Trial Outcomes & Findings for Implementation Effectiveness and Safety of Tenofovir Gel Provision Through Family Planning Services (NCT NCT01691768)

NCT ID: NCT01691768

Last Updated: 2019-11-26

Results Overview

The primary endpoint is the mean number of returned used applicators per month. Since participants in the intervention arm followed two and three monthly schedule (as opposed to monthly in the intervention arm), the number of returned used applicators per month for each participant will be estimated as the total number of returned applicators at that visit divided by the number of days since the previous visit, multiplied by 30. Thus a uniform distribution of gel use will be assumed in participants whom we did not see monthly. Intent to treat and per protocol analyses were carried out of this outcome. Intent to treat population includes all participants who were randomized, met pre-randomization eligibility criteria and who have post-enrollment follow-up data. The per protocol population is a subset of the intent to treat population.The per-protocol analysis excluded visits where no gel had been dispensed for \>120 days.

• Recruitment status: COMPLETED
• Study phase: PHASE2/PHASE3
• Target enrollment: 372 participants
• Primary outcome timeframe: Between 2012 to 2015, up to 28 months
• Results posted on: 2019-11-26

Participant Flow

448 were assessed for eligibility and 382 were randomized. However, only 372 were eligible for study participation. Of the 10 who were ineligibly enrolled: 6 were HIV positive at enrollment, 2 were co-enrolled in another trial, 1 had no post-randomization follow-up data and 1 was pregnant at enrollment.

Participant milestones

Measure	Intervention 1% tenofovir gel provision through a public sector family planning services with 2-3 monthly provision and monitoring and the use of Quality Improvement methodology to promote reliable service delivery 1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either: * Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or * The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).	Control monthly 1% tenofovir gel provision and monitoring through CAPRISA research clinics 1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either: * Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or * The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).
Overall Study STARTED	189	183
Overall Study COMPLETED	174	167
Overall Study NOT COMPLETED	15	16

Reasons for withdrawal

Measure	Intervention 1% tenofovir gel provision through a public sector family planning services with 2-3 monthly provision and monitoring and the use of Quality Improvement methodology to promote reliable service delivery 1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either: * Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or * The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).	Control monthly 1% tenofovir gel provision and monitoring through CAPRISA research clinics 1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either: * Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or * The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).
Overall Study Death	0	2
Overall Study Lost to Follow-up	4	3
Overall Study Withdrawal by Subject	10	9
Overall Study Relocated	0	1
Overall Study Investigator decision	1	1

Baseline Characteristics

A total of 9 participants had equivocal results and 2 had missing results.

