HIV risk perception and sexual behavior among HIV-uninfected men and transgender women who have sex with men in sub-Saharan Africa: Findings from the HPTN 075 qualitative sub-study.

There remains a limited understanding of how men who have sex with men (MSM) and transgender women (TGW) in sub-Saharan Africa (SSA) perceive their risk for HIV and how risk influences behavior during sexual interactions. We performed thematic analysis on in-depth interviews from the qualitative sub-study of HPTN 075 in Kenya, Malawi, and South Africa. Using the Integrated Behavioral Model (IBM) constructs, we found that most MSM and TGW perceived themselves to be at risk for HIV, leading them to regularly engage in safer sexual behaviors. Notably, even though these MSM and TGW perceived themselves to be at risk for HIV, some of them reported engaging in transactional sex, sex under the influence of alcohol, and intentional non-use of condoms. This indicates that HIV risk perception was not always associated with safer sexual behaviors or a reduction in risk behaviors. Attitudes (negative attitudes toward condom use), perceived norms (social pressures), and environment constraints (contextual barriers) were related to MSM and TGW not engaging in safe sexual behavior. Hearing the perspectives of MSM and TGW on their sexual behavior continues to be important for the development and implementation of effective prevention policies and interventions. Eliminating structural barriers such as stigma, discrimination, and criminalization of same-sex sexuality is a crucial prerequisite for the success of interventions to promote sexual health among MSM and TGW in SSA

Raltegravir-intensified initial antiretroviral therapy in advanced HIV in Africa: a randomized controlled trial

BACKGROUND: In sub-Saharan Africa, severely immunocompromised HIV-infected individuals have high mortality (10%) shortly after starting antiretroviral therapy (ART). This group also have the greatest risk of morbidity and mortality associated with immune reconstitution inflammatory syndrome (IRIS), a paradoxical response to successful ART. Integrase inhibitors lead to significantly more rapid declines in HIV viral load (VL) than all other ART classes. We hypothesised that intensifying standard triple-drug ART with the integrase inhibitor, raltegravir, would reduce HIV VL faster, and hence reduce early mortality, although this strategy could also risk more IRIS events. METHODS AND FINDINGS: In a 2x2x2 factorial open-label parallel-group trial, treatment-naïve HIV-infected adults, adolescents and children >5 years with CD4 0.7), and despite significantly greater VL suppression with raltegravir-intensified-ART at 4-weeks (343/836 (41.0%) vs 113/841 (13.4%) standard-ART, p<0.001) and 12-weeks (567/789 (71.9%) vs 415/803 (51.7%) standard-ART, p<0.001). Through 48-weeks there was no evidence of differences in mortality (aHR=0.98 (95%CI 0.76-1.28) p=0.91); serious (aHR=0.99 (0.81-1.21) p=0.88), grade-4 (aHR=0.88 (0.71-1.09) p=0.29) or ART-modifying (aHR=0.90 (0.63-1.27) p=0.54) adverse events (the latter occurring in occurring in 59 (6.5%) raltegravir-intensified-ART vs 66 (7.3%) standard-ART); in events judged compatible with IRIS (occurring in 89 (9.9%) raltegravir-intensified-ART vs 86 (9.5%) standard-ART, p=0.79) or hospitalizations (aHR=0.94 (95%CI 0.76-1.17) p=0.59). At 12 weeks, one and two raltegravir-intensified participants had predicted intermediate-level and high-level raltegravir resistance respectively. At 48 weeks, the NRTI mutation K219E/Q (p=0.004), and the NNRTI mutations K101E/P (p=0.03) and P225H (p=0.007), were less common in raltegravir-intensified-ART, with weak evidence of less intermediate or high-level resistance to tenofovir (p=0.06), abacavir (p=0.08) and rilpivirine (p=0.07). Limitations were limited clinical, radiological and/or microbiological information for some participants, reflecting available services at the centres, and lack of baseline genotypes. CONCLUSIONS: Although 12-weeks raltegravir-intensification was well-tolerated and reduced HIV viraemia significantly faster than standard triple-drug ART during the time of greatest risk for early death, this strategy did not reduce mortality or clinical events, and is not warranted. There was no excess of IRIS-compatible events, suggesting integrase inhibitors can be used safely as part of standard triple-drug first-line therapy in severely immuno-compromised individuals

