The V-BRCH Project: Strengthening HIV Research Capacity in Nigeria through Intensive Workshops in Implementation Science and Grant Writing.

As persons with HIV live longer as the result of antiretroviral therapy, morbidity from HIV-associated noncommunicable diseases (NCDs) is increasing. The Vanderbilt-Nigeria Building Research Capacity in HIV and Noncommunicable Diseases program is a training platform created with the goal of training a cohort of successful Nigerian investigators to become leaders in HIV-associated NCD research. We describe survey findings from two week-long workshops in Kano, Nigeria, where trainees received instruction in implementation science and grant writing. Surveys assessed participants' self-perceived knowledge and confidence in topics taught during these workshops. Thirty-seven participants (all assistant professors) attended the implementation science workshop; 30 attended the grant-writing workshop. Response rates for the implementation science workshop were 89.2% for the preworkshop survey and 91.9% for the postworkshop survey. For the grant-writing workshop, these values were 88.2% and 85.3%, respectively. Improvement in participant knowledge and confidence was observed in every domain measured for both workshops. On average, a 101.4% increase in knowledge and a 118.0% increase in confidence was observed across measured domains among participants in the implementation science workshop. For the grant-writing workshop, there was a 68.8% increase in knowledge and a 70.3% increase in confidence observed. Participants rated the workshops and instructors as effective for both workshops. These workshops improved participants' knowledge and competence in implementation science and grant writing, and provide a model for training programs that aim to provide physician scientists with the skills needed to compete for independent funding, conduct locally relevant research, and disseminate research findings.

Prevalence and Determinants of Endothelial Dysfunction among Adults Living with HIV in Northwest Nigeria.

Background: Endothelial dysfunction constitutes an early pathophysiological event in atherogenesis and cardiovascular disease. This study aimed to assess the prevalence, determinants, and degree of endothelial dysfunction in antiretroviral therapy (ART)-treated people living with HIV (PLWH) in northwestern Nigeria using brachial flow-mediated dilatation (FMD). Methods: This was a comparative, cross-sectional study. A total of 200 ART-treated adults living with HIV with no evidence of kidney disease were compared with 200 HIV-negative participants attending a tertiary hospital in Kano, Nigeria, between September 2020 and May 2021. Endothelial function was evaluated by measuring FMD with a high-resolution vascular ultrasound transducer. FMD was calculated as the ratio of the brachial artery diameter after reactive hyperemia to baseline diameter and expressed as a percentage of change. Blood and urine samples were obtained from participants in both arms. Urine albumin-to-creatinine ratio (uACR) was calculated using the 2021 CKD-EPI estimated glomerular filtration rate (eGFR) creatinine-cystatin C equation without the race variable, and low-density lipoprotein (LDL) cholesterol was measured using enzymatic method. Results: The overall mean age (± standard deviation) of the study participants was 42 ± 11 years. Participants in the comparison arm were younger than PLWH (38 ± 11 versus 46 ± 10 years, respectively). The median (interquartile range) uACR was 41.6 (23.2-162.9) mg/g for the ART-treated PLWH versus 14.5 (7.4-27.0) mg/g for healthy controls. PLWH had a significantly lower mean percent FMD when compared to HIV-negative participants (9.8% ± 5.4 versus 12.1% ± 9.2, respectively). Reduced FMD was independently associated with HIV infection (ß = -2.83%, 95% CI, -4.44% to -1.21%, p = 0.001), estimated glomerular filtration rate (ß = -0.04%, 95% CI, -0.07% to -0.01%, p = 0.004) and LDL cholesterol (ß = -1.12%, 95% CI, -2.13% to -0.11%, p = 0.029). Conclusion: HIV-positive status, lower estimated GFR, and higher LDL cholesterol levels were independently associated with endothelial dysfunction. Future prospective studies with larger cohorts of persons living with HIV (and age- and sex-matched HIV-negative controls) are needed to gain further insight into these important findings. In the interim, aggressive management of modifiable risk factors is warranted.

