CClinicalTrials.gg
Sign In
CompletedNCT01691768Updated Nov 26, 2019Results posted

Implementation Effectiveness and Safety of Tenofovir Gel Provision Through Family Planning Services

A Phase 2/3 interventional study of 1% tenofovir gel in HIV, sponsored by Centre for the AIDS Programme of Research in South Africa. Completed at 2 sites in South Africa. Open to female participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-11-26.

Sponsored by Centre for the AIDS Programme of Research in South Africa · Phase 2/3, Interventional, and Prevention

Phase
Phase 2/3
Study type
Interventional
Enrollment
372
Allocation
Randomized
Ages
18 Years and older
Sex
Female
01

Study summary

The purpose of this study is to assess the effectiveness of an implementation model which integrates tenofovir gel provision into existing family planning services.

Read the detailed description

The CAPRISA 008 trial is a two-arm, open-label, randomized controlled trial that is being conducted at the CAPRISA eThekwini and CAPRISA Vulindlela Clinics and their neighboring public sector family planning services in KwaZulu-Natal, South Africa. Up to 700 consenting sexually active, HIV-uninfected women aged 18 years and older who previously participated in an antiretroviral (ARV) prevention study will be enrolled and followed for a maximum 30 months. All women will be provided with 1% tenofovir gel but will be randomised to either receive their gel through a public sector family planning services with 2-3 monthly provision (intervention arm) or through the CAPRISA research clinics with monthly provision (control arm).

All women in the trial will be provided with the standard package of HIV prevention and reproductive health services. Participants in both study arms will be provided with a supply of single-use, pre-filled applicators of 1% tenofovir gel. While in the study, participants will be advised and supported to follow the CAPRISA 004 pre- and post-dosing strategy, namely BAT24, where the first dose of tenofovir gel is applied within 12 hours before anticipated coitus and a second dose as soon as possible but within 12 hours after coitus, with a maximum of two doses of gel in a 24-hour period.

The primary objective of this trial is to assess the effectiveness of an implementation model for tenofovir gel provision through family planning services.

02

Conditions studied

  • HIV

Keywords

  • microbicides
  • women
  • HIV prevention
  • PrEP
  • Tenofovir gel
03

In context

Lead sponsor

Centre for the AIDS Programme of Research in South Africa is the lead sponsor of 16 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
Female
Accepts healthy volunteers
Yes

Inclusion criteria

  • Age 18 years and older
  • Women who previously participated in an ARV prevention study
  • Currently utilizing or agreeing to attend designated public sector family planning services
  • Able and willing to provide first person informed consent to be screened for, and to enroll in, the study
  • Able and willing to provide adequate locator information for study retention purposes
  • Sexually active (at least one coital act in the last 3 months prior to screening)
  • HIV negative (by HIV testing performed by study staff within 30 days of enrollment)
  • Negative pregnancy test performed by study staff within 21 days of enrollment
  • Agree to use a non-barrier form of contraceptive
  • Agree to adhere to study visits and procedures

Exclusion criteria

Exclusion Criteria:

  • Has a creatinine clearance \< 50ml/min
  • Has any other condition that, based on the opinion of the Investigator or designee, would preclude provision of informed consent, make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives
05

Study design

Phase
Phase 2 / Phase 3
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
372 participants (actual)

Study arms

  • Experimental
    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

    Drug: 1% tenofovir gel

  • Active comparator
    Control

    monthly 1% tenofovir gel provision and monitoring through CAPRISA research clinics

    Drug: 1% tenofovir gel

Interventions

  • Drug1% 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).

06

What researchers measure

Primary outcomes

  1. Mean Number of Returned Used Applicators Per Month (i.e in 30 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.

    Time frame: Between 2012 to 2015, up to 28 months

Secondary outcomes

  1. HIV Incidence Rates

    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.

    Time frame: Between 2012 and 2015, up to 28 months

  2. Pregnancy Incidence Rates

    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.

