Sickle cell trait, APOL1 risk allele status and chronic kidney disease among ART-experienced adults living with HIV in northern Nigeria.

BACKGROUND: We sought to determine the prevalence of sickle cell trait (SCT) and apolipoprotein-1 (APOL1) risk variants in people living with HIV (PLWH) in Nigeria, and to establish if SCT and APOL1 high-risk status correlate with estimated glomerular filtration rate (eGFR) and/or prevalent chronic kidney disease (CKD). METHODS: Baseline demographic and clinical data were obtained during three cross-sectional visits. CKD was defined as having an eGFR<60 mL/min/1.73 m2. We collected urine specimens to determine urine albumin-creatine ratio and blood samples for sickle cell genotyping, APOL1 testing, and for creatinine/cystatin C assessment. The associations between SCT, APOL1 genotype, and eGFR/CKD stages/CKD were investigated using linear/ordinal logistic/logistic regression models, respectively. RESULTS: Of 2443 participants, 599 (24.5%) had SCT, and 2291 (93.8%) had a low-risk APOL1 genotype (0 or 1 risk variant), while 152 (6.2%) had high-risk genotype (2 allele copies). In total, 108 participants (4.4%) were diagnosed with CKD. In adjusted analyses, SCT was associated with lower eGFR (adjusted mean difference [aMD]= -2.33, 95% CI -4.25, -0.42), but not with worse CKD stages, or increased odds of developing CKD. Participants with the APOL1 high risk genotype were more likely to have lower eGFR (aMD= -5.45, 95% CI -8.87, -2.03), to develop CKD (adjusted odds ratio [aOR] = 1.97, 95% CI: 1.03, 3.75), and to be in worse CKD stages (aOR = 1.60, 95% CI: 1.12, 2.29) than those with the low-risk genotype. There was no evidence of interaction between SCT and APOL1 genotype on eGFR or risk of CKD. CONCLUSION: Our findings highlight the multifaceted interplay of genetic factors in the pathogenesis of CKD in PLWH.

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.

Prevalence and clinical profile of heart failure patients with atrial fibrillation in a tertiary hospital in Kano, Nigeria.

Introduction: Atrial fibrillation (AF) is one of the most prevalent sustained arrhythmias that is seen in clinical practice. AF commonly coexists with heart failure (HF) and there is growing evidence that it confers an adverse prognostic impact on the natural course of the disease. We set out to describe the prevalence and clinical profile of HF patients with AF in Aminu Kano Teaching Hospital (AKTH), Kano, Nigeria. Materials and Methods: We conducted a cross-sectional study of all adults aged 18 years and above, who presented at the AKTH, Kano, and were hospitalised for HF. Those who consented were consecutively recruited into the study. Sociodemographic and clinical characteristics of patients at presentation were documented. Thromboembolic risk was assessed using CHA2DS2-VASc scoring system. A 12-lead electrocardiogram recording was obtained from each of the recruited patients to confirm the presence of AF. The prevalence of AF was determined amongst the admitted HF patients. Those with AF were compared with those without AF in terms of sociodemographic and clinical characteristics. Results: A total of 240 Nigerians were recruited. Sixty per cent were female and the whole group had a mean age of 50.85 ± 18.90 years. The prevalence of AF was found to be 12.5% amongst the recruited HF patients. The HF patients with AF had a significantly higher mean age (58 ± 16.7 years vs. 49.8 ± 19.0 years) (P = 0.021), and they also had a higher prevalence of palpitation and body swelling. The mean CHA2DS2-VASc score of the AF patients was 3.4 ± 1.0. Conclusion: AF is prevalent amongst HF patients in our environment with high thrombotic risk. More studies are needed to fully study the prevalence of AF and its clinical profile amongst HF patients in our country.

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.

Factors influencing postpartum haemorrhage detection and management and the implementation of a new postpartum haemorrhage care bundle (E-MOTIVE) in Kenya, Nigeria, and South Africa.

BACKGROUND: Postpartum haemorrhage (PPH) is the leading cause of global maternal deaths, accounting for 30-50% of maternal deaths in sub-Saharan Africa. Most PPH-related deaths are preventable with timely detection and initiation of care, which may be facilitated by using a clinical care bundle. We explore influences on current PPH detection and management and on the future implementation of a new PPH bundle (E-MOTIVE) in low-resource, high-burden settings. METHODS: Semi-structured qualitative interviews based on the Theoretical Domains Framework were conducted with 45 healthcare providers across nine hospitals in Nigeria, Kenya and South Africa, to identify barriers and enablers to current PPH detection and management and future implementation of a new PPH care bundle. Data were analysed using thematic and framework analysis. The Behaviour Change Wheel was used to identify potential interventions to address identified barriers and enablers. RESULTS: Influences on current PPH detection and management fell under 12 domains: Environmental Context and Resources (drug and staff shortages), Skills (limited in-service training), Knowledge (variable understanding of the recommended practice), Behaviour Regulation (limited quality improvement culture), Beliefs about Consequences (drawbacks from inaccurate detection), Emotion (stress from the unpredictability of PPH), Social Influence (teamwork), Memory, Attention and Decision-making (limited guideline use), Social/Professional Role and Identity (role clarity), Beliefs about Capabilities (confidence in managing PPH), Reinforcement (disciplinary procedures) and Goals (PPH as a priority). Influences on bundle uptake included: Beliefs about Consequences (perceived benefits of new blood loss measurement tool), Environmental Context and Resources (high cost of drugs and new tools), Memory, Attention and Decision-making (concerns about whether bundle fits current practice), Knowledge (not understanding 'bundled' approach), Social Influence (acceptance by women and staff) and Intention (limited acceptance of 'bundled' approach over existing practice). These influences were consistent across countries. Proposed interventions included: Education, Training, Modelling (core and new skills), Enablement (monitoring uptake), Persuasion (leadership role) and Environmental Restructuring (PPH emergency trolley/kit). CONCLUSIONS: A wide range of individual, socio-cultural and environmental barriers and enablers to improving PPH detection and management exist in these settings. We identified a range of interventions that could improve PPH care and the implementation of new care bundles in this context. TRIAL REGISTRATION: ClinicalTrials.gov : NCT04341662.

