Undetectable viral load means untransmittable HIV: Does this mean zero infection risk?
What is undetectable is untransmittable, and this extends to HIV risk in serodiscordant gay couples on effective antiretroviral treatment (ART), the PARTNER 2 study has shown.
There was zero transmission between gay couples when the HIV-positive partner had a fully suppressed viral load (<200 copies/mL) in the blood and despite 77,000 condomless anal intercourse between them in 1,600 couple-years of follow-up. [AIDS2018, abstract WEAX01]
“Finally, we’ve evidence to suggest that a patient on suppressive ART is sexually noninfectious, with no risk of transmission,” said PARTNER 2 principal investigator Dr Alison Rodger from the University College London, London, UK at the AIDS 2018 Congress.
What matters in HIV
The PARTNER 1 study first demonstrated in 2016 that in terms of viral load, undetectable equals untransmittable (U=U). The finding was not as robust for gay couples as it was for heterosexual couples. [JAMA 2016;316:171-181] The concern then by many was that U=U was counterintuitive for it encourages unprotected sex.
PARTNER 2 sought to find whether U=U holds true for gay couples with a suppressed viral load on ART. “We didn’t find a single case despite couples having sex without condoms,” said Rodger. The more important message, she added, is early treatment and adherence matter in HIV.
PARTNER 1 was conducted from September 2010 to May 2014, PARTNER 2 from May 2014 to April 2018. In PARTNER 1, there were 888 couples, 337 of whom were gay couples. As there were fewer gay couples than heterosexual couples in PARTNER 1, PARTNER 2 recruited 635 additional gay couples from 14 European countries for a total of 972 gay couples and 516 heterosexual couples. In both studies, one partner was HIV-positive, the other negative. HIV-negative partners were tested every 6-12 months for HIV, the HIV-positive partners for viral load. HIV-negative partners did not use pre- or post-exposure prophylaxis during the study course. HIV-negative partners at baseline who later tested positive for HIV were tested again to check if the virus was passed on to them by someone other than their HIV-positive partners on suppressive ART.
Key results from PARTNER-2
During follow-up, both HIV-positive and -negative men had STIs (27 and 23 percent, respectively) in about 20 percent of follow-up time. Thirty-seven percent of HIV-negative men reported that they were in an open relationship and had anal sex with other men without condoms. “Couples had on average 42 episodes of condomless sex a year or roughly 3–4 times a month,” said Rodger. “Over the entire follow-up period, we accumulated approximately 77,000 condomless sex acts, and in the absence of ART, we would have expected a significant number of transmissions to have occurred.”
While 15 of the HIV-negative men at baseline tested positive during follow-up, by looking at the genetic characteristics of the virus using phylogenetic sequencing, we could clearly see that not one HIV infection came from their HIV-positive regular partners on suppressive ART, she added.
“Due to the large study size, the precision of confidence we now have around the assessment of zero is dramatically improved. At the very worse-case scenario, the upper limit of the confidence interval for gay men engaging in condomless anal sex takes 420 years to have one transmission,” Rodger explained.
Of the 15 with new infections, three out of four reported recent sex without a condom and with a different partner. Six had a completely different HIV subtype.
Time for excuses over
For clinicians who may be hesitant to share with their patients the robust results of PARTNER 2, Rodger said, “the time for excuses is over.” As to how often viral load monitoring should be done to check for whether they’ve no longer detectable, Rodger said, “each patient is different.”
Generally, the higher the viral load the more likely the virus can be transmitted. ART stops the virus from replicating itself and spreading, effectively suppressing the viral load when ART is taken as prescribed. But the downside is that ART requires life-long therapy. When ART is stopped, patients experience a rebound.
Professor Jens Lundgren, co-author of PARTNER 2 from the University of Copenhagen in Copenhagen, Germany, said they’ve proven early on that early treatment works for HIV. “Now, we have the evidence that effective treatment prevents sexual transmission.”
To the community of gay men, Rodger’s message was loud and clear: “The risk of HIV transmission in gay men with suppressive ART is effectively zero. Our data support the message of the U=U campaign. I’ve to pay tribute to prevention access campaign for effectively promoting the science behind PARTNER 2 and other transmission studies so effectively.”