Source of new infections in generalised HIV epidemics

Source of new infections in generalised HIV epidemics

Correspondence We did not see a significant difference in HIV by group among the women participants from Zambia and South Africa, although we are conce...

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Correspondence

We did not see a significant difference in HIV by group among the women participants from Zambia and South Africa, although we are concerned about potential for bias in post-hoc analyses of subgroups. If disinhibition was an important effect of our intervention, we would expect it to occur among men as well, and among women in Zimbabwe. We are assessing unblinding and perceived randomisation during the trial. Although the results are preliminary, we are seeing little association between what participants report about their perceived assignment to aciclovir or placebo and their actual randomisation. The issues of behavioural risk compensation and adherence to prevention interventions are critical in HIV prevention trials, as described by the US Institute of Medicine report on methodological challenges in biomedical HIV prevention trials.1,2 However, we have no indication that either behavioural disinhibition or unblinding were significant factors in explaining the lack of efficacy in reducing HIV acquisition among women in our trial. CC has received research grant support from GlaxoSmithKline and has served on an advisory board for GlaxoSmithKline. AW has received grant support from GlaxoSmithKline, Antigenics, 3M, Roche, Astellas, and Vical. She is a consultant for Novartis, Powdermed, and Medigene, and a speaker for Merck Vaccines. The University of Washington Virology Division Laboratories have received grant funding from GlaxoSmithKline and Novartis to do HSV serological assays and PCR assays for studies funded by these companies. LC directs these laboratories but receives no salary support from these grants. JH declares that he has no conflict of interest.

*Connie Celum, Anna Wald, Jim Hughes, Larry Corey [email protected] University of Washington, Harborview Medical Center, Box 359927, 325 Ninth Avenue, Seattle, WA 98104, USA 1

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Lagakos SW, Gable AR. Challenges to HIV prevention—seeking effective measures in the absence of a vaccine. N Engl J Med 2008; 358: 1543–45. Lagakos SW, Gable AR, eds. Methodological challenges in biomedical HIV prevention trials. Washington, DC: National Academies Press, 2008.

www.thelancet.com Vol 372 October 11, 2008

Source of new infections in generalised HIV epidemics Kristin Dunkle and colleagues (June 28, p 2183)1 address a profoundly important question for HIV prevention: the source of new infections in generalised epidemics. However, their modelling has at least two crucial weaknesses. First, Dunkle and colleagues assume an annual rate of infection from one infected partner to another of 20%. Of the two older studies they reference, the first2 was predominantly based on individuals with advanced disease (AIDS and AIDS-related complex) who are highly infectious and hence not representative. The other study3 had no direct data on uncounselled couples, but imputed a rate of infection indirectly. By contrast, evidence from the well observed cohort studies in Rakai, Masaka, and Mwanza from the 1990s are all consistent in finding infection rates of about 5–10% in the multiyear latent phase of infection. Dunkle and colleagues discount such estimates, arguing that participants might have been aware of their HIV status. However, in the case of Rakai,4 knowing ones status had no effect on HIV acquisition even with counselling. The second major flaw is to assume no infections occur over the course of a year within “couples” where both are uninfected. In reality, rapid transmission occurs among people who have concurrent partnerships, as one highly infectious new infection begets another. Such transmission probably drives much of the generalised epidemics. Seroprevalence data clearly rebut both assumptions. For example, in Rwanda,5 among couples in whom at least one partner is infected, 44% involve partners who both have HIV. If the intracouple infection rate were 20% per year, in a mature epidemic, the proportion of couples in which both are infected should be

far higher than 44%. Additionally, if virtually all infections occur within established discordant partnerships, where did the large proportion of couples with only one infected partner (56%) come from? Clearly many infections are occurring outside of established dyads. We agree with Dunkle and colleagues’ interpretation that counselling and testing among couples should be promoted, but their modelling greatly overestimates its potential benefit. We declare that we have no conflict of interest.

*James D Shelton, David L Stanton [email protected] Bureau for Global Health, US Agency for International Development, Washington, DC 20523, USA 1

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Dunkle KL, Stephenson R, Karita E, et al. New heterosexually transmitted infections in married or cohabitating couple in urban Zambia and Rwanda: an analysis of survey and clinical data. Lancet 2008; 371: 2183–91. Hira SK, Nkowane BM, Kamanga J, et al. Epidemiology of human immunodeficiency virus in families in Lusaka, Zambia. J Acquir Immun Defic Syndr 1990; 3: 83–86. Allen S, Tice J, Van de Perre P, et al. Effect of serotesting with counselling on condom use and seroconversion among HIV discordant couples in Africa. BMJ 1992; 302: 1605–09. Matovu JKB, Gray RH, Makumbi F, et al. Voluntary HIV counseling and testing acceptance, sexual risk behavior and HIV incidence in Rakai, Uganda. AIDS 2005; 19: 503–11. Institut National de la Statistique du Rwanda (INSR) and ORC Macro 2006. Rwanda demographic and health survey 2005. http:// www.measuredhs.com/pubs/pub_details. cfm?ID=594&ctry_id=35&SrchTp=type (accessed July 2, 2008).

In their Article on HIV transmission in married and cohabiting couples in urban Zambia and Rwanda,1 Kristin Dunkle and colleagues estimate that 55–93% of newly heterosexually acquired HIV infections in these populations “occurred within serodiscordant marital or cohabiting relationships”. These estimates are too high, since logically a maximum of 50% of new infections can be within couples, because in any stable couple, at least one partner had to acquire the initial infection outside the relationship. (In actual populations the proportion will be less than 50% because of 1299