Letters to the Editor: Author's Response
To the Editor:
When commenting on the ability of our model to represent the spread of HIV in sub-Saharan Africa, Brewer et al1 focus on our choice of parameters rather than what we consider more important: our representation of the sexual network structure. It was not our objective to precisely replicate observed epidemics, a task we believe requires a more sophisticated description of sexual networks, but to explore some of the issues surrounding different modes of transmission. Our main conclusion remains that heterogeneity in risk is required to generate the size of epidemics observed by transmission through either sexual contact or unsafe injections.
Our range of transmission probabilities per sex act was taken from a systematic review and meta-analysis,2 which incorporated studies where STI cofactors were present and of populations involved in commercial sex. We still believe this provides a better estimate than the figure quoted by Brewer et al. The prospective study of discordant couples in Rakai3 provides an accurate figure for transmission but suffers from selection bias, including only couples within which transmission had not yet occurred at recruitment. As this study shows, transmission is dependent on the viral load of the infected partner, which means that transmission probability will vary with time since HIV infection. The recruitment of couples when HIV prevalence was declining in Rakai would suggest that transmission during primary viraemia was missed. In a more recent analysis from the same population, Wawer et al estimate the transmission probability per sex act at different stages of infection, including within the first 15 months after seroconversion and the last 25 months before death.4 We start to observe infection in the model population with transmission probabilities per sex act of around 0.0045, well within the confidence intervals estimated in this recent study. When estimating the corresponding transmission probability from iatrogenic exposures, the inability to study unsafe practices is a barrier that we believe cannot be solved by retrospectively studying 4 of 8 outbreaks where more than 10 people were infected, because this excludes an unknown number of cases where HIV failed to spread.
Measures of the number of sexual partners suffer from social desirability biases.5 This is particularly a problem in large, household-based surveys where sexual behavior is not the main focus, as is the case in the Demographic and Health Surveys quoted by Brewer et al. Furthermore, behaviors recorded recently are likely to have changed significantly from the behaviors existing during the initial spread of HIV. Nonetheless, it is likely that we have used an overestimate of the number of new sexual partners per year. This is because the model, which is typical of many others, equates risk of sexual HIV acquisition with turnover of partners, using ‘new partners' to approximate both new and existing partners and concurrent partners. The model structure with instantaneous formation of partnerships does not allow for concurrent sexual partnerships, which we believe is a major factor for transmission. A more complex, individual-based model would be required to explore these characteristics fully.
As Brewer et al note, Apetrei et al found detectable HIV RNA in 33% of needles previously used by HIV-infected individuals in Cameroon.6 However, the presence of HIV in needles does not necessitate transmission; it is only if those needles are then reused that transmission may occur. The existing evidence is that reuse of needles is relatively rare.7 However, empirical evidence is lacking with which to assess heterogeneity of risk.
Brewer et al criticize our decision to allow only one transmission per contaminated needle by citing an article in which they suggest that multiple infections are possible from a single reused needle or syringe. We, however, based this decision on results from work by Abdala et al, who observed that recovery of viable HIV-1 from syringes that had been flushed once was dramatically reduced.8
Our initial aim in comparing a model of iatrogenic and sexual transmission was to explore the parameter regimes and patterns of epidemics in more detail. However, we acknowledge that more work is needed both in model development and in empirical study. We agree with Brewer et al that comparing the risks of those with and without incident HIV is important. Prevalent HIV infections were once incident infections, and we have found that lifetime number of sex partners best predicted prevalent HIV infections in rural Zimbabwe.9 However, risk may differ by location and over time and further studies are required to generate a more measured view of the relative importance of sexual and iatrogenic routes of infection.
1. Brewer D, Rothenberg R, Potterat J, et al. Data-free modeling of HIV transmission in Sub-Saharan Africa. Sex Transm Dis 2007; 34: 54–56.
2. Baggaley RF. The impact of antiretroviral use in resource-poor settings: Insights from mathematical models. Ph.D. Thesis, Imperial College, London, 2006.
3. Gray RH, Wawer MJ, Brookmeyer R, et al. Probability of HIV-1 transmission per coital act in monogamous, heterosexual, HIV-1-discordant couples in Rakai, Uganda. Lancet 2001; 357:1149–1153.
4. Wawer MJ, Gray RH, Sewankambo NK, et al. Rates of HIV-1 transmission per coital act, by stage of HIV-1 infection, in Rakai, Uganda. J Infect Dis 2005; 191:1403–1409.
5. Fenton KA, Johnson AM, McManus S, et al. Measuring sexual behaviour: Methodological challenges in survey research. Sex Transm Infect 2001; 77:84–92.
6. Apetrei C, Becker J, Metzger M, et al. Potential for HIV transmission through unsafe injections. AIDS 2006; 20:1074–1076.
7. Hutin YJ, Hauri AM, Armstrong GL. Use of injections in healthcare settings worldwide, 2000: Literature review and regional estimates. BMJ 2003; 327:1075.
8. Abdala N, Gleghorn AA, Carney JM, et al. Can HIV-1-contaminated syringes be disinfected? Implications for transmission among injection drug users. J Acquir Immune Defic Syndr 2001; 28:487–494.
9. Lopman BA, Garnett GP, Mason PR, et al. Individual level injection history: A lack of association with HIV incidence in rural Zimbabwe. PLoS Med 2005; 2:e37.