HIV This Week

Attia S, Egger M, Müller M, Zwahlen M, Low N. Sexual transmission of HIV according to viral load and antiretroviral therapy: systematic review and meta-analysis. AIDS. 2009 Apr 17. [Epub ahead of print]

Attia and colleagues aimed to synthesize the evidence on the risk of HIV transmission through unprotected sexual intercourse according to viral load and treatment with combination antiretroviral therapy. They conducted a systematic review and meta-analysis, searching Medline, Embase, and conference abstracts from 1996-2009. The authors included longitudinal studies of serodiscordant couples reporting on HIV transmission according to plasma viral load or use of antiretroviral therapy and used random-effects Poisson regression models to obtain summary transmission rates [with 95% confidence intervals, (CI)]. If there were no transmission events they estimated an upper 97.5% confidence limit. They identified 11 cohorts reporting on 5021 heterosexual couples and 461 HIV-transmission events. The rate of transmission overall from antiretroviral therapy-treated patients was 0.46 (95% CI 0.19-1.09) per 100 person-years, based on five events. The transmission rate from a seropositive partner with viral load below 400 copies/ml on antiretroviral therapy, based on two studies, was zero with an upper 97.5% confidence limit of 1.27 per 100 person-years, and 0.16 (95% CI 0.02-1.13) per 100 person-years if not on antiretroviral therapy , based on five studies and one event. There were insufficient data to calculate rates according to the presence or absence of sexually transmitted infections, condom use, or vaginal or anal intercourse. Studies of heterosexual discordant couples observed no transmission in patients treated with antiretroviral therapy and with viral load below 400 copies/ml, but data were compatible with one transmission per 79 person-years. Further studies are needed to better define the risk of HIV transmission from patients on antiretroviral therapy.

Editors’ note: This study underscores the considerable uncertainty about the risk of HIV transmission under ‘Swiss Commission’ conditions, that is, viral load below 40 copies/ml, no other sexually transmitted infection, and consistent adherence to antiretroviral treatment. The Commission stated ‘much lower than one per 100,000 acts of sexual intercourse’ whereas this systematic review and meta-analysis of existing data found them compatible with one new infection for every 79 person-years of follow-up (or 7900 acts of sexual intercourse, if the yearly average is 100 contacts). Further studies are needed to quantify HIV transmission risk in different populations, including men who have sex with men for whom there are no comparable published data. In the meantime, since the Swiss Commission statement January 2008 UNAIDS has continued to reassert the importance of correct and consistent condom use – a key part of positive prevention and a cornerstone of HIV prevention for people without HIV.

Wood E, Kerr T, Marshall BD, Li K, Zhang R, Hogg RS, Harrigan PR, Montaner JS. Longitudinal community plasma HIV-1 RNA concentrations and incidence of HIV-1 among injecting drug users: prospective cohort study. BMJ. 2009 Apr 30;338:b1649.

To examine the relation between plasma HIV-1 RNA concentrations in the community and HIV incidence among injecting drug users, Wood and colleagues conducted a prospective cohort study in an inner city community in Vancouver, Canada. Injecting drug users, with and without HIV, were followed up every six months between 1 May 1996 and 30 June 2007. The main outcome measures were estimated community plasma HIV-1 RNA in the six months before each HIV-negative participant’s follow-up visit and associated HIV incidence. Among 622 injecting drug users with HIV, 12 435 measurements of plasma HIV-1 RNA were obtained. Among 1429 injecting drug users without HIV, there were 155 HIV seroconversions, resulting in an incidence density of 2.49 (95% confidence interval 2.09 to 2.88) per 100 person years. In a Cox model that adjusted for unsafe sexual behaviours and using nonsterile syringes, the estimated community plasma HIV-1 RNA concentration remained independently associated with the time to HIV seroconversion (hazard ratio 3.32 (1.82 to 6.08, P<0.001), per log(10) increase). When the follow-up period was limited to observations after 1 January 1998 (when the median plasma HIV RNA concentration was <20 000 copies/ml), the median viral load was no longer statistically associated with HIV incidence (1.70 (0.79 to 3.67, P=0.175), per log(10) increase). The authors concluded that a longitudinal measure of community plasma HIV-1 RNA concentration was correlated with the community HIV incidence rate and predicted HIV incidence independent of unsafe sexual behaviours and sharing used syringes. If these findings are confirmed, they could help to inform both HIV prevention and treatment interventions.

Editors’ note: This ecological study estimated community plasma viral load from the viral loads of injecting drug users on treatment in this urban community which has a centralised antiretroviral dispensation programme and HIV laboratory. The proportion of patients on 3 or more antiretroviral drugs increased from 8.4% in 1996 to 98.8% in 2007 while both median estimated community plasma HIV-1 RNA concentrations and HIV incidence fell. The likelihood that an HIV-negative injecting drug user had seroconverted since the last clinic visit was correlated with the median estimated community viral load during the prior 6 months. It is not possible to conclude from these data that the association was causal but the fact that the highest rates of HIV seroconversion occurred in the year after the highest community plasma HIV-2 concentration support this hypothesis. These findings no doubt influenced the provincial government to fund an innovative programme to expand access to treatment for street-involved people living in Vancouver’s downtown eastside and downtown Prince George, British Columbia.