

Measure	H1N1 Vaccine Pregnant women received two doses of H1N1 vaccine administered 21 days apart. Each dose consisted of two 15-microgram intramuscular injections.
Overall Study STARTED	128
Overall Study Received Both Study Vaccinations	124
Overall Study Received Only One Study Vaccination	4
Overall Study COMPLETED	118
Overall Study NOT COMPLETED	10

Reasons for withdrawal

Measure	H1N1 Vaccine Pregnant women received two doses of H1N1 vaccine administered 21 days apart. Each dose consisted of two 15-microgram intramuscular injections.
Overall Study Lost to Follow-up	2
Overall Study Withdrawal by Subject	2
Overall Study Unable to get to clinic	5
Overall Study Not adhere to study requirements	1

Baseline Characteristics

Safety of and Immune Response to an H1N1 Influenza Vaccine in HIV Infected Pregnant Women

Baseline characteristics by cohort

Measure	H1N1 Vaccine n=128 Participants Pregnant women received two doses of H1N1 vaccine administered 21 days apart. Each dose consisted of two 15-microgram intramuscular injections.
Age, Continuous	28 years STANDARD_DEVIATION 6 • n=5 Participants
Sex: Female, Male Female	128 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Region of Enrollment United States	112 participants n=5 Participants
Region of Enrollment Puerto Rico	16 participants n=5 Participants
CD4 Cells Count	504 cells / mm^3 STANDARD_DEVIATION 264 • n=5 Participants
Percentage of CD4 Cells	30 percentage of CD4 cells STANDARD_DEVIATION 11 • n=5 Participants
Gestational Age	25 Weeks STANDARD_DEVIATION 6 • n=5 Participants

PRIMARY outcome

Timeframe: Measured up to 6 months after delivery

Population: All 128 pregnant women who received at least one vaccination are included in this analysis.

Shows the number of participants who had at least one adverse event (AE) in each category. These include: abnormal laboratory values, signs and symptoms, or diagnoses; solicited local AEs; and solicited systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.

Outcome measures

Measure	H1N1 Vaccine n=128 Participants Pregnant women enrolled in the study.
The Number of Participants Who Had at Least One Adverse Event (AE) Overall (New AEs after start of treatment)	118 Participants
The Number of Participants Who Had at Least One Adverse Event (AE) Grade 4 AEs (New, after start of treatment)	11 Participants
The Number of Participants Who Had at Least One Adverse Event (AE) Grade 3 AEs (New, after start of treatment)	8 Participants
The Number of Participants Who Had at Least One Adverse Event (AE) Grade >=2 local and systemic AEs to injection	0 Participants

PRIMARY outcome

Timeframe: Measured up to 6 months after delivery

Population: All 128 pregnant women who received at least one vaccination are included.

Shows the number of participants who experienced any events that were thought to be at least possibly related to study treatment. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.

Outcome measures

Measure	H1N1 Vaccine n=128 Participants Pregnant women enrolled in the study.
The Number of Participants Who Had at Least One AE Attributed to the Study Vaccine	0 Participants

PRIMARY outcome

Timeframe: Measured at Day 21

Population: All 128 pregnant women who received at least one vaccination are included.

Outcome measures

Measure	H1N1 Vaccine n=128 Participants Pregnant women enrolled in the study.
Withholding of Second Vaccine Dose Due to Adverse Reactions Attributed to First Dose	0 Participants

PRIMARY outcome

Timeframe: Measured at 21 days after first dose and at 10 days after second dose of study vaccine

Population: The analysis population consists of the eligible pregnant women with nonmissing HAI titers, who had not delivered prior to the evaluation, and had received all doses of vaccine up to that timepoint. The N for the analyses of HAI titers after the first and second vaccinations were 118 and 108, respectively.

Antibodies to Influenza A (H1N1) 2009 were measured using an HAI assay. The potential titer read-outs from the assay used were <10 (considered undetectable), 10, 20, 40, 60, 80, 160, 320, 640, and >=1280. Seroprotection was defined as having a titer of >=40 following vaccination.