    Time frame: Between 2012 and 2015, up to 28 months

  3. Percentage of Participants Achieving Adherence >80%.

    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.

    Time frame: Between 2012 and 2015, up to 28 months

  4. HIV Viral Load Among HIV Seroconverters

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

    Time frame: Between 2012 and 2015, up to 28 months

  5. Tenofovir Resistance Among HIV Seroconverters

    Time frame: Between 2012 and 2015, up to 28 months

  6. Human Papillomavirus Incidence Rates

    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.

    Time frame: Between 2012 and 2015, up to 28 months

  7. Percentage of Participants With Detectable Tenofovir Levels From Vaginal Samples 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.

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

  8. Product Acceptability

    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.

    Time frame: At study completion, up to 28 months

07

Results

Posted Nov 26, 2019
Limitations and caveats
The 2-3 monthly intervals between clinic appointments in the control arm is likely to introduce recall bias in this arm, unlike the monthly intervals in the intervention arm.

Participant flow

Participant flow — Overall Study
MilestoneInterventionControl
Started189183
Completed174167
Not completed1516
Withdrew: Death02
Withdrew: Lost to follow-up43
Withdrew: Withdrawal by subject109
Withdrew: Relocated01
Withdrew: Investigator decision11

Outcome measures

PrimaryMean Number of Returned Used Applicators Per Month (i.e in 30 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.

Time frame:
Between 2012 to 2015, up to 28 months
Reported as:
Least squares mean · Used gel applicators per month
Mean Number of Returned Used Applicators Per Month (i.e in 30 Days)
Used gel applicators per monthInterventionControl
Intent to treat analyses5.2 (4.7 to 5.7)5.7 (5.2 to 6.2)
Per protocol analyses5.5 (5.0 to 6.1)5.8 (5.3 to 6.3)
Statistical analysis
  • Intervention vs Control · Mean difference (final values): -0.47 · 95% CI -1.16 to 0.21The least square mean from the intervention arm was the minuend and the least square mean from the control arm was the subtrahend.
  • Intervention vs Control · Median difference (final values): -0.25 · 95% CI -0.98 to 0.48We calculated the difference in means between the two arms. The mean from the intervention arm was the minuend and the mean from the control arm was the subtrahend.
SecondaryHIV Incidence Rates

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.

Time frame:
Between 2012 and 2015, up to 28 months
Reported as:
Number · Incidence rate/100 women years
HIV Incidence Rates
Incidence rate/100 women yearsInterventionControl
HIV Incidence Rates3.5 (1.8 to 6.0)3.6 (1.9 to 6.3)
Statistical analysis
  • Intervention vs Control · z-test · p = 0.928 · Incidence rate ratio: 0.96 · 95% CI 0.40 to 2.35We calculated incidence rate ratio, where the HIV incidence rate for the intervention arm represents the numerator and the HIV incidence rate for the control arm represents the denominator.
SecondaryPregnancy Incidence Rates

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.

Time frame:
Between 2012 and 2015, up to 28 months
Reported as:
Number · Incidence rate/100 women years
Pregnancy Incidence Rates
Incidence rate/100 women yearsInterventionControl
Pregnancy Incidence Rates4.9 (2.8 to 7.9)5.1 (2.9 to 8.3)
Statistical analysis
  • Intervention vs Control · z-test · p = 0.895 · Incidence rate ratio: 0.96 · 95% CI 0.45 to 2.04We calculated incidence rate ratio, where the pregnancy incidence rate for the intervention arm represents the numerator and the pregnancy incidence rate for the control arm represents the denominator.
SecondaryPercentage of Participants Achieving Adherence >80%.

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.

