TDF/FTC (Truvada) is the only ARV combination currently approved by the FDA for use as preexposure prophylaxis (PrEP). The multinational Phase 3 DISCOVER Study compared the efficacy and safety of TAF/FTC (Descovy) with TDF/FTC, in HIV-uninfected cisgender MSM and transgender women at high risk of sexually acquired HIV.
The study randomized 5,313 cisgender MSM and 74 transgender women to receive TAF/FTC or TDF/FTC, in a double-blind protocol, PO once daily. Participants received clinical follow-up every 12 weeks, with HIV and STI testing, safety labs, adherence assessment and support, and HIV risk behavior assessment. The median age of participants was 34 years; 84% were white, 9% black, and 24% Latinx. At 48 weeks, 7 HIV infections were detected in the TAF/FTC arm, and 15 in the TDF/FTC arm. These results met the study's prespecified criteria for noninferiority.
Further analysis showed that 1 subject in the TAF/FTC arm and 4 in the TDF/FTC arm likely had acute but undetected HIV at baseline. Of the remaining subjects who were infected while taking PrEP, 5 in the TAF/FTC arm and 10 in the TDF/FTC had low levels of tenofovir (TFV)-diphosphate (DP) in dried blood spots at the time of HIV diagnosis, suggesting suboptimal PrEP adherence. One person in each study arm had medium or high TFV-DP levels at the time of HIV diagnosis.
In those with HIV infection, HIV resistance to FTC was found in 4 of the subjects who were thought to have HIV infection at baseline (all were in the TDF/FTC arm) and in none of the subjects who became infected with HIV while on PrEP. No resistance to TFV was found in any of those with HIV infection.
The HIV incidence rate for the TAF/FTC recipients was 0.08/100 person-years (95% confidence interval [CI]: 0.01, 0.28) and 0.45/100 PY (95% CI: 0.23, 0.78) for the TDF/FTC recipients. The study of course did not have a placebo arm, so investigators could not compare these findings with the incidence rate of a similar group of at-risk MSM who were not taking PrEP (investigators did show a comparison with CDC data, but it should be noted that the composition of the DISCOVER study group was quite different [eg, largely white] than the general at-risk male population in the United States).
Rates and types of symptomatic adverse effects were about the same in both arms. Renal impairment led to study discontinuation in 2 persons in the TAF/FTC group and 6 in the TDF/FTC arm, and, overall, markers of bone mineral density and renal function worsened modestly in the TDF/FTC group.
Clinical Bottom Line
The DISCOVER study demonstrated that TAF/FTC was noninferior to TDF/FTC as daily PrEP in MSM. It was not possible (ie, not ethical) to include a placebo arm in this study, unlike the earlier TDF/FTC PrEP studies in MSM, which included a placebo arm (iPrEx, IPERGAY) or a delayed PrEP arm (PROUD). Thus, the study cannot tell us how much TAF/FTC reduces HIV incidence compared with use of no chemoprophylaxis. Still, given the very high rates of STIs reported in this study, it appears that the study group was truly at substantial risk of HIV infection and, thus, that TAF/FTC was highly effective in this (mostly white) MSM cohort.
Questions about TAF/FTC that remain after this study include the following:
- Efficacy of TAF/FTC in populations other than MSM. Few trans women were included in the cohort, and no data on outcomes in trans women were presented. TAF/FTC as PrEP has not been studied at all in cisgender women, or in trans men.
- Potential for TAF/FTC use in intermittent (2:1:1) PrEP
- Safety and efficacy of TAF/FTC as PrEP in persons with renal dysfunction
Until we have data on TAF/FTC-PrEP use in these populations and these clinical scenarios, TAF/FTC should not be used as PrEP, or should be used with caution and very close monitoring. Note that TAF/FTC is not approved by the FDA for use as PrEP.
- Hare CB, Coll J, Ruane P, et al. The Phase 3 DISCOVER Study: daily F/TAF or F/TDF for HIV preexposure prophylaxis. In: Program and abstracts of the 2019 Conference on Retroviruses and Opportunistic Infections; March 4-7, 2109; Seattle. Abstract 104LB.