A meta-analysis of numerous major studies of pre-exposure prophylaxis against HIV has concluded what has become increasingly apparent in recent years: PrEP works. Publishing their findings in the journal AIDS, researchers included in their analysis 18 studies of PrEP, which comprised data from 39 articles and six conference abstracts and included 19,491 participants, of whom 11,901 received active drug.
The studies were either a randomized controlled trial, an open-label extension or a demonstration project testing PrEP containing TDF (in some studies, participants received just TDF instead of Truvada, which also contains emtricitabine). The research included injection drug users, men who have sex with men and transgender women, mixed-HIV status couples, women and heterosexual men. The trials were conducted in low-, middle- and high-income nations.
Across the placebo-controlled trials, PrEP was associated with a 51 percent reduction in the risk of HIV acquisition compared with receiving a placebo. Adherence significantly moderated the effectiveness of PrEP. Studies in which participants adhered at a high level saw a 70 percent HIV risk reduction, while those studies with moderate adherence levels saw some protection against the virus and studies with low adherence did not see any protection from PrEP.
PrEP was similarly effective across modes of acquisition of HIV; it was associated with a 66 percent reduction for rectal exposure to the virus and a 46 percent reduction for vaginal intercourse. There were no significant differences in PrEP effectiveness based on the sex of individuals, drug regimens or dosing strategies. However, there was only one study looking at intermittent, or intercourse-based, dosing of Truvada.
Adverse health events were similar between the PrEP and placebo arms of studies. Looking at studies in which participants received PrEP immediately or on a deferred basis, two studies saw occasional interruptions of PrEP taking due to medical events, such as gastrointestinal symptoms, among participants; however, in most cases these individuals resumed taking PrEP. Several studies reported small decreases in kidney function levels among PrEP users, although these declines were subclinical, meaning they did not lead to actual symptoms, and the levels returned to normal after these individuals stopped taking PrEP. Some studies also reported small decreases in liver function and bone mineral density among those taking PrEP; both of these effects were also subclinical.
Six trials looked at reported cases of resistance to the two components of Truvada, emtricitabine and tenofovir. Eight (18 percent) of 44 individuals who turned out to be acutely infected when enrolling in the study showed resistance to either drug, including two people who received the placebo and six people who received PrEP. Additionally, six infections (2 percent) resistant to either drug occurred out of 533 new HIV cases in which the transmission took place after participants were randomized into the studies, including five mutations related to emtricitabine among those randomized to PrEP and one mutation among those randomized to the placebo.
PrEP was consistently not associated with an increase in sexual risk taking (also known as risk compensation), according to several measures, including reported condom use, number of sexual partners and sexually transmitted infection rates.
PrEP was also not linked to an increased risk in pregnancy-related adverse health events or the effectiveness of hormonal contraceptives.
The authors concluded: “PrEP is protective against HIV infection across populations, presents few significant safety risks, and [there is] no evidence of [associated] behavioral risk compensation. The effective and cost-effective use of PrEP will require development of best practices for fostering uptake and adherence among people at substantial HIV risk.”
To read the study abstract, click here.