New infections by HIV occurred at a low rate of about 1 per 100 person-years among people taking Truvada for pre-exposure prophylaxis (PrEP), with seroconversions mainly seen when they stopped taking their tablets, according to an analysis of more than 30 studies and demonstration projects presented last week at the ASM 2016 Boston Microbiology conference.
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 have not taken Truvada effectively and regularly. In one study open-label extension of the iPrEx, anyone who took Truvada at least 4 times a week was infected. However, in use in the real world, a man in Toronto, Canada was contaminated by a multidrug resistant strain of HIV despite very clear signs of adherence consistent with PreP.
Scott McCallister and colleagues at Gilead Sciences conducted an analysis of HIV seroconversion rates across a number of studies and demonstration projects using PrEP in various populations, comparing rates in clinical trials.
Seroconversion rates in carefully managed clinical studies ranged between 0,9 and 1,2 per 100 person-years (PY) among gay men and bisexual men in French Ipergay studies e UK PROUD ; 2,2 by 100 PY between gay / bi men and transgender women in International Study iPrEx; 0,5 and 1,2 by 100 PY among serodiscordant couples and heterosexual men and women in the studies PrEP and TDF2 Partners; and up to 4,7 by 100 PY among African women in the Fem-PrEP E VOICE studies, which were able to show a protective effect, which the researchers noted as profound.
This analysis included a total of 8478 participants who received treatment in an open-label (non-blind) study of Truvada as PrEP in 32 studies and demonstration projects in 16 countries; deferred persons or control arms or observation alone were excluded. Fully 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). Most (28) included men who have sex with men and 23 transgender women also included, with fewer studies including heterosexual women (12), heterosexual men (5), serodiscordant couples (6), and adolescents (1). Two were made after the US Food and Drug Administration approved tenofovir / emtricitabine for PrEP in July of 2012.
Dry 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 seronegative 32.
- A total of 67 cases of HIV infection occurred between daily seroconversions using Truvada once during the study period, for a rate of 0,95 per 100 PY (IC 95% 0,74-1,21).
- The mean age was 25.
- The highest rate of seroconversion - 7,7 by 100 PY - was observed in a study of young gay / bi men aged 18-25.
- Categorized by sex / gender, studies included 7002 men, 1378 women and 76 transsexuals; 64 gay men, 2 non-trans, heterosexual women and a transsexual woman became HIV positive, resulting in seroconversion rates of 1,03, 0,25 and 2,07 by 100 PY, respectively.
- 25 of which seroconverteram were black, 14 were white, 1 was Asian, 23 were crossbred and 4 were not categorized.
- The largest number of new infections (29) occurred in the US, with 18 in Peru and 5 or less in all other countries included.
- Most projects (17) - with a combined total of 2467 participants and 1315 Person-years of exposure - did not result in new infections.
- 9 projects (4230 participants, 3801 Person-years of exposure) had 0,1-1,5 seroconversion rates per 100 PY, while 6 projects (1781 participants, 1941 Person-years of exposure) had rates above 1,5 per 100 PY.
- Of the 67 seroconversions, 6 happened during the post-treatment phase of the projects - when participants were no longer taking Truvada.
- Among 32 seroconverters with dry blood analysis results, 17 had tenofovir diphosphate levels below the quantification limit, while 14 levels suggested that they took less than 2 Truvada tablets one week.
The overall 0,95 seroconversion rate per 100 person-years in these studies and demonstration projects “compares favorably with rates in controlled clinical trials,” the researchers concluded, and the low 0,25 seroconversion rate per 100 person years among women is “ encouraging ”.
“Available intracellular data have shown undetectable or very low [tenofovir diphosphate] levels in almost all those with seroconversion, they add.
Posted on Thursday, 30 June 2016 00: 00 on hivandhepatitis.com
Written by Liz Highleyman
Translated by Claudio Souza's original ASM Microbe 2016: HIV seroconversion Is Rare If PrEP Is Used Consistently
S McCallister, D Magnuson, R Guzman et al. HIV-1 seroconversion in 17 International Demonstration Projects with Pre-Exposure Prophylaxis (PREP) with Oral Emtricitabine / Tenofovir Disoproxil Fumarate (FTC / TDF). The ASM microbe. June 16-20, 2016. 371 session (abstract).