Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER 2)

Background

• the level of evidence for HIV transmission risk through condomless sex in serodifferent gay couples with the HIV-positive partner taking virally suppressive antiretroviral therapy (ART) is limited compared with the evidence available for transmission risk in heterosexual couples
• aim of the second phase of the PARTNER study (PARTNER2) was to provide precise estimates of transmission risk in gay serodifferent partnerships.

Methodology:

• PARTNER study was a prospective observational study done at 75 sites in 14 European countries
  • first phase of the study (PARTNER1; Sept 15, 2010, to May 31, 2014) recruited and followed up both heterosexual and gay serodifferent couples (HIV-positive partner taking suppressive ART) who reported condomless sex, whereas the PARTNER2 extension (to April 30, 2018) recruited and followed up gay couples only
    • first phase of the PARTNER study (PARTNER1) estimated the risks for different types of sex and in a broader population. The study reported no linked transmissions in 888 serodifferent couples (548 heterosexual and 340 gay couples) who reported condomless penetrative sex during 1238 couple-years of follow-up when the HIV-positive partner was on virally suppressive ART
      
      
  • PARTNER2 extension (to April 30, 2018) recruited and followed up gay couples only
    
    
    • at study visits, data collection included sexual behaviour questionnaires, HIV testing (HIV-negative partner), and HIV-1 viral load testing (HIV-positive partner)
      • if a seroconversion occurred in the HIV-negative partner, anonymised phylogenetic analysis was done to compare HIV-1 pol and env sequences in both partners to identify linked transmissions
        
        
      • couple-years of follow-up were eligible for inclusion if condomless sex was reported, use of pre-exposure prophylaxis or postexposure prophylaxis was not reported by the HIV-negative partner, and the HIV-positive partner was virally suppressed (plasma HIV-1 RNA <200 copies per mL) at the most recent visit (within the past year)
        
        
      • incidence rate of HIV transmission was calculated as the number of phylogenetically linked HIV infections that occurred during eligible couple-years of follow-up divided by eligible couple-years of follow-up
        
        
      • two-sided 95% CIs for the incidence rate of transmission were calculated using exact Poisson methods. Findings Between Sept 15, 2010, and July 31, 2017, 972 gay couples were 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)
        
        
      • during eligible couple-years of follow-up, couples reported condomless anal sex a total of 76 088 times. 288 (37%) of 777 HIV-negative men reported condomless sex with other partners. 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)
        
        
• Study author's conclusions
  • "... Our results provide a similar level of evidence on viral suppression and HIV transmission risk for gay men to that previously generated for heterosexual couples and suggest that the risk of HIV transmission in gay couples through condomless sex when HIV viral load is suppressed is effectively zero. Our findings support the message of the U=U (undetectable equals untransmittable) campaign, and the benefits of early testing and treatment for HIV..."

Notes:

• Partner 2 - also provides further evidence that detectable HIV RNA shedding may not correspond to infection risk
  • well recognised that HIV-positive people on ART with suppressed viral load in blood can have intermittent shedding and detectable HIV RNA in semen and other genital tract fluids
    • HIV RNA in semen has been detected in 6-8% of men with suppressed HIV-1 RNA concentrations in blood in the absence of STIs.
    • however, this study gives further evidence towards the hypothesis that scientific detection of small amounts of HIV RNA in semen does not appear to correlate with risk of HIV transmission if plasma viral load is suppressed. The finding of HIV RNA might be because the virus present is not whole virus, is not replication competent, or is present at insufficient levels to cause transmission (2)

Reference:

• Rodger AJ et al. Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER): final results of a multicentre, prospective, observational study. Lancet. 2019 May 2. pii: S0140-6736(19)30418-0
• Coombs RW et al Association between culturable human immunodeficiency virus type 1 (HIV-1) in semen and HIV-1 RNA levels in semen and blood: evidence for compartmentalization of HIV-1 between semen and blood. J Infect Dis. 1998; 177: 320-330.