An HIV-1 risk assessment tool for women aged 15-49 in African countries: A pooled analysis across 15 nationally representative surveys.

BACKGROUND: Women in Africa disproportionately acquire HIV-1. Understanding which women are most likely to acquire HIV-1 can guide focused prevention with pre-exposure prophylaxis (PrEP). Our objective is to identify women at highest risk of HIV-1 and estimate PrEP efficiency at different sensitivity levels. METHODS: Nationally representative data were collected from 2015-2019 from 15 population-based household surveys. This analysis included women aged 15-49 who tested HIV-1 sero-negative or had recent HIV-1. Least absolute shrinkage and selection operator regression models were fit with 28 variables to predict recent HIV-1. Models were trained on the full population and internally cross-validated. Performance was evaluated using area under the receiver-operating-characteristic curve (AUC), sensitivity, and number needed to treat (NNT) with PrEP to avert one infection. RESULTS: Among 209,012 participants 248 had recent HIV-1 infection, representing 118 million women and 402,000 (95% CI: 309,000-495,000) new annual infections. Two variables were retained in the model: living in a subnational area with high HIV-1 viremia and having a sexual partner living outside the home. Full-population AUC was 0.80 (95% CI: 0.76-0.84); cross-validated AUC was 0.79 (95% CI: 0.75-0.84). At a sensitivity of 33%, up to 130,000 cases could be averted if 7.9 million women were perfectly adherent to PrEP; NNT would be 61. At a sensitivity of 67%, up to 260,000 cases could be averted if 25.1 million women were perfectly adherent to PrEP; the NNT would be 96. CONCLUSIONS: This risk assessment tool was generalizable, predictive, and parsimonious with tradeoffs between reach and efficiency.

Impact of a Multi-Institutional Initiative to Engage Students and Early-Stage Scholars From Underrepresented Racial and Ethnic Minority Groups in HIV Research: The Centers for AIDS Research Diversity, Equity, and Inclusion Pathway Initiative.

BACKGROUND: The Centers for AIDS Research Diversity, Equity, and Inclusion Pathway Initiative (CDEIPI) aims to establish programs to develop pathways for successful careers in HIV science among scholars from underrepresented racial and ethnic populations. This article describes cross-site evaluation outcomes during the first 18 months (July 2021-December 2022) across 15 programs. METHODS: The aims of the evaluation were to characterize participants, describe feasibility, challenges, and successes of the programs and provide a basis for the generalizability of best practices to Diversity, Equity, and Inclusion (DEI) programs in the United States. Two primary data collection methods were used: a quarterly programmatic monitoring process and a centrally managed, individual-level, participant quantitative and qualitative survey. RESULTS: During the first year of evaluation data collection, 1085 racially and ethnically diverse scholars ranging from the high school to postdoctoral levels applied for CDEIPI programs throughout the United States. Of these, 257 (23.7%) were selected to participate based on program capacity and applicant qualifications. Participants were trained by 149 mentors, teachers, and staff. Of the N = 95 participants responding to the individual-level survey, 95.7% agreed or strongly agreed with statements of satisfaction with the program, 96.8% planned to pursue further education, and 73.7% attributed increased interest in a variety of HIV science topics to the program. Qualitative findings suggest strong associations between mentorship, exposure to scientific content, and positive outcomes. CONCLUSIONS: These data provide evidence to support the feasibility and impact of novel DEI programs in HIV research to engage and encourage racially and ethnically diverse scholars to pursue careers in HIV science.

Centers for AIDS Research (CFAR) Diversity, Equity, and Inclusion Pathway Initiative (CDEIPI): Developing Career Pathways for Early-Stage Scholars From Racial and Ethnic Groups Underrepresented in HIV Science and Medicine.

BACKGROUND: There is an urgent need to increase diversity among scientific investigators in the HIV research field to be more reflective of communities highly affected by the HIV epidemic. Thus, it is critical to promote the inclusion and advancement of early-stage scholars from racial and ethnic groups underrepresented in HIV science and medicine. METHODS: To widen the HIV research career pathway for early-stage scholars from underrepresented minority groups, the National Institutes of Health supported the development of the Centers for AIDS Research (CFAR) Diversity, Equity, and Inclusion Pathway Initiative (CDEIPI). This program was created through partnerships between CFARs and Historically Black Colleges and Universities and other Minority Serving Institutions throughout the United States. RESULTS: Seventeen CFARs and more than 20 Historically Black Colleges and Universities and Minority Serving Institutions have participated in this initiative to date. Programs were designed for the high school (8), undergraduate (13), post baccalaureate (2), graduate (12), and postdoctoral (4) levels. Various pedagogical approaches were used including didactic seminar series, intensive multiday workshops, summer residential programs, and mentored research internship opportunities. During the first 18 months of the initiative, 257 student scholars participated in CDEIPI programs including 150 high school, 73 undergraduate, 3 post baccalaureate, 27 graduate, and 4 postdoctoral students. CONCLUSION: Numerous student scholars from a wide range of educational levels, geographic backgrounds, and racial and ethnic minority groups have engaged in CDEIPI programs. Timely and comprehensive program evaluation data will be critical to support a long-term commitment to this unique training initiative.

