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Introduction: Despite widespread success in reducing vertical HIV transmission, most antenatal care (ANC) programmes in eastern and southern Africa have not emphasized primary prevention of maternal HIV acquisition during pregnancy and lactation/breastfeeding. We hypothesized that combination HIV prevention interventions initiated alongside ANC could substantially reduce maternal HIV incidence. Methods: We constructed a multi‐state model describing male‐to‐female HIV transmission in steady heterosexual partnerships during pregnancy and lactation/breastfeeding, with initial conditions based on population distribution estimates for Malawi and Zambia in 2020. We modelled individual and joint increases in three HIV prevention strategies at or soon after ANC initiation: (1) HIV testing of male partners, resulting in HIV diagnosis and less condomless sex among those with previously undiagnosed HIV; (2) initiation (or re‐initiation) of suppressive antiretroviral therapy (ART) for male partners with diagnosed but unsuppressed HIV; and (3) adherent pre‐exposure prophylaxis (PrEP) for HIV‐negative female ANC patients with HIV‐diagnosed or unknown‐status male partners. We estimated the percentage of within‐couple, male‐to‐female HIV transmissions that could be averted during pregnancy and lactation/breastfeeding with these strategies, relative to base‐case conditions in which 45% of undiagnosed male partners become newly HIV diagnosed via testing, 75% of male partners with diagnosed but unsuppressed HIV initiate/re‐initiate ART and 0% of female ANC patients start PrEP. Results: Increasing uptake of any single strategy by 20 percentage points above base‐case levels averted 10%−11% of maternal HIV acquisitions during pregnancy and lactation/breastfeeding in the model. Joint uptake increases of 20 percentage points in two interventions averted an estimated 19%−23% of transmissions, and with a 20‐percentage‐point increase in uptake of all three interventions, 29% were averted. Strategies achieving 95% male testing, 90% male ART initiation/re‐initiation and 40% female PrEP use reduced incident infections by 45%. Conclusions: Combination HIV prevention strategies provided alongside ANC and sustained through the post‐partum period could substantially reduce maternal HIV incidence during pregnancy and lactation/breastfeeding in eastern and southern Africa. [ABSTRACT FROM AUTHOR]

Women's empowerment is associated with engagement in some areas of healthcare, but its role in prevention of mother-to-child HIV transmission (PMTCT) services has not been previously considered. In this secondary analysis, we investigated the association of women's decision-making and uptake of health services for PMTCT. Using data from population-based household surveys, we included women who reported delivery in the 2-year period prior to the survey and were HIV-infected. We measured a woman's self-reported role in decision-making in her own healthcare, making of large purchases, schooling of children, and healthcare for children. For each domain, respondents were categorized as having an “active” or “no active” role. We investigated associations between decision-making and specific steps along the PMTCT cascade: uptake of maternal antiretroviral drugs, uptake of infant HIV prophylaxis, and infant HIV testing. We calculated unadjusted and adjusted odds ratios via logistic regression. From March to December 2011, 344 HIV-infected mothers were surveyed and 276 completed the relevant survey questions. Of these, 190 (69%) took antiretroviral drugs during pregnancy; 175 (64%) of their HIV-exposed infants received antiretroviral prophylaxis; and 160 (58%) had their infant tested for HIV. There was no association between decision-making and maternal or infant antiretroviral drug use. We observed a significant association between decision-making and infant HIV testing in univariate analyses (OR 1.56–1.85;p < 0.05); however, odds ratios for the decision-making indicators were no longer statistically significant predictors of infant HIV testing in multivariate analyses. In conclusion, women who reported an active role in decision-making trended toward a higher likelihood of uptake of infant testing in the PMTCT cascade. Larger studies are needed to evaluate the impact of empowerment initiatives on the PMTCT service utilization overall and infant testing in particular. [ABSTRACT FROM AUTHOR]