Outcome measures

Measure	H1N1 Vaccine n=118 Participants Pregnant women enrolled in the study.
Percent of Pregnant Women With a Hemagglutination Inhibition (HAI) Titer of >= 40 Percent with titers >= 40 post dose 1 (N=118)	73.7 Percent of participants Interval 64.8 to 81.4
Percent of Pregnant Women With a Hemagglutination Inhibition (HAI) Titer of >= 40 Percent with titers >= 40 post dose 2 (N=108)	80.6 Percent of participants Interval 71.8 to 87.5

SECONDARY outcome

Timeframe: Measured at delivery of the baby, and at 3 months and 6 months after delivery

Population: The population consists of eligible pregnant women with nonmissing HAI titers, who had not delivered before the evaluation post second dose, and received two doses of vaccine. The N for the analyses of HAI titers at delivery, and at 3 and 6 months after were 102, 92 and 58, respectively. Only some women had a clinic visit at 6 months post delivery.

Antibodies to Influenza A (H1N1) 2009 were measured using an HAI assay. The potential titer read-outs from the assay used were <10 (considered undetectable), 10, 20, 40, 60, 80, 160, 320, 640, and >=1280. Seroprotection was defined as having a titer of >=40 following vaccination.

Outcome measures

Measure	H1N1 Vaccine n=102 Participants Pregnant women enrolled in the study.
Percent of Pregnant Women With an HAI Titer of >= 40 at Delivery, 3 Months and 6 Months After Delivery % with titers >= 1:40 at delivery (N=102)	65.7 Percent of participants Interval 55.6 to 74.8
Percent of Pregnant Women With an HAI Titer of >= 40 at Delivery, 3 Months and 6 Months After Delivery % with titers >= 1:40 at 3 mo post delivery (N=92)	55.4 Percent of participants Interval 44.7 to 65.8
Percent of Pregnant Women With an HAI Titer of >= 40 at Delivery, 3 Months and 6 Months After Delivery % with titers >= 1:40 at 6 mo post delivery (N=58)	60.3 Percent of participants Interval 46.6 to 73.0

SECONDARY outcome

Timeframe: Measured at birth (via cord blood) and at 3 months and 6 months of age

Population: The population consists of infants born to eligible women with nonmissing HAI titers, who had not delivered before the evaluation post second dose, and received two doses of vaccine. The N for analyses at birth, 3 and 6 months were 96, 87 and 52, respectively. Cord blood was used when available. Only some infants had a clinic visit at 6 months.

Antibodies to Influenza A (H1N1) 2009 were measured using an HAI assay. The potential titer read-outs from the assay used were <10 (considered undetectable), 10, 20, 40, 60, 80, 160, 320, 640, and >=1280. Seroprotection was defined as having a titer of >=40 following vaccination.

Outcome measures

Measure	H1N1 Vaccine n=96 Participants Pregnant women enrolled in the study.
Percent of Infants With an HAI Titer of >= 40 % infants with titers >= 1:40 at birth (N=96)	64.6 Percent of participants Interval 54.2 to 74.1
Percent of Infants With an HAI Titer of >= 40 % infants with titers >= 1:40 at 3 months (N=87)	23.0 Percent of participants Interval 14.6 to 33.2
Percent of Infants With an HAI Titer of >= 40 % infants with titers >= 1:40 at 6 months (N=52)	11.5 Percent of participants Interval 4.4 to 23.4

SECONDARY outcome

Timeframe: Measured after the first and second doses of the vaccine, at delivery, and at 3 and 6 months after delivery

Population: The population consists of eligible women with nonmissing HAI titers, who had not delivered before the evaluation post first or second dose, and received all vaccines up to that point, respectively. The N for analyses after the first and second vaccinations, at delivery, 3 and 6 months after were 104, 94, 102, 92 and 58, respectively.

Presents the value of the geometric mean titer at each time point. Antibodies to Influenza A (H1N1) 2009 were measured using an HAI assay. The potential titer read-outs from the assay used were <10 (considered undetectable), 10, 20, 40, 60, 80, 160, 320, 640, and >=1280.

Outcome measures

Measure	H1N1 Vaccine n=104 Participants Pregnant women enrolled in the study.
Maternal Geometric Mean Titers (GMT) of Antibodies HAI Post first vaccination (N=104)	83 titers Interval 63.0 to 110.0
Maternal Geometric Mean Titers (GMT) of Antibodies HAI Post second vaccination (N=94)	81 titers Interval 62.0 to 106.0
Maternal Geometric Mean Titers (GMT) of Antibodies HAI At delivery (N=102)	50 titers Interval 39.0 to 65.0
Maternal Geometric Mean Titers (GMT) of Antibodies HAI At 3 months post delivery (N=92)	36 titers Interval 28.0 to 46.0
Maternal Geometric Mean Titers (GMT) of Antibodies HAI At 6 months post delivery (N=58)	38 titers Interval 29.0 to 50.0

SECONDARY outcome

Timeframe: Measured at birth and at 3 and 6 months of age

Population: The population consists of infants born to eligible women with nonmissing HAI titers, who had not delivered before the evaluation post second dose, and received two doses of vaccine. The N for analyses at birth, 3 and 6 months were 96, 87 and 52, respectively. Cord blood was used when available. Only some infants had a clinic visit at 6 months.

