Estimating male circumcision coverage in 15 priority countries in sub-Saharan Africa.

INTRODUCTION: Given the importance of voluntary medical male circumcision (VMMC) in reducing HIV incidence, access to and use of quality data for programme planning and management are essential. Unfortunately, such data are currently not standardized for reliable and consistent programme use in priority countries. To redress this, the UNAIDS Reference Group (RG) on Estimates, Modelling, and Projection worked with partner Avenir Health to use the Decision Makers Program Planning Toolkit (DMPPT) 2 Online to provide estimates of VMMC coverage and to support countries to set age- and geographic-specific targets. This article describes the methods and tools used for assembling, reviewing and validating VMMC programme data as part of the 2021 Estimates process. DISCUSSION: The approach outlined for integrating VMMC data using the DMPPT2 Online required significant country engagement as well as upgrades to the DMPPT2 Online. The process brought together local-level VMMC stakeholders, for example Ministries of Health, the Joint United Nations Programme on HIV/AIDS (UNAIDS), the US President's Emergency Plan for AIDS Relief, the World Health Organization (WHO), VMMC implementers and so on, to review, amend and agree on historical and more recent VMMC data. The DMPPT2 Online was upgraded to align with the Spectrum and Naomi models used in the Annual HIV Estimates process. In addition, new and revised inputs were incorporated to enhance accuracy of modelled outputs. The process was successful in mobilizing stakeholders behind efforts to integrate VMMC into the annual HIV Estimates process and generating comprehensive, country-owned and validated VMMC data that will enhance programme monitoring and planning. CONCLUSIONS: VMMC programme data from most of the priority countries were successfully reviewed, updated, validated and incorporated into the annual HIV Estimates process in 2020. It is important to ensure that these data continue to be used for programme planning and management. Current and future data issues will need to be addressed, and countries will need ongoing support to do so. The integration of the DMPPT2 Online into the annual HIV Estimates process is a positive step forward in terms of streamlining country-owned planning and analytical practices for the HIV response.

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

BACKGROUND: The epidemiological and programmatic implications of inclusivity of HIV-positive males in voluntary medical male circumcision (VMMC) programs are uncertain. We modeled these implications using Zambia as an illustrative example. METHODS AND FINDINGS: We used the Age-Structured Mathematical (ASM) model to evaluate, over an intermediate horizon (2010-2025), the effectiveness (number of VMMCs needed to avert one HIV infection) of VMMC scale-up scenarios with varying proportions of HIV-positive males. The model was calibrated by fitting to HIV prevalence time trend data from 1990 to 2014. We assumed that inclusivity of HIV positive males may benefit VMMC programs by increasing VMMC uptake among higher risk males, or by circumcision reducing HIV male-to-female transmission risk. All analyses were generated assuming no further antiretroviral therapy (ART) scale-up. The number of VMMCs needed to avert one HIV infection was projected to increase from 12.2 VMMCs per HIV infection averted, in a program that circumcises only HIV-negative males, to 14.0, in a program that includes HIV-positive males. The proportion of HIV-positive males was based on their representation in the population (e.g. 12.6% of those circumcised in 2010 would be HIV-positive based on HIV prevalence among males of 12.6% in 2010). However, if a program that only reaches out to HIV-negative males is associated with 20% lower uptake among higher-risk males, the effectiveness would be 13.2 VMMCs per infection averted. If improved inclusivity of HIV-positive males is associated with 20% higher uptake among higher-risk males, the effectiveness would be 12.4. As the assumed VMMC efficacy against male-to-female HIV transmission was increased from 0% to 20% and 46%, the effectiveness of circumcising regardless of HIV status improved from 14.0 to 11.5 and 9.1, respectively. The reduction in the HIV incidence rate among females increased accordingly, from 24.7% to 34.8% and 50.4%, respectively. CONCLUSION: Improving inclusivity of males in VMMC programs regardless of HIV status increases VMMC effectiveness, if there is moderate increase in VMMC uptake among higher-risk males and/or if there is moderate efficacy for VMMC against male-to-female transmission. In these circumstances, VMMC programs can reduce the HIV incidence rate in males by nearly as much as expected by some ART programs, and additionally, females can benefit from the intervention nearly as much as males.

Gene expression diversity among Mycobacterium tuberculosis clinical isolates.

Intraspecies genetic diversity has been demonstrated to be important in the pathogenesis and epidemiology of several pathogens, such as HIV, influenza, Helicobacter and Salmonella. It is also important to consider strain-to-strain variation when identifying drug targets and vaccine antigens and developing tools for molecular diagnostics. Here, the authors present a description of the variability in gene expression patterns among ten clinical isolates of Mycobacterium tuberculosis, plus the laboratory strains H37Rv and H37Ra, growing in liquid culture. They identified 527 genes (15 % of those tested) that are variably expressed among the isolates studied. The remaining genes were divided into three categories based on their expression levels: unexpressed (38 %), low to undetectable expression (31 %) and consistently expressed (16 %). The expression categories were compared with functional categories and three biologically interesting gene lists: genes that are deleted among clinical isolates, T-cell antigens and essential genes. There were significant associations between expression variability and the classification of genes as T-cell antigens, involved in lipid metabolism, PE/PPE, insertion sequences and phages, and deleted among clinical isolates. This survey of mRNA expression among clinical isolates of M. tuberculosis demonstrates that genes with important functions can vary in their expression levels between strains grown under identical conditions.