LMIC Research Centers' Experiences Hosting U.S. and LMIC Trainees: Evaluation of the Fogarty Global Health Fellows and Scholars Program, 2012 to 2020.

In this mixed-methods study, we explore themes that emerged from a survey assessing the programmatic experiences of mentors and administrators at institutions in low- and middle-income countries (LMICs) hosting trainees supported by the Fogarty International Center's Global Health Program for Fellows and Scholars. A total of 89 of 170 potential respondents representing 31 countries completed the survey (response rate, 52.4%). There was agreement among respondents that their institutions received sufficient funds to support trainees and had the capacity to manage operational and financial aspects of the program. A majority also agreed that both LMIC and U.S. trainees were beneficial to the host institutions, and that trainee projects were relevant to the needs of the host country. Respondents felt that program benefits to LMIC trainees could be improved by increasing the research consumables budget, increasing the flexibility of program timelines, and increasing engagement between LMIC and U.S. trainees and institutions. Respondents indicated that both U.S. and LMIC trainees behaved professionally (including demonstrating respectful and ethical behavior) and took appropriate initiative to conduct their research projects. Findings from this study will help inform innovations to similar training initiatives that will enhance sustainability and improve program performance, and will be responsive to local needs.

Building Physician-Scientist Skills in R Programming:A Short Workshop Report.

Introduction: Statistical analysis programs require coding experience and a basic understanding of programming, skills which are not taught as part of medical school or residency curricula. Methods: We conducted a five-day course for early-career Nigerian physician-scientists interested in learning common statistical tests and acquiring R programming skills. The workshop included didactic presentations, small group learning activities, and interactive discussions. A baseline questionnaire captured participant demographics and solicited participants' level of confidence in understanding/performing common statistical tests. REDCap questionnaires were emailed to obtain feedback on educational format and content. A post-workshop assessment covered participants' overall impression of the program. Results: A total of 23 participants attended the program. Most participants were male (n=14, 60.9%) and at an early stage in their career (assistant professor, n=20, 87.0%). Approximately 70% of respondents indicated having received some prior training in statistics. The proportion of participants without experience using R and SAS software (90% and 85%, respectively) was greater than the corresponding proportions for Stata (55%) and SPSS (20%). Prior to the workshop, most respondents expressed being "not at all confident" in performing one-way ANOVA (60%), logistic regression (68%), simple linear regression (60%), and McNemar's test (80%). There was a statistically significant post-workshop improvement in the level of confidence in understanding and performing common statistical tests. The course was rated on a 0-100 scale as "moderately difficult" (mean ± SD: 51.7 ± 19.5). Most participants felt comfortable in putting the knowledge learned into practice (82.2 ± 17.1). Conclusion and Public Health Implications: Introductory R can be taught to junior physician-scientists in resource-limited settings and can inform the development and implementation of similar training initiatives in analogous settings.

Building Research Capacity in HIV and Noncommunicable Diseases in Africa: A Mentorship and Leadership Workshop Report.

INTRODUCTION: Few structured mentoring programs target early-stage investigators in Africa, creating a gap in mentorship skills where HIV burden is greatest. We describe findings from a Nigeria-based workshop for early-career physician scientists to build mentoring and leadership capacity in HIV and noncommunicable disease research. METHODS: Baseline surveys captured participant demographics, confidence in implementing mentoring competencies, and perceived importance of workshop training domains. The workshop included didactic presentations, small group activities, and interactive discussions. Daily surveys evaluated sessions, and postworkshop surveys solicited overall course impressions. RESULTS: Of the 33 participants, most were male (n = 21, 63.6%) and from medicine, laboratory sciences, and surgical specialties. "Building mentees' confidence" and "setting mentees' research goals" were ranked as areas where participants most believed they needed training. Sessions were rated favorably across five areas. Greatest improvements in mean scores were for confidence in identifying personal temperament styles, describing mentoring and leadership theories/frameworks, and developing mentoring plans. Additional identified workshop strengths were content relevance, leadership case series, interactive nature, and collegial atmosphere. All respondents indicated learning something new/useful/helpful in each session. At 6-month postworkshop, most respondents (25 of 26, 96%) had replicated or plan to replicate parts of the workshop in their departments/institutions. DISCUSSION: Effective mentoring training initiatives targeting future academic leaders have the potential to create skilled academicians who can impart mentoring skills and competencies to their mentees.

