Two recent papers below raise issues about 'Treatment as Prevention'. TasP is more of a religion than an established and proven tool. The fact is that most sexually transmitted epidemics are declining because people have changed their behaviour and use condoms or both. Only a few are not declining.
Jamie
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Model shows potential for substantial long-term HIV risk for serodifferent couples, even with new prevention tools
Model may contain pessimistic assumptions about efficacy of PrEP, antiretroviral treatment and condoms
Michael Carter, Gus Cairns
Published: 27 May 2014
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%.
Reference
Lasry A et al. HIV sexual transmission risk among serodiscordant couples: assessing the effects of combining prevention strategies. AIDS 28, online edition. DOI: 10.1097/QAD0000000000000307, 2014.
http://www.aidsmap.com/page/2856038/?utm_source=NAM-Email-Promotion&utm_medium=aidsmap-news&utm_campaign=aidsmap-news
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Second analysis concludes that we can't eliminate the long-term possibility of HIV transmission from someone on treatment
Gus Cairns
Published: 31 May 2014
A study that estimates the risk that someone living with HIV and taking antiretroviral therapy could transmit the virus reports that, on the basis of the few transmissions from heterosexual partners on treatment that have been reported, it is not possible to dismiss the risk of infection as zero.
The analysis by French researchers 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. However, the researchers stressed to aidsmap.com that this is the highest-likely risk: the actual risk may be lower than this and could indeed be zero.
This implies that the accumulated highest-likely risk of HIV transmission would rise to 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.
This is the second recent study to find that the long-term risk from a partner on antiretroviral therapy (ART), while very much lower than from a partner not on treatment, may not be negligible in the long term.
The other study, by the Centers for Disease Control and Prevention (CDC) in the USA, used a mathematical model to calculate the one- and ten-year risks of HIV infection in heterosexual and gay couples. It then added in the mitigating effects of ART, condom use, circumcision and pre-exposure prophylaxis (PrEP). It used 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 actual reported cases of HIV transmission within a heterosexual couple where the partner living with HIV 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 studies 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, serodiscordant 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 study participants had an undetectable viral load at various time points. At the start of the studies, sexual frequency in participants varied from three to twelve times a month; 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 cited for the highest-likely risk of transmission of 8.7 or 13 transmissions per 100,000.
The researchers’ calculation that the chance of transmission from a partner on treatment in a heterosexual couple could rise up to 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 highest-likely risk after 720 sex acts (equivalent to ten years in the US model) was either 1.85% or 3.7% (depending on the timing of that one transmssion). This is compatible with the American estimates, though the CDC study computes an average risk of transmission from rather conservative assumptions about the efficacy of different prevention methods, while the French study computes a range of risk, from zero (the lowest-likely risk) to the uppermost-likely risk quoted.
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, say, one in 100,000, it would have taken the HPTN 052 study, which provided an answer of "at least 96%" for the reduction in infections conferred by ART, 27 years to establish such a fact.
This French study tells us nothing about the risk of transmission within a gay couple. The American model suggests that the long-term risks could be very much higher for gay men simply because the risk of transmission via anal sex (where the HIV-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 likely to transmit HIV – because no completely undisputed and verified transmission from a partner on ART in a gay couple has been documented.
It is important to reiterate that the true likelihood of a person on fully suppressive ART transmitting the virus may be much closer to zero than these two studies suggest. Nonetheless, the ten-year risk may not be negligible, and research into even more effective prevention methods is still needed.
Reference
Supervie V et al. Heterosexual risk of HIV transmission per sexual act under combined antiretroviral therapy: systematic review and Bayesian modelling. Clinical Infectious Diseases, early online edition. See abstract here.
http://www.aidsmap.com/page/2857022/?utm_source=NAM-Email-Promotion&utm_medium=aidsmap-news&utm_campaign=aidsmap-news