A mobile-optimized artificial intelligence system for gestational age and fetal malpresentation assessment.

Background: Fetal ultrasound is an important component of antenatal care, but shortage of adequately trained healthcare workers has limited its adoption in low-to-middle-income countries. This study investigated the use of artificial intelligence for fetal ultrasound in under-resourced settings. Methods: Blind sweep ultrasounds, consisting of six freehand ultrasound sweeps, were collected by sonographers in the USA and Zambia, and novice operators in Zambia. We developed artificial intelligence (AI) models that used blind sweeps to predict gestational age (GA) and fetal malpresentation. AI GA estimates and standard fetal biometry estimates were compared to a previously established ground truth, and evaluated for difference in absolute error. Fetal malpresentation (non-cephalic vs cephalic) was compared to sonographer assessment. On-device AI model run-times were benchmarked on Android mobile phones. Results: Here we show that GA estimation accuracy of the AI model is non-inferior to standard fetal biometry estimates (error difference -1.4 ± 4.5 days, 95% CI -1.8, -0.9, n = 406). Non-inferiority is maintained when blind sweeps are acquired by novice operators performing only two of six sweep motion types. Fetal malpresentation AUC-ROC is 0.977 (95% CI, 0.949, 1.00, n = 613), sonographers and novices have similar AUC-ROC. Software run-times on mobile phones for both diagnostic models are less than 3 s after completion of a sweep. Conclusions: The gestational age model is non-inferior to the clinical standard and the fetal malpresentation model has high AUC-ROCs across operators and devices. Our AI models are able to run on-device, without internet connectivity, and provide feedback scores to assist in upleveling the capabilities of lightly trained ultrasound operators in low resource settings.

Measuring for Success: Evaluating Leadership Training Programs for Sustainable Impact.

Background: In an era of global health security challenges such as the COVID-19 pandemic, there is greater need for strong leadership. Over the past decades, significant investments have been made in global health leadership development programs by governments and philanthropic organizations to address this need. Evaluating the societal impact of these programs remains challenging, despite consensus on the importance of public health leadership. Objective: This article identifies the gaps and highlights the critical role of monitoring and evaluation approaches in assessing the impact of global health leadership programs. Importantly, we also propose the theory of change (TOC) as a common framework and identify a set of tools and indicators that leadership programs can adapt and use. Methods: We carried out an informal review of major global health leadership programs, including a literature review on leadership program evaluation approaches. Current practices in assessing the short- to long-term outcomes of leadership training programs were explored and synthesized. We also examined use of program theory frameworks, such as theory of change to guide the evaluation strategy. We find the TOC approach can be enhanced by integrating evaluation-specific frameworks and establishing broad stakeholder buy-in. We highlight measurement challenges, proposed outcome indicators and evaluation methodologies, and outline the future direction for such efforts. Findings: Most evaluation of current leadership programs is focused on short-term individual-level outcomes, while reports on long-term societal impact were limited. Reciprocal impacts on and benefits for the "host" organizations were not included in evaluation metrics. Most programs had program logic or result chains, but with no well-articulated program theories. Conclusion: Key stakeholders involved in leadership training programs benefit from the evidence of rigorous program evaluations to inform decisions that address barriers in fostering global health leadership and improving population health outcomes. Insight into reciprocal change in host organizations is important. Evaluation of global health leadership training must go beyond the individual trainee and encompass organizational and community-level impacts. Documentation of long-lasting organizational and societal impacts is essential for donors to appreciate the return on their investment. Key Takeaways: Evaluation plays an important role in understanding how leadership development takes place and how it contributes to improving public health outcomes.Making the case for investments in leadership development programs requires robust evidence from monitoring and evaluation strategies that link investments beyond the individual-level to longer-term societal impacts.The first critical step towards a strategy for success is for leadership programs to clearly build, articulate, share, and use their program theories or theories of change.Theories of change help identify the pathways (and potential tensions) through which leadership development programs effect change at the individual, organizational and community levels.Evaluation methods that examine outcomes of leadership programs should be multi-method, multi-level, and where possible include counterfactual outcomes.Allocation of funds to evaluate on-going and long-lasting societal impact of leadership programs should be a routine practice.