Time frame:
Between 2012 and 2015, up to 28 months
Reported as:
Number · percentage of participants
Percentage of Participants Achieving Adherence >80%.
percentage of participantsInterventionControl
Percentage of Participants Achieving Adherence >80%.70.2 (63.1 to 76.7)65.2 (57.8 to 72.1)
Statistical analysis
  • Intervention vs Control · Regression, Log-binomial · p = 0.304 · Risk ratio (rr): 1.08 · 95% CI 0.94 to 1.24
SecondaryHIV Viral Load Among HIV Seroconverters

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

Time frame:
Between 2012 and 2015, up to 28 months
Reported as:
Mean · log10 copies/ml
HIV Viral Load Among HIV Seroconverters
log10 copies/mlInterventionControl
HIV Viral Load Among HIV Seroconverters4.4 ± 1.34.8 ± 0.9
Statistical analysis
  • Intervention vs Control · t-test, 2 sided · p = 0.455
SecondaryTenofovir Resistance Among HIV Seroconverters
Time frame:
Between 2012 and 2015, up to 28 months

No measurements were reported for this outcome.

SecondaryHuman Papillomavirus Incidence Rates

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.

Time frame:
Between 2012 and 2015, up to 28 months
Reported as:
Number · Incidence rate/100 women years
Human Papillomavirus Incidence Rates
Incidence rate/100 women yearsInterventionControl
Human Papillomavirus Incidence Rates1.0 (0.2 to 2.9)3.0 (1.4 to 5.8)
Statistical analysis
  • Intervention vs Control · z-test · p = 0.097 · Incidence rate ratio: 0.33 · 95% CI 0.06 to 1.32We calculated incidence rate ratio, where the HPV incidence rate for the intervention arm represents the numerator and the HPV incidence rate for the control arm represents the denominator.
SecondaryPercentage of Participants With Detectable Tenofovir Levels From Vaginal Samples 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.

Time frame:
All participants with drug levels at 12 months of follow-up
Reported as:
Number · percentage of participants
Percentage of Participants With Detectable Tenofovir Levels From Vaginal Samples at 12 Months of Follow-up
percentage of participantsInterventionControl
Percentage of Participants With Detectable Tenofovir Levels From Vaginal Samples at 12 Months of Follow-up39.5 (32.2 to 47.3)43.6 (36.1 to 51.4)
Statistical analysis
  • Intervention vs Control · Regression, Log-binomial · p = 0.462 · Risk ratio (rr): 0.91 · 95% CI 0.70 to 1.18
SecondaryProduct Acceptability

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.

Time frame:
At study completion, up to 28 months
Reported as:
Count of participants · Participants
Product Acceptability
ParticipantsInterventionControl
Product Acceptability180170

Adverse events

Collected over Between 2012 and 2015, up to 28 months.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Intervention0/189 (0%)13/189 (6.9%)166/189 (87.8%)
Control2/183 (1.1%)17/183 (9.3%)181/183 (98.9%)
Most frequent serious events
Showing 10 of 29
Most frequent serious events
EventInterventionControl
Caesarean sectionSurgical and medical procedures5/1893/183
GastritisGastrointestinal disorders2/1890/183
Cardiac failure congestiveCardiac disorders0/1891/183
Crohn's diseaseGastrointestinal disorders0/1891/183
CholecystitisHepatobiliary disorders0/1891/183
Oesophageal candidiasisInfections and infestations0/1891/183
Post procedural sepsisInfections and infestations0/1891/183
Postoperative wound infectionInfections and infestations0/1891/183
Ankle fractureInjury, poisoning and procedural complications0/1891/183
Hand fractureInjury, poisoning and procedural complications0/1891/183
Most frequent other events
Showing 10 of 25
Most frequent other events
EventInterventionControl
Vaginal dischargeReproductive system and breast disorders67/18973/183
NasopharyngitisInfections and infestations23/18966/183
HeadacheNervous system disorders28/18962/183
DiarrhoeaGastrointestinal disorders21/18945/183
Blood pressure diastolic increasedInvestigations42/18927/183
Blood pressure systolic increasedInvestigations42/18920/183
VulvovaginitisInfections and infestations25/18939/183
Upper respiratory tract infectionInfections and infestations27/18924/183
CoughRespiratory, thoracic and mediastinal disorders11/18926/183
TonsillitisInfections and infestations20/18925/183

Baseline characteristics

Intent to treat population was analyzed. All participants who were randomized and met the pre-enrollment eligibility criteria.