The cost‐effectiveness of prophylaxis strategies for individuals with advanced HIV starting treatment in Africa

Introduction Many HIV‐positive individuals in Africa have advanced disease when initiating antiretroviral therapy (ART) so have high risks of opportunistic infections and death. The REALITY trial found that an enhanced‐prophylaxis package including fluconazole reduced mortality by 27% in individuals starting ART with CD4 <100 cells/mm3. We investigated the cost‐effectiveness of this enhanced‐prophylaxis package versus other strategies, including using cryptococcal antigen (CrAg) testing, in individuals with CD4 <200 cells/mm3 or <100 cells/mm3 at ART initiation and all individuals regardless of CD4 count. Methods The REALITY trial enrolled from June 2013 to April 2015. A decision‐analytic model was developed to estimate the cost‐effectiveness of six management strategies in individuals initiating ART in the REALITY trial countries. Strategies included standard‐prophylaxis, enhanced‐prophylaxis, standard‐prophylaxis with fluconazole; and three CrAg testing strategies, the first stratifying individuals to enhanced‐prophylaxis (CrAg‐positive) or standard‐prophylaxis (CrAg‐negative), the second to enhanced‐prophylaxis (CrAg‐positive) or enhanced‐prophylaxis without fluconazole (CrAg‐negative) and the third to standard‐prophylaxis with fluconazole (CrAg‐positive) or without fluconazole (CrAg‐negative). The model estimated costs, life‐years and quality‐adjusted life‐years (QALY) over 48 weeks using three competing mortality risks: cryptococcal meningitis; tuberculosis, serious bacterial infection or other known cause; and unknown cause. Results Enhanced‐prophylaxis was cost‐effective at cost‐effectiveness thresholds of US$300 and US$500 per QALY with an incremental cost‐effectiveness ratio (ICER) of US$157 per QALY in the CD4 <200 cells/mm3 population providing enhanced‐prophylaxis components are sourced at lowest available prices. The ICER reduced in more severely immunosuppressed individuals (US$113 per QALY in the CD4 <100 cells/mm3 population) and increased in all individuals regardless of CD4 count (US$722 per QALY). Results were sensitive to prices of the enhanced‐prophylaxis components. Enhanced‐prophylaxis was more effective and less costly than all CrAg testing strategies as enhanced‐prophylaxis still conveyed health gains in CrAg‐negative patients and savings from targeting prophylaxis based on CrAg status did not compensate for costs of CrAg testing. CrAg testing strategies did not become cost‐effective unless the price of CrAg testing fell below US$2.30. Conclusions The REALITY enhanced‐prophylaxis package in individuals with advanced HIV starting ART reduces morbidity and mortality, is practical to administer and is cost‐effective. Efforts should continue to ensure that components are accessed at lowest available prices

Late Presentation With HIV in Africa: Phenotypes, Risk, and Risk Stratification in the REALITY Trial.

