ASM Microbe 2016: HIV Seroconversion Is Rare If PrEP Is Used Consistently

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New HIV infections occurred at a low rate of about 1 per 100 person-years among people who took Truvada for pre-exposure prophylaxis (PrEP), with seroconversions mostly seen in those who stopped taking their pills, according to an analysis of more than 30 studies and demonstration projects presented last week at the ASM Microbe 2016 conference in Boston.

Research has shown that Truvada (tenofovir/emtricitabine) reduces the risk of HIV infection by more than 90% if used consistently.In studies to date, new HIV infections have occurred among people who did not actually take Truvada regularly. In an open-label extension of the iPrExtrial, no one who took Truvada at least 4 times per week became infected. However, in real-world use, a man in Toronto became infected with a multidrug-resistant strain of HIV despite apparently very consistent adherence to PrEP.

Scott McCallister and colleagues from Gilead Sciences did an analysis of HIV seroconversion rates in various studies and demonstration projects of PrEP use in diverse populations, comparing them to rates in clinical trials.

Seroconversion rates in carefully managed clinical studies have ranged from 0.9 and 1.2 per 100 person-years (PY) among gay and bisexual men in the French Ipergay and U.K. PROUD studies; 2.2 per 100 PY among gay/bi men and transgender women in the international iPrExtrial; 0.5 and 1.2 per 100 PY among serodiscordant couples and heterosexual men and women in the Partners PrEP and TDF2studies; and up to 4.7 per 100 PY among African women in the Fem-PrEP and VOICE trials, which were unable to show a protective effect, the researchers noted as background.

This analysis included a total of 8478 participants who received open-label (not blinded) once-daily Truvada PrEP in 32 studies and demonstration projects in 16 countries; people in deferred or observation-only control arms were excluded. Altogether they contributed 7061 cumulative person-years of tenofovir/emtricitabine exposure.

Most of these studies (19) were conducted in North America, followed by Africa (9), Europe (3), Asia (2), Australia (2), and South America (2). A majority (28) included men who have sex with men and 23 also included transgender women, with fewer studies including heterosexual women (12), heterosexual men (5), serodiscordant couples (6), and adolescents (1). All but 2 were conducted after the U.S. Food and Drug Administration approved tenofovir/emtricitabine for PrEP in July 2012.

Dried blood spots were used to measure levels of tenofovir diphosphate (the active form of the drug) in red blood cells, as an indicator of adherence; these were available for 32 seroconverters.

Results

The overall seroconversion rate of 0.95 per 100 person-years in these studies and demonstration projects "compares favorably with rates in controlled clinical trials," the researchers concluded, and the low seroconversion rate of 0.25 per 100 person years among women is "encouraging."

"Available intracellular data demonstrates undetectable or very low [tenofovir diphosphate] levels in nearly all of those with seroconversion," they added.

6/30/16

Reference

S McCallister, D Magnuson, R Guzman, et al. HIV-1 Seroconversion Across 17 International Demonstration Projects with Pre- Exposure Prophylaxis (PREP) with Oral Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF). ASM Microbe. June 16-20, 2016. Session 371 (abstract).