Should HIV-Serodiscordant Couples Always Take Preventive Measures? Experts Debate

Executive Editor
Should HIV-Serodiscordant Couples Always Take Preventive Measures? Experts Debate

You're in a long-term, committed, monogamous relationship with a loving partner. You are not HIV infected, but your partner is. However, your partner is on stable antiretroviral therapy and has had a fully suppressed HIV viral load for several months.

Should the two of you still take measures (condoms, pre-exposure prophylaxis [PrEP], etc.) to reduce the risk of HIV transmission? Or is unprotected sex "safe enough"?

This is the question faced every day by thousands of couples in the U.S., and many thousands more throughout the world. It was also the issue vigorously debated by two prominent HIV clinician-researchers at a session entitled "Clinical Controversies" at IDWeek 2013. Roy "Trip" Gulick, M.D., took to the podium to argue the "pro" position in favor of continued prevention measures, while Paul Sax, M.D., was the standard-bearer for the "con" position.

The Argument for Continuing HIV Prevention Efforts

"What does suppressed HIV RNA really mean?" Gulick asked rhetorically. "The fact is, it does not mean that there's no virus in the blood." On the contrary, Gulick said, research has shown that HIV is still potentially present in the blood plasma of patients with an "undetectable" viral load (the term typically applied to a viral load below the level of detection in blood using widely available assays, usually less than 50 copies/mL), and that in fact cases of transmission have indeed occurred in this setting.

Further, Gulick added, virus has also been found to potentially be present in the tissue, semen and cervicovaginal fluid of patients with an undetectable plasma viral load, suggesting a very real risk of transmission during activities that traditionally expose an individual to HIV. He cited two examples, in published research, of HIV transmission from an infected partner with an undetectable viral load to a previously uninfected partner. (One was a case report from 2008; the other was a case report from 2012 involving an elite HIV controller.)

It is these sorts of data that feed into an HIV risk calculation model that was published in The Lancet in 2008, which found a small per-sexual-act risk of HIV transmission from females to males (1 in 50,000), males to females (1 in 25,000) and males to males (1 in 2,500) -- risks that appear remote until one takes into account that the average couple engages in sexual intercourse 100 times per year, Gulick said.

In addition, HIV is not the only transmissible pathogen that couples should be concerned about, Gulick noted. Hepatitis C, gonorrhea, herpes simplex (and other herpes viruses), and human papillomavirus are just a few examples of additional, harmful microorganisms that can bring potentially severe consequences to the HIV-infected and uninfected partner alike -- and against which safer sex is the best protection.

Gulick also took a cynical, if realistic, approach on the nature of human fallibility and relationships. Citing results from HPTN 052 and the Partners PrEP studies in which extra-relationship transmission of HIV occurred despite partners saying they were in a "committed" union, Gulick questioned the value of a public health approach based on a trust between partners that was often broken. "Do we really want to advise our HIV positive patients to have unsafe sex?" he asked.

To which Sax responded: Absolutely.

The Argument for Stopping HIV Prevention Efforts

Sax's counterargument largely revolved around a desire for what he considered a more realistic approach to prevention set within the modern context of the epidemic. In the early 1990s, when Sax and Gulick were both fellows at Massachusetts General Hospital, AIDS was a leading cause of death among youth and one of their mentors "basically made us feel that having unprotected sex was the equivalent of a death sentence," according to Sax.

"What Trip is telling you is that he's a product of his time," he said. But what the data show -- "in humans ... not in laboratory experiments, not in models" -- is that the actual HIV transmission rate from a virologically suppressed, HIV-infected person to an HIV-uninfected partner is "essentially zero," Sax asserted.

Sax cited a systematic review of 11 cohort studies that found zero cases of HIV transmission from an HIV-infected partner to an HIV-uninfected partner when the HIV-infected partner's viral load was below 400 copies/mL -- even if the partner was not on antiretroviral therapy.

Sax also referred to the well-known "Swiss statement," a landmark 2008 publication by highly respected clinician-researchers in Switzerland that unequivocally supported the argument that HIV cannot be transmitted sexually by an HIV-infected person who is fully compliant with therapy, is monitored by an attending physician, has had an undetectable viral load for at least six months, and has no other sexually transmitted diseases. "Precision, orderliness ... those are some of the things that come to mind when you say 'Switzerland.' You do not think, 'Oh, they are going to give irresponsible statements about public health,'" Sax said. "And you'll note that the people on this statement were people who are leading figures in our field of HIV research."

Sax also called attention to the 2011 publication of results from HPTN 052, which he suggested may be the most important HIV prevention study to date. That study (a randomized investigation comparing HIV transmission rates in early versus late treatment initiators who were in serodiscordant relationships) found seven cases of transmission in the delayed therapy group, but only one in the early treatment group -- and that single case occurred prior to the patient achieving virologic suppression.

Not that HPTN 052 was the only study to see such findings; Sax noted several additional studies published between 2008 and 2011 -- elucidated in a PLoS One article earlier this year -- showing a nonexistent transmission rate among patients with an undetectable viral load.

"Protection for these individuals is no longer needed," Sax concluded. "Are we actually going to be taking no risks in our life? ... Unprotected sexual intercourse is a viable option -- I'm not saying recommend that they stop using protection, but it's up to them -- for serodiscordant couples in long-term, monogamous relationships."

Where do you stand on the issue? The audience present at this debate -- a collection of infectious disease clinicians and researchers -- overwhelmingly sided with Gulick's assertion (by a margin of 63% to 37% among those who voted via remote controls located near many seats) that serodiscordant couples should perpetually take preventive measures to curb the risk of HIV transmission. But surely that won't be the final word on this challenging, complicated question.

Myles Helfand is the editorial director of and

Follow Myles on Twitter: @MylesatTheBody.