Research Mentorship Crowdsourcing Contest: Toward Global Health Good.

As one of the six consortia funded through the NIH Fogarty International Center, the University of North Carolina at Chapel Hill, Johns Hopkins University, Morehouse School of Medicine, and Tulane University (UJMT) Fogarty Global Health Fellows Program provides postdoctoral trainees and doctoral students support and training for yearlong research attachments at selected low- and middle-income countries. To understand the current impact of this global health research training opportunity, the UJMT consortium conducted a crowdsourcing contest to gather creative messages to promote and improve the impact of the program in partnership with Social Entrepreneurship to Spur Health. Between January and March 2019, the contest received a total of 47 submissions from 14 countries; 44 were found eligible. After judging, 19 (41.2%) submissions received a mean score of 7 or higher. We examined both textual and descriptive submissions for emergent themes and identified a range of facilitators who can be used to further improve the training programs; examples include exceptional mentorship, acquisition of research skills, career development, personal development, and multisite training opportunities. In conclusion, the crowdsourcing mentorship contest demonstrated the feasibility and acceptability of leveraging existing research networks for community engagement and how useful information can be effectively collected to highlight the effectiveness of a program and expand the reach.

HIV Research Training Partnership of the University of Zambia and Vanderbilt University: Features and Early Outcomes.

Background: Despite the burden of HIV being highest in sub-Saharan Africa (SSA), research expertise and capacity to address scientific questions regarding complications of HIV and ART, especially chronic non-communicable conditions, is limited in the region. The comorbidities prevalent in persons with HIV are mediated through diverse mechanisms, many of which can be context or region-specific and are yet to be elucidated. The phenotype, risk factors, and effective interventions for these conditions may differ between populations and settings, and therefore there is an urgent need for research to help understand these processes and how to best address them in SSA. Here, we report the research capacity building activities in SSA conducted by the University of Zambia (UNZA)-Vanderbilt Training Partnership for HIV-Nutrition-Metabolic Research (UVP), drawing lessons and challenges for a wide global health audience. Methods: We reviewed program data and conducted interviews with program leaders and participants to understand and document the progress and outcomes of the partnership. We report the program's early achievements, highlighting drivers and challenges. Results: Between 2015 and 2019, UVP made substantial progress on its goals of training new UNZA PhD scientists to investigate complex nutritional and metabolic factors related to long-term HIV complications and comorbidities. The program has supported 11 UNZA PhD students with dual UNZA-Vanderbilt mentorship; three have graduated, and other candidates are progressing in their PhD studies. The project also supported institutional capacity through UNZA faculty participation in Vanderbilt grant writing workshops, with strong success in obtaining grants among those who participated. UVP also supported development of greater structure to UNZA's PhD program and a mentorship curriculum, both now adopted by UNZA. The major drivers for success included UVP's alignment of goals between UNZA and Vanderbilt, and local institutional ownership. The longstanding history of collaborations between the two institutions contributed substantially to alignment and mutual support of UVP's goals. Several challenges were noted, including limits on direct research funding for students and a relatively small pool of funded investigators at UNZA. Conclusions: Despite some challenges, UVP has achieved positive outcomes over its first four years. Longstanding partnerships and local institutional ownership were the main drivers. We expect the challenges to mitigated as the project continues and produces more UNZA researchers and teams and more funded projects, collectively building the local research community. With continued resources and clear focus, we expect that UNZA's investigators and partners will attract research funding and generate high-impact research outputs across a broad range of studies in HIV as well as newer threats from non-communicable conditions experienced by long-term survivors of HIV and by the general population.

Evaluating Academic Mentorship Programs in Low- and Middle-Income Country Institutions: Proposed Framework and Metrics.

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.

Strengthening Mentoring in Low- and Middle-Income Countries to Advance Global Health Research: An Overview.

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.

The National Institutes of Health Fogarty International Center Global Health Scholars and Fellows Program: Collaborating Across Five Consortia to Strengthen Research Training.

