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Tenofovir PrEP Reduces HIV Transmission Risk By Up To 99%: Adherence Critical to Protection From HIV in Partners PrEP Trial of TDF and TDF/FTC
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19th Conference on Retroviruses and Opportunistic Infections, March 5-8, 2012, Seattle
Mark Mascolini
Having detectable blood levels of tenofovir dramatically improved chances of protection from HIV among people taking tenofovir (TDF) or tenofovir/emtricitabine (TDF/FTC) as pre-exposure prophylaxis (PrEP) in the Partners PrEP trial [1]. That finding complements results of a FEM-PrEP analysis that implicated poor adherence as a major reason why TDF/FTC failed to protect high-risk women from HIV in that study (reviewed separately by NATAP) [2].
Partners PrEP enrolled 4758 HIV-discordant couples (one partner positive and one negative) in Kenya and Uganda and randomized positive partners to take daily oral TDF, TDF/FTC, or placebo. Compared with the placebo group, those taking TDF had a 67% lower risk of HIV infection and those taking TDF/FTC had a 75% lower risk (P < 0.0001 for both comparisons) [3]. TDF and TDF/FTC protected both women and men from HIV infection.
To determine how adherence reflected in blood levels of tenofovir affected HIV risk, Partners PrEP conducted this comparison of 17 people who became infected in the TDF-only arm, 12 who became infected in the TDF/FTC arm, and 198 randomly selected people from both arms who did not get infected with HIV during the study [1]. In the people who did get infected, researchers measured tenofovir levels from the visit when they tested positive. People in the control group had their tenofovir levels measured in study months 1, 3, 6, 12, 18, 24, 30, and 36 (908 samples in all). The assay used can detect TDF levels down to 0.3 ng/mL.
Among participants in this substudy who got infected with HIV during the trial, only 6 of 17 (35%) assigned to TDF and only 3 of 12 (25%) assigned to TDF/FTC had detectable tenofovir in plasma on the day they tested positive. In contrast, tenofovir could be measured in 363 of 437 samples (83%) of HIV-negative control participants assigned to TDF and in 375 of 465 samples (81%) from those assigned to TDF/FTC.
In the uninfected control group, median tenofovir concentrations were 70 ng/mL (interquartile range [IQR] 33 to 111) in the TDF-only arm and 67 ng/mL (IQR 16 to 99) in the TDF/FTC arm.
Among people randomized to take TDF alone, having a detectable drug level cut the risk of HIV infection 86% (95% confidence interval [CI]) 57% to 94%, P < 0.001) compared with having an undetectable level. Among people randomized to TDF/FTC, having a detectable tenofovir level sliced the HIV risk 90% (95% CI 56% to 98%) (P = 0.002). Adjusting these analyses for demographic and HIV risk factors did not change results.
A separate study of intracellular tenofovir concentrations in men who participated in the iPrEx trial of daily TDF/FTC PrEP found that an intracellular level of 15.6 fmol/M cells lowered the risk of HIV acquisition 90% when compared with the placebo group [4]. Taking TDF daily 7 days a week yielded tenofovir concentrations high enough to lower HIV risk 99%. Taking TDF 4 days a week yielded concentrations high enough to lower HIV risk 96%. The protection rate slipped to 76% with only 2 doses every week.
References
1. Donnell D, Baeten J, C Hendrix C, et al. Tenofovir disoproxil fumarate drug levels indicate PrEP use is strongly correlated with HIV-1 protective effects: Kenya and Uganda. 19th Conference on Retroviruses and Opportunistic Infections. March 5-8, 2012. Seattle. Abstract 30.
2. Van Damme L, Corneli A, Ahmed K, et al. The FEM-PrEP trial of emtricitabine/tenofovir disoproxil fumarate (Truvada) among African women. 19th Conference on Retroviruses and Opportunistic Infections. March 5-8, 2012. Seattle. Abstract 32LB.
3. Baeten J, Donnell D, Ndase P, et al. ARV PrEP for HIV-1 prevention among heterosexual men and women. 19th Conference on Retroviruses and Opportunistic Infections. March 5-8, 2012. Seattle. Abstract 29.
4. Anderson P, Liu A, Buchbinder S, et al. Intracellular tenofovir-DP concentrations associated with PrEP efficacy in MSM from iPrEx. 19th Conference on Retroviruses and Opportunistic Infections. March 5-8, 2012. Seattle. Abstract 31LB.
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