Research Article

Effectiveness and Safety of Tenofovir Gel, an Antiretroviral Microbicide, for the Prevention of HIV Infection in Women

See allHide authors and affiliations

Science  03 Sep 2010:
Vol. 329, Issue 5996, pp. 1168-1174
DOI: 10.1126/science.1193748
  • Fig. 1

    Screening, enrollment, randomization, and follow-up of the study participants.

  • Fig. 2

    Kaplan-Meier estimates of cumulative probability of HIV infection in the tenofovir and placebo gel arms. The table provides the cumulative number of HIV endpoints, corresponding HIV incidence rates, and effectiveness of tenofovir gel for each additional 6 months of follow-up.

  • Fig. 3

    Trends in coital frequency, condom use, and gel use (gel use by HIV status) in relation to duration of follow-up.

  • Table 1

    Baseline demographic characteristics, sexual history, and contraceptive use by study participants in the CAPRISA 004 tenofovir gel trial.

    SiteStudy arms
    Rural
    (n = 611 women)
    Urban
    (n = 278 women)
    P valueTenofovir
    (n = 445 women)
    Placebo
    (n = 444 women)
    P value
    Demographic characteristics
       ;Mean age (years)23.325.1<0.00124.223.60.131
       ;Monthly income <1000
       ;South African rand
    86.1%69.1%<0.00181.1%80.4%0.799
       ;Married6.5%3.6%0.0855.8%5.4%0.884
       ;Stable partner77.0%93.1%<0.00187.6%88.5%0.756
    Sexual behavior
       ;Mean age sexual debut17.317.70.01417.417.40.782
       ;Mean number sexual partners
       ;(lifetime)
    2.16.0<0.0013.03.60.780
       ;Mean age of oldest partner
       ;(past 30 days)
    26.429.6<0.00127.727.10.299
       ;Reported sex in the past
       ;7 days
    58.9%68.3%0.00763.6%60.1%0.301
       ;Always use condom during sex22.9%42.8%<0.00128.8%29.5%0.825
       ;New partner (past 30 days)0.5%2.5%0.0141.3%0.9%0.753
       ;Anal sex (past 30 days)0.5%0.4%1.0000.4%0.5%1.000
       ;HSV-2 prevalence47.6%59.6%0.00153.5%49.2%0.202
    Contraception
    Injectable83.179.90.606*80.7%83.6%0.288*
       ;Oral14.617.616.4%14.6%
       ;Tubal ligation2.12.52.9%1.6%
       ;Hysterectomy0.20.000.2%

    *P value applicable to comparison for all forms of contraception.

    • Table 2

      Impact of adherence and non-endpoint HIV infections on the effectiveness of tenofovir gel in HIV prevention in the CAPRISA 004 tenofovir gel trial.

      No. of HIV infections/women yearsHIV incidence
      TenofovirPlaceboNTenofovir gel (95% CI)Placebo gel (95% CI)Incidence rate ratioEffectiveness95% CIP value
      Overall effectiveness of tenofovir gel
         HIV endpoints38/680.660/660.78895.6 (4.0, 7.7)9.1 (6.9, 11.7)0.6139%6, 600.017
      Site-specific effectiveness
         Rural25/484.742/461.26115.2 (3.3, 7.6)9.1 (6.6, 12.3)0.5743%5, 670.023
         Urban13/195.918/199.52786.6 (3.5, 11.3)9.0 (5.3, 14.3)0.7426%-59, 670.380
      HIV endpoints by levels of adherence*
         High adherers
            (>80% gel adherence)
      11/259.225/269.43364.2 (2.1, 7.6)9.3 (6.0, 13.7)0.4654%4, 800.025
         Intermediate adherers
            (50–80% adherence)
      10/159.810/99.71816.3 (3.0, 11.5)10.0 (4.8, 18.4)0.6238%-67, 770.343
         Low adherers
            (<50% gel adherence)
      16/258.525/290.63676.2 (3.5, 10.1)8.6 (5.6, 12.7)0.7228%-40, 640.303
         Sensitivity analyses
         HIV endpoints plus
      HIV infection not meeting
         protocol definition
      39/680.660/660.78895.7 (4.1, 7.8)9.1 (6.9, 11.7)0.6337%4, 590.023
         HIV endpoints
            plus ineligibly enrolled
      40/720.163/698.610755.6 (4.0, 7.6)9.0 (6.9, 11.5)0.6238%7, 600.015
         HIV endpoints plus women
            with post-trial infection
      39/680.664/660.78895.7 (4.1, 7.8)9.7 (7.5, 12.4)0.5941%11, 610.015
         Per protocol analysis†32/589.253/575.48895.4 (3.7, 7.7)9.2 (6.9, 12.0)0.5941%7, 630.017
         All HIV infections‡43/720.176/698.810856.0 (4.3, 8.0)10.9 (8.6, 13.6)0.5545%19, 630.003
         Adjusted analysis§3860889Hazard ratio = 0.6337%6, 580.025

      *Adherence could not be calculated for the five women who reported no sex during their follow-up in the study.