As demand for global health research training continues to grow, many universities are striving to meet the needs of trainees in a manner complementary to research priorities of the institutions hosting trainees, while also increasing capacity for conducting research. We provide an overview of the first 4 years of the Global Health Program for Fellows and Scholars, a collaboration of 20 U.S. universities and institutions spread across 36 low- and middle-income countries funded through the National Institutes of Health Fogarty International Center. We highlight many aspects of our program development that may be of interest to other multinational consortia developing global health research training programs.

Cost-Effectiveness of Pre-exposure HIV Prophylaxis During Pregnancy and Breastfeeding in Sub-Saharan Africa.

INTRODUCTION: Antiretroviral pre-exposure prophylaxis (PrEP) for the prevention of HIV acquisition is cost-effective when delivered to those at substantial risk. Despite a high incidence of HIV infection among pregnant and breastfeeding women in sub-Saharan Africa (SSA), a theoretical increased risk of preterm birth on PrEP could outweigh the HIV prevention benefit. METHODS: We developed a decision analytic model to evaluate a strategy of daily oral PrEP during pregnancy and breastfeeding in SSA. We approached the analysis from a health care system perspective across a lifetime time horizon. Model inputs were derived from existing literature and local sources. The incremental cost-effectiveness ratio (ICER) of PrEP versus no PrEP was calculated in 2015 U.S. dollars per disability-adjusted life year (DALY) averted. We evaluated the effect of uncertainty in baseline estimates through one-way and probabilistic sensitivity analyses. RESULTS: PrEP administered to pregnant and breastfeeding women in SSA was cost-effective. In a base case of 10,000 women, the administration of PrEP averted 381 HIV infections but resulted in 779 more preterm births. PrEP was more costly per person ($450 versus $117), but resulted in fewer disability-adjusted life years (DALYs) (3.15 versus 3.49). The incremental cost-effectiveness ratio of $965/DALY averted was below the recommended regional threshold for cost-effectiveness of $6462/DALY. Probabilistic sensitivity analyses demonstrated robustness of the model. CONCLUSIONS: Providing PrEP to pregnant and breastfeeding women in SSA is likely cost-effective, although more data are needed about adherence and safety. For populations at high risk of HIV acquisition, PrEP may be considered as part of a broader combination HIV prevention strategy.

Premature adult mortality in urban Zambia: a repeated population-based cross-sectional study.

OBJECTIVES: To measure the sex-specific and community-specific mortality rates for adults in Lusaka, Zambia, and to identify potential individual-level, household-level and community-level correlates of premature mortality. We conducted 12 survey rounds of a population-based cross-sectional study between 2004 and 2011, and collected data via a structured interview with a household head. SETTING: Households in Lusaka District, Zambia, 2004-2011. PARTICIPANTS: 43,064 household heads (88% female) who enumerated 123,807 adult household members aged between 15 and 60 years. PRIMARY OUTCOME: Premature adult mortality. RESULTS: The overall mortality rate was 16.2/1000 person-years for men and 12.3/1000 person-years for women. The conditional probability of dying between age 15 and 60 (45q15) was 0.626 for men and 0.537 for women. The top three causes of death for men and women were infectious in origin (ie, tuberculosis, HIV and malaria). We observed an over twofold variation of mortality rates between communities. The mortality rate was 1.98 times higher (95% CI 1.57 to 2.51) in households where a family member required nursing care, 1.44 times higher (95% CI 1.22 to 1.71) during the cool dry season, and 1.28 times higher (95% CI 1.06 to 1.54) in communities with low-cost housing. CONCLUSIONS: To meet Zambia's development goals, further investigation is needed into the factors associated with adult mortality. Mortality can potentially be reduced through focus on high-need households and communities, and improved infectious disease prevention and treatment services.

Implementation and Operational Research: Risk Charts to Guide Targeted HIV-1 Viral Load Monitoring of ART: Development and Validation in Patients From Resource-Limited Settings.

BACKGROUND: HIV-1 RNA viral load (VL) testing is recommended to monitor antiretroviral therapy (ART) but not available in many resource-limited settings. We developed and validated CD4-based risk charts to guide targeted VL testing. METHODS: We modeled the probability of virologic failure up to 5 years of ART based on current and baseline CD4 counts, developed decision rules for targeted VL testing of 10%, 20%, or 40% of patients in 7 cohorts of patients starting ART in South Africa, and plotted cutoffs for VL testing on colour-coded risk charts. We assessed the accuracy of risk chart-guided VL testing to detect virologic failure in validation cohorts from South Africa, Zambia, and the Asia-Pacific. RESULTS: In total, 31,450 adult patients were included in the derivation and 25,294 patients in the validation cohorts. Positive predictive values increased with the percentage of patients tested: from 79% (10% tested) to 98% (40% tested) in the South African cohort, from 64% to 93% in the Zambian cohort, and from 73% to 96% in the Asia-Pacific cohort. Corresponding increases in sensitivity were from 35% to 68% in South Africa, from 55% to 82% in Zambia, and from 37% to 71% in Asia-Pacific. The area under the receiver operating curve increased from 0.75 to 0.91 in South Africa, from 0.76 to 0.91 in Zambia, and from 0.77 to 0.92 in Asia-Pacific. CONCLUSIONS: CD4-based risk charts with optimal cutoffs for targeted VL testing maybe useful to monitor ART in settings where VL capacity is limited.

