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Safety and Effectiveness of Vaginal Microbicides BufferGel and 0.5% PRO 2000/5 Gel for the Prevention of HIV Infection in Women: Results of the HPTN 035 Trial
Salim Abdool Karim*1, A Coletti2, B Richardson3, G Ramjee4, I Hoffman5, M Chirenje6, T Taha7, M Kapina8, L Maslankowski9, and L Soto-Torres10
1Ctr for the AIDS Prgm of Res in South Africa, Durban; 2Family Hlth Intl, Medford, MA, US; 3Univ of Washington, Seattle, US; 4South African Med Res Council, Durban; 5Univ of North Carolina at Chapel Hill, US; 6Univ of Zimbabwe, Harare; 7Johns Hopkins Univ Bloomberg Sch of Publ Hlth, Baltimore, MD, US; 8Ctr for Infectious Disease in Zambia, Lusaka; 9Univ of Pennsylvania, Philadelphia, US; and 10NIAID, NIH, Bethesda, MD, US
Background: The development of female initiated HIV
prevention methods is a high priority. The purpose of this study was to assess
the safety and effectiveness of 2 microbicides—BufferGel and 0.5% PRO 2000/5
gel—for the prevention of male to female HIV transmission.
Methods: A phase 2/2B, four-arm, randomized,
placebo-controlled trial was conducted in Malawi, South Africa, Zambia, Zimbabwe, and the US. The 3 study gel arms were double-blinded, while the no gel arm was
open label. The study participants were followed monthly for pregnancy, safety
assessments, and study product resupply; and quarterly to assess gel and condom
use and HIV infection. Gel products were temporarily discontinued at the time
of first positive pregnancy test. The primary analysis of HIV effectiveness is
a comparison of HIV incidence, in each active gel arm compared to each control
arm.
Results: We randomized 3099 women and followed them for
an average of 20.4 months with a retention rate of 93.6%. There were no
statistically significant differences in adverse events. Adherence to gel use
was 81% across gel arms. Condom use was 72% in gel arms and 81% in no gel arm (p
<0.05). There were 610 pregnancies for a rate of 11.3 per 100 woman-years. In
a per-protocol analysis excluding time off product (5.9% of total woman-years
of those on gel), 0.5% PRO 2000/5 Gel was 36% protective against HIV compared
to no gel (p = 0.04). The 0.5% PRO 2000/5 Gel was most
effective among women who reported low condom use and high gel adherence.
|
Intention-to-treat
analysis
|
HIV Events
[woman-years]
|
Incidence
per 100 woman-years
|
Hazards Ratio
vs Placebo
|
Hazards Ratio
vs No Gel
|
|
0.5% PRO 2000/5
Gel
|
36 [1332]
|
2.70
|
0.7 (0.5 to 1.1), p = 0.10
|
0.7 (0.4 to 1.0), p = 0.06
|
|
BufferGel
|
54 [1304]
|
4.14
|
1.1 (0.8 to 1.6), p = 0.63
|
1.1 (0.7 to 1.6), p = 0.78
|
|
Placebo Gel
|
51 [1305]
|
3.91
|
|
|
|
No Gel
|
53 [1318]
|
4.02
|
|
|
|
Overall
|
194 [5258]
|
3.69
|
|
|
Conclusions: Women in the 0.5% PRO 2000/5 Gel arm had a 30%
lower rate of HIV acquisition compared to controls, although not statistically
significant in the intent-to-treat analysis. BufferGel did not alter the risk
of HIV infection. Both products were safe.
|