The CircumVent Project: a CPAP/O2 helmet solution for non-invasive ventilation using an implementation research framework.

BACKGROUND: Acute respiratory failure, a major cause of death in COVID-19, is managed with high-flow oxygen therapy via invasive mechanical ventilation. In resource-limited settings like Nigeria, the shortage of ventilators and oxygen supply makes this option challenging. Evidence-based non-invasive alternatives to mechanical ventilation such as the use of continuous positive airway pressure (CPAP) devices exist, but there have been concerns that non-invasive ventilation may expose healthcare workers to infection from aerosolized dispersion of SARS-CoV-2. We propose to evaluate the feasibility, adaptability and acceptability of a CPAP/O2 helmet solution for non-invasive ventilation among patients with COVID-19 and health workers in eight COVID-19 treatment and isolation centers in Nigeria. METHODS: The study will occur in 4 stages: (1) convene a Steering Committee of key stakeholders and recruit implementation sites; (2) use the integrated Promoting Action on Research Implementation in Health Services (i-PARiHS) framework to guide a needs assessment of treatment centers' capacity to use high-flow oxygen therapy to treat COVID-19 patients and utilize the findings to develop an implementation strategy for the use of a CPAP/O2 helmet solution; (3) build infrastructure to support training and data monitoring processes and to develop implementation protocols to evaluate the adaptability of the strategy for the use of the CPAP/O2 helmet; and (4) train health workers, distribute a CPAP/O2 helmet solution for non-invasive ventilation, pilot test the implementation strategy, and assess feasibility of its use and acceptability that includes monitoring altered risk of SARS-CoV-2 infection among healthcare workers. DISCUSSION: The CPAP/O2 helmet solution for non-invasive ventilation in Nigeria can serve as a scalable model for resource-poor countries, and beyond the COVID-19 pandemic, has the potential to be deployed for the treatment of pneumonia and other respiratory diseases. TRIAL REGISTRATION: NCT04929691. Registered June 18, 2021-retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04929691.

Strategies for Successful Clinical Trial Recruitment of People Living with HIV in Low- and Middle-Income Countries: Lessons Learned and Implementation Implications from the Nigeria Renal Risk Reduction (R3) Trial.

PURPOSE OF REVIEW: Clinical trials represent a bedrock for measuring efficacy of interventions in biomedical research, but recruitment into clinical trials remains a challenge. Few data have focused on recruitment strategies from the perspective of clinical trial teams, especially in low- and middle-income countries (LMIC), where HIV is most prevalent. RECENT FINDINGS: We summarized data from the literature and our experience with recruitment for the Renal Risk Reduction trial, aimed at reducing risk of kidney complications among people living with HIV in Nigeria. Using an implementation science framework, we identified strategies that contributed to successful clinical trial recruitment. For strategies that could not be categorized by this framework, we summarized key features according to selected action, actor, target, context, and time. We identified how these identified strategies could map to subsequent implementation outcomes at the patient and provider/health system level, as well as capacity-building efforts to meet needs identified by LMIC partners, which is a priority for success. Our experience highlights the importance of considering implementation outcomes, and the strategies necessary to achieve those outcomes early, in the planning and execution of clinical trials. Clinical trial recruitment can be optimized via methodologies grounded in implementation science.

Apolipoprotein-1 risk variants and associated kidney phenotypes in an adult HIV cohort in Nigeria.