Baseline characteristics by cohort

Measure	Intervention n=189 Participants 1% tenofovir gel provision through a public sector family planning services with 2-3 monthly provision and monitoring and the use of QI methodology to promote reliable service delivery 1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either: * Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or * The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).	Control n=183 Participants monthly 1% tenofovir gel provision and monitoring through CAPRISA research clinics 1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either: * Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or * The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).	Total n=372 Participants Total of all reporting groups
Age, Continuous	29.5 years STANDARD_DEVIATION 5.8 • n=189 Participants	29.3 years STANDARD_DEVIATION 5.3 • n=183 Participants	29.4 years STANDARD_DEVIATION 5.5 • n=372 Participants
Sex: Female, Male Female	189 Participants n=189 Participants	183 Participants n=183 Participants	372 Participants n=372 Participants
Sex: Female, Male Male	0 Participants n=189 Participants	0 Participants n=183 Participants	0 Participants n=372 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=189 Participants	0 Participants n=183 Participants	0 Participants n=372 Participants
Race (NIH/OMB) Asian	0 Participants n=189 Participants	0 Participants n=183 Participants	0 Participants n=372 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=189 Participants	0 Participants n=183 Participants	0 Participants n=372 Participants
Race (NIH/OMB) Black or African American	189 Participants n=189 Participants	183 Participants n=183 Participants	372 Participants n=372 Participants
Race (NIH/OMB) White	0 Participants n=189 Participants	0 Participants n=183 Participants	0 Participants n=372 Participants
Race (NIH/OMB) More than one race	0 Participants n=189 Participants	0 Participants n=183 Participants	0 Participants n=372 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=189 Participants	0 Participants n=183 Participants	0 Participants n=372 Participants
Region of Enrollment South Africa	189 participants n=189 Participants	183 participants n=183 Participants	372 participants n=372 Participants
Sex acts in past 30 days	4 Acts n=189 Participants	4 Acts n=183 Participants	4 Acts n=372 Participants
Contraception Injectable	139 Participants n=189 Participants	140 Participants n=183 Participants	279 Participants n=372 Participants
Contraception Oral	43 Participants n=189 Participants	32 Participants n=183 Participants	75 Participants n=372 Participants
Contraception Sterilized	7 Participants n=189 Participants	11 Participants n=183 Participants	18 Participants n=372 Participants
HSV-2 prevalence	174 Participants n=182 Participants • A total of 9 participants had equivocal results and 2 had missing results.	159 Participants n=179 Participants • A total of 9 participants had equivocal results and 2 had missing results.	333 Participants n=361 Participants • A total of 9 participants had equivocal results and 2 had missing results.
HPV prevalence	20 Participants n=186 Participants • Total of 5 participants had equivocal and 2 had missing results.	11 Participants n=179 Participants • Total of 5 participants had equivocal and 2 had missing results.	31 Participants n=365 Participants • Total of 5 participants had equivocal and 2 had missing results.

PRIMARY outcome

Timeframe: Between 2012 to 2015, up to 28 months

Population: Intent to treat population and the per protocol population (excluding all subsequent data collected from participants who were not dispensed product for more than 120 days).

The primary endpoint is the mean number of returned used applicators per month. Since participants in the intervention arm followed two and three monthly schedule (as opposed to monthly in the intervention arm), the number of returned used applicators per month for each participant will be estimated as the total number of returned applicators at that visit divided by the number of days since the previous visit, multiplied by 30. Thus a uniform distribution of gel use will be assumed in participants whom we did not see monthly. Intent to treat and per protocol analyses were carried out of this outcome. Intent to treat population includes all participants who were randomized, met pre-randomization eligibility criteria and who have post-enrollment follow-up data. The per protocol population is a subset of the intent to treat population.The per-protocol analysis excluded visits where no gel had been dispensed for >120 days.

Outcome measures

Measure	Intervention n=189 Participants 1% tenofovir gel provision through a public sector family planning services with 2-3 monthly provision and monitoring and the use of QI methodology to promote reliable service delivery 1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either: * Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or * The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).	Control n=183 Participants monthly 1% tenofovir gel provision and monitoring through CAPRISA research clinics 1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either: * Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or * The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).
Mean Number of Returned Used Applicators Per Month (i.e in 30 Days) Intent to treat analyses	5.2 Used gel applicators per month Interval 4.7 to 5.7	5.7 Used gel applicators per month Interval 5.2 to 6.2
Mean Number of Returned Used Applicators Per Month (i.e in 30 Days) Per protocol analyses	5.5 Used gel applicators per month Interval 5.0 to 6.1	5.8 Used gel applicators per month Interval 5.3 to 6.3

SECONDARY outcome

Timeframe: Between 2012 and 2015, up to 28 months

Population: Intent to treat population(all participants who were randomized, met pre-randomization eligibility criteria and who have post-enrollment follow-up data).

Time to HIV infection was calculated as the difference between estimated date of infection (midpoint between the last negative HIV test date and the first confirmed positive HIV test date) and enrolment date, plus one. Where a participant has a positive PCR and a negative rapid test on the same date, the date of infection is calculated as 14 days prior to this date. Women who do not become HIV positive before their last study visit will be censored on the day of their last negative HIV test. Their follow-up time will be calculated as the difference between date of censoring and enrolment date, plus one.

