Model shows potential for substantial long-term HIV risk for serodifferent couples, even with new prevention tools

A mathematical model derived from current knowledge about the efficacy of various different prevention strategies has found that, based on these data, the risk of HIV transmission from a person living with HIV to an HIV-negative partner in a serodifferent couple could still be substantial over a ten-year period.

The authors state they undertook their research because people in serodifferent couples (often referred to as serodiscordant) require guidance about the likely impact of emergent prevention strategies (such as treatment as prevention and pre-exposure prophylaxis) alone, or in combination with each other, on the risk of HIV transmission.

They therefore estimated the risk of sexual transmission of HIV over one-year and ten-year periods for gay and heterosexual couples. The risk for heterosexual couples was modelled separately according to whether the male or female partner was living with HIV. The authors, publishing in the online edition of AIDS, emphasise that their model does not say what the actual risk will be. “This model was not designed to predict actual transmission risk for real-world serodiscordant couples over the course of a multiyear relationship,” they say. “Our intent is to emphasize how risk accumulates over time under various strategies and show the relative differences between strategies.”

Antiretroviral therapy is the intervention most likely to reduce the risk of sexual transmission of HIV in such couples but even with antiretroviral therapy for the partner living with HIV, the model computes that the ten-year risk of transmission in gay couples is 25%, with a 2% risk for heterosexual couples.

The only way of reducing transmission risk further was to use an unrealistic combination of prevention interventions.

“Modest HIV transmission probabilities per sex act translate into substantial cumulative risks over time,” comment the authors. “In serodiscordant couples, particularly those practicing anal sex, some strategies (including consistent condom use) may not provide sufficient levels of protection over an extended time when used alone.”

The study has a number of limitations. The authors acknowledge that they did not factor in whether the partner on HIV therapy achieved viral load suppression. They also used pessimistic estimates of the efficacy of various prevention strategies.

The model assumes the following reductions in risk: 80% with consistent condom use; 54% from circumcision of the male partner in a heterosexual couple; 73% for PrEP in heterosexual couples; 44% for PrEP in gay couples; and 96% from antiretroviral therapy when used by the partner with HIV.

The model also assumes that male circumcision reduces the risk of HIV by 73% for the HIV-negative partner in a gay relationship where the partner is exclusively insertive (top) over the whole ten-year period but even over one year surveys suggest that no more than one-in-five HIV-negative men maintain this role exclusively and one in seven are exclusively receptive: almost all studies show that circumcision has no protective effect in gay men in general.

The model also assumes that couples have penetrative sex six times per month. Gay couples had three episodes of receptive anal sex and three episodes of insertive anal sex.

A substantial risk of HIV transmission remained when couples relied on any single prevention strategy.

For gay men relying on condom use the risk of HIV transmission is 13% over one year, which adds up to 76% over ten years. When antiretroviral therapy is the sole prevention method used there is a 3% risk of transmission over one year, equating to a 25% risk over ten years.

A strategy of antiretroviral therapy with condoms, PrEP, circumcision and no receptive anal sex for the HIV-negative partner was needed to reduce the one-year risk to 0.1% and the ten-year risk to 1%.

For heterosexual couples with an HIV-negative male partner, the transmission risk with consistent condom use was 1% over one year and 11% over ten years. The one- and ten-year risks with antiretroviral therapy alone were 0.2% and 2%, respectively. The risk associated with PrEP alone was 2% over one year and 15% over ten years. Combining HIV therapy, condoms, PrEP and circumcision reduced the risk to 0.01% over one year and 0.1% over ten years.

In heterosexual couples where the female partner was HIV negative, consistent condom use alone resulted in a 1% one-year transmission risk and a 11% ten-year risk. HIV therapy alone was associated with a 0.2% and a 2% risk over one and ten years, respectively. A combination of antiretroviral therapy, condoms and PrEP reduced the one- and ten-year risks to 0.05% and 0.5%, respectively.

It is important to note that this model uses the most pessimistic assumptions about efficacy. The 44% efficacy of PrEP in gay men, for instance, was based on a study in which 50% of participants turned out not to have taken PrEP at all, and some more recent PrEP studies have found higher levels of sufficient adherence. The 96% efficacy for HIV therapy is based on the HPTN052 study in which the one transmission from a partner on treatment came from someone who had only just started treatment and was not virally suppressed. And some analyses of condom use suggest that efficacy can be improved with behavioural support.

The model used may be based on data that are already out of date. Recently, the PARTNER study showed no HIV transmissions in couples – gay and straight – when the HIV-positive partner was taking treatment and had an undetectable viral load. The results so far predict that in the most pessimistic likely scenario, the ten-year risk of transmission via anal sex is 10%.