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Second analysis concludes that treatment doesn't eliminate the long-term risk of HIV transmission
Gus Cairns, 2014-05-31 07:40:00

A mathematical model that estimates the risk of HIV transmission from someone taking antiretroviral therapy reports that, on the basis of the few transmissions from heterosexual partners on treatment that have been reported, it is impossible to dismiss the risk of infection as zero.

The analysis in Clinical Infectious Diseases estimates that the highest-likely risk of HIV being transmitted is between 8.7 and 13 transmissions per 100,000 sex acts; in other words, from one in about 11,500 to one in about 7700 acts.

The researchers from INSERM (Institut National de la Santé et de la Recherche Médicale) in Paris calculate that this means the accumulated risk of HIV transmission would rise to over 1% after between 195 and 389 occasions of sex.

A couple who have vaginal sex around six times a month would take two and a half years to have sex 195 times, or five and a half years to have sex 389 times. A couple having sex three times a month would take double the time; a couple having sex twelve times a month would take half the time.

This is the second recent modelling study to warn that the long-term risk from a partner on antiretroviral therapy (ART), while very much lower than from a partner not on treatment, is not negligible, especially in the long term.

The other model, developed by the CDC in the USA, calculated the one- and ten-year risks of HIV infection in heterosexual and gay couples, and the mitigating effects of ART, condom use, circumcision and PrEP, by feeding in estimates of the likelihood of transmission, and the efficacy of the different prevention methods, from various studies.

The French researchers tackled the question by searching out the few reported cases of HIV transmission within a heterosexual couple where the HIV positive person was on ART, and where the virus was unequivocally shown to have come from them. They then calculated the highest-likely probability of transmission from someone on ART based on these cases.

The researchers found six trials that were set up sufficiently well to document such cases. They identified four cases of viral transmission from a partner on ART during 2773 person-years in 1672 heterosexual, discordant couples. (An additional 182 transmissions occurred when people were not taking ART). Four of the studies took place in Africa and one each in Spain and Brazil. Between 70 and 100% of subjects were virally undetectable at various time points. At the start of the studies, sexual frequency in subjects varied from three to twelve times a month. (In contrast, the American model assumed an unvarying frequency of six times a month).

In three of these transmissions, which were proven to come from the HIV positive partner by genetic analysis, that partner had been taking ART for less than six months. In the fourth transmission the person had been taking ART for less than a year. As the Swiss Statement says that people who have had an undetectable viral load and no sexually transmitted infections for more than six months may be regarded as non-infectious, the researchers did two calculations for the likelihood of transmission risk, based on whether the transmission in that study had taken place less or more than six months after the start of therapy. This explains the two figures (8.7 or 13 transmissions per 100,000) cited.

The researchers’ calculation that the chance of transmission from a partner on treatment in a heterosexual couple would rise beyond 1% after 195 to 389 occasions of sex allows a comparison with the American model. The CDC estimated the ten-year risk of HIV transmission from a partner on ART to be 2%. According to the French researchers, the risk after 720 sex acts (equivalent to ten years in the US model) ranges from 1.85% to 3.7% - compatible with the American estimates.

The researchers argue that we may never be able to get a more precise answer for the long-term risk of transmission than this. Because transmission from someone on treatment is so rare, if the highest likely ‘true’ risk is actually one in 100,000, it would have taken the HPTN 052 study, which provided a convincing answer of at least 96% for the reduction in infections conferred by ART, 27 years to establish such a fact.

This current study tells us nothing about the risk of transmission within a gay couple. The American analysis suggests that the long-term risks are very much higher for gay men simply because the risk of transmission via anal sex, where the negative partner is the receptive one, is 18 times higher than in vaginal sex. But we do not know if a partner on ART is 18 times more infectious because no completely undisputed and verified transmission from a partner on ART in a gay couple has been documented.

It is important to note that both the American and French analyses are deliberately establishing the most conservative scenarios in the interests of prevention policy. The true likelihood of a person on fully-suppressive ART transmitting the virus may be much closer to zero than these figures suggest. Nonetheless, the ten-year risk is not negligible, and should spur further research into even more prevention methods.