Outcome measures

Measure	Intervention n=189 Participants 1% tenofovir gel provision through a public sector family planning services with 2-3 monthly provision and monitoring and the use of QI methodology to promote reliable service delivery 1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either: * Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or * The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).	Control n=183 Participants monthly 1% tenofovir gel provision and monitoring through CAPRISA research clinics 1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either: * Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or * The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).
HIV Incidence Rates	3.5 Incidence rate/100 women years Interval 1.8 to 6.0	3.6 Incidence rate/100 women years Interval 1.9 to 6.3

SECONDARY outcome

Timeframe: Between 2012 and 2015, up to 28 months

Population: Intent to treat population(all participants who were randomized, met pre-randomization eligibility criteria and who have post-enrollment follow-up data).

Time to pregnancy, was as the difference between the estimated date of conception and the enrolment date, plus one. The date of conception was defined as 14 days after the last normal menstrual period or the estimated date of delivery minus 40 weeks if the first date of last normal menstrual period is not available or the midpoint between the date of the first positive pregnancy test and the date of the previous negative pregnancy test. The censoring time for a woman who did not become pregnant during the study equals the difference between the calculated censoring date and the enrolment date, plus one.

Outcome measures

Measure	Intervention n=189 Participants 1% tenofovir gel provision through a public sector family planning services with 2-3 monthly provision and monitoring and the use of QI methodology to promote reliable service delivery 1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either: * Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or * The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).	Control n=183 Participants monthly 1% tenofovir gel provision and monitoring through CAPRISA research clinics 1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either: * Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or * The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).
Pregnancy Incidence Rates	4.9 Incidence rate/100 women years Interval 2.8 to 7.9	5.1 Incidence rate/100 women years Interval 2.9 to 8.3

SECONDARY outcome

Timeframe: Between 2012 and 2015, up to 28 months

Population: This is a subset of intent to treat population. It includes all participants who returned used gel applicators and also reported sex during follow-up.

Self-reported adherence to the tenofovir gel dosing strategy.Gel adherence was defined as the estimated proportion of reported sex acts covered by two gel doses and calculated for each woman by dividing half the number of returned used applicators each month by the number of reported sex acts that month.For participants attending 2-3 monthly clinic visits, their number of gels used in the last 30 days will be estimated as the total number of returned used gels, divided by the number of days between the current and the previous visit, times 30.

Outcome measures

Measure	Intervention n=188 Participants 1% tenofovir gel provision through a public sector family planning services with 2-3 monthly provision and monitoring and the use of QI methodology to promote reliable service delivery 1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either: * Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or * The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).	Control n=181 Participants monthly 1% tenofovir gel provision and monitoring through CAPRISA research clinics 1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either: * Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or * The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).
Percentage of Participants Achieving Adherence >80%.	70.2 percentage of participants Interval 63.1 to 76.7	65.2 percentage of participants Interval 57.8 to 72.1

SECONDARY outcome

Timeframe: Between 2012 and 2015, up to 28 months

Population: All participants who became HIV infected

This is mean log transformed HIV viral load measured at the first visit post HIV infection.

Outcome measures

Measure	Intervention n=12 Participants 1% tenofovir gel provision through a public sector family planning services with 2-3 monthly provision and monitoring and the use of QI methodology to promote reliable service delivery 1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either: * Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or * The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).	Control n=12 Participants monthly 1% tenofovir gel provision and monitoring through CAPRISA research clinics 1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either: * Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or * The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).
HIV Viral Load Among HIV Seroconverters	4.4 log10 copies/ml Standard Deviation 1.3	4.8 log10 copies/ml Standard Deviation 0.9

SECONDARY outcome

Timeframe: Between 2012 and 2015, up to 28 months

Population: Due to lack of funding, tenofovir resistance testing was not done in this study. However, we do have stored samples to fall back onto, should we secure funding.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Between 2012 and 2015, up to 28 months

Population: This is the subset of intent to treat population. It includes all participants who had HPV negative results at randomisation.

