Final Results of the PARTNER 2 Study Confirm Undetectable = Untransmittable (U=U) (5/19)

Christopher J. Hoffmann, MD, MPH, Johns Hopkins University School of Medicine

Dr. Alison Rodger presented the final results of the PARTNER2 study at the 22nd International AIDS Conference in Amsterdam in July 2018. The findings of the study increased the precision of estimates for the risk of HIV transmission during condomless anal sex between serodifferent gay men when the man with HIV has a viral load <200 copies/mL. At the AIDS Conference, Rodger reported that there were zero linked HIV transmissions during approximately 77,000 acts of condomless anal sex.

Rodger and colleagues have now published these results in an article that provides important details about the study population [Rodger A, Cambiano V, Bruun, T, et al. Lancet. 2019 May 04;393(10183)]. The PARTNER2 study recruited serodifferent gay men between September 2010 and July 2017 from 75 clinical sites in 14 European countries. Gay men with HIV were eligible if they were taking antiretroviral therapy (ART) and expected to stay on it, and they had condomless penetrative sex (anal receptive without ejaculation, anal receptive with ejaculation, and insertive anal) in the past month with a partner who did not have HIV. Data on demographics, sexual behavior, ART, viral load, CD4 count, and sexually transmitted infections (STIs) were collected at baseline and every 4 to 6 months. Men with HIV were expected to have viral load testing every 6 to 12 months, and their partners without HIV were expected to have HIV testing every 6 to 12 months. Phylogenetic testing was performed when there was evidence of seroconversion to determine whether the transmission was linked within the couple.

The primary analysis estimated the risk of phylogenetically linked HIV transmission during the follow-up period. Criteria for inclusion of a couple in the follow-up period were as follows:

  • The couple reported condomless anal sex.
  • The man with HIV had viral load testing in the past 12 months.
  • The most recent viral load for the man with HIV was <200 copies/mL.
  • The man who did not have HIV had HIV testing in the past 12 months.
  • The man who did not have HIV did not use pre- or post-exposure prophylaxis (PrEP or PEP).

Of the 972 gay male couples who participated, 88% were white, the median age was about 40 years, and 97% had viral loads <50 copies/mL at enrollment. There were 2,072 couple-years of follow-up and approximately 76,000 episodes of condomless sex during eligible observation periods. Approximately 25% reported an STI during the most recent follow-up period, and 4% of men who did not have HIV reported injection drug use.

There were 15 incident HIV infections detected, none of which were linked phylogenetically to the partner with HIV in the study, resulting in an estimated risk of transmission of zero, with an upper bound of the risk estimate of 0.23 per 100 couple-years for condomless anal sex when the man with HIV has a viral load <200 copies/mL (95% confidence interval). In other words, the researchers reported a possible risk of zero and a maximum risk of one transmission of HIV per 435 years of condomless anal sex; this was interpreted by the authors as follows: “Our findings provide conclusive evidence that the risk of HIV transmission through anal sex when HIV viral load is suppressed is effectively zero.” Without virologic suppression due to ART, 472 within-couple transmissions would have been expected.

Important caveats to consider are that the study population was older (median age 40 years) and the individuals with HIV had been taking ART for several years. Both characteristics are associated with continued viral suppression. Other populations may struggle to maintain a viral load <200 copies/mL and may need greater support to adhere to ART regimens and achieve and maintain the virologic suppression required for U=U.