The Risk of HIV in Mixed-Status Couples

Antiretroviral therapy (ART) and HIV transmission risk in mixed-status couples

Research has shown that antiretroviral therapy (ART) can significantly reduce the risk of HIV in serodiscordant couples (in which one partner is HIV-positive and the other is HIV-negative). Strategies include treatment as prevention (TasP), in which ART reduces the infectivity of the HIV-positive partner, and pre-exposure prophylaxis (PrEP), in which ART reduces the susceptibility in the HIV-negative partner.

The current body of evidence has shown that the benefits of ART can be great in mixed-status couples, effectively eliminating the risk of HIV if the virus is fully suppressed (undetectable).

Couple hugging in bed
kupicoo / Getty Images

PARTNER 1 Reports Zero Infections

At the 2014 Conference on Retroviruses and Opportunistic Infections (CROI) in Boston, researchers with the ongoing PARTNER1 study reported that among 767 mixed-status couples using TasP alone, not one infection occurred despite over 44,000 condomless sex acts. The study included both heterosexual and gay couples who reported an average of 37 to 43 condomless sex acts per year.

While the results of the PARTNER1 research strongly suggested that TasP alone could prevent HIV transmission, researchers at the time were reluctant to draw such conclusions.

Based on a number of highly variable factors—including the types of sex acts and whether ejaculation occurred or not—the confidence interval (used to measure the certainty of the estimates) was placed at 96 percent.

This translated to a 4 percent risk of infection. For those engaging in anal sex, the estimated risk increased to 10 percent. Subsequent studies cast even greater doubt as to how well TasP could reduce infections over the longer term.

Study Casts Doubt on TasP

In a study conducted by the Centers for Disease Control and Prevention (CDC), scientists analyzed current data on the efficacy of TasP, PrEP, and condoms in serodiscordant heterosexual and gay couples. The aim of the study was not to predict actual transmission risk in a real-world setting, but to demonstrate how risk accumulates over time—namely, after a one- and 10-year period.

Based on the number of potentially confounding factors, the likelihood of infection among mixed-status couples using ART alone was estimated to be two percent for heterosexuals and an astonishing 25 percent in gay couples. The findings were based on a number of assumptions, including:

  • 80 percent reduction in risk from condom usage
  • 96 percent reduction in risk when HIV-infected partners are on TasP
  • 73 percent reduction in risk for uninfected heterosexual partners on PrEP
  • 44 percent reduction in risk for uninfected gay partners on PrEP
  • 54 percent reduction in risk for the uninfected heterosexual male partner who is circumcised
  • 73 percent reduction in risk for the uninfected, circumcised gay male partner who is exclusively insertive ("top") during anal sex
  • An average of six penetrative sex acts per month

Based on these variables, the researchers suggested that the "real-world" risk of infection over 10 years was between 1 percent and 11 percent for heterosexual couples and a whopping 76 percent for gay couples. The news sent ripples of alarm through the research community, suggesting that TasP in a real-world setting was inherently flawed.

Others derided the study, claiming that the conclusions were based on the false assumption that gay men were less likely to benefit from PrEP due to their sexual practices.

This essentially compared apples to oranges, they argued, applying two different standards of measurement for gays and heterosexuals.

PARTNER2: The Game Changer

Between 2010 and 2018, the PARTNER2 study extended the PARTNER1 investigation by evaluating the effectiveness of TasP in gay couples only. The study was conducted among 782 gay couples in 14 countries in which the HIV-infected partner maintained an undetectable viral.

Of the partners on ART, 98 percent maintained greater than 90 percent adherence to treatment. All couples practiced condomless anal sex. None used PrEP.

By the end of the 18-month trial, not one HIV infection was reported among any of the couples despite the absence of condoms during anal sex.

Based on these results of the PARTNER1 and PARTNER2 studies, the researchers concluded that, irrespective of sexual orientation, the risk of HIV transmission when the viral load is fully suppressed is zero.

The results were communicated to the public under a new health campaign called "U=U" (Undetectable = Untransmittable).

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By James Myhre & Dennis Sifris, MD
Dennis Sifris, MD, is an HIV specialist and Medical Director of LifeSense Disease Management. James Myhre is an American journalist and HIV educator.