NATAP/CROI: Tenofovir PrEP Up to 99% Reduced HIV Risk

[Guest guest]

Subject: NATAP/CROI: Tenofovir PrEP Up to 99% Reduced HIV Risk

Adherence Critical to Protection From

HIV in Partners PrEP Trial of TDF and TDF/FTC

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 taken 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. 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.