Presents the value of the geometric mean titer at each time point. Antibodies to Influenza A (H1N1) 2009 were measured using an HAI assay. The potential titer read-outs from the assay used were <10 (considered undetectable), 10, 20, 40, 60, 80, 160, 320, 640, and >=1280.

Outcome measures

Measure	H1N1 Vaccine n=96 Participants Pregnant women enrolled in the study.
Infant GMT of Antibodies HAI At birth (N=96 infants)	56 units on the HAI titer scale Interval 43.0 to 72.0
Infant GMT of Antibodies HAI At 3 months (N=87 infants)	13 units on the HAI titer scale Interval 11.0 to 16.0
Infant GMT of Antibodies HAI At 6 months (N=52 infants)	14 units on the HAI titer scale Interval 11.0 to 17.0

SECONDARY outcome

Timeframe: Measured at entry, at 21 days after first dose of vaccine, at 10 days after second dose

Population: The pregnant women who had not delivered prior to the evaluation, had received all doses of vaccine up to that timepoint and had sufficient samples for testing.

The median and interquartile range (IQR) of B-Cell ELISPOT-measured IgG antibody-secreting cells (ASC)/10^6 PBMC and the median and interquartile range (IQR) of T-Cell ELISPOT-measured pH1N1 IFNgamma spot-forming cells (SFC)/10^6 PBMC.

Outcome measures

Measure	H1N1 Vaccine n=45 Participants Pregnant women enrolled in the study.
Maternal Cell-mediated Immunity (CMI) Responses, as Measured by B-cell and T-cell Enzyme-linked Immunosorbent Spot (ELISPOT) Assay Values pH1N1 IFNgamma SFC/10^6 PBMC, Post Dose 2 (N=43)	76 ASC or SFC/10^6 PBMC Interval 32.0 to 336.0
Maternal Cell-mediated Immunity (CMI) Responses, as Measured by B-cell and T-cell Enzyme-linked Immunosorbent Spot (ELISPOT) Assay Values IgG ASC/10^6 PBMC, Week 0 (N=36)	6 ASC or SFC/10^6 PBMC Interval 2.0 to 28.0
Maternal Cell-mediated Immunity (CMI) Responses, as Measured by B-cell and T-cell Enzyme-linked Immunosorbent Spot (ELISPOT) Assay Values IgG ASC/10^6 PBMC, Post Dose 1 (N=36)	15 ASC or SFC/10^6 PBMC Interval 4.0 to 46.0
Maternal Cell-mediated Immunity (CMI) Responses, as Measured by B-cell and T-cell Enzyme-linked Immunosorbent Spot (ELISPOT) Assay Values IgG ASC/10^6 PBMC, Post Dose 2 (N=39)	14 ASC or SFC/10^6 PBMC Interval 6.0 to 70.0
Maternal Cell-mediated Immunity (CMI) Responses, as Measured by B-cell and T-cell Enzyme-linked Immunosorbent Spot (ELISPOT) Assay Values pH1N1 IFNgamma SFC/10^6 PBMC, Week 0 (N=45)	166 ASC or SFC/10^6 PBMC Interval 38.0 to 324.0
Maternal Cell-mediated Immunity (CMI) Responses, as Measured by B-cell and T-cell Enzyme-linked Immunosorbent Spot (ELISPOT) Assay Values pH1N1 IFNgamma SFC/10^6 PBMC, Post Dose 1 (N=44)	117 ASC or SFC/10^6 PBMC Interval 40.0 to 506.0

SECONDARY outcome

Timeframe: Measured at entry

Population: Pregnant women who received the first H1N1 immunization.

Presents the value of the median titer as well as the interquartile range at study entry. Antibodies to seasonal Influenza vaccine were measured using an HAI assay. The potential titer read-outs from the assay used were <10 (considered undetectable), 10, 20, 40, 60, 80, 160, 320, 640, and >=1280.