For the calculation of the incidence rate, seroconversion was assumed to have occurred at the midpoint between the first positive HPV test and the previous HPV negative test.

Outcome measures

Measure	Intervention n=166 Participants 1% tenofovir gel provision through a public sector family planning services with 2-3 monthly provision and monitoring and the use of QI methodology to promote reliable service delivery 1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either: * Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or * The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).	Control n=168 Participants monthly 1% tenofovir gel provision and monitoring through CAPRISA research clinics 1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either: * Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or * The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).
Human Papillomavirus Incidence Rates	1.0 Incidence rate/100 women years Interval 0.2 to 2.9	3.0 Incidence rate/100 women years Interval 1.4 to 5.8

SECONDARY outcome

Timeframe: All participants with drug levels at 12 months of follow-up

Population: All participants with drug levels measured at 12 months of follow-up

Percentage of participants with detectable tenofovir levels from vaginal samples at 12 months of follow-up. All drug levels below limit of quantification were considered to be undetectable.

Outcome measures

Measure	Intervention n=157 Participants 1% tenofovir gel provision through a public sector family planning services with 2-3 monthly provision and monitoring and the use of QI methodology to promote reliable service delivery 1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either: * Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or * The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).	Control n=156 Participants monthly 1% tenofovir gel provision and monitoring through CAPRISA research clinics 1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either: * Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or * The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).
Percentage of Participants With Detectable Tenofovir Levels From Vaginal Samples at 12 Months of Follow-up	39.5 percentage of participants Interval 32.2 to 47.3	43.6 percentage of participants Interval 36.1 to 51.4

SECONDARY outcome

Timeframe: At study completion, up to 28 months

Population: Participants who completed product acceptability questionnaire at study exit

This is the number of participants who reported that they liked the study product. The questionnaire was administered at study exit, therefore participants who were loss to follow-up and those who died could not complete the questionnaire.

Outcome measures

Measure	Intervention n=184 Participants 1% tenofovir gel provision through a public sector family planning services with 2-3 monthly provision and monitoring and the use of QI methodology to promote reliable service delivery 1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either: * Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or * The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).	Control n=177 Participants monthly 1% tenofovir gel provision and monitoring through CAPRISA research clinics 1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either: * Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or * The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).
Product Acceptability	180 Participants	170 Participants

