Susanne F. Awad

Mapping HIV clustering: a strategy for identifying populations at high risk of HIV infection in sub-Saharan Africa

BackgroundThe geographical structure of an epidemic is ultimately a consequence of thedrivers of the epidemic and the population susceptible to the infection. The‘know your epidemic’ concept recognizes this geographicalfeature as a key element for identifying populations at higher risk of HIVinfection where prevention interventions should be targeted. In an effort toclarify specific drivers of HIV transmission and identify prioritypopulations for HIV prevention interventions, we conducted a comprehensivemapping of the spatial distribution of HIV infection across sub-SaharanAfrica (SSA).MethodsThe main source of data for our study was the Demographic and Health Surveyconducted in 20 countries from SSA. We identified and compared spatialclusters with high and low numbers of HIV infections in each country usingKulldorff spatial scan test. The test locates areas with higher and lowernumbers of HIV infections than expected under spatial randomness. For eachidentified cluster, a likelihood ratio test was computed. A P-valuewas determined through Monte Carlo simulations to evaluate the statisticalsignificance of each cluster.ResultsOur results suggest stark geographic variations in HIV transmission patternswithin and across countries of SSA. About 14% of the population in SSA islocated in areas of intense HIV epidemics. Meanwhile, another 16% of thepopulation is located in areas of low HIV prevalence, where some behavioralor biological protective factors appear to have slowed HIV transmission.ConclusionsOur study provides direct evidence for strong geographic clustering of HIVinfection across SSA. This striking pattern of heterogeneity at themicro-geographical scale might reflect the fact that most HIV epidemics inthe general population in SSA are not far from their epidemic threshold. Ourfindings identify priority geographic areas for HIV programming, and supportthe need for spatially targeted interventions in order to maximize theimpact on the epidemic in SSA.

Sources of HIV incidence among stable couples in sub-Saharan Africa

The recent availability of efficacious prevention interventions among stable couples offers new opportunities for reducing HIV incidence in sub‐Saharan Africa. Understanding the dynamics of HIV incidence among stable couples is critical to inform HIV prevention strategy across sub‐Saharan Africa.

Estimation of hepatitis C virus infections resulting from vertical transmission in Egypt

Despite having the highest hepatitis C virus (HCV) prevalence in the world, the ongoing level of HCV incidence in Egypt and its drivers are poorly understood. Whereas HCV mother‐to‐child infection is a well‐established transmission route, there are no estimates of HCV infections resulting from vertical transmission for any country, including Egypt. The aim of this study was to estimate the absolute number of new HCV infections resulting from vertical transmission in Egypt. We developed a conceptual framework of HCV vertical transmission, expressed in terms of a mathematical model and based on maternal HCV antibody and viremia. The mathematical model estimated the number of HCV vertical infections nationally and for six subnational areas. Applying two vertical transmission risk estimates to the 2008 Egyptian birth cohort, we estimated that between 3,080 and 5,167 HCV infections resulted from vertical transmission among children born in 2008. HCV vertical transmission may account for half of incident cases in the <5‐year age group. Disproportionately higher proportions of vertical infections were estimated in Lower Rural and Upper Rural subnational areas. This geographical clustering was a result of higher‐area‐level HCV prevalence among women and higher fertility rates. Conclusion: Vertical transmission is one of the primary HCV infection routes among children <5 years in Egypt. The absolute number of vertical transmissions and the young age at infection highlight a public health concern. These findings also emphasize the need to quantify the relative contributions of other transmission routes to HCV incidence in Egypt. (Hepatology 2015;61:834–842)

The risk of HIV transmission within HIV-1 sero-discordant couples appears to vary across sub-Saharan Africa.

BACKGROUND Representative and precise estimates for the annual risk of HIV transmission (ϕ) from the infected to the uninfected partner in a stable HIV-1 sero-discordant couple (SDC) are not available. Nevertheless, quantifying HIV infectiousness is critical to understanding HIV epidemiology and implementing prevention programs. MATERIALS AND METHODS We estimated ϕ and examined its variation across 23 countries in sub-Saharan Africa (SSA) by constructing and analyzing a mathematical model that describes HIV dynamics among SDCs. The model was parameterized using empirical measures such as those of the nationally representative Demographic and Health Surveys. Uncertainty and sensitivity analyses were conducted to assess the robustness of the findings. RESULTS We estimated a median ϕ of 11.1 per 100 person-years across SSA. A clustering based on HIV population prevalence was observed with a median ϕ of 7.5 per 100 person-years in low HIV prevalence countries (<5%) compared to 19.5 per 100 person-years in high prevalence countries (>5%). The association with HIV prevalence explained 67% of the variation in ϕ, and suggested an increase of 0.95 per 100 person-years in ϕ for every 1% increase in HIV prevalence. CONCLUSIONS Empirical measures from cohort studies appear to underestimate HIV infectiousness in SSA. The risk of HIV transmission among SDCs appears also to vary across SSA, and this may have contributed to the contrasting HIV epidemic trajectories in this continent.

