Ap Cox

Remodelling core group theory: the role of sustaining populations in HIV transmission

Background and objectives Core group theory describes the central role of groups with high rates of sexual partner change in HIV transmission. Research illustrates the heterogeneous and dynamic nature of commercial sex, and that some men involved in the organisation or policing of sex work regularly have sex with sex workers. These findings are used to explore gaps in core group theory. Methods Evidence from developing countries on the duration that women sell and men buy sex was reviewed. Simple compartmental dynamic models were used to derive analytical expressions for the relative HIV equilibrium levels among sex workers and partners, incorporating partner change rates and duration in commercial sex settings. Simulations explored the degree to which HIV infection can be attributable to men with low partner change rates who remain in sex work settings for long periods, and their influence on the impact of HIV intervention. Results Partner change rates and duration of time in a setting determine equilibrium HIV levels. Modelling projections suggest that men with low mobility can substantially contribute to HIV prevalence among sex workers, especially in settings with prevalences <50%. This effect may reduce the impact of sex-worker interventions on HIV incidence in certain scenarios by one-third. Reductions in impact diminish at higher sex-worker prevalences. Conclusion In commercial sex settings, patterns of HIV risk and transmission are influenced by both partner change rates and duration in a setting. The latter is not reflected in classic core group theory. Men who control the sex industry and regular clients may form an important ‘sustaining population’ that increases infection and undermines the impact of intervention. Intervention activities should include these groups, and examine the social organisation of sex work that underpins many of these relationships.

Tuberculosis Control in South African Gold Mines: Mathematical Modeling of a Trial of Community-Wide Isoniazid Preventive Therapy

A recent major cluster randomized trial of screening, active disease treatment, and mass isoniazid preventive therapy for 9 months during 2006–2011 among South African gold miners showed reduced individual-level tuberculosis incidence but no detectable population-level impact. We fitted a dynamic mathematical model to trial data and explored 1) factors contributing to the lack of population-level impact, 2) the best-achievable impact if all implementation characteristics were increased to the highest level achieved during the trial (“optimized intervention”), and 3) how tuberculosis might be better controlled with additional interventions (improving diagnostics, reducing treatment delay, providing isoniazid preventive therapy continuously to human immunodeficiency virus–positive people, or scaling up antiretroviral treatment coverage) individually and in combination. We found the following: 1) The model suggests that a small proportion of latent infections among human immunodeficiency virus–positive people were cured, which could have been a key factor explaining the lack of detectable population-level impact. 2) The optimized implementation increased impact by only 10%. 3) Implementing additional interventions individually and in combination led to up to 30% and 75% reductions, respectively, in tuberculosis incidence after 10 years. Tuberculosis control requires a combination prevention approach, including health systems strengthening to minimize treatment delay, improving diagnostics, increased antiretroviral treatment coverage, and effective preventive treatment regimens.

Cost-effectiveness of tenofovir gel in urban South Africa: model projections of HIV impact and threshold product prices

BackgroundThere is urgent need for effective HIV prevention methods that women can initiate. The CAPRISA 004 trial showed that a tenofovir-based vaginal microbicide had significant impact on HIV incidence among women. This study uses the trial findings to estimate the population-level impact of the gel on HIV and HSV-2 transmission, and price thresholds at which widespread product introduction would be as cost-effective as male circumcision in urban South Africa.MethodsThe estimated ‘per sex-act’ HIV and HSV-2 efficacies were imputed from CAPRISA 004. A dynamic HIV/STI transmission model, parameterised and fitted to Gauteng (HIV prevalence of 16.9% in 2008), South Africa, was used to estimate the impact of gel use over 15 years. Uptake was assumed to increase linearly to 30% over 10 years, with gel use in 72% of sex-acts. Full economic programme and averted HIV treatment costs were modelled. Cost per DALY averted is estimated and a microbicide price that equalises its cost-effectiveness to that of male circumcision is estimated.ResultsUsing plausible assumptions about product introduction, we predict that tenofovir gel use could lead to a 12.5% and 4.9% reduction in HIV and HSV-2 incidence respectively, by year 15. Microbicide introduction is predicted to be highly cost-effective (under

Prevalence and under-detection of gambiense human African trypanosomiasis during mass screening sessions in Uganda and Sudan

300 per DALY averted), though the dose price would need to be just

Attaining realistic and substantial reductions in HIV incidence: model projections of combining microbicide and male circumcision interventions in rural Uganda

0.12 to be equally cost-effective as male circumcision. A single dose or highly effective (83% HIV efficacy per sex-act) regimen would allow for more realistic threshold prices (

The impact of syphilis screening among female sex workers in China: A modelling study

0.25 and

Identifying optimal strategies for microbicide distribution in India and South Africa: modelling and cost-effectiveness analyses.

