The potential impact and cost of focusing HIV prevention on young women and men: A modeling analysis in western Kenya.

OBJECTIVE: We compared the impact and costs of HIV prevention strategies focusing on youth (15-24 year-old persons) versus on adults (15+ year-old persons), in a high-HIV burden context of a large generalized epidemic. DESIGN: Compartmental age-structured mathematical model of HIV transmission in Nyanza, Kenya. INTERVENTIONS: The interventions focused on youth were high coverage HIV testing (80% of youth), treatment at diagnosis (TasP, i.e., immediate start of antiretroviral therapy [ART]) and 10% increased condom usage for HIV-positive diagnosed youth, male circumcision for HIV-negative young men, pre-exposure prophylaxis (PrEP) for high-risk HIV-negative females (ages 20-24 years), and cash transfer for in-school HIV-negative girls (ages 15-19 years). Permutations of these were compared to adult-focused HIV testing coverage with condoms and TasP. RESULTS: The youth-focused strategy with ART treatment at diagnosis and condom use without adding interventions for HIV-negative youth performed better than the adult-focused strategy with adult testing reaching 50-60% coverage and TasP/condoms. Over the long term, the youth-focused strategy approached the performance of 70% adult testing and TasP/condoms. When high coverage male circumcision also is added to the youth-focused strategy, the combined intervention outperformed the adult-focused strategy with 70% testing, for at least 35 years by averting 94,000 more infections, averting 5.0 million more disability-adjusted life years (DALYs), and saving US$46.0 million over this period. The addition of prevention interventions beyond circumcision to the youth-focused strategy would be more beneficial if HIV care costs are high, or when program delivery costs are relatively high for programs encompassing HIV testing coverage exceeding 70%, TasP and condoms to HIV-infected adults compared to combination prevention programs among youth. CONCLUSION: For at least the next three decades, focusing in high burden settings on high coverage HIV testing, ART treatment upon diagnosis, condoms and male circumcision among youth may outperform adult-focused ART treatment upon diagnosis programs, unless the adult testing coverage in these programs reaches very high levels (>70% of all adults reached) at similar program costs. Our results indicate the potential importance of age-targeting for HIV prevention in the current era of 'test and start, ending AIDS' goals to ameliorate the HIV epidemic globally.

Quantitative assessment of the impact of partially protective anti-schistosomiasis vaccines.

BACKGROUND: Mass drug administration (MDA) of praziquantel has been the intervention of choice against schistosomiasis but with limited success in interrupting the transmission. The development of anti-Schistosoma vaccines is underway. Our objective is to quantify the population-level impact of anti-Schistosoma vaccines when administered alone and in combination with mass drug administration (MDA) and determine factors in vaccine design and public health implementation that optimize vaccination role in schistosomiasis control and elimination. METHODS AND FINDINGS: We developed a deterministic compartmental model simulation of schistosomiasis transmission in a high-risk Kenyan community, including stratification by age, parasite burden, and vaccination status. The modeled schistosomiasis vaccines differed in terms of vaccine duration of protection (durability) and three biological efficacies. These are vaccine susceptibility effect (SE) of reducing person's susceptibility to Schistosoma acquisition, vaccine mortality effect (ME) of reducing established worm burden and vaccine fecundity effect (FE) of reducing egg release by mature worms. We quantified the population-level impact of vaccination over two decades under diverse vaccination schemes (childhood vs. mass campaigns), with different age-targeting scenarios, different risk settings, and with combined intervention with MDA. We also assessed the sensitivity of our predictions to uncertainties in model parameters. Over two decades, our base case vaccine with 80% SE, FE, and ME efficacies, 10 years' durability, provided by mass vaccination every 10 years, reduced host prevalence, mean intensity, incidence, and patent snail prevalence to 31%, 20 eggs/10-ml sample/person, 0.87 worm/person-year, and 0.74%, from endemic-state values of 71%, 152, 3.3, and 0.98%, respectively. Lower impact was found when coverage did not encompass all potential contaminators, and childhood-only vaccination schemes showed delayed and lower impact. In lower prevalence settings, the base case vaccine generated a proportionately smaller impact. A substantially larger vaccine program effect was generated when MDA + mass vaccination was provided every 5 years, which could be achieved by an MDA-only program only if drug was offered annually. Vaccine impact on schistosomiasis transmission was sensitive to a number of parameters including vaccine efficacies, human contact rates with water, human density, patent snails' rate of patency and lifespan, and force of infection to snails. CONCLUSIONS: To be successful a vaccine-based control strategy will need a moderately to highly effective formulation combined with early vaccination of potential contaminators and aggressive coverage in repeated rounds of mass vaccination. Compared to MDA-only program, vaccination combined with MDA accelerates and prolongs the impact by reducing the acquisition of new worms and reducing egg release from residual worms.