HIV-positive adults are at risk for various kidney diseases, and apolipoprotein 1 (APOL1) high-risk genotypes increase this risk. This study aimed to determine the prevalence and ethnic distribution of APOL1 risk genotypes among a cohort of HIV-positive Nigerian adults and explore the relationship between APOL1 risk variant status with albuminuria and estimated glomerular filtration rate (eGFR). We conducted a cross-sectional study among 2 458 persons living with HIV who attended an HIV clinic in northern Nigeria and had received antiretroviral therapy for a minimum of six months. We collected two urine samples four-eight weeks apart to measure albumin excretion, and blood samples to measure eGFR and determine APOL1 genotype. The frequency of APOL1 high-risk genotype was 6.2%, which varied by ethnic group: Hausa/Fulani (2.1%), Igbo (49.1%), and Yoruba (14.5%). The prevalence of microalbuminuria (urine/albumin creatinine ratio 30- 300 mg/g) was 37%, and prevalence of macroalbuminuria (urine/albumin creatinine ratio over 300 mg/g) was 3%. The odds of microalbuminuria and macroalbuminuria were higher for participants with the APOL1 high-risk genotype compared to those carrying the low-risk genotype ([adjusted odds ratio 1.97, 95% confidence interval 1.37-2.82] and [3.96, 1.95-8.02] respectively). APOL1 high-risk genotype participants were at higher risk of having both an eGFR under 60 ml/min/1.73m2 and urine/albumin creatinine ratio over 300 mg/g (5.56, 1.57-19.69). Thus, we found a high proportion of HIV-positive, antiretroviral therapy-experienced, and largely virologically suppressed adults had microalbuminuria. Hence, although the high-risk APOL1 genotype was less prevalent than expected, it was strongly associated with some level of albuminuria.

The V-BRCH Project: building clinical trial research capacity for HIV and noncommunicable diseases in Nigeria.

Antiretroviral therapy has turned HIV into a chronic condition, with morbidity from HIV-associated noncommunicable diseases (NCDs) becoming more common as HIV-infected individuals live longer. In Nigeria, the additional challenge of an under-capacitated health system highlights the need for skilled clinical investigators who can generate evidence to tackle the double burden of HIV and NCDs. The Vanderbilt-Nigeria Building Research Capacity in HIV and Non-communicable Diseases (V-BRCH) programme is a training platform to create a cohort of skilled Nigerian investigators with the capacity to lead independent clinical trial research focused on the intersection of HIV and NCDs. V-BRCH will solidify an atmosphere of continuous mentoring and skills acquisition for physician faculty at the Aminu Kano Teaching Hospital via short- and medium-term learning opportunities, paired mentoring arrangements, and mentored research projects. Trainees will attend an annual faculty enrichment programme in Nashville, in addition to on-site workshops in Nigeria on HIV-associated NCD epidemiology, clinical trials methodology, evidence synthesis, qualitative research methods, stakeholder engagement, knowledge translation, and grant writing. Research-oriented junior faculty will undergo focused training in clinical trials administration and regulatory oversight. Scholars will share best practices through mentoring panels, regular 'Works in Progress' meetings, and monthly career development seminars. Competitive seed grants will be provided to mentor-mentee teams to promote targeted in-country pilot studies focused on HIV-associated NCDs. For long-term training, physician scientists will be supported to undergo enhanced Master of Public Health (MPH) training at Bayero University in Nigeria and Master of Science in Clinical Investigation (MSCI) training at Vanderbilt. Short-term regional courses, staff development workshops, and MPH curriculum refinement will help to strengthen institutional capacity in HIV-associated NCD clinical trial research. V-BRCH will create a cohort of skilled Nigerian scientists who will be able to compete for independent funding and design and implement high quality research that will generate evidence to inform policy and practice and lead to improved outcomes for Nigerians impacted by HIV-associated NCDs.

The burden of extended-spectrum ß-lactamase-producing Enterobacteriaceae in Nigeria: a systematic review and meta-analysis.