0.33 per dose, respectively).ConclusionsThese findings show that an effective coitally-dependent microbicide could reduce HIV incidence by 12.5% in this setting, if current condom use is maintained. For microbicides to be in the range of the most cost-effective HIV prevention interventions, product costs will need to decrease substantially.

How Different Efficacy, Consistency of Usage and Uptake/Distribution Factors Affect the Relative Impact of Microbicide Interventions: Analytical Insights

BackgroundActive case detection through mass community screening is a major control strategy against human African trypanosomiasis (HAT, sleeping sickness) caused by T. brucei gambiense. However, its impact can be limited by incomplete attendance at screening sessions (screening coverage) and diagnostic inaccuracy.MethodsWe developed a model-based approach to estimate the true prevalence and the fraction of cases detected during mass screening, based on observed prevalence, and adjusting for incomplete screening coverage and inaccuracy of diagnostic algorithms for screening, confirmation and HAT stage classification. We applied the model to data from three Médecins Sans Frontières projects in Uganda (Adjumani, Arua-Yumbe) and Southern Sudan (Kiri).ResultsWe analysed 604 screening sessions, targeting about 710 000 people. Cases were about twice as likely to attend screening as non-cases, with no apparent difference by stage. Past incidence, population size and repeat screening rounds were strongly associated with observed prevalence. The estimated true prevalence was 0.46% to 0.90% in Kiri depending on the analysis approach, compared to an observed prevalence of 0.45%; 0.59% to 0.87% in Adjumani, compared to 0.92%; and 0.18% to 0.24% in Arua-Yumbe, compared to 0.21%. The true ratio of stage 1 to stage 2 cases was around two-three times higher than that observed, due to stage misclassification. The estimated detected fraction was between 42.2% and 84.0% in Kiri, 52.5% to 79.9% in Adjumani and 59.3% to 88.0% in Arua-Yumbe.ConclusionsIn these well-resourced projects, a moderate to high fraction of cases appeared to be detected through mass screening. True prevalence differed little from observed prevalence for monitoring purposes. We discuss some limitations to our model that illustrate several difficulties of estimating the unseen burden of neglected tropical diseases.

Model projections of the population-level impact, on HIV and herpes simplex virus type-2 (HSV-2), and cost-effectiveness of tenofovir gel, an antiretroviral microbicide

Objectives This study simulates the potential impact of male circumcision and female microbicide interventions, singularly and in combination, in rural Uganda. Methods A dynamic model was parameterised and fitted to setting-specific data, and used to estimate the impact on HIV transmission of a microbicide and/or male circumcision intervention over 15 years. The proportion of circumcised men or women using microbicides was assumed to increase linearly from 0.18 (male circumcision) or 0.00 (microbicide use) to the final proportion 10 years later, then remain constant for 5 years. Women using microbicides were assumed to use the product in 80% of penile–vaginal sex acts. Male circumcision or microbicide use was assumed to reduce the per-act probability of HIV acquisition in men or women, respectively, by 60%. Results Independently, to obtain a 30% relative reduction in HIV incidence at 15 years, the model suggests that the final proportion of women using microbicides would need to be 0.91 (95% CI 0.75 to 1.00) or the proportion of circumcised men would need to be 0.96 (0.83 to impact not possible). The same impact could be achieved by combining the interventions, eg, if the proportion of women using microbicides was 0.49 (0.39 to 0.56) and the proportion of circumcised men was 0.67 (0.57 to 0.74). Conclusions Under these assumptions, as separate interventions it is unlikely that increases in either the proportion of men circumcised or of women using microbicides could reduce HIV incidence by 30% or more at 15 years. A combination-prevention strategy using complementary interventions may be a more feasible approach to achieve substantial reductions in incidence.