Adverse Events

Intervention

Serious events: 13 serious events

Other events: 166 other events

Deaths: 0 deaths

Control

Serious events: 17 serious events

Other events: 181 other events

Deaths: 2 deaths

Serious adverse events

Measure	Intervention n=189 participants at risk 1% tenofovir gel provision through a public sector family planning services with 2-3 monthly provision and monitoring and the use of QI methodology to promote reliable service delivery 1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either: * Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or * The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).	Control n=183 participants at risk monthly 1% tenofovir gel provision and monitoring through CAPRISA research clinics 1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either: * Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or * The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).
Blood and lymphatic system disorders Neutropenia	0.53% 1/189 • Number of events 1 • Between 2012 and 2015, up to 28 months.	0.00% 0/183 • Between 2012 and 2015, up to 28 months.
Cardiac disorders Cardiac failure congestive	0.00% 0/189 • Between 2012 and 2015, up to 28 months.	0.55% 1/183 • Number of events 1 • Between 2012 and 2015, up to 28 months.
Gastrointestinal disorders Abdominal pain	0.53% 1/189 • Number of events 2 • Between 2012 and 2015, up to 28 months.	0.00% 0/183 • Between 2012 and 2015, up to 28 months.
Gastrointestinal disorders Anal sphincter atony	0.53% 1/189 • Number of events 1 • Between 2012 and 2015, up to 28 months.	0.00% 0/183 • Between 2012 and 2015, up to 28 months.
Gastrointestinal disorders Crohn's disease	0.00% 0/189 • Between 2012 and 2015, up to 28 months.	0.55% 1/183 • Number of events 1 • Between 2012 and 2015, up to 28 months.
Gastrointestinal disorders Gastritis	1.1% 2/189 • Number of events 2 • Between 2012 and 2015, up to 28 months.	0.00% 0/183 • Between 2012 and 2015, up to 28 months.
Hepatobiliary disorders Cholecystitis	0.00% 0/189 • Between 2012 and 2015, up to 28 months.	0.55% 1/183 • Number of events 1 • Between 2012 and 2015, up to 28 months.
Infections and infestations Acute sinusitis	0.53% 1/189 • Number of events 1 • Between 2012 and 2015, up to 28 months.	0.00% 0/183 • Between 2012 and 2015, up to 28 months.
Infections and infestations Oesophageal candidiasis	0.00% 0/189 • Between 2012 and 2015, up to 28 months.	0.55% 1/183 • Number of events 1 • Between 2012 and 2015, up to 28 months.
Infections and infestations Post procedural sepsis	0.00% 0/189 • Between 2012 and 2015, up to 28 months.	0.55% 1/183 • Number of events 1 • Between 2012 and 2015, up to 28 months.
Infections and infestations Postoperative wound infection	0.00% 0/189 • Between 2012 and 2015, up to 28 months.	0.55% 1/183 • Number of events 1 • Between 2012 and 2015, up to 28 months.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/189 • Between 2012 and 2015, up to 28 months.	0.55% 1/183 • Number of events 1 • Between 2012 and 2015, up to 28 months.