Investigating Voluntary Medical Male Circumcision Program Efficiency Gains through Subpopulation Prioritization: Insights from Application to Zambia.

Background Countries in sub-Saharan Africa are scaling-up voluntary male medical circumcision (VMMC) as an HIV intervention. Emerging challenges in these programs call for increased focus on program efficiency (optimizing program impact while minimizing cost). A novel analytic approach was developed to determine how subpopulation prioritization can increase program efficiency using an illustrative application for Zambia. Methods and Findings A population-level mathematical model was constructed describing the heterosexual HIV epidemic and impact of VMMC programs (age-structured mathematical (ASM) model). The model stratified the population according to sex, circumcision status, age group, sexual-risk behavior, HIV status, and stage of infection. A three-level conceptual framework was also developed to determine maximum epidemic impact and program efficiency through subpopulation prioritization, based on age, geography, and risk profile. In the baseline scenario, achieving 80% VMMC coverage by 2017 among males 15–49 year old, 12 VMMCs were needed per HIV infection averted (effectiveness). The cost per infection averted (cost-effectiveness) was USD

Could there have been substantial declines in sexual risk behavior across sub-Saharan Africa in the mid-1990s?

1,089 and 306,000 infections were averted. Through age-group prioritization, effectiveness ranged from 11 (20–24 age-group) to 36 (45–49 age-group); cost-effectiveness ranged from

A Reevaluation of the Voluntary Medical Male Circumcision Scale-Up Plan in Zimbabwe.

888 (20–24 age-group) to

Estimate of vertical transmission of Hepatitis C virus in Pakistan in 2007 and 2012 birth cohorts

3,300 (45–49 age-group). Circumcising 10–14, 15–19, or 20–24 year old achieved the largest incidence rate reduction; prioritizing 15–24, 15–29, or 15–34 year old achieved the greatest program efficiency. Through geographic prioritization, effectiveness ranged from 9–12. Prioritizing Lusaka achieved the highest effectiveness. Through risk-group prioritization, prioritizing the highest risk group achieved the highest effectiveness, with only one VMMC needed per infection averted; the lowest risk group required 80 times more VMMCs. Conclusion Epidemic impact and efficiency of VMMC programs can be improved by prioritizing young males (sexually active or just before sexual debut), geographic areas with higher HIV prevalence than the national, and high sexual-risk groups.

Are Geographical “Cold Spots” of Male Circumcision Driving Differential HIV Dynamics in Tanzania?

BACKGROUND HIV prevalence is decreasing in much of sub-Saharan Africa (SSA), but the drivers of the decline are subject to much dispute. Using mathematical modeling as a tool for hypothesis generation, we demonstrate how the hypothesis that the drop in prevalence reflects declines in sexual risk behavior is self-consistent. We characterize these potential declines in terms of their scale, duration, and timing, and theorize on how small changes in sexual behavior at the individual-level could have driven large declines in HIV prevalence. MATERIALS AND METHODS A population-level deterministic compartmental model was constructed to describe the HIV epidemics in 24 countries in SSA with sufficient trend data. The model was parameterized by national HIV prevalence and HIV natural history and transmission data. The temporal evolution of sexual risk behavior was characterized using established tools and uncertainty and sensitivity analyses on the results were conducted. RESULTS Declines in the scale of sexual risk behavior between 31.8% (Botswana) and 89.3% (Liberia) can explain the declining HIV prevalence across countries. The average decline across countries was 68.9%. The transition in sexual risk behavior lasted between 2.7 (Botswana) and 16.6 (Gabon) years with an average of 8.2 years. The turning point year of the transition occurred between 1993 (Burundi) and 2001 (Namibia), but clustered around 1995 for most countries. The uncertainty and sensitivity analyses affirmed our model predictions. CONCLUSION The hypothesis that HIV prevalence declines in SSA have been driven by declines in sexual risk behavior is self-consistent and provides a convincing narrative for an evolving HIV epidemiology in this region. The hypothesized declines must have been remarkable in their intensity, rapidity, and synchronicity to explain the temporal trends in HIV prevalence. These findings provide contextual support for the hypothesis that changes in sexual behavior that materialized in the 1990s are a dominant driver of the recent decreases in HIV prevalence.

Could Circumcision of HIV-Positive Males Benefit Voluntary Medical Male Circumcision Programs in Africa? Mathematical Modeling Analysis

Background The voluntary medical male circumcision (VMMC) program in Zimbabwe aims to circumcise 80% of males aged 13–29 by 2017. We assessed the impact of actual VMMC scale-up to date and evaluated the impact of potential alterations to the program to enhance program efficiency, through prioritization of subpopulations. Methods and Findings We implemented a recently developed analytical approach: the age-structured mathematical (ASM) model and accompanying three-level conceptual framework to assess the impact of VMMC as an intervention. By September 2014, 364,185 males were circumcised, an initiative that is estimated to avert 40,301 HIV infections by 2025. Through age-group prioritization, the number of VMMCs needed to avert one infection (effectiveness) ranged between ten (20–24 age-group) and 53 (45–49 age-group). The cost per infection averted ranged between