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Persons living with HIV (PLWH) receiving tenofovir disoproxil fumarate (TDF)-based antiretroviral therapy (ART) risk suffering TDF-associated nephrotoxicity (TDFAN). TDFAN can result in short- and long-term morbidity, including permanent loss of kidney function, chronic kidney disease (CKD), and end-stage kidney disease (ESKD) requiring dialysis. Currently, there is no model to predict this risk or discern which patients to initiate TDF-based therapy. Consequently, some patients suffer TDFAN within the first few months of initiating therapy before switching to another suitable antiretroviral or a lower dose of TDF. In a prospective observational cohort study of adult Zambian PLWH, we modelled the risk for TDFAN before initiating therapy to identify individuals at high risk for experiencing AKI after initiating TDF-based therapy. We enrolled 205 HIV-positive, ART-naïve adults initiating TDF-based therapy followed for a median of 3.4 months for TDFAN at the Adult Infectious Disease Research Centre (AIDC) in Lusaka, Zambia. We defined TDFAN as meeting any of these acute kidney disease (AKD) criteria: 1) An episode of estimated glomerular filtration rate (eGFR)< 60ml/ min/1.73m2 within 3 months, 2) reduced eGFR by> 35% within 3 months or 3) increased serum creatinine by> 50% within 3 months. A total of 45 participants (22%) developed acute kidney disease (AKD) after TDF-based therapy. The development of AKD within the first 3 months of commencing TDF-based therapy was associated with an increase in baseline serum creatinine, age, baseline eGFR and female sex. We concluded that baseline characteristics and baseline renal function biomarkers predicted the risk for AKD within the first 3-months of TDF-based therapy.

Background In much of sub-Saharan Africa, male partners play influential roles in women's access to maternal-child healthcare, including prevention of mother-to-child transmission of HIV services. We explored male partner perspectives on women’s access to maternal-child healthcare in North-Central Nigeria. Methods Three focus groups were conducted with 30 men, purposefully-selected on the basis of being married, and rural or urban residence. Major themes explored were men’s maternal-child health knowledge, gender power dynamics in women’s access to healthcare, and peer support for pregnant and postpartum women. Data were manually analyzed using Grounded Theory, which involves constructing theories out of data collected, rather than applying pre-formed theories. Results Mean participant age was 48.3 years, with 36.7% aged Conclusions Strategic engagement of community leaders, including traditional and religious leaders, is needed to address harmful norms and practices underlying gender inequity in health decision-making. Gender mainstreaming, where the needs and concerns of both men and women are considered, should be applied in maternal-child healthcare education and delivery. Clinic fee reductions or elimination can facilitate service access. Finally, professional organizations can do more to reinforce respectful maternity care among healthcare workers.

Introduction The knowledge, attitude, and practice of emergency neonatal resuscitation are critical requirements in any facility that offers obstetric and neonatal services. This study aims to conduct a needs assessment survey and obtain individual and facility-level data on expertise and readiness for neonatal resuscitation. We hypothesize that neonatal emergency preparedness among healthcare providers in Kano, Nigeria is associated with the level of knowledge, attitudinal disposition, practice and equipment availability at the facility level. Methods A semi-structured, self-administered questionnaire was administered to a cross-section of health providers directly involved with neonatal care (n = 112) and attending a neonatal resuscitation workshop in Kano state. Information regarding knowledge, attitude, practice and facility preparedness for neonatal resuscitation was obtained. Bloom’s cut-off score and a validated basic emergency obstetric and neonatal care assessment tool were adopted to categorize outcomes. Multivariable logistic regression was employed to determine independent predictors of knowledge and practice. Results Almost half (48% and 42% respectively) of the respondents reported average level of self-assessed knowledge and comfort during resuscitation. Only 7% (95% CI:3.2–13.7) and 5% (95% CI:2.0–11.4) of health providers demonstrated good knowledge and practice scores respectively, with an overall facility preparedness of 46%. Respondents’ profession as a physician compared to nurses and midwives predicted good knowledge (aOR = 0.08, 95% CI: 0.01–0.69; p = 0.01), but not practice. Conclusion Healthcare provider’s knowledge and practice including facility preparedness for emergency neonatal resuscitation were suboptimal, despite the respondents’ relatively high self-assessed attitudinal perception. Physicians demonstrated higher knowledge compared to other health professionals. The low level of respondents’ awareness, practice, and facility readiness suggest the current weak state of secondary health systems in Kano.