Outcome measures

Measure	H1N1 Vaccine n=128 Participants Pregnant women enrolled in the study.
Response to Seasonal Trivalent Influenza Vaccine (TIV)	20 titer Interval 10.0 to 40.0

Adverse Events

H1N1 Vaccine

Serious events: 21 serious events

Other events: 118 other events

Deaths: 0 deaths

Serious adverse events

Measure	H1N1 Vaccine n=128 participants at risk Pregnant women received two doses of H1N1 vaccine administered 21 days apart. Each dose consisted of two 15-microgram intramuscular injections.
Gastrointestinal disorders Vomiting	0.78% 1/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
General disorders Influenza like illness	0.78% 1/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Infections and infestations Pneumonia	0.78% 1/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Infections and infestations Wound infection	0.78% 1/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Injury, poisoning and procedural complications Wound dehiscence	0.78% 1/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Musculoskeletal and connective tissue disorders Flank pain	0.78% 1/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Nervous system disorders Hypoaesthesia	0.78% 1/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Nervous system disorders Paraesthesia	0.78% 1/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Nervous system disorders VIIth nerve paralysis	0.78% 1/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Pregnancy, puerperium and perinatal conditions Complication of pregnancy	0.78% 1/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Pregnancy, puerperium and perinatal conditions Intra-uterine death	0.78% 1/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Pregnancy, puerperium and perinatal conditions Placenta accreta	0.78% 1/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Pregnancy, puerperium and perinatal conditions Pre-eclampsia	3.9% 5/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Pregnancy, puerperium and perinatal conditions Premature labour	2.3% 3/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Pregnancy, puerperium and perinatal conditions Premature rupture of membranes	0.78% 1/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Psychiatric disorders Conversion disorder	0.78% 1/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Vascular disorders Deep vein thrombosis	0.78% 1/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.

Other adverse events

Measure	H1N1 Vaccine n=128 participants at risk Pregnant women received two doses of H1N1 vaccine administered 21 days apart. Each dose consisted of two 15-microgram intramuscular injections.
Blood and lymphatic system disorders Iron deficiency anaemia	7.0% 9/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Gastrointestinal disorders Abdominal pain	9.4% 12/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Gastrointestinal disorders Diarrhoea	8.6% 11/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Gastrointestinal disorders Nausea	18.8% 24/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Gastrointestinal disorders Vomiting	11.7% 15/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
General disorders Fatigue	7.0% 9/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
General disorders Pyrexia	6.2% 8/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Infections and infestations Bacterial disease carrier	5.5% 7/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Infections and infestations Vaginitis bacterial	6.2% 8/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Infections and infestations Vulvovaginal candidiasis	12.5% 16/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Investigations Alanine aminotransferase increased	7.8% 10/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Investigations Aspartate aminotransferase increased	6.2% 8/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Investigations Blood albumin abnormal	23.4% 30/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Investigations Blood alkaline phosphatase increased	5.5% 7/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Investigations Blood bicarbonate abnormal	10.9% 14/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Investigations Blood glucose decreased	12.5% 16/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Investigations Blood sodium decreased	19.5% 25/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Investigations Haemoglobin decreased	16.4% 21/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Musculoskeletal and connective tissue disorders Back pain	8.6% 11/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Musculoskeletal and connective tissue disorders Pain in extremity	8.6% 11/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Nervous system disorders Dizziness	7.0% 9/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Nervous system disorders Headache	24.2% 31/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Pregnancy, puerperium and perinatal conditions Pre-eclampsia	5.5% 7/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Reproductive system and breast disorders Vaginal discharge	14.8% 19/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Reproductive system and breast disorders Vaginal haemorrhage	7.0% 9/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Reproductive system and breast disorders Vulvovaginal pruritus	8.6% 11/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Respiratory, thoracic and mediastinal disorders Cough	17.2% 22/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Respiratory, thoracic and mediastinal disorders Nasal congestion	14.1% 18/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	8.6% 11/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Skin and subcutaneous tissue disorders Rash	5.5% 7/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Vascular disorders Hypertension	8.6% 11/128 • Adverse events were collected from the date of enrollment in the study until 6 months after delivery. Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.

Additional Information

Melissa Allen, Director, IMPAACT Operations Center

Family Health International (FHI 360)

Phone: 919-405-1429

Email: mallen@fhi360.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place