Injury, poisoning and procedural complications Hand fracture	0.00% 0/189 • Between 2012 and 2015, up to 28 months.	0.55% 1/183 • Number of events 1 • Between 2012 and 2015, up to 28 months.
Investigations Investigation	0.00% 0/189 • Between 2012 and 2015, up to 28 months.	0.55% 1/183 • Number of events 2 • Between 2012 and 2015, up to 28 months.
Metabolism and nutrition disorders Diabetic ketoacidosis	0.00% 0/189 • Between 2012 and 2015, up to 28 months.	0.55% 1/183 • Number of events 1 • Between 2012 and 2015, up to 28 months.
Musculoskeletal and connective tissue disorders Soft tissue mass	0.00% 0/189 • Between 2012 and 2015, up to 28 months.	0.55% 1/183 • Number of events 1 • Between 2012 and 2015, up to 28 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ameloblastoma	0.00% 0/189 • Between 2012 and 2015, up to 28 months.	0.55% 1/183 • Number of events 1 • Between 2012 and 2015, up to 28 months.
Nervous system disorders Cerebrovascular accident	0.00% 0/189 • Between 2012 and 2015, up to 28 months.	0.55% 1/183 • Number of events 1 • Between 2012 and 2015, up to 28 months.
Pregnancy, puerperium and perinatal conditions Complication of pregnancy	0.53% 1/189 • Number of events 1 • Between 2012 and 2015, up to 28 months.	0.00% 0/183 • Between 2012 and 2015, up to 28 months.
Pregnancy, puerperium and perinatal conditions Gestational hypertension	0.00% 0/189 • Between 2012 and 2015, up to 28 months.	0.55% 1/183 • Number of events 1 • Between 2012 and 2015, up to 28 months.
Pregnancy, puerperium and perinatal conditions Pre-eclampsia	0.00% 0/189 • Between 2012 and 2015, up to 28 months.	0.55% 1/183 • Number of events 1 • Between 2012 and 2015, up to 28 months.
Pregnancy, puerperium and perinatal conditions Premature labour	0.53% 1/189 • Number of events 1 • Between 2012 and 2015, up to 28 months.	0.55% 1/183 • Number of events 1 • Between 2012 and 2015, up to 28 months.
Pregnancy, puerperium and perinatal conditions Ruptured ectopic pregnancy	0.53% 1/189 • Number of events 1 • Between 2012 and 2015, up to 28 months.	0.00% 0/183 • Between 2012 and 2015, up to 28 months.
Psychiatric disorders Completed suicide	0.00% 0/189 • Between 2012 and 2015, up to 28 months.	0.55% 1/183 • Number of events 1 • Between 2012 and 2015, up to 28 months.
Psychiatric disorders Schizoaffective disorder	0.00% 0/189 • Between 2012 and 2015, up to 28 months.	0.55% 1/183 • Number of events 1 • Between 2012 and 2015, up to 28 months.
Renal and urinary disorders Calculus ureteric	0.00% 0/189 • Between 2012 and 2015, up to 28 months.	0.55% 1/183 • Number of events 1 • Between 2012 and 2015, up to 28 months.
Renal and urinary disorders Neurogenic bladder	0.53% 1/189 • Number of events 1 • Between 2012 and 2015, up to 28 months.	0.00% 0/183 • Between 2012 and 2015, up to 28 months.
Surgical and medical procedures Anoplasty	0.53% 1/189 • Number of events 1 • Between 2012 and 2015, up to 28 months.	0.00% 0/183 • Between 2012 and 2015, up to 28 months.
Surgical and medical procedures Caesarean section	2.6% 5/189 • Number of events 5 • Between 2012 and 2015, up to 28 months.	1.6% 3/183 • Number of events 3 • Between 2012 and 2015, up to 28 months.