Background: Population-based evaluations of programs for prevention of mother-to-child HIV transmission (PMTCT) are scarce. We measured PMTCT service coverage, regimen use, and HIV-free survival among children ≤24 mo of age in Cameroon, Côte D'Ivoire, South Africa, and Zambia. Methods and Findings: We randomly sampled households in 26 communities and offered participation if a child had been born to a woman living there during the prior 24 mo. We tested consenting mothers with rapid HIV antibody tests and tested the children of seropositive mothers with HIV DNA PCR or rapid antibody tests. Our primary outcome was 24-mo HIV-free survival, estimated with survival analysis. In an individual-level analysis, we evaluated the effectiveness of various PMTCT regimens. In a community-level analysis, we evaluated the relationship between HIV-free survival and community PMTCT coverage (the proportion of HIV-exposed infants in each community that received any PMTCT intervention during gestation or breastfeeding). We also compared our community coverage results to those of a contemporaneous study conducted in the facilities serving each sampled community. Of 7,985 surveyed children under 2 y of age, 1,014 (12.7%) were HIV-exposed. Of these, 110 (10.9%) were HIV-infected, 851 (83.9%) were HIV-uninfected, and 53 (5.2%) were dead. HIV-free survival at 24 mo of age among all HIV-exposed children was 79.7% (95% CI: 76.4, 82.6) overall, with the following country-level estimates: Cameroon (72.6%; 95% CI: 62.3, 80.5), South Africa (77.7%; 95% CI: 72.5, 82.1), Zambia (83.1%; 95% CI: 78.4, 86.8), and Côte D'Ivoire (84.4%; 95% CI: 70.0, 92.2). In adjusted analyses, the risk of death or HIV infection was non-significantly lower in children whose mothers received a more complex regimen of either two or three antiretroviral drugs compared to those receiving no prophylaxis (adjusted hazard ratio: 0.60; 95% CI: 0.34, 1.06). Risk of death was not different for children whose mothers received a more complex regimen compared to those given single-dose nevirapine (adjusted hazard ratio: 0.88; 95% CI: 0.45, 1.72). Community PMTCT coverage was highest in Cameroon, where 75 of 114 HIV-exposed infants met criteria for coverage (66%; 95% CI: 56, 74), followed by Zambia (219 of 444, 49%; 95% CI: 45, 54), then South Africa (152 of 365, 42%; 95% CI: 37, 47), and then Côte D'Ivoire (3 of 53, 5.7%; 95% CI: 1.2, 16). In a cluster-level analysis, community PMTCT coverage was highly correlated with facility PMTCT coverage (Pearson's r = 0.85), and moderately correlated with 24-mo HIV-free survival (Pearson's r = 0.29). In 14 of 16 instances where both the facility and community samples were large enough for comparison, the facility-based coverage measure exceeded that observed in the community. Conclusions: HIV-free survival can be estimated with community surveys and should be incorporated into ongoing country monitoring. Facility-based coverage measures correlate with those derived from community sampling, but may overestimate population coverage. The more complex regimens recommended by the World Health Organization seem to have measurable public health benefit at the population level, but power was limited and additional field validation is needed. Please see later in the article for the Editors' Summary [ABSTRACT FROM AUTHOR]

Background: Although patient attrition is recognized as a threat to the long-term success of antiretroviral therapy programs worldwide, there is no universal definition for classifying patients as lost to follow-up (LTFU). We analyzed data from health facilities across Africa, Asia, and Latin America to empirically determine a standard LTFU definition. Methods and Findings: At a set "status classification" date, patients were categorized as either "active" or "LTFU" according to different intervals from time of last clinic encounter. For each threshold, we looked forward 365 d to assess the performance and accuracy of this initial classification. The best-performing definition for LTFU had the lowest proportion of patients misclassified as active or LTFU. Observational data from 111 health facilities-representing 180,718 patients from 19 countries-were included in this study. In the primary analysis, for which data from all facilities were pooled, an interval of 180 d (95% confidence interval [CI]: 173-181 d) since last patient encounter resulted in the fewest misclassifications (7.7%, 95% CI: 7.6%-7.8%). A secondary analysis that gave equal weight to cohorts and to regions generated a similar result (175 d); however, an alternate approach that used inverse weighting for cohorts based on variance and equal weighting for regions produced a slightly lower summary measure (150 d). When examined at the facility level, the best-performing definition varied from 58 to 383 d (mean = 150 d), but when a standard definition of 180 d was applied to each facility, only slight increases in misclassification (mean = 1.2%, 95% CI: 1.0%-1.5%) were observed. Using this definition, the proportion of patients classified as LTFU by facility ranged from 3.1% to 45.1% (mean = 19.9%, 95% CI: 19.1%-21.7%). Conclusions: Based on this evaluation, we recommend the adoption of $180 d since the last clinic visit as a standard LTFU definition. Such standardization is an important step to understanding the reasons that underlie patient attrition and establishing more reliable and comparable program evaluation worldwide. [ABSTRACT FROM AUTHOR]

The article discusses a study which measured the coverage of services aimed at preventing mother-to-child human immunodeficiency virus (HIV) transmission in four African countries. The cross-sectional surveillance study of mother-infant pairs used umbilical cord blood samples from selected facilities that provide delivery services in several countries, including Cameroon and South Africa. The authors found that only 51 percent of HIV-exposed infants received the minimal regimen of single-dose nevirapine.

