HIV transmission among serodiscordant monogamous couples in which the HIV-positive partner has an undetectable viral load due to effective treatment might rise fourfold over a decade if condom use is abandoned, suggests a mathematical model published this week.
The study, published in the July 26th edition of The Lancet coincides with the publication of a joint Australasian statement developed in response to the Swiss statement, which concludes that consistent condom use and early and effective treatment for sexually transmitted infections “is the only way to prevent HIV spread.”
The impact of antiretroviral therapy on sexual transmission has been the subject of intense debate this year, following publication of guidance from the Swiss Federal AIDS Commission (EKAF) stating that an individual with a blood plasma undetectable viral load is not infectious under certain conditions.
Although much of the debate has been due to concerns about increased sexual risk-taking on a population level cancelling out any gains in antiretroviral therapy’s effect on infectiousness some of the concerns have been about the scientific accuracy of the Swiss statement.
In particular there are no data on the residual transmission risk that may exist when an individual has an undetectable viral load on therapy, even when they are in a monogamous relationship – which may reduce the risk of acquiring new sexually transmitted infections (STIs), but does not address the potential impact of untreated chronic viral STIs such as herpes. Other factors that may affect the risk of unprotected sex while taking effective treatment include potential variations in concentrations between individual antiretroviral drugs in the genital tract and anal mucosa; the effect of adherence on antiretroviral drug levels; and the impact of intermittent viraemia (‘blips’).
In order to estimate the per act and cumulative risks of HIV transmission from individuals with a blood plasma viral load below 10 copies per mL, investigators from the National Centre in HIV Epidemiology and Clinical Research at the University of New South Wales in Sydney used a simple mathematical model.
The model used previous published data estimating the relationship between viral load and transmission risk (based on data from heterosexual couples in Uganda practising vaginal sex) as well as previously published estimates of HIV transmission risk per sexual act for men to women; women to men; and men to men. It also assumed that each monogamous couple had 100 instances of sexual intercourse each year; that no heterosexual couple had anal intercourse; and that men in same-sex relationships had equal amounts of insertive and receptive anal sex.
Importantly, however, the model assumes that HIV transmission is possible at all viral load levels, rather than assuming that there is threshold below which transmission cannot occur.
An accompanying editorial commentary from Professor Geoffrey Garnett of Imperial College London and Professor Brian Gazzard, of Chelsea and Westminster Hospital, London notes, “the authors extrapolate the model beyond the available data, assuming that there is continuous reduction in risk rather than a threshold below which no transmission is possible. The Swiss statement is based on the different assumption that there is such a threshold, as was observed in a study in Rakai, Uganda, where no transmission event occurred when viral copy numbers were below 1500 copies per mL. Unfortunately, small sample sizes mean that neither assumption is secure.”
Nevertheless, the model found that the cumulative probability of transmission to the serodiscordant partner for each year is 0.0022 (range 0.0008–0·0058) for female-to-male transmission; 0.0043 (range 0·0016–0·0115) for male-to-female transmission; and 0.043 (range 0·0159–0·1097) for male-to-male transmission.
The investigators point out the public health implications if their calculations were to hold true: over ten years and 10,000 serodiscordant couples they would expect to see 215 (range, 80–564) female-to-male transmissions; 425 (range, 159–1096) male-to-female transmissions; and 3524 (range, 1477–6871) male-to-male transmissions, ”corresponding to an increase in incidence of four times compared with incidence under current rates of condom use.”
In their discussion, however, they point out that “under our assumptions, the effectiveness of treatment in reducing the risk of HIV transmission per sexual act was about the same as has been reported for condoms. Although we agree that effective antiretroviral treatment which leads to undetectable viral load is likely to have a substantial effect on reducing infectiousness, our analyses suggest that it should not replace condoms.”
On the basis of the data presented here,” the Australian researchers conclude, “we believe that the Swiss statement is not a sensible public-health message because its logical outcome would be the abandonment of condoms by people with effectively treated HIV infection…As a population strategy, treatment as prevention has the potential to reduce HIV epidemics only if consistent condom use is maintained. Indeed, our analysis suggests that there is large potential for more harm than good."
That was also the conclusion of the Australasian consensus statement to which the study’s authors contributed. The statement, from the Australasian Society for HIV Medicine, the Australian Federation of AIDS Organisations, the National Association of People Living with HIV/AIDS, and the National Centre in HIV Epidemiology and Clinical Research notes the following:
“Consistent use of effective antiretroviral therapy (ART) will, in most cases, lead to an undetectable viral load (VL), as measured in blood, semen and vaginal fluids. As a result, the average viral load of the community of people living with the human immunodeficiency virus (HIV) will be reduced. By reducing the VL, ART will also complement the benefits of consistent condom use and effective sexually transmitted infections (STI) detection and treatment, in preventing HIV transmission that may otherwise occur due to condom failure. However, there are no data to suggest that a population HIV prevention strategy based solely or predominately on the use of ART and associated with a reduction in condom use, will lead to fewer people becoming infected in the Australian and New Zealand populations, especially in the context of rising rates of STI.”
The statement then summarises available knowledge on the effect of treatment on transmission and weighs the pros and cons of making a public statement that encourages individuals with an undetectable viral load to abandon safer sex. It also acknowledges the legal implications for jurisdictions that have HIV exposure laws, such as New South Wales.
It concludes by saying that, “for the present and in light of our current knowledge, safe sex is the only way to prevent HIV spread. Safer sex includes correct and consistent male and female condom use, and early and effective detection and treatment for STIs.”
The editorial commentary from Professors Garnett and Gazzard is more pragmatic: “Denying an effect of treatment on risk of transmission would be dishonest and futile, because well-informed patients will assume an effect,” they write.
It is also more welcoming of the Swiss statement that marked the end of “muted discussion” on the effects of treatment on prevention. “In many ways,” it concludes, “the Swiss statement provides the opportunity for positive public-health messages, by promoting adherence to treatment and concern over other sexually transmitted infections. The use of condoms, in addition to antiretrovirals, to further reduce risk and prevent other sexually transmitted infections can then also be promoted.”
Wilson DP et al. Relation between HIV viral load and infectiousness: a model-based analysis. Lancet 372: 314-20, 2008.
Garnett GP and Gazzard B. Risk of HIV transmission in discordant couples. Lancet 372: 270-71, 2008.
Australasian Society for HIV Medicine, National Centre in HIV Epidemiology and Clinical Research, Australian Federation of AIDS Organisations and National Association of People Living with HIV/AIDS. Australasian statement on HIV antiretroviral therapy and infectiousness.Published online July 18, 2008.