Age, Continuous
Age, Continuous(years)InterventionControlTotal
Mean29.5 ± 5.829.3 ± 5.329.4 ± 5.5
Sex: Female, Male
Sex: Female, Male(Participants)InterventionControlTotal
Female189183372
Male000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)InterventionControlTotal
American Indian or Alaska Native000
Asian000
Native Hawaiian or Other Pacific Islander000
Black or African American189183372
White000
More than one race000
Unknown or Not Reported000
Region of Enrollment
Region of Enrollment(participants)InterventionControlTotal
South Africa189183372
Sex acts in past 30 days
Sex acts in past 30 days(Acts)InterventionControlTotal
Median4 (3 to 8)4 (2 to 8)4 (2 to 8)
Contraception
Contraception(Participants)InterventionControlTotal
Injectable139140279
Oral433275
Sterilized71118
HSV-2 prevalence
HSV-2 prevalence(Participants)InterventionControlTotal
Count of participants174159333
HPV prevalence
HPV prevalence(Participants)InterventionControlTotal
Count of participants201131
08

Study locations

2 sites
  • CAPRISA eThekwini Clinical Research Site
    Durban, KwaZulu-Natal 4001, South Africa
  • CAPRISA Vulindlela Clinical Research Site
    Pietermaritzburg, KwaZulu-Natal, South Africa
09

References and documents

Publications

  • Abdool Karim Q, Abdool Karim SS, Frohlich JA, Grobler AC, Baxter C, Mansoor LE, Kharsany AB, Sibeko S, Mlisana KP, Omar Z, Gengiah TN, Maarschalk S, Arulappan N, Mlotshwa M, Morris L, Taylor D; CAPRISA 004 Trial Group. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science. 2010 Sep 3;329(5996):1168-74. doi: 10.1126/science.1193748. Epub 2010 Jul 19. Erratum In: Science. 2011 Jul 29;333(6042):524. PubMed 20643915 ↗
  • Mngadi KT, Singh JA, Mansoor LE, Wassenaar DR. Undue inducement: a case study in CAPRISA 008. J Med Ethics. 2017 Dec;43(12):824-828. doi: 10.1136/medethics-2016-103414. Epub 2017 Mar 27. PubMed 28348164 ↗
  • Mansoor LE, Abdool Karim Q, Mngadi KT, Dlamini S, Montague C, Nkomonde N, Mvandaba N, Baxter C, Gengiah TN, Samsunder N, Dawood H, Grobler A, Frohlich JA, Abdool Karim SS. Assessing the implementation effectiveness and safety of 1% tenofovir gel provision through family planning services in KwaZulu-Natal, South Africa: study protocol for an open-label randomized controlled trial. Trials. 2014 Dec 19;15:496. doi: 10.1186/1745-6215-15-496. PubMed 25527071 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Nov 26, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01691768
Lead sponsor
Centre for the AIDS Programme of Research in South Africa
Collaborators
CONRAD, Gilead Sciences, FHI 360, Institute for Healthcare Improvement
Responsible party
Dr Quarraisha Abdool Karim (Associate Scientific Director, Centre for the AIDS Programme of Research in South Africa) — Principal investigator
First posted
Sep 25, 2012
Start date
Oct 2012
Primary completion
Apr 2015
Completion
Dec 2015
Results posted
Nov 26, 2019
Last update
Nov 26, 2019

Study contacts

Quarraisha Abdool Karim, PhD
principal investigator · Centre for the AIDS Programme of Research in South Africa

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Nov 2019. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies from this sponsor

Centre for the AIDS Programme of Research in South Africa

Start the discussion