This article has been accepted for publication in Clinical Infectious Diseases Published by Oxford University PressBackground: Severely immunocompromised human immunodeficiency virus (HIV)-infected individuals have high mortality shortly after starting antiretroviral therapy (ART). We investigated predictors of early mortality and "late presenter" phenotypes. Methods: The Reduction of EArly MortaLITY (REALITY) trial enrolled ART-naive adults and children ≥5 years of age with CD4 counts .1). Results: Among 1711 included participants, 203 (12%) died. Mortality was independently higher with older age; lower CD4 count, albumin, hemoglobin, and grip strength; presence of World Health Organization stage 3/4 weight loss, fever, or vomiting; and problems with mobility or self-care at baseline (all P < .04). Receiving enhanced antimicrobial prophylaxis independently reduced mortality (P = .02). Of five late-presenter phenotypes, Group 1 (n = 355) had highest mortality (25%; median CD4 count, 28 cells/µL), with high symptom burden, weight loss, poor mobility, and low albumin and hemoglobin. Group 2 (n = 394; 11% mortality; 43 cells/µL) also had weight loss, with high white cell, platelet, and neutrophil counts suggesting underlying inflammation/infection. Group 3 (n = 218; 10% mortality) had low CD4 counts (27 cells/µL), but low symptom burden and maintained fat mass. The remaining groups had 4%-6% mortality. Conclusions: Clinical and laboratory features identified groups with highest mortality following ART initiation. A screening tool could identify patients with low CD4 counts for prioritizing same-day ART initiation, enhanced prophylaxis, and intensive follow-up. Clinical Trials Registration: ISRCTN43622374.REALITY was funded by the Joint Global Health Trials Scheme (JGHTS) of the UK Department for International Development, the Wellcome Trust, and Medical Research Council (MRC) (grant number G1100693). Additional funding support was provided by the PENTA Foundation and core support to the MRC Clinical Trials Unit at University College London (grant numbers MC_UU_12023/23 and MC_UU_12023/26). Cipla Ltd, Gilead Sciences, ViiV Healthcare/GlaxoSmithKline, and Merck Sharp & Dohme donated drugs for REALITY, and ready-to-use supplementary food was purchased from Valid International. A. J. P. is funded by the Wellcome Trust (grant number 108065/Z/15/Z). J. A. B. is funded by the JGHTS (grant number MR/M007367/1). The Malawi-Liverpool–Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine (grant number 101113/Z/13/Z) and the Kenya Medical Research Institute (KEMRI)/Wellcome Trust Research Programme, Kilifi (grant number 203077/Z/16/Z) are supported by strategic awards from the Wellcome Trust, United Kingdom. Permission to publish was granted by the Director of KEMRI. This supplement was supported by funds from the Bill & Melinda Gates Foundation

“He does not have to wait under a tree”: perceptions of men, women and health care workers on male partner involvement in prevention of mother to child transmission of human immunodeficiency virus services in Malawi

Abstract Background The perception of male involvement (MI) in maternal child health services is multifaceted and differs among varying programs and populations. In the Prevention of Mother to Child Transmission (PMTCT) context, MI includes men’s attendance at antenatal care (ANC) clinics, undertaking an HIV tests within the ANC and financial and psychological support. Contexualising the definition of MI is fundamental in the development of MI in PMTCT policy and interventions. The objective of this study was to explore the perceptions of men, women and health care workers on male partner involvement in PMTCT services in Malawi. Methods A qualitative descriptive study was conducted at South Lunzu Health Centre (SLHC) in Blantyre, Malawi from December 2012 to January 2013. We conducted s Key Informant Interviews (KIIs) with 6 health care workers and moderated four Focus Group Discussions (FGDs) among 18 men and 17 pregnant women attending antenatal care at SLHC. We divided FGDs participants according to sex and age. We digitally recorded all FGDs and KIIs and simultaneously transcribed and translated verbatim into English. We employed thematic analysis to identify codes and themes. Results Men and women described MI in PMTCT as either a) Positive participation or b) Negative participation. Positive participation included total involvement of the male partner in PMTCT interventions, reminding the spouse of clinic and treatment schedules, and resource provision. Health care workers described MI as either a) Involvement along the pregnancy continuum or b) Passive Involvement. Participants’ preferred positive involvement of male partners. Conclusions There are multiple perceptions of MI in PMTCT with participants preferring positive involvement. There is a need to have a uniform description of MI in PMTCT to optimize development of strategies and interventions that accommodate and optimize MI in PMTCT. A uniform description will be useful in assessing a country’s progress towards achieving MI in PMTCT goals

Facility assessment and qualitative analysis of health worker perspectives on neonatal health in Malawi

Objectives The “Integrating a neonatal healthcare package for Malawi” (IMCHA#108030) project conducted mixed-methods to understand facility-based implementation factors for newborn health innovations in low-resourced health settings. The objective of the two datasets was to evaluate: (a) capacity of quality newborn care in three districts in southern Malawi, and (b) barriers and facilitators the scale up of bubble continuous positive airway pressure (CPAP), a newborn health innovation to support babies with respiratory distress. Data description The Integrated Maternal, Neonatal and Child Quality of Care Assessment and Improvement Tool (version April-2014) is a standardized facility assessment tool developed by the World Health Organization (WHO) that examines quality as well as quantity and availability. The facility survey is complemented by a qualitative dataset of illustrative quotes from health service providers and supervisors on bubble CPAP implementation factors. Research was conducted in one primary health centre (facility assessment only), three district-level hospitals (both) and a tertiary hospital (qualitative only) in southern Malawi. These datasets may be used by other researchers for insights into health systems of low-income countries and implementation factors for the roll-out of neonatal health innovations as well as to frame future research questions or preliminary exploratory research on similar topics.Medicine, Faculty ofNon UBCObstetrics and Gynaecology, Department ofPathology and Laboratory Medicine, Department ofReviewedFacult