Background HIV-positive persons of African descent are disproportionately affected by chronic kidney disease (CKD). Deterioration to end-stage kidney disease (ESKD) also occurs in this population at a higher frequency. There remains a lot to learn about the genetic susceptibility to CKD in HIV positive patients, and the pathophysiology of progression to ESKD. Objectives We will conduct an exploratory genotype-phenotype study in HIV-positive persons with CKD in Aminu Kano Teaching Hospital, Nigeria, to determine blood-based differential gene expression biomarkers in different kidney risk groups according to the KDIGO 2012 criteria. Methods We will consecutively screen 150 HIV-positive adults (≥18 years of age) attending the HIV clinic of Aminu Kano Teaching Hospital, Kano, Nigeria, for CKD based on proteinuria and elevation of estimated glomerular filtration rate. Among these, two separate groups of 16 eligible participants each (n = 32) will be selected in the four (4) KDIGO 2012 kidney risk categories. The groups will be matched for age, sex, viral suppression level and antiretroviral (ARV) regimen. In the first group (n = 16), we will determine differential gene expression markers in peripheral blood mononuclear cells using mRNA-sequencing (RNA-Seq). We will validate the differential expression markers in the second group (n = 16) using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Using a systems-based approach, we will construct, visualize and analyze gene-gene interaction networks to determine the potential biological roles of identified differential expression markers based on published literature and publicly available databases. Results Our exploratory study will provide valuable information on the potential roles of differential expression biomarkers in the pathophysiology of HIV-associated kidney disease by identifying novel biomarkers in different risk categories of CKD in a sub-Saharan African population. The results of this study will provide the basis for population-based genome-wide association studies to guide future personalized medicine approaches. Conclusion Validated biomarkers can be potential targets for the development of stage-specific therapeutic interventions, an essential paradigm in precision medicine.

Background There are few studies that characterize sex-related differences in HIV outcomes among adolescents and young adults (AYA) 15–24 years of age. Methods We conducted a retrospective cohort study among AYA who enrolled in a comprehensive HIV program in Mozambique between 2012–2016. We assessed patients by sex and pregnancy/lactation status, comparing time to combination antiretroviral therapy (ART) initiation using Cox proportional hazard models. We employed multivariable logistic regression to investigate pre- and post-ART retention. Patients were defined as ‘retained pre-ART’ if they attended at least 3 of 4 required visits or started ART in the 6 months after enrollment, and ‘retained post-ART’ if they had any ART pickup or clinical visit during the last 90 days of the one-year follow-up period. Results Of 47,702 patients in the cohort, 81% (n = 38,511) were female and 19% (n = 9,191) were male. Of the females, 57% (n = 21,770) were non-pregnant and non-lactating (NPNL) and 43% (n = 16,741) were pregnant or lactating (PL). PL (aHR 2.64, 95%CI:2.47–2.81) and NPNL females (aHR 1.36, 95%CI:1.30–1.42) were more likely to initiate ART than males. PL females had higher odds of pre-ART retention in care (aOR 3.56, 95%CI: 3.30–3.84), as did NPNL females (aOR 1.71, 95%CI: 1.62–1.81), compared to males. This was also true for retention post-ART initiation, with higher odds for both PL (aOR 1.78, 95%CI:1.63–1.94) and NPNL females (aOR 1.50, 95%CI:1.35–1.65) compared to males. Conclusions PL females were most likely to initiate ART and remain in care post-ART in this AYA cohort, likely reflecting expansion of Option B+. Despite pregnancy and policy driven factors, we observed important sex-related disparities in this cohort. NPNL females were more likely to initiate ART and be retained in care before and after ART initiation than males. These data suggest that young males need targeted interventions to improve these important care continuum outcomes.

The transition to PEPFAR 2.0 with its focus on country ownership was accompanied by substantial funding cuts. We describe the impact of this transition on HIV care in a large network of HIV clinics in Nigeria. We surveyed 30 comprehensive HIV treatment clinics to assess services supported before (October 2013-September 2014) and after (October 2014-September 2015) the PEPFAR funding policy change, the impact of these policy changes on service delivery areas, and response of clinics to the change. We compared differences in support for staffing, laboratory services, and clinical operations pre- and post-policy change using paired t-tests. We used framework analysis to assess answers to open ended questions describing responses to the policy change. Most sites (83%, n = 25) completed the survey. The majority were public (60%, n = 15) and secondary (68%, n = 17) facilities. Clinics had a median of 989 patients in care (IQR: 543-3326). All clinics continued to receive support for first and second line antiretrovirals and CD4 testing after the policy change, while no clinics received support for other routine drug monitoring labs. We found statistically significant reductions in support for viral load testing, staff employment, defaulter tracking, and prevention services (92% vs. 64%, p = 0.02; 80% vs. 20%, 100% vs. 44%, 84% vs. 16%, respectively, p

BackgroundGlobal HIV funding cutbacks have been accompanied by the adoption of user fees to address funding gaps in treatment programs. Our objective was to assess the impact of user fees on HIV care utilization and medication adherence in Nigeria.MethodsWe conducted a retrospective analysis of patients enrolled in care before (October 2012-September 2013) and after (October 2014-September 2015) the introduction of user fees in a Nigerian clinic. We assessed pre- vs. post-user fee patient characteristics and enrollment trends, and determined risk of care interruption, loss to follow-up, and optimal medication adherence.ResultsAfter fees were instituted, there was a 66% decline in patient enrollment and 75% decline in number of ART doses dispensed. There was no difference in the proportion of female clients (64% vs 63%, p = 0.46), average age (36 vs. 37 years, p = 0.15), or median baseline CD4 (220/ul vs. 222/uL, p = 0.24) in pre- and post-fee cohorts. There was an increase in clients employed and/or had tertiary education (24% vs. 32%, pConclusionsPatients enrolled in care after introduction of user fees in Nigeria were more likely to be educated or employed, and effectively retained in care after starting ART. However, fees were accompanied by a drastic reduction in new patient enrollment, suggesting that many patients may have been marginalized from HIV care.