Temporal Trends and Predictors of Modern Contraceptive Use in Lusaka, Zambia, 2004-2011.

INTRODUCTION: Although increasing access to family planning has been an important part of the global development agenda, millions of women continue to face unmet need for contraception. MATERIALS AND METHODS: We analyzed data from a repeated cross-sectional community survey conducted in Lusaka, Zambia, over an eight-year period. We described prevalence of modern contraceptive use, including long-acting reversible contraception (LARC), among female heads of household aged 16-50 years. We also identified predictors of LARC versus short-term contraceptive use among women using modern methods. RESULTS AND DISCUSSION: Twelve survey rounds were completed between November 2004 and September 2011. Among 29,476 eligible respondents, 17,605 (60%) reported using modern contraception. Oral contraceptive pills remained the most popular method over time, but use of LARC increased significantly, from less than 1% in 2004 to 9% by 2011 (p < 0.001). Younger women (OR: 0.46, 95% CI: 0.34, 0.61) and women with lower levels of education (OR: 0.70, 95% CI: 0.56, 0.89) were less likely to report LARC use compared to women using short-term modern methods. CONCLUSIONS: Population-based assessments of contraceptive use over time can guide programs and policies. To achieve reproductive health equity and reduce unmet contraceptive need, future efforts to increase LARC use should focus on young women and those with less education.

Estimating the cost-effectiveness of nutrition supplementation for malnourished, HIV-infected adults starting antiretroviral therapy in a resource-constrained setting.

BACKGROUND: Low body mass index (BMI) individuals starting antiretroviral therapy (ART) for HIV infection in sub-Saharan Africa have high rates of death and loss to follow-up in the first 6 months of treatment. Nutritional supplementation may improve health outcomes in this population, but the anticipated benefit of any intervention should be commensurate with the cost given resource limitations and the need to expand access to ART in the region. METHODS: We used Markov models incorporating historical data and program-wide estimates of treatment costs and health benefits from the Zambian national ART program to estimate the improvements in 6-month survival and program retention among malnourished adults necessary for a combined nutrition support and ART treatment program to maintain cost-effectiveness parity with ART treatment alone. Patients were stratified according to World Health Organization criteria for severe (BMI <16.0 kg/m(2)), moderate (16.00-16.99 kg/m(2)), and mild (17.00-18.49 kg/m(2)) malnutrition categories. RESULTS: 19,247 patients contributed data between May 2004 and October 2010. Quarterly survival and retention were lowest in the BMI <16.0 kg/m(2) category compared to higher BMI levels, and there was less variation in both measures across BMI strata after 180 days. ART treatment was estimated to cost $556 per year and averted 7.3 disability-adjusted life years. To maintain cost-effectiveness parity with ART alone, a supplement needed to cost $10.99 per quarter and confer a 20% reduction in both 6-month mortality and loss to follow-up among BMI <16.0 kg/m(2) patients. Among BMI 17.00-18.49 kg/m(2) patients, supplement costs accompanying a 20% reduction in mortality and loss to follow-up could not exceed $5.18 per quarter. In sensitivity analyses, the maximum permitted supplement cost increased if the ART program cost rose, and fell if patients classified as lost to follow-up at 6 months subsequently returned to care. CONCLUSIONS: Low BMI adults starting ART in sub-Saharan Africa are at high risk of early mortality and loss to follow-up. The expense of providing nutrition supplementation would require only modest improvements in survival and program retention to be cost-effective for the most severely malnourished individuals starting ART, but interventions are unlikely to be cost-effective among those in higher BMI strata.

Prevention of mother-to-child HIV transmission within the continuum of maternal, newborn, and child health services.