Etiology of Persistent Microalbuminuria in Nigeria (P_MICRO study): protocol and study design.

BACKGROUND: Microalbuminuria is an independent risk factor for cardiovascular and kidney disease and a predictor of end organ damage, both in the general population and in persons with HIV (PWH). Microalbuminuria is also an important risk factor for mortality in PWH treated with antiretroviral therapy (ART). In the ongoing Renal Risk Reduction (R3) study in Nigeria, we identified a high prevalence of microalbuminuria confirmed by two measurements 4-8 weeks apart in ART-experienced, virologically suppressed PWH. Although Stage 1 or 2 hypertension and exposure to potentially nephrotoxic antiretroviral medications were common in R3 participants, other traditional risk factors for albuminuria and kidney disease, including diabetes, APOL1 high-risk genotype, and smoking were rare. Co-infection with endemic pathogens may also be significant contributors to albuminuria, but co-infections were not evaluated in the R3 study population. METHODS: In Aim 1, we will cross-sectionally compare the prevalence of albuminuria and established kidney disease risk factors in a cohort of PWH to age- and sex-matched HIV-negative adults presenting for routine care at the Aminu Kano Teaching Hospital in Kano, Nigeria. We will leverage stored specimens from 2500 R3 participants and enroll an additional 500 PLWH recently initiated on ART (≤ 24 months) and 750 age- and sex-matched HIV-negative adults to determine the contribution of HIV, hypertension, and other comorbid medical conditions to prevalent albuminuria. In Aim 2, we will follow a cohort of 1000 HIV-positive, ART-treated and 500 HIV-negative normoalbuminuric adults for 30 months to evaluate the incidence and predictors of albuminuria. DISCUSSION: The findings from this study will support the development of interventions to prevent or address microalbuminuria in PWH to reduce kidney and cardiovascular morbidity and mortality. Such interventions might include more intensive monitoring and treatment of traditional risk factors, the provision of renin-angiotensin aldosterone system or sodium-glucose cotransporter-2 inhibitors, consideration of changes in ART regimen, and screening and treatment for relevant co-infections.

Differences in obstetric practices and outcomes of postpartum hemorrhage across Nigerian health facilities.

OBJECTIVE: To explore differences in obstetric practices and clinical outcomes of postpartum hemorrhage (PPH) in Nigerian facilities. METHODS: A descriptive cross-sectional study of public health facilities providing maternal healthcare services in Nigeria. Surveys were conducted across 38 purposively sampled facilities (January 2020-March 2021) to collect information on obstetric practices related to the management of the third stage of labor, treatment of postpartum hemorrhage, and clinical outcomes related to postpartum hemorrhage in the preceding 12 months. RESULTS: The median number of annual births per facility was 2230 (IQR, 1952-3283). The cesarean section rate was 21.6% (range 2.1%-52.6%). There was large variability in PPH rate (median 3%, range 0.4%-16.8%) and blood transfusions for PPH (median 2.8%, range 0.4%-48.6%) after vaginal birth. There was less variability for laparotomies (median 0.25%, range 0%-2.8%) and maternal deaths (median 0.11%, range 0%-0.64%) due to PPH after vaginal birth. The number of maternal deaths from all causes varied (median 0.27%, range 0%-3.5%). The rates of PPH and adverse maternal outcomes did not vary substantially between state or federal facilities, region, type of facility, and the number of clinical staff. CONCLUSION: Across the Nigerian facilities surveyed there was large variation in PPH rates and adverse maternal outcomes due to PPH. This variability remains largely unexplained and requires further insights and detailed data to gain a deeper understanding of the root causes and challenges to implement customized solutions to improve maternal outcomes.

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.

Usability, acceptability, and feasibility of the World Health Organization Labour Care Guide: A mixed-methods, multicountry evaluation.

INTRODUCTION: The World Health Organization's (WHO) Labour Care Guide (LCG) is a "next-generation" partograph based on WHO's latest intrapartum care recommendations. It aims to optimize clinical care provided to women and their experience of care. We evaluated the LCG's usability, feasibility, and acceptability among maternity care practitioners in clinical settings. METHODS: Mixed-methods evaluation with doctors, midwives, and nurses in 12 health facilities across Argentina, India, Kenya, Malawi, Nigeria, and Tanzania. Purposively sampled and trained practitioners applied the LCG in low-risk women during labor and rated experiences, satisfaction, and usability. Practitioners were invited to focus group discussions (FGDs) to share experiences and perceptions of the LCG, which were subjected to framework analysis. RESULTS: One hundred and thirty-six practitioners applied the LCG in managing labor and birth of 1,226 low-risk women. The majority of women had a spontaneous vaginal birth (91.6%); two cases of intrapartum stillbirths (1.63 per 1000 births) occurred. Practitioner satisfaction with the LCG was high, and median usability score was 67.5%. Practitioners described the LCG as supporting precise and meticulous monitoring during labor, encouraging critical thinking in labor management, and improving the provision of woman-centered care. CONCLUSIONS: The LCG is feasible and acceptable to use across different clinical settings and can promote woman-centered care, though some design improvements would benefit usability. Implementing the LCG needs to be accompanied by training and supportive supervision, and strategies to promote an enabling environment (including updated policies on supportive care interventions, and ensuring essential equipment is available).