Other adverse events

Measure	Intervention n=189 participants at risk 1% tenofovir gel provision through a public sector family planning services with 2-3 monthly provision and monitoring and the use of QI methodology to promote reliable service delivery 1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either: * Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or * The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).	Control n=183 participants at risk monthly 1% tenofovir gel provision and monitoring through CAPRISA research clinics 1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either: * Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or * The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).
Eye disorders Conjunctivitis allergic	2.1% 4/189 • Number of events 4 • Between 2012 and 2015, up to 28 months.	7.7% 14/183 • Number of events 14 • Between 2012 and 2015, up to 28 months.
Gastrointestinal disorders Abdominal pain	2.6% 5/189 • Number of events 5 • Between 2012 and 2015, up to 28 months.	9.3% 17/183 • Number of events 17 • Between 2012 and 2015, up to 28 months.
Gastrointestinal disorders Abdominal pain lower	7.4% 14/189 • Number of events 15 • Between 2012 and 2015, up to 28 months.	9.3% 17/183 • Number of events 19 • Between 2012 and 2015, up to 28 months.
Gastrointestinal disorders Diarrhoea	11.1% 21/189 • Number of events 22 • Between 2012 and 2015, up to 28 months.	24.6% 45/183 • Number of events 60 • Between 2012 and 2015, up to 28 months.
Infections and infestations Body tinea	6.9% 13/189 • Number of events 15 • Between 2012 and 2015, up to 28 months.	9.3% 17/183 • Number of events 18 • Between 2012 and 2015, up to 28 months.
Infections and infestations Gastroenteritis	5.8% 11/189 • Number of events 13 • Between 2012 and 2015, up to 28 months.	3.8% 7/183 • Number of events 7 • Between 2012 and 2015, up to 28 months.
Infections and infestations Influenza	7.9% 15/189 • Number of events 20 • Between 2012 and 2015, up to 28 months.	9.8% 18/183 • Number of events 22 • Between 2012 and 2015, up to 28 months.
Infections and infestations Nasopharyngitis	12.2% 23/189 • Number of events 27 • Between 2012 and 2015, up to 28 months.	36.1% 66/183 • Number of events 112 • Between 2012 and 2015, up to 28 months.
Infections and infestations Pelvic inflammatory disease	4.2% 8/189 • Number of events 9 • Between 2012 and 2015, up to 28 months.	8.7% 16/183 • Number of events 19 • Between 2012 and 2015, up to 28 months.
Infections and infestations Tonsillitis	10.6% 20/189 • Number of events 22 • Between 2012 and 2015, up to 28 months.	13.7% 25/183 • Number of events 31 • Between 2012 and 2015, up to 28 months.
Infections and infestations Upper respiratory tract infection	14.3% 27/189 • Number of events 36 • Between 2012 and 2015, up to 28 months.	13.1% 24/183 • Number of events 34 • Between 2012 and 2015, up to 28 months.
Infections and infestations Urinary tract infection	7.9% 15/189 • Number of events 15 • Between 2012 and 2015, up to 28 months.	9.3% 17/183 • Number of events 20 • Between 2012 and 2015, up to 28 months.
Infections and infestations Vaginitis bacterial	5.8% 11/189 • Number of events 12 • Between 2012 and 2015, up to 28 months.	7.7% 14/183 • Number of events 14 • Between 2012 and 2015, up to 28 months.
Infections and infestations Vulvovaginitis	13.2% 25/189 • Number of events 29 • Between 2012 and 2015, up to 28 months.	21.3% 39/183 • Number of events 49 • Between 2012 and 2015, up to 28 months.
Investigations Blood pressure diastolic increased	22.2% 42/189 • Number of events 50 • Between 2012 and 2015, up to 28 months.	14.8% 27/183 • Number of events 31 • Between 2012 and 2015, up to 28 months.
Investigations Blood pressure increased	11.6% 22/189 • Number of events 26 • Between 2012 and 2015, up to 28 months.	6.0% 11/183 • Number of events 13 • Between 2012 and 2015, up to 28 months.
Investigations Blood pressure systolic increased	22.2% 42/189 • Number of events 53 • Between 2012 and 2015, up to 28 months.	10.9% 20/183 • Number of events 27 • Between 2012 and 2015, up to 28 months.
Metabolism and nutrition disorders Abnormal loss of weight	5.8% 11/189 • Number of events 13 • Between 2012 and 2015, up to 28 months.	5.5% 10/183 • Number of events 13 • Between 2012 and 2015, up to 28 months.
Musculoskeletal and connective tissue disorders Arthralgia	2.1% 4/189 • Number of events 5 • Between 2012 and 2015, up to 28 months.	11.5% 21/183 • Number of events 25 • Between 2012 and 2015, up to 28 months.
Musculoskeletal and connective tissue disorders Back pain	4.8% 9/189 • Number of events 11 • Between 2012 and 2015, up to 28 months.	10.4% 19/183 • Number of events 19 • Between 2012 and 2015, up to 28 months.
Nervous system disorders Headache	14.8% 28/189 • Number of events 30 • Between 2012 and 2015, up to 28 months.	33.9% 62/183 • Number of events 91 • Between 2012 and 2015, up to 28 months.
Reproductive system and breast disorders Genital ulceration	5.3% 10/189 • Number of events 10 • Between 2012 and 2015, up to 28 months.	8.2% 15/183 • Number of events 16 • Between 2012 and 2015, up to 28 months.
Reproductive system and breast disorders Vaginal discharge	35.4% 67/189 • Number of events 91 • Between 2012 and 2015, up to 28 months.	39.9% 73/183 • Number of events 102 • Between 2012 and 2015, up to 28 months.
Respiratory, thoracic and mediastinal disorders Cough	5.8% 11/189 • Number of events 12 • Between 2012 and 2015, up to 28 months.	14.2% 26/183 • Number of events 33 • Between 2012 and 2015, up to 28 months.
Vascular disorders Hypertension	9.5% 18/189 • Number of events 18 • Between 2012 and 2015, up to 28 months.	6.0% 11/183 • Number of events 14 • Between 2012 and 2015, up to 28 months.

Additional Information

Nonhlanhla Yende-Zuma

CAPRISA

Phone: +27 31 260 4392

Email: nonhlanhla.yende@caprisa.org

Results disclosure agreements

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