      †Excludes all visits after 3 months’ interruption of drug supply.

      ‡All HIV infections = protocol-defined HIV endpoints (n = 98 women) + HIV infection not meeting protocol definition (n = 1 woman who did not have 2 RNA PCR results) + HIV infections among ineligibly enrolled women (n = 5 women) + posttrial HIV infections (n = 5 women) + window period HIV infections in eligible women (n = 8 women) + window period HIV infections in ineligibly enrolled women (n = 2 women).

      §Adjusted for the following baseline covariates: age, site, parity, number of sexual partners (past 30 days), presence of STI, anal sex, contraceptive method, HSV-2 antibody status, and condom use; HSV-2 status is indeterminate in four women and missing in five women.

      • Table 3

        Adverse events and other safety markers in the CAPRISA 004 tenofovir gel trial.

        Tenofovir gelPlacebo gelP value
        Events/participants/(percent with ≥ 1 event)Events/participants/(percent with ≥ 1 event)
        Number of adverse events2419/423/(95.1)2273/415/(93.5)0.32
        Deaths0/0/(0)1/1/(0.2)0.50
        Serious adverse events:
           total serious adverse events
        23/21/(4.7)16/16/(3.6)0.50
              Pregnancy-related serious adverse events8/8/(1.8)8/8/(1.8)1.00
              Grade 3* adverse events19/15/(3.4)18/16/(3.6)0.86
              Grade 4* adverse events4/4/(0.9)4/3/(0.7)1.00
        Common adverse events
           Influenza365/216/(48.5)314/220/(49.5)0.79
           Vaginal discharge203/156/(35.1)239/156/(35.1)1.00
           Headache126/93/(20.9)133/102/(23.0)0.53
           Urinary tract infection135/100/(22.5)120/93/(20.9)0.63
           Diarrhea and gastrointestinal infections91/75/(16.9)65/49/(11.0)0.02
           Upper respiratory tract infections162/114/(25.6)145/100/(22.5)0.31
        Genital adverse events
        Disrupted epithelium, e.g., genital ulceration18/18/(4.0)14/13/(2.9)0.47
           Intact epithelium, e.g., erythema48/41/(9.2)42/33/(7.4)0.40
           Urogenital symptoms (such as menorrhagia)312/210/(47.2)394/238/(53.6)0.06
           Vaginal candidiasis156/114/(25.6)187/130/(29.3)0.23
           Other182/131/(29.4)176/123/(27.7)0.60
        Laboratory parameters: any abnormality after randomization
           Hepatic
              Aspartate aminotransferase (AST)29/21/(4.7)36/29/(6.5)0.25
              Alanine transaminase (ALT)42/33/(7.4)50/40/(9.0)0.38
           Renal
              Raised creatinine3/3/(0.7)1/1/(0.2)0.62
              Low potassium119/95/(21.3)99/83/(18.7)0.36
              Abnormal sodium54/48/(10.8)43/41/(9.2)0.50
           Hematological
              Anemia52/34/(7.6)46/29/(6.5)0.60
              Neutropenia19/16/(3.6)13/11/(2.5)0.44
           Bone
              Low phosphate79/62/(13.9)65/51/(11.5)0.31
              Abnormal calcium16/15/(3.4)14/13/(2.9)0.85
              Fractures5/4/(0.9)2/2/(0.5)0.69
        Pregnancy rate per 100 women-years3.24.70.18
        Proportion of pregnancies resulting in live births66.751.90.38

        *Grade 3 and 4 adverse events refer to the grading for severity according to the Division of AIDS Table for Grading Adult and Pediatric Adverse Events, 2004 (http://rsc.tech-res.com/safetyandpharmacovigilance/).

        Additional Files


        • Effectiveness and Safety of Tenofovir Gel, an Antiretroviral Microbicide, for the Prevention of HIV Infection in Women
          Quarraisha Abdool Karim, Salim S. Abdool Karim, Janet A. Frohlich, Anneke C. Grobler, Cheryl Baxter, Leila E. Mansoor, Ayesha B.M. Kharsany, Sengeziwe Sibeko, Koleka P. Mlisana, Zaheen Omar, Tanuja N Gengiah, Silvia Maarschalk, Natasha Arulappan, Mukelisiwe Mlotshwa, Lynn Morris, Douglas Taylor, on behalf of the CAPRISA 004 Trial Group

          Supporting Online Material

          This supplement contains:
          Materials and Methods
          Table S1
          References

          This file is in Adobe Acrobat PDF format.

        Navigate This Article