The article reports on the Six-Week Extended-Dose Nevirapine (SWEN) Study involving HIV-exposed breastfeeding infants in Africa and India. The article describes the randomised study, and the results are detailed. The SWEN regimen is compared with another, more effective randomised trial, the PEPI study. The article contends that pediatric HIV-prevention services need to be improved globally and argues that extended infant prophylaxis with nevirapine is the solution.

Background: Single-dose nevirapine is the cornerstone of the regimen for prevention of mother-to-child transmission of human immunodeficiency virus (HIV) in resource-limited settings, but nevirapine frequently selects for resistant virus in mothers and children who become infected despite prophylaxis. The optimal antiretroviral treatment strategy for children who have had prior exposure to single-dose nevirapine is unknown. Methods: We conducted a randomized trial of initial therapy with zidovudine and lamivudine plus either nevirapine or ritonavir-boosted lopinavir in HIV-infected children 6 to 36 months of age, in six African countries, who qualified for treatment according to World Health Organization (WHO) criteria. Results are reported for the cohort that included children exposed to single-dose nevirapine prophylaxis. The primary end point was virologic failure or discontinuation of treatment by study week 24. Enrollment in this cohort was terminated early on the recommendation of the data and safety monitoring board. Results: A total of 164 children were enrolled. The median percentage of CD4+ lymphocytes was 19%; a total of 56% of the children had WHO stage 3 or 4 disease. More children in the nevirapine group than in the ritonavir-boosted lopinavir group reached a primary end point (39.6% vs. 21.7%; weighted difference, 18.6 percentage-points; 95% confidence interval, 3.7 to 33.6; nominal P=0.02). Baseline resistance to nevirapine was detected in 18 of 148 children (12%) and was predictive of treatment failure. No significant between-group differences were seen in the rate of adverse events. Conclusions: Among children with prior exposure to single-dose nevirapine for perinatal prevention of HIV transmission, antiretroviral treatment consisting of zidovudine and lamivudine plus ritonavir-boosted lopinavir resulted in better outcomes than did treatment with zidovudine and lamivudine plus nevirapine. Since nevirapine is used for both treatment and perinatal prevention of HIV infection in resource-limited settings, alternative strategies for the prevention of HIV transmission from mother to child, as well as for the treatment of HIV infection, are urgently required. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00307151.) N Engl J Med 2010;363:1510-20. [ABSTRACT FROM AUTHOR]

Mentoring is a proven path to scientific progress, but it is not a common practice in low- and middle-income countries (LMICs). Existing mentoring approaches and guidelines are geared toward high-income country settings, without considering in detail the differences in resources, culture, and structure of research systems of LMICs. To address this gap, we conducted five Mentoring-the-Mentor workshops in Africa, South America, and Asia, which aimed at strengthening the capacity for evidence-based, LMIC-specific institutional mentoring programs globally. The outcomes of the workshops and two follow-up working meetings are presented in this special edition of the American Journal of Tropical Medicine and Hygiene . Seven articles offer recommendations on how to tailor mentoring to the context and culture of LMICs, and provide guidance on how to implement mentoring programs. This introductory article provides both a prelude and executive summary to the seven articles, describing the motivation, cultural context and relevant background, and presenting key findings, conclusions, and recommendations.

A growing number of low- and middle-income country (LMIC) institutions have developed and implemented formal programs to support mentorship. Although the individual-level benefits of mentorship are well established, such activities can also sustainably build institutional capacity, bridge inequities in health care, and catalyze scientific advancement. To date, however, evaluation of these programs remains limited, representing an important gap in our understanding about the impact of mentoring. Without rigorous and ongoing evaluation, there may be missed opportunities for identifying best practices, iteratively improving program activities, and demonstrating the returns on investment in mentorship. In this report, we propose a framework for evaluating mentorship programs in LMIC settings where resources may be constrained. We identify six domains: 1) mentor-mentee relationship, 2) career guidance, 3) academic productivity, 4) networking, 5) wellness, and 6) organizational capacity. Within each, we describe specific metrics and how they may be considered as part of evaluation plans. We emphasize the role of measurement and evaluation at the institutional level, so that programs may enhance their mentoring capacity and optimize the management of their resources. Although we advocate for a comprehensive approach to evaluation, we recognize that-depending on stage and relative maturity-some domains may be prioritized to address short- and medium-term program goals.