PURPOSE OF REVIEW: To reach virtual elimination of pediatric HIV, programs for the prevention of mother-to-child HIV transmission (PMTCT) must expand coverage and achieve long-term retention of mothers and infants. Although PMTCT have been traditionally aligned with maternal, newborn, and child health (MNCH) services, novel approaches are needed to address the increasing demands of evolving global PMTCT policies. RECENT FINDINGS: PMTCT-MNCH integration has improved the uptake and timely initiation of antiretroviral therapy (ART) among treatment-eligible pregnant women in public health settings. Postpartum engagement of HIV-infected mothers and HIV-exposed infants has been insufficient, although alignment of visits to the childhood immunization schedule and establishment of integrated mother-infant clinics may increase retention. Evidence also suggests that the integration of maternal HIV testing into childhood immunization clinics can significantly increase the identification of at-risk HIV-exposed infants previously missed by traditional PMTCT models. SUMMARY: Targeted service integration models can improve PMTCT uptake. However, as global PMTCT policy shifts to universal provision of maternal ART during pregnancy (i.e., Option B/B+), these findings must be reexamined in the context of increased service demand and systems burden. Intensive evaluation is needed to ensure quality clinical care is maintained both for PMTCT and for underpinning MNCH services.

Measuring coverage in MNCH: population HIV-free survival among children under two years of age in four African countries.

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.

The causal effect of switching to second-line ART in programmes without access to routine viral load monitoring.

OBJECTIVES: We examined the effect of switching to second-line antiretroviral therapy (ART) on mortality in patients who experienced immunological failure in ART programmes without access to routine viral load monitoring in sub-Saharan Africa. DESIGN AND SETTING: Collaborative analysis of two ART programmes in Lusaka, Zambia and Lilongwe, Malawi. METHODS: We included all adult patients experiencing immunological failure based on WHO criteria. We used Cox proportional hazards models weighted by the inverse probability of switching to compare mortality between patients who switched and patients who did not; and between patients who switched immediately and patients who switched later. Results are expressed as hazard ratios with 95% credible intervals (95% CI). RESULTS: Among 2411 patients with immunological failure 324 patients (13.4%) switched to second-line ART during 3932 person-years of follow-up. The median CD4 cell count at start of ART and failure was lower in patients who switched compared to patients who did not: 80 versus 155 cells/µl (P < 0.001) and 77 versus 146 cells/µl (P < 0.001), respectively. Adjusting for baseline and time-dependent confounders, mortality was lower among patients who switched compared to patients remaining on failing first-line ART: hazard ratio 0.25 (95% CI 0.09-0.72). Mortality was also lower among patients who remained on failing first-line ART for shorter periods: hazard ratio 0.70 (95% CI 0.44-1.09) per 6 months shorter exposure. CONCLUSION: In ART programmes switching patients to second-line regimens based on WHO immunological failure criteria appears to reduce mortality, with the greatest benefit in patients switching immediately after immunological failure is diagnosed.

Determinants of stillbirth in Zambia.

OBJECTIVE: The objective of this study was to estimate the rates and determinants of stillbirth in an urban African obstetric population. METHODS: In this retrospective cohort study, we reviewed vital outcomes of newborns whose mothers received antenatal care, delivery care, or both antenatal and delivery care in the Lusaka, Zambia, public sector between February 2006 and March 2009. We excluded newborns weighing less than 1,000 g, those whose mothers died before delivery, and those born outside Lusaka. RESULTS: There were 100,454 deliveries that met criteria for inclusion. The median maternal age at the initial visit was 24 years (interquartile range 21-29) and the median gestational age was 22 weeks (interquartile range 19-26). The median gestational age at birth was 38 weeks (interquartile range 36-40), and the median neonatal birth weight was 3,000 g (interquartile range 2,750-3,300). A total of 2,109 fetuses were stillborn (crude rate, 21 per 1,000 live births, 95% confidence interval 20.1 per 1,000 to 21.9 per 1,000). This included 1,049 (49.7%) stillbirths classified as "recent" (presumed to have occurred within 12 hours of delivery) and 1,060 (50.3%) classified as "macerated" (presumed to have occurred more than 12 hours before delivery). In adjusted analysis, increasing maternal age, baseline body mass index greater than 26, history of stillbirth, placental abruption, maternal untreated syphilis, cesarean delivery, operative vaginal delivery, assisted breech delivery, and extremes of neonatal birth weight were all significantly associated with stillbirth. CONCLUSION: Stillbirth is a major contributor to poor perinatal outcomes in Lusaka. Many deaths appear avoidable through investment in antenatal screening and better labor monitoring. Stillbirth should be adopted as a routine health indicator by the World Health Organization.