Antibiotic resistance on account of extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-PE) has become a major public health concern in developing countries. The presence of ESBL-PE is associated with increased morbidity, mortality and healthcare costs. There is no active antimicrobial surveillance mechanism in Nigeria. The aim of this study is to determine a precise estimate of the burden of ESBL-PE in Nigeria. We employed Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and searched electronic databases for suitable studies. We derived pooled prevalence estimates using random effects models and assessed trends with meta-regression. We found 208 studies, with 38 satisfying our inclusion criteria. The overall pooled prevalence of ESBL-PE in Nigeria was 34.6% (95% CI 26.8 to 42.3%) and increased at a rate of 0.22% per year (p for trend=0.837). In summary, we found the prevalence of ESBL-PE in Nigeria to be high and recommend a robust national survey to provide a more detailed picture of the epidemiology of ESBL-PE in Nigeria.

Optimal management of HIV- positive adults at risk for kidney disease in Nigeria (Renal Risk Reduction "R3" Trial): protocol and study design.

BACKGROUND: Individuals with two copies of the apolipoprotein-1 (APOL1) gene risk variants are at high risk (HR) for non-diabetic kidney disease. The presence of these risk variants is highest in West Africa, specifically in Nigeria. However, there is limited availability of dialysis and kidney transplantation in Nigeria, and most individuals will die soon after developing end-stage renal disease. Blocking the renin angiotensin aldosterone system with angiotensin-converting enzyme inhibitors (ACEi) is a well-recognized strategy to slow renal disease progression in patients with diabetes mellitus with chronic kidney disease (CKD) and in patients with HIV-associated nephropathy. We propose to determine whether presence of the APOL1 HR genotype alters or predicts responsiveness to conventional therapy to treat or prevent CKD and if addition of an ACEi to standard combination antiretroviral therapy (ART) reduces the risk of kidney complications among non-diabetic Nigerian adults. METHODS/DESIGN: We will screen 2600 HIV-positive adults who have received ART to (1) determine the prevalence of APOL1 risk variants and assess whether APOL1 HR status correlates with prevalent albuminuria, estimated glomerular filtration rate (eGFR), and/or prevalent CKD; (2) assess, via a randomized, placebo-controlled trial (RCT) in a subset of these participants with microalbuminura (n = 280) whether addition of the ACEi, lisinopril, compared to standard of care, significantly reduces the incidence or progression of albuminuria; and (3) determine whether the APOL1 HR genotype is associated with worse kidney outcomes (i.e. eGFR slope or regression of albuminuria) among participants in the RCT. CONCLUSIONS: This study will examine the increasing prevalence of kidney diseases in HIV-positive adults in a West African population, and the relationship between these diseases and the APOL1 high-risk genotype. By evaluating the addition of an ACEi to the care of individuals with HIV infection who have albuminuria, our trial will provide definitive evidence to guide strategies for management and clinical care in this population, with the goal of reducing HIV-related kidney complications. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03201939 . Registered on 26 August 2016.

Prevalence and Risk Factors for Diabetes Mellitus in Nigeria: A Systematic Review and Meta-Analysis.