BACKGROUND: Despite availability of effective cure, tuberculosis (TB) remains a leading cause of death in children. In many high-burden countries, childhood TB is underdiagnosed and underreported, and care is often accessed too late, resulting in adverse treatment outcomes. In this study, we examined the time to death and its associated factors among a cohort of children that commenced TB treatment in a large treatment centre in northern Nigeria. METHODS: This is a retrospective cohort study of children that started TB treatment between 2010 and 2014. We determined mortality rates per 100 person-months of treatment, as well as across treatment and calendar periods. We used Cox proportional hazards regression to determine adjusted hazard ratios (aHR) for factors associated with mortality. RESULTS: Among 299 children with a median age 4 years and HIV prevalence of 33.4%; 85 (28.4%) died after 1,383 months of follow-up. Overall mortality rate was 6.1 per 100 person-months. Deaths occurred early during treatment and declined from 42.4 per 100 person-months in the 1st week of treatment to 2.2 per 100 person-months after at the 3rd month of treatment. Mortality was highest between October to December period (9.1 per 100 pm) and lowest between July and September (2.8 per 100 pm). Risk factors for mortality included previous TB treatment (aHR 2.04:95%CI;1.09-3.84); HIV infection (aHR 1.66:95%CI;1.02-2.71), having either extra-pulmonary disease (aHR 2.21:95%CI;1.26-3.89) or both pulmonary and extrapulmonary disease (aHR 3.03:95%CI;1.70-5.40). CONCLUSIONS: Mortality was high and occurred early during treatment in this cohort, likely indicative of poor access to prompt TB diagnosis and treatment. A redoubling of efforts at improving universal health coverage are required to achieve the End TB Strategy target of zero deaths from TB.

Background Despite decades of efforts to eliminate tuberculosis (TB) in the United States (US), TB still contributes to adverse ill health, especially among racial/ethnic minorities. According to the Centers for Disease Control and Prevention, in 2016, about 87% of the TB cases reported in the US were among racial and ethnic minorities. The objective of this study is to explore the risks for pregnancy complications and in-hospital death among mothers diagnosed with TB across racial/ethnic groups in the US. Methods This retrospective cohort study utilized National Inpatient Sample data for all inpatient hospital discharges in the US. We analyzed pregnancy-related hospitalizations and births in the US from January 1, 2002 through December 31, 2014 (n = 57,393,459). Multivariable logistic regression was applied to generate odds ratios for the association between TB status and the primary study outcomes (i.e., pregnancy complications and in-hospital death) across racial/ethnic categories. Results The prevalence of TB was 7.1 per 100,000 pregnancy-related hospitalizations. The overall prevalence of pregnancy complications was 80% greater among TB-infected mothers than their uninfected counterparts. Severe pre-eclampsia, eclampsia, placenta previa, post-partum hemorrhage, sepsis and anemia occurred with greater frequency among mothers with a TB diagnosis than those without TB, irrespective of race/ethnicity. The rate of in-hospital death among TB patients was 37 times greater among TB-infected than in non-TB infected mothers (468.8 per 100,000 versus 12.6 per 100,000). A 3-fold increased risk of in-hospital death was observed among black TB-negative mothers compared to their white counterparts. No racial/ethnic disparities in maternal morbidity or in-hospital death were found among mothers with TB disease. Conclusion TB continues to be an important cause of morbidity and mortality among pregnant women in the US. Resources to address TB disease should also target pregnant women, especially racial/ethnic minorities who bear the greatest burden of the disease.

Background Multidrug resistant tuberculosis (MDR-TB), is an emerging public health problem in sub-Saharan Africa (SSA). This study aims to determine the trends in prevalence of MDR-TB among new TB cases in sub-Saharan Africa over two decades. Methods We searched electronic data bases and accessed all prevalence studies of MDR-TB within SSA between 2007 and 2017. We determined pooled prevalence estimates using random effects models and determined trends using meta-regression. Results Results: We identified 915 studies satisfying inclusion criteria. Cumulatively, studies reported on MDR-TB culture of 34,652 persons. The pooled prevalence of MDR-TB in new cases was 2.1% (95% CI; 1.7-2.5%). There was a non-significant decline in prevalence by 0.12% per year. Conclusion We found a low prevalence estimate of MDR-TB, and a slight temporal decline over the study period. There is a need for continuous MDR-TB surveillance among patients with TB.