PrEP'd to reduce transmission
HIV is a disease of major importance in the UK—and despite increased HIV testing and a move towards earlier initiation of antiretroviral therapy, a reduction in new cases each year proved hard to achieve. While the prognosis is excellent, treatment is lifelong with inescapable rising costs to the NHS.
The PROUD study was designed to assess the effectiveness of PrEP, including the net effect of efficacy, adherence, and any change in sexual behaviour because of PrEP. This initial study was a pilot to test the feasibility of a large-scale trial; however, the unexpectedly large number of HIV infections enabled researchers to present findings on the effectiveness of PrEP. PROUD was an open-label randomised trial undertaken at 13 sexual health clinics in England. Eligibility criteria were: 18+ years; male at birth; previously attended the enrolling clinic; been screened for HIV and other sexually transmitted infections; HIV-negative in the previous 4 weeks or on the day of enrolment; reported anal intercourse without a condom in the previous 90 days and likely to have anal intercourse without a condom in the next 90 days.
Participants were randomly assigned (1:1) to either receive daily PrEP immediately or after a deferral period of 1 year. Neither participant nor researcher was blinded to the allocation of medication.
There were 544 participants (275 immediate, 269 deferred) enrolled between November 2012 and April 2014. Based on early evidence of effectiveness, the trial steering committee recommended in October 2014, that all deferred participants be offered PrEP. Follow-up for HIV incidence was complete for 243 (94%) of 259 patient-years in the immediate group versus 222 (90%) of 245 patient-years in the deferred group. HIV incidence was significantly lower in the immediate group (1·2 cases per 100 person-years, 90% CI 0·4–2·9) than in the deferred group (9·0 per 100 person-years, 90% CI 6·1–12·8; p=0·0001). This difference corresponds to a proportionate reduction of 86% (90% CI 64–96). No serious adverse drug reactions were recorded although 28 adverse events, most commonly nausea, headache, and arthralgia, resulted in interruption of PrEP. There was no detected difference in the occurrence of sexually transmitted infections between groups, despite a suggestion of risk compensation among some PrEP recipients. The findings strongly support the addition of PrEP to the standard of prevention for men who have sex with men at risk of HIV infection.
Undetectable equals untransmittable
Understanding the risk of HIV transmission through condomless sex in gay couples where one partner is HIV-positive and taking virally suppressive antiretroviral therapy (ART), and the other HIV-negative (serodifferent couple), is essential to reducing transmission of the virus. The PARTNER1 and later PARTNER2 studies were designed to provide precise estimates of transmission risk in gay serodifferent partnerships.
This prospective observational study was undertaken at 75 sites across 14 European countries. The initial phase (PARTNER1) recruited and followed up both heterosexual and gay serodifferent couples who reported condomless sex, whereas the PARTNER2 extension recruited and followed up gay couples only.
Data collection included sexual behaviour questionnaires, HIV testing (HIV-negative partner), and HIV-1 viral load testing (HIV-positive partner). The primary analysis was estimation of the incidence rate of HIV transmission through condomless anal sex. Couple-years of follow-up were included under the following circumstances:
There were 972 gay couples enrolled, of which 782 provided 1593 eligible couple-years of follow-up with a median follow-up of 2·0 years (IQR 1·1–3·5). At baseline, median age for HIV-positive partners was 40 years (IQR 33–46) and couples reported condomless sex for a median of 1·0 years (IQR 0·4–2·9). During eligible couple-years of follow-up, couples reported condomless anal sex a total of 76 088 times. Of 777 HIV-negative men, 288 (37%) reported condomless sex with other partners. In total, 15 new HIV infections occurred during eligible couple-years of follow-up, but none were phylogenetically linked within-couple transmissions, resulting in an HIV transmission rate of zero (upper 95% CI 0·23 per 100 couple-years of follow-up). Findings support the message of the U=U (undetectable equals untransmittable) campaign, and the benefits of early testing and treatment for HIV.