INTRODUCTION: There has been no nationwide health (diabetes) survey in Nigeria since 1992, when a diabetes mellitus (DM) prevalence of 2.2% was reported. We aimed to determine the prevalence of and risk factors for DM in Nigeria by performing a systematic review and meta-analysis. METHODS: We searched Medline, EMBASE, PubMed, PapersFirst, the Cochrane Library, Scopus, Bioline, African Journals Online, Institute of Scientific Information, and Google Scholar from the year 1990 to 2017. Using MeSH headings, the terms "diabetes mellitus," "risk factors," "prevalence," and "Nigeria" as well as variations thereof were searched for. The last search was performed on 26 November 2017. We only included studies that utilized the random plasma glucose test, the fasting plasma glucose test, the oral glucose tolerance test (OGTT), or HbA1c to diagnose DM. A total of 23 studies (n = 14,650 persons) were evaluated. A random effects model was used to estimate the pooled prevalence of DM. We estimated the overall pooled prevalence of DM and subgroup-specific DM prevalences while accounting for inter-study and intra-study variability/heterogeneity. RESULTS: The overall pooled prevalence of DM was 5.77% (95% CI 4.3-7.1). The pooled prevalences of DM in the six geopolitical zones of Nigeria were 3.0% (95% CI 1.7-4.3) in the north-west, 5.9% (95% CI 2.4-9.4) in the north-east, 3.8% (95% CI 2.9-4.7) in the north-central zone, 5.5% (95% CI 4.0-7.1) in the south-west, 4.6% (95% CI 3.4-5.9) in the south-east, and 9.8% (95% CI 7.2-12.4) in the south-south zone. Risk factors for the pooled prevalence of DM were a family history of DM (4.6%; 95% CI 3.5-5.6); urban dwelling (6.0%; 95% CI 4.3-7.8); unhealthy dietary habits (8.0%; 95% CI 5.4-10.5); cigarette smoking (4.4%; 95% CI 1.3-10.2); older age (6.6%; 95% CI 4.5-8.7); physical inactivity (4.8%; 95% CI 3.2-6.4); and obesity (5.3%; 95% CI 3.8-6.9). CONCLUSION: There has been an increase in the prevalence of DM in Nigeria. All regions of the country have been affected, with the highest prevalence seen in the south-south geopolitical zone. Urban dwelling, physical inactivity, advanced age, and unhealthy diet are important risk factors for DM among Nigerians. A national diabetes care and prevention policy is highly recommended.

HIV treatment and monitoring patterns in routine practice: a multi-country retrospective chart review of patient care.

Background: A study of patient records in four HIV clinics in three sub-Saharan African countries examined routine clinical care patterns and variations. Methods: Clinic characteristics were described, and patient data extracted from a sample of medical records. Data on treatment, CD4 count and viral load (VL) were obtained for the last visit in the records, dates mainly between 2015 and 2017, patient demographic data were obtained from the first clinic visit. Results: Four clinics, two in Nigeria, one in Zambia and one in Uganda, all public facilities, using national HIV treatment guidelines were included. Numbers of patients and health professionals varied, with some variation in stated frequency of testing for CD4 count and VL. Clinical guidelines were available in each clinic, and most drugs were available free to patients. The proportion of patients with a CD4 count in the records varied from 84 to 100 percent, the latest median count varied from 269 to 593 between clinics. 35% had a record of a VL test, varying from 1% to 63% of patients. Lamivudine (3TC) was recorded for more than 90% of patients in each clinic, and although there was variation between clinics in the choice of antiretroviral therapy (ART), the majority were on first line drugs consistent with guidelines.  Only about 2% of the patients were on second-line ARTs. In two clinics, 100% and 99% of patients were prescribed co-trimoxazole, compared with 7% and no patients in the two other clinics. Conclusions: The wide variation in available clinic health work force, levels and frequency of CD4 counts, and VL assessment and treatment indicate sub-optimal adherence to current guidelines in routine clinical care. There is room for further work to understand the reasons for this variation, and to standardise record keeping and routine care of HIV positive patients.

Cost-effectiveness of expanding childhood routine immunization against Neisseria meningitidis serogroups C, W and Y with a quadrivalent conjugate vaccine in the African meningitis belt.