Understanding the potential impact of a combination HIV prevention intervention in a hyper-endemic community.

OBJECTIVES: Despite demonstrating only partial efficacy in preventing new infections, available HIV prevention interventions could offer a powerful strategy when combined. In anticipation of combination HIV prevention programs and research studies we estimated the population-level impact of combining effective scalable interventions at high population coverage, determined the factors that influence this impact, and estimated the synergy between the components. METHODS: We used a mathematical model to investigate the effect on HIV incidence of a combination HIV prevention intervention comprised of high coverage of HIV testing and counselling, risk reduction following HIV diagnosis, male circumcision for HIV-uninfected men, and antiretroviral therapy (ART) for HIV-infected persons. The model was calibrated to data for KwaZulu-Natal, South Africa, where adult HIV prevalence is approximately 23%. RESULTS: Compared to current levels of HIV testing, circumcision, and ART, the combined intervention with ART initiation according to current guidelines could reduce HIV incidence by 47%, from 2.3 new infections per 100 person-years (pyar) to 1.2 per 100 pyar within 4 years and by almost 60%, to 1 per 100 pyar, after 25 years. Short-term impact is driven primarily by uptake of testing and reductions in risk behaviour following testing while long-term effects are driven by periodic HIV testing and retention in ART programs. If the combination prevention program incorporated HIV treatment upon diagnosis, incidence could be reduced by 63% after 4 years and by 76% (to about 0.5 per 100 pyar) after 15 years. The full impact of the combination interventions accrues over 10-15 years. Synergy is demonstrated between the intervention components. CONCLUSION: High coverage combination of evidence-based strategies could generate substantial reductions in population HIV incidence in an African generalized HIV epidemic setting. The full impact could be underestimated by the short assessment duration of typical evaluations.

Will circumcision provide even more protection from HIV to women and men? New estimates of the population impact of circumcision interventions.

BACKGROUND: Mathematical modelling has indicated that expansion of male circumcision services in high HIV prevalence settings can substantially reduce population-level HIV transmission. However, these projections need revision to incorporate new data on the effect of male circumcision on the risk of acquiring and transmitting HIV. METHODS: Recent data on the effect of male circumcision during wound healing and the risk of HIV transmission to women were synthesised based on four trials of circumcision among adults and new observational data of HIV transmission rates in stable partnerships from men circumcised at younger ages. New estimates were generated for the impact of circumcision interventions in two mathematical models, representing the HIV epidemics in Zimbabwe and Kisumu, Kenya. The models did not capture the interaction between circumcision, HIV and other sexually transmitted infections. RESULTS: An increase in the risk of HIV acquisition and transmission during wound healing is unlikely to have a major impact of circumcision interventions. However, it was estimated that circumcision confers a 46% reduction in the rate of male-to-female HIV transmission. If this reduction begins 2 years after the procedure, the impact of circumcision is substantially enhanced and accelerated compared with previous projections with no such effect-increasing by 40% the infections averted by the intervention overall and doubling the number of infections averted among women. CONCLUSIONS: Communities, and especially women, may benefit much more from circumcision interventions than had previously been predicted, and these results provide an even greater imperative to increase scale-up of safe male circumcision services.

Population level impact of an imperfect prophylactic vaccine for herpes simplex virus-2.

