The Risk of HIV in Mixed-Status Couples

While low, studies suggest risk cannot be fully eliminated

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Clinical research has shown that antiretroviral therapy (ART) can significantly reduce the risk of HIV infection in mixed-status (serodiscordant) couples—where one partner is HIV-positive and the other is HIV-negative. Strategies include the reduction of infectivity of the HIV-infected partner by ensuring a sustained undetectable viral load (often referred to as treatment as prevention, or TasP), as well as the daily use of an antiretroviral pill to reduce HIV susceptibility in the uninfected partner (known as pre-exposure prophylaxis, or PrEP).

Also considered key are non-ART prevention tools, such as condoms and voluntary male circumcision (known to reduce HIV risk in uninfected men). While early research has shown that the benefits of ART can be great in mixed-status couples—with TasP reducing HIV risk by up to 96 percent and PrEP lowering risk by as much as 75 percent—some have questioned whether these figures will hold up in a real-world setting. 

Condomless Sex and HIV Risk

At the 2014 Conference on Retroviruses and Opportunistic Infections (CROI) in Boston, researchers with the ongoing PARTNER study showed 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.

However, even by the researchers' own admission, the figures are a bit tricky. 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) stood at 96 percent.

This translates to an estimated 4 percent risk of infection—and not the 0 percent that some might presume. For those engaging in anal sex, estimated risk increased to 10 percent. Subsequent studies have cast even greater doubt as to how well these prevention tools can reduce infection risk over the longer term.

Variations In Risk Between Heterosexual and Gay Couples

In a study conducted by the U.S. Centers for Disease Control and Prevention (CDC), scientists analyzed current data into 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 2 percent for heterosexuals and an astonishing 25 percent in gay couples. The findings were based on a number of evaluative assumptions, including:

  • 80 percent reduction in risk from condom usage
  • 96 percent reduction in risk when HIV-infected partners are on ART/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

It is important to note that variations in rates between heterosexual and gay couples are not confined solely to the greater likelihood of infection through anal sex, but to current research that suggests lower rates of PrEP among gay couples. The researchers concede that greater PrEP uptake and/or improved adherence sufficiency data may improve these estimates.

Additionally, a number of recent studies have strongly suggested that interim PrEP usage in MSM may have the same protective benefit as daily PrEP usage. If such results can be confirmed, as many are expecting, the impact on PrEP efficacy in MSM couples would be greatly enhanced.

Short- and Long-Term Risk Factors

The investigators further demonstrated that couples using only one prevention method had a far greater risk of infection, both in the short and long term. Among their findings:

  • Gay couples who relied solely on condoms had a 13 percent risk of HIV in one year and an astonishing 76 percent risk over 10 years, based on current consistency usage data. By contrast, heterosexual males were shown to have 1 percent and 11 percent risk, respectively.
  • Gay couples who relied solely on TasP had a 3 percent risk over one year and a 25 percent risk over 10 years. By comparison, heterosexual couples had a 0.2 percent and 2 percent risk, respectively.
  • Of gay couples who combined TasP, PrEP, and circumcision, used condoms consistently, and engaged in no receptive anal sex for the uninfected partner, HIV risk dropped to 0.1 percent over one year and 1 percent over 10 years.
  • Similarly, drops were seen in heterosexual couples who combined TasP, PrEP, circumcision, and consistent condom use. For men, the risk over one year was 0.1 percent and 1 percent over 10 years. Risk among women was even lower at 0.05 percent and 0.5 percent, respectively.

These results were supported, in part, by a 2014 analysis by the Sorbonne Université in Paris, which analyzed data from six different studies on the use of TasP among mixed-status heterosexual couples. The couples included in the study had sexual intercourse between three and 12 times per month, with 80 percent consistent condom usage.

The investigators concluded that the available data does not support the suggestion that ART can reduce HIV risk to zero. Instead, their analysis determines that, while the risk of infection is extremely low during the first two years, that risk can increase to 1 percent after 18 months. The study did not assess the long-term effectiveness of ART in serodiscordant gay couples.

Sources:

Baeten, J.; Donnell, D.; Ndase, P.; et al. "Antiretroviral Prophylaxis for HIV Prevention in Heterosexual Men and Women." New England Journal of Medicine. August 2, 2012; 367(5):399-410.

Rodger, A.: Bruun, T.; Cambiano, V.; et al. "HIV transmission risk through condomless sex if HIV+ partner on suppressive ART: PARTNER study." 21st Conference on Retroviruses and Opportunistic Infections (CROI); Boston, Massachusetts; March 3-6, 2014; abstract 153LB.

Lasry, A; Sansom, S.;  Wolitski,R.; et al. "HIV sexual transmission risk among serodiscordant couples: assessing the effects of combining prevention strategies." AIDS. June 14, 2014; 28(10):1521-1529.

Supervie, V.; Viard, J; Costagliola, D.; et al. "Heterosexual risk of HIV transmission per sexual act under combined antiretroviral therapy: systematic review and Bayesian modeling." Clinical Infectious Diseases. April 19, 2014; 223 [Epub ahead of print].

Molina, J; Fonsart, C.; Spire, B; et al. "On Demand PrEP With Oral TDF-FTC in MSM: Results of the ANRS Ipergay Trial." 2015 Conference on Retroviruses and Opportunistic Infections (CROI); July 24, 2015; Seattle, Washington; abstract 23LB

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