HIV This Week

Wilson DP, Law MG, Grulich AE, Cooper DA, Kaldor JM. Relation between HIV viral load and infectiousness: a model-based analysis. Lancet. 2008;372(9635):314-20.

A consensus statement released on behalf of the Swiss Federal Commission for HIV/AIDS suggests that people receiving effective antiretroviral therapy-ie, those with undetectable plasma HIV RNA (<40 copies per mL)-are sexually non-infectious. Wilson and colleagues analysed the implications of this statement at a population level. They used a simple mathematical model to estimate the cumulative risk of HIV transmission from effectively treated HIV-infected patients (HIV RNA <10 copies per mL) over a prolonged period. The authors investigated the risk of unprotected sexual transmission per act and cumulatively over many exposures, within couples initially discordant for HIV status. Assuming that each couple had 100 sexual encounters per year, the cumulative probability of transmission to the serodiscordant partner each year is 0.0022 (uncertainty bounds 0.0008-0.0058) for female-to-male transmission, 0.0043 (0.0016-0.0115) for male-to-female transmission, and 0.043 (0.0159-0.1097) for male-to-male transmission. In a population of 10 000 serodiscordant partnerships, over 10 years the expected number of seroconversions would be 215 (80-564) for female-to-male transmission, 425 (159-1096) for male-to-female transmission, and 3524 (1477-6871) for male-to-male transmission, corresponding to an increase in incidence of four times compared with incidence under current rates of condom use. The analyses suggest that the risk of HIV transmission in heterosexual partnerships in the presence of effective treatment is low but non-zero and that the transmission risk in male homosexual partnerships is high over repeated exposures. If the claim of non-infectiousness in effectively treated patients was widely accepted, and condom use subsequently declined, then there is the potential for substantial increases in HIV incidence.

Editors’ note: This modelling suggests that, at the population level, treatment as a prevention strategy would not be an improvement over condom use. This model assumes that a threshold viral load under which transmission is very difficult does not exist, something that we do not know, and uses estimates of average HIV transmission probabilities that are unlikely to apply to all discordant couples. Nonetheless, the estimates are sobering and suggest that as a population strategy, treatment as prevention has the potential to reduce HIV epidemics only if consistent condom use is maintained. This conclusion is supported by resurgence of HIV among populations with high levels of treatment, such as men who have sex with men in Amsterdam.

Lima and colleagues developed a mathematical model using a multiple source of infection framework to assess the potential effect of the expansion of highly active antiretroviral therapy coverage among those in medical need on the number of individuals testing newly positive for human immunodeficiency virus (HIV) and on related costs in British Columbia, Canada, over the next 25 years. The model was calibrated using retrospective data describing antiretroviral therapy utilization and individuals testing newly positive for HIV in the province. Different scenarios were investigated on the basis of varying assumptions regarding drug resistance, adherence to highly active antiretroviral therapy, therapeutic guidelines, degree of highly active antiretroviral therapy coverage, and the timing of highly active antiretroviral therapy uptake. Expansion of highly active antiretroviral therapy leads to substantial reductions in the growth of the HIV epidemic and related costs. These results provide powerful additional motivation to accelerate the roll out of highly active antiretroviral therapy programmes aggressively targeting those in medical need, both for their own benefit and as a means of decreasing new HIV infections.

Editors’ note: This model estimates encouraging effects of treatment at the population level when all current HIV prevention modalities are maintained. These include promotion and provision of condoms, needles and syringes, and methadone maintenance, in addition to reduction in the number of sex partners. The model suggests that for expansion of treatment to be a successful complementary strategy, HIV testing must expand to increase knowledge of serostatus. Clearly, expanded access to antiretroviral treatment could be a supplement but not a replacement for current HIV prevention programming.