BACKGROUND: The continuation of developing Herpes simplex virus type-2 (HSV-2) prophylactic vaccines requires parallel mathematical modeling to quantify the effect on the population of these vaccines. METHODS: Using mathematical modeling we derived 3 summary measures for the population effect of imperfect HSV-2 vaccines as a function of their efficacies in reducing susceptibility (VES), genital shedding (VEP), and infectivity during shedding (VEI). In addition, we studied the population level effect of vaccine intervention using representative vaccine efficacies. RESULTS: A vaccine with limited efficacy of reducing shedding frequency (VEP = 10%) and infectivity (VEI = 0%) would need to reduce susceptibility by 75% (VES = 75%) to substantially reduce the sustainability of HSV-2 infection in a population. No reduction in susceptibility would be required to reach this target in a vaccine that decreased shedding by 75% (VES = 0%, VEP = 75%, VEI = 0%). Mass vaccination using a vaccine with imperfect efficacies (VES = 30%, VEP = 75%, and VEI = 0%) in Kisumu, Kenya, in 2010 would decrease prevalence and incidence in 2020 by 7% and 30%, respectively. For lower prevalence settings, vaccination is predicted to have a lower effect on prevalence. CONCLUSION: A vaccine with substantially high efficacy of reducing HSV-2 shedding frequency would have a desirable effect at the population level. The vaccine's short-term impact in a high prevalence setting in Africa would be a substantial decrease in incidence, whereas its immediate impact on prevalence would be small and would increase slowly over time.

HSV-2 serology can be predictive of HIV epidemic potential and hidden sexual risk behavior in the Middle East and North Africa.

BACKGROUND: HIV prevalence is low in the Middle East and North Africa (MENA) region, though the risk or potential for further spread in the future is not well understood. Behavioral surveys are limited in this region and when available have serious limitations in assessing the risk of HIV acquisition. We demonstrate the potential use of herpes simplex virus-2 (HSV-2) seroprevalence as a marker for HIV risk within MENA. METHODS: We designed a mathematical model to assess whether HSV-2 prevalence can be predictive of future HIV spread. We also conducted a systematic literature review of HSV-2 seroprevalence studies within MENA. RESULTS: We found that HSV-2 prevalence data are rather limited in this region. Prevalence is typically low among the general population but high in established core groups prone to sexually transmitted infections such as men who have sex with men and female sex workers. Our model predicts that if HSV-2 prevalence is low and stable, then the risk of future HIV epidemics is low. However, expanding or high HSV-2 prevalence (greater than about 20%), implies a risk for a considerable HIV epidemic. Based on available HSV-2 prevalence data, it is not likely that the general population in MENA is experiencing or will experience such a considerable HIV epidemic. Nevertheless, the risk for concentrated HIV epidemics among several high-risk core groups is present. CONCLUSIONS: HSV-2 prevalence surveys provide a useful mechanism for identifying and corroborating populations at risk for HIV within MENA. HSV-2 serology offers an effective tool for probing hidden sexual risk behaviors in a region where quality behavioral data are limited.

Quantitative assessment of the role of male circumcision in HIV epidemiology at the population level.

OBJECTIVE: Three recent randomized trials have shown that male circumcision (circumcision) reduces HIV incidence in heterosexual men by about 60%. Mathematical models are needed to assess the historical role of circumcision in the observed disparate levels of prevalence in sub-Saharan Africa and to translate these findings into estimates of the population-level impact of circumcision on HIV prevalence. METHODS AND FINDINGS: A deterministic compartmental model of HIV dynamics with circumcision was parameterized by empirical data from the Rakai, Masaka, and Four-City studies. Circumcision was found to account for about two-thirds of the differential HIV prevalence between West Africa and East and Southern Africa. We found that in Kisumu, Kenya, and in Rakai, Uganda, universal circumcision implemented in 2008 would reduce HIV prevalence by 19% and 14%, respectively, by 2020. In Kisumu, a setting with high HIV prevalence, about 6 circumcisions would be needed for each infection averted while in Rakai, 11 circumcisions would be needed. Females will also benefit from circumcision with a substantial reduction in prevalence of about 8% in Kisumu and 4% in Rakai within a few years of universal circumcision. The beneficial impact of circumcision for both males and females will not be undermined by risk behavior compensation unless the increase in risk behavior is in excess of 30%. The effectiveness of circumcision as an intervention is maximized by universal circumcision within 2-3 years. CONCLUSIONS: In West Africa, circumcision may have "quarantined" the spread of HIV by limiting sustainable transmission to within high risk groups and bridge populations. Our findings indicate that circumcision is an effective intervention in both high and intermediate HIV prevalence settings. Circumcision coverage should be expanded as soon as possible to optimize the epidemiological impact.