Background: Given the ambitious targets to reduce pediatric AIDS worldwide, ongoing assessment of programs to prevent mother-to-child HIV transmission (PMTCT) is critical. The concept of a "PMTCT cascade" has been used widely to identify bottlenecks in program implementation; however, most efforts to reconstruct the cascade have relied on facility-based approaches that may limit external validity., Methods: We analyzed data from the PEARL household survey, which measured PMTCT effectiveness in 26 communities across Zambia, South Africa, Cote d'Ivoire, and Cameroon. We recruited women who reported a delivery in the past 2 years. Among mothers confirmed to be HIV infected at the time of survey, we reconstructed the PMTCT cascade with self-reported participant information. We also analyzed data about the child's vital status; for those still alive, HIV testing was performed by DNA polymerase chain reaction testing., Results: Of the 976 eligible women, only 355 (36%) completed every step of the PMTCT cascade. Among the 621 mother-child pairs who did not, 22 (4%) reported never seeking antenatal care, 103 (17%) were not tested for HIV during pregnancy, 395 (64%) reported testing but never received their HIV-positive result, 48 (8%) did not receive maternal antiretroviral prophylaxis, and 53 (9%) did not receive infant antiretroviral prophylaxis. The lowest prevalence of infant HIV infection or death was observed in those completing the cascade (10%, 95% confidence interval: 7% to 12%)., Conclusions: Future efforts to measure population PMTCT impact should incorporate dimensions explored in the PEARL study-including HIV testing of HIV-exposed children in household surveys-to better understand program effectiveness.

Among 6789 HIV-infected Zambian adults screened for hepatitis B virus (HBV) coinfection, estimated glomerular filtration rate (eGFR) was 50-90 mL/minute/1.73 m(2) in 17.6% and <50 mL/minute/1.73 m(2) in 2.5%. Human immunodeficiency virus/HBV coinfection was associated with eGFR <50 mL/minute/1.73 m(2) (adjusted odds ratio, 1.96 [95% confidence interval, 1.34-2.86]), adjusted for age, sex, CD4(+) count, and World Health Organization disease stage., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Health facility characteristics associated with effective prevention of mother-to-child transmission of HIV (PMTCT) coverage in sub-Saharan are poorly understood., Methodology/principal Findings: We conducted surveys in health facilities with active PMTCT services in Cameroon, Cote d'Ivoire, South Africa, and Zambia. Data was compiled via direct observation and exit interviews. We constructed composite scores to describe provision of PMTCT services across seven topical areas: antenatal quality, PMTCT quality, supplies available, patient satisfaction, patient understanding of medication, and infrastructure quality. Pearson correlations and Generalized Estimating Equations (GEE) to account for clustering of facilities within countries were used to evaluate the relationship between the composite scores, total time of visit and select individual variables with PMTCT coverage among women delivering. Between July 2008 and May 2009, we collected data from 32 facilities; 78% were managed by the government health system. An opt-out approach for HIV testing was used in 100% of facilities in Zambia, 63% in Cameroon, and none in Côte d'Ivoire or South Africa. Using Pearson correlations, PMTCT coverage (median of 55%, (IQR: 33-68) was correlated with PMTCT quality score (rho = 0.51; p = 0.003); infrastructure quality score (rho = 0.43; p = 0.017); time spent at clinic (rho = 0.47; p = 0.013); patient understanding of medications score (rho = 0.51; p = 0.006); and patient satisfaction quality score (rho = 0.38; p = 0.031). PMTCT coverage was marginally correlated with the antenatal quality score (rho = 0.304; p = 0.091). Using GEE adjustment for clustering, the, antenatal quality score became more strongly associated with PMTCT coverage (p<0.001) and the PMTCT quality score and patient understanding of medications remained marginally significant., Conclusions/results: We observed a positive relationship between an antenatal quality score and PMTCT coverage but did not identify a consistent set of variables that predicted PMTCT coverage.