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Not using Descovy for HIV PrEP defies logic

Issue: March 2018

ByStephen M. Smith, MD

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Recently, the Canadian HIV Trials Network published its guidelines for pre-exposure prophylaxis, or PrEP, and nonoccupational post-exposure prophylaxis.

PrEP for HIV infection has been studied extensively. Once-daily tenofovir/emtricitabine (TDF/FTC) has been used almost exclusively in these studies.

Clinical trials of TDF/FTC conducted between 2010 and 2012 yielded different results.

In two studies of heterosexual women — FEM-PrEP and VOICE — TDF/FTC had no effect on HIV-1 transmission.

In iPrEx — a study of men who have sex with men (MSM) — TDF/FTC reduced HIV-1 transmission by 44%. TDF2, a study on heterosexuals, was affected by a low retention rate, but it did show a 62% reduction in HIV-1 infection among those completing the study.

Finally, in Partners PrEP — a study of serodiscordant heterosexual couples — TDF/FTC had 75% efficacy in preventing new HIV-1 infections.

Bone density was shown to decrease measurably in some of these studies. Breakthrough infections were often associated with resistance to TDF or FTC.

With these data in 2012, the FDA approved once-daily Truvada (Gilead Sciences) and, more recently, generic TDF/FTC for use in HIV-1-uninfected, at-risk individuals.

The Canadian guidelines differ little from those published by the U.S. Public Health Service in 2014. There, too, only TDF/FTC is recommended for PrEP. The Canadian guidelines state that Descovy (Gilead Sciences), which contains tenofovir alafenamide (TAF) with FTC, is not recommended for PrEP simply because TAF has not been studied for PrEP. Although it has not been studied for PrEP, TAF has been studied extensively for other purposes and has had similar or improved efficacy compared with TDF. The argument that TAF/FTC should not be used for PrEP is strange for the following reasons:

• TDF was approved by the FDA for HIV treatment based on very limited clinical trial data in patients with appreciable viral loads, despite the use of other antiretroviral medications.
• Monotherapy with TAF had a much greater effect on HIV-1 viral load than the addition of TDF to ART regimens.
• The TDF data on PrEP are not impressive. Even among monogamous, heterosexual discordant couples, TDF/FTC had limited efficacy. No clinical trial has demonstrated a clear protective effect in women. In MSM, the efficacy rate was only 44%.
• TDF has been shown to decrease bone density in many PrEP populations.
• TAF works very well in treatment of HIV-1.
• TAF produces similar body fluid levels of the active agent, tenofovir.
• TAF is safer than TDF.
• The FDA accepts bioequivalence and bioavailability studies.

To me, the argument that TAF/FTC should not be used in PrEP not only lacks logic but also suggests an ulterior motive. Perhaps, some researchers are concerned about the relative cost of TAF/FTC compared with Truvada. However, TDF/FTC has known substantial risks, especially when used over the long term, whereas TAF/FTC does not.

Truvada’s U.S. patent expires in 2021. Gilead started a TAF/FTC PrEP trial, called Discover, in late 2016. Presumably, the data from the Discover trial will be available before 2021.

Finally, as HIV therapy evolves, why not study a more active, perhaps longer acting combination of drugs for PrEP? After all, the idea of using two drugs, TDF and FTC, is not based on science, and no one any longer suggests using just two drugs for postoccupational exposure to HIV-1.

• References:
• Baeten JM, et al. N Engl J Med. 2012;doi:10.1056/NEJMoa1108524.
• Gallant JE, et al. Clin Infect Dis. 2003;doi:10.1086/378068.
• Grant PM, et al. Curr Opin HIV AIDS. 2016;doi:10.1097/COH.0000000000000248.
• Grant RM, et al. N Engl J Med. 2010;doi:10.1056/NEJMoa1011205.
• Marrazzo JM, et al. N Engl J Med. 2015;doi:10.1056/NEJMoa1402269.
• Ray AS, et al. Antiviral Res. 2016;doi:10.106/j.antiviral.2015.11.009.
• Ruane PJ, et al. J Acquir Immune Defic Syndr. 2013;doi:10.1097/QAI.0b013e3182965d45.
• Thigpen MC, et al. N Engl J Med. 2012;doi:10.1056/NEJMoa1110711.
• Van Damme L, et al. N Engl J Med. 2012;doi:10.1056/NEJMoa1202614.
• Wang H, et al. Medicine (Baltimore). 2016;doi:10.1097/MD.0000000000005146.

• For more information:
• Stephen M. Smith, MD, is the founder and medical director of the Smith Center for Infectious Diseases and Urban Health in East Orange, N.J., and an Infectious Disease News Editorial Board Member.

Disclosure: Smith reports no relevant financial disclosures.