BACKGROUND: Neisseria meningitidis constitutes a major public health problem among countries in the African meningitis belt. Following regional vaccination campaigns for serogroup A and subsequent increases in protection against this serogroup, non-A serogroups such as C and W now pose significant epidemic threats, particularly in young children. OBJECTIVE: To evaluate the cost-effectiveness of broadening coverage from conjugate serogroup A to quadrivalent ACWY vaccination. METHODS: We developed a 40-year Markov state transition model with annual cycles to simulate costs and clinical outcomes in children aged 1 to 10 in the 26 countries of the African meningitis belt. The incidence of CWY meningitis cases among an unvaccinated population was held constant at inter-epidemic rates of 50 per 100,000/year and 150 per 100,000/year. The country-specific cost and probability of access to meningitis care, vaccine efficacy, the mortality risk among treated and untreated meningitis cases, the risk of clinical sequelae and their respective disability weights were based on published sources. Vaccination cost was based on international prices lists, presented in 2014 US$. RESULTS: At an incidence rate of 50 per 100,000/year, routine conjugate vaccination is highly cost-effective in 14 out of 26 countries with a cost/DALY averted ranging from US$555-US$787. At the higher incidence rate of 150 per 100,000/year, quadrivalent vaccination is cost-effective in all 26 countries with a cost/DALY averted ranging from US$105-US$250. The annual incidence rate at which routine conjugate quadrivalent vaccination is expected to be economically justifiable ranges from 13 per 100,000/year in Nigeria to 142 per 100,000/year in Burundi. CONCLUSION: Routine quadrivalent conjugate vaccination against Neisseria meningitidis is cost-effective at incidence rates well below the epidemic threshold among children living in the African meningitis belt.

Sex disparities in outcomes among adults on long-term antiretroviral treatment in northern Nigeria.

BACKGROUND: There are conflicting reports of sex differences in HIV treatment outcomes in Africa. We investigated sex disparities in treatment outcomes for adults on first line antiretroviral treatment (ART) in Nigeria. METHODS: We compared clinical and immunologic responses to ART between HIV-infected men (n=205) and women (n=140) enrolled in an ART program between June 2004 and December 2007, with follow-up through June 2014. We employed Kaplan-Meier estimates to examine differences in time to immunologic failure and loss to follow-up (LTFU), and generalized estimating equations to assess changes in CD4+ count by sex. RESULTS: Men had lower baseline mean CD4+ count compared to women (327.6 cells/µL vs 413.4, respectively, p<0.01). Women had significantly higher rates of increase in CD4+ count than men, even after adjusting for confounders, p<0.0001. There was no significant difference in LTFU by sex: LTFU rate was 2.47/1000 person-months (95% CI 1.6-3.9) in the first five years for men vs 1.98/1000 person-months (95% CI (1.3-3.0) for women. There was no difference in time to LTFU by sex over the study period. CONCLUSIONS: Women achieved better long-term immune response to ART at baseline and during treatment, but had similar rates of long-term retention in care to men. Targeted efforts are needed to improve immune outcomes in men in our setting.

Higher prevalence of wheezing and lower FEV1 and FVC percent predicted in adults with sickle cell anaemia: A cross-sectional study.

BACKGROUND AND OBJECTIVE: Respiratory symptoms including wheezing are common in adults with sickle cell anaemia (SCA), even in the absence of asthma. However, the prevalence of spirometry changes and respiratory symptoms in adults with SCA is unknown. METHODS: Using a cross-sectional study design, we tested the hypothesis that adults with SCA (cases) would have higher rates of lower airway obstruction and wheezing than those without SCA (controls) using the American Thoracic Society Division of Lung Diseases' questionnaire. Patients were adults with SCA aged between 18 and 65 years. Controls were consecutive unselected individuals without SCA who presented to an outpatient general medicine clinic. RESULTS: We enrolled 150 adults with SCA and 287 consecutive controls without SCA. The median age was 23.0 and 27.0 years for adults with and without SCA, respectively. Cases were more likely to report cough without a cold (35.0% vs 18.6%, P < 0.001), lower forced expiratory volume in 1 s (FEV1 ) % predicted (70.1% vs 82.1%, P = 0.001) and lower forced vital capacity (FVC) % predicted (67.4% vs 74.9%, P = 0.001) than controls. In the multivariable model, wheezing was significantly associated with SCA status (OR = 1.69, 95% CI = 1.08-2.65, P = 0.024). Similarly, FEV1 % predicted was significantly associated with SCA status and wheezing (P = 0.001 for both). CONCLUSION: Adults with SCA experience a higher rate of wheezing and impaired respiratory functions compared with controls from the same region.

