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

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 $811 (20–24 age-group) and $5,518 (45–49 age-group). By 2025, the largest reductions in HIV incidence rate (up to 27%) were achieved by prioritizing 10–14, 15–19, or 20–24 year old. The greatest program efficiency was achieved by prioritizing 15–24, 15–29, or 15–34 year old. Prioritizing males 13–29 year old was programmatically efficient, but slightly inferior to the 15–24, 15–29, or 15–34 age groups. Through geographic prioritization, effectiveness varied from 9–12 VMMCs per infection averted across provinces. Through risk-group prioritization, effectiveness ranged from one (highest sexual risk-group) to 60 (lowest sexual risk-group) VMMCs per infection averted.

Conclusion

The current VMMC program plan in Zimbabwe is targeting an efficient and impactful age bracket (13–29 year old), but program efficiency can be improved by prioritizing a subset of males for demand creation and service availability. The greatest program efficiency can be attained by prioritizing young sexually active males and males whose sexual behavior puts them at higher risk for acquiring HIV.     

Tumour eradication and induction of memory against murine mesothelioma by combined immunotherapy

Numerous immunotherapy treatments for cancer are undergoing clinical trials or are already approved for use. One particular area of interest is targeting mechanisms of immune tolerance. Using a murine model of mesothelioma, we investigated the roles of regulatory T-cells, intratumoural transforming growth factor (TGF)-β and the negative regulator molecule cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) in immune tolerance to tumours. It was found that treatments targeting a single negative regulator molecule mechanism were not as effective against tumours as targeting multiple mechanisms simultaneously. Most importantly, it was found that a combined triple treatment of anti-CD25 monoclonal antibody (mAb), anti-CTLA-4 mAb and TGF-β soluble receptor resulted in long-term clearance of tumours and memory against tumour rechallenge. These data suggest that clinical application of immunotherapies against tumours may be improved by simultaneously targeting multiple mechanisms of immune suppression.     

Distinct Effects of Different Phosphatidylglycerol Species on Mouse Keratinocyte Proliferation

We have previously shown that liposomes composed of egg-derived phosphatidylglycerol (PG), with a mixed fatty acid composition (comprising mainly palmitate and oleate), inhibit the proliferation and promote the differentiation of rapidly dividing keratinocytes, and stimulate the growth of slowly proliferating epidermal cells. To determine the species of PG most effective at modulating keratinocyte proliferation, primary mouse keratinocytes were treated with different PG species, and proliferation was measured. PG species containing polyunsaturated fatty acids were effective at inhibiting rapidly proliferating keratinocytes, whereas PG species with monounsaturated fatty acids were effective at promoting proliferation in slowly dividing cells. Thus, palmitoyl-arachidonyl-PG (16∶0/20∶4), palmitoyl-linoleoyl-PG (16∶0/18∶2), dilinoleoyl-PG (18∶2/18∶2) and soy PG (a PG mixture with a large percentage of polyunsaturated fatty acids) were particularly effective at inhibiting proliferation in rapidly dividing keratinocytes. Conversely, palmitoyl-oleoyl-PG (16∶0/18∶1) and dioleoyl-PG (18∶1/18∶1) were especially effective proproliferative PG species. This result represents the first demonstration of opposite effects of different species of a single class of phospholipid and suggests that these different PG species may signal to diverse effector enzymes to differentially affect keratinocyte proliferation and normalize keratinocyte proliferation. Thus, different PG species may be useful for treating skin diseases characterized by excessive or insufficient proliferation.     

Factors Associated with Ever Being HIV-Tested in Zimbabwe: An Extended Analysis of the Zimbabwe Demographic and Health Survey (2010–2011)

Introduction

Zimbabwe has a high human immunodeficiency virus (HIV) burden. It is therefore important to scale up HIV-testing and counseling (HTC) as a gateway to HIV prevention, treatment and care.

Objective

To determine factors associated with being HIV-tested among adult men and women in Zimbabwe.

Methods

Secondary analysis was done using data from 7,313 women and 6,584 men who completed interviewer-administered questionnaires and provided blood specimens for HIV testing during the Zimbabwe Demographic and Health Survey (ZDHS) 2010–11. Factors associated with ever being HIV-tested were determined using multivariate logistic regression.

Results

HIV-testing was higher among women compared to men (61% versus 39%). HIV-infected respondents were more likely to be tested compared to those who were HIV-negative for both men [adjusted odds ratio (AOR) = 1.53; 95% confidence interval (CI) (1.27–1.84)] and women [AOR = 1.42; 95% CI (1.20–1.69)]. However, only 55% and 74% of these HIV-infected men and women respectively had ever been tested. Among women, visiting antenatal care (ANC) [AOR = 5.48, 95% CI (4.08–7.36)] was the most significant predictor of being tested whilst a novel finding for men was higher odds of testing among those reporting a sexually transmitted infection (STI) in the past 12 months [AOR = 1.86, 95%CI (1.26–2.74)]. Among men, the odds of ever being tested increased with age ≥20 years, particularly those 45–49 years [AOR = 4.21; 95% CI (2.74–6.48)] whilst for women testing was highest among those aged 25–29 years [AOR = 2.01; 95% CI (1.63–2.48)]. Other significant factors for both sexes were increasing education level, higher wealth status and currently/formerly being in union.

Conclusions

There remains a high proportion of undiagnosed HIV-infected persons and hence there is a need for innovative strategies aimed at increasing HIV-testing, particularly for men and in lower-income and lower-educated populations. Promotion of STI services can be an important gateway for testing more men whilst ANC still remains an important option for HIV-testing among pregnant women.