Initiation of antiretroviral therapy based on the 2015 WHO guidelines.

OBJECTIVE: In 2015, the WHO recommended initiation of antiretroviral therapy (ART) in all HIV-positive patients regardless of CD4 cell count. We evaluated the cost-effectiveness of immediate versus deferred ART initiation among patients with CD4 cell counts exceeding 500cells/µl in four resource-limited countries (South Africa, Nigeria, Uganda, and India). DESIGN: A 5-year Markov model with annual cycles, including patients at CD4 cell counts more than 500 cells/µl initiating ART or deferring therapy until historic ART initiation criteria of CD4 cell counts more than 350 cells/µl were met. METHODS: The incidence of opportunistic infections, malignancies, cardiovascular disease, unscheduled hospitalizations, and death, were informed by the START trial results. Risk of HIV transmission was obtained from a systematic review. Disability weights were based on published literature. Cost inputs were inflated to 2014 US dollars and based on local sources. Results were expressed in cost per disability-adjusted life years averted and measured against WHO cost-effectiveness thresholds. RESULTS: Immediate initiation of ART is associated with a cost per disability-adjusted life years averted of -$317 [95% confidence interval (CI): -$796-$817] in South Africa; -$507 (95% CI: -$765-$837) in Nigeria; -$136 (-$382-$459) in Uganda; and -$78 (-$256-$374) in India. The results are largely driven by the impact of ART on reducing the risk of new HIV transmissions. CONCLUSIONS: In HIV-positive patients with CD4 counts above 500 cells/µl in the four studied countries, immediate initiation of ART versus deferred therapy until historic eligibility criteria are met is cost-effective and likely even cost-saving over time.

Mobilising the alumni of a Master of Public Health degree to build research and development capacity in low- and middle-income settings: The Peoples-uni.

BACKGROUND: Peoples-uni (People's Open Access Education Initiative) was established to help build Public Health capacity in low- and middle-income countries (LMICs) through postgraduate level online courses. Graduates are invited to join a virtual alumni group. We report the results of efforts to meet the need for health research capacity building by exploring how the course alumni could be mobilised to perform collaborative research into the health problems of their populations. METHODS: Two online surveys of Peoples-uni graduates were conducted with graduates from the first two and first four cohorts in 2013 and 2014, respectively, to explore the formation of an alumni group that would collaborate to further the research and development agenda in LMICs. This was followed by feedback on research-related activity and outcomes via the online alumni and tutors' forum to estimate early indicators of alumni success in relation to capacity building in both the conduct and utilisation of research. RESULTS: Responses were received from 26 (87% response rate) graduates of the first survey and 42 (60% response rate) of the second survey. Overall, 92% of the respondents to the first survey supported the creation of an alumni group, especially if it helped to develop their own research skills and improve the health of their populations. Findings from the second survey showed that study with Peoples-uni was felt to have had a major or potential impact on the careers of the respondents, with 19% of graduates having progressed to a PhD programme to further their research skills, and a further 48% being in the process of applying or intending to apply for doctoral studies. Further feedback shows that at least one collaborative study has been completed and published by alumni members with other collaborative studies planned. Ongoing support has been provided to graduates to help them publish their work and apply for individual or collaborative research grants. CONCLUSIONS: Harnessing the alumni of a Masters level course to perform collaborative research has considerable potential to build research capacity in LMICs.

Xanthoma disseminatum in a black African woman.

PURPOSE: To report a partial steroid response of xanthoma disseminatum in a black African woman. DESIGN: Case report and literature review. METHODS: Histopathologic study of cutaneous tumour and clinical follow-up. RESULTS: A 32-year-old black African woman with mucocutaneous xanthomatosis and dysphonia, which partially responded to treatment with steroids. CONCLUSIONS: Xanthoma dissseminatum is a rare condition for which there is no medical treatment. We reported the condition in a black African woman whose skin and CNS symptoms regressed remarkably within 22 weeks of steroid therapy.