Barriers and facilitators to implementing bubble CPAP to improve neonatal health in sub-Saharan Africa: a systematic review

Background: Bubble continuous positive airway pressure (CPAP) has been shown to be effective in supporting breathing in newborns with respiratory distress. The factors that influence implementation in resource-constrained settings remain unclear. The objective of this review is to evaluate the barriers and facilitators of CPAP implementation for newborn care at sub-Saharan African health facilities and how different facility levels and types of bubble CPAP systems may impact utilization. Methods: A systematic search (database inception to July 2019) was performed on MEDLINE Ovid, EMBASE, CINAHL, The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), the WHO Regional Database for Africa, African Index Medicus (AIM), African Journals Online, grey literature and the references of relevant articles. Studies that met the inclusion criteria (primary research, bubble CPAP implementation with neonates ≤ 28 days old at a health facility in sub-Saharan Africa) were included in the review and assessed with National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH) quality assessment tools. The review protocol was published to PROSPERO (CRD42018116082). Results: Seventeen studies were included in the review. Reliable availability of equipment, effectively informing and engaging caregivers and staffing shortages were frequently mentioned barriers to the implementation of bubble CPAP. Understaffed neonatal units and high turnover of nurses and doctors compromised effective training. Provider-to-provider clinical mentorship models as well as affordability and cost-effectiveness of innovative bubble CPAP systems were identified as frequently mentioned facilitators of implementation. Conclusions: With a strong recommendation by the World Health Organization for its use with premature infants with respiratory distress, it is important to understand the barriers and facilitators that can inform the implementation of bubble CPAP. More research is needed into health system factors that can support or impede the use of this potentially promising intervention.Medicine, Faculty ofOther UBCNon UBCObstetrics and Gynaecology, Department ofPathology and Laboratory Medicine, Department ofReviewedFacult

Barriers and facilitators for early and exclusive breastfeeding in health facilities in Sub-Saharan Africa: a systematic review

Background Sub-Saharan Africa carries a disproportionate burden of under-five child deaths in the world and appropriate breastfeeding practices can support efforts to reduce child mortality rates. Health facilities are important in the promotion of early and exclusive breastfeeding. The purpose of this review was to examine facility-based barriers and facilitators to early and exclusive breastfeeding in Sub-Saharan Africa. Methods A systematic search was conducted on Medline, Web of Science, CINAHL, African Journals Online and African Index Medicus from database inception to April 29, 2021 and primary research studies on breastfeeding practices in health facilities in Sub-Saharan Africa were included in the review. We assessed qualitative studies with the Critical Appraisal Skills Programme Qualitative Checklist and quantitative studies using the National Heart, Lung, and Blood Institute tool. The review protocol was registered to Prospero prior to conducting the review (CRD42020167414). Results Of the 56 included studies, relatively few described health facility infrastructure and supplies-related issues (5, 11%) while caregiver factors were frequently described (35, 74%). Facility-based breastfeeding policies and guidelines were frequently available but challenged by implementation gaps, especially at lower health service levels. Facilitators included positive caregiver and health worker attitudes, knowledge and support during the postpartum period. Current studies have focused on caregiver factors, particularly around their knowledge and attitudes, while health facility infrastructure and supplies factors appear to be growing concerns, such as overcrowding and lack of privacy during breastfeeding counselling that lowers the openness and comfort of mothers especially those HIV-positive. Conclusion There has been a dramatic rise in rates of facility births in Sub-Saharan Africa, which must be taken into account when considering the capacities of health facilities to support breastfeeding practices. As the number of facility births rise in Sub-Saharan Africa, so does the responsibility of skilled healthcare workers to provide the necessary breastfeeding support and advice to caregivers. Our review highlighted that health facility infrastructure, supplies and staffing appears to be a neglected area in breastfeeding promotion and a need to strengthen respectful maternity care in the delivery of breastfeeding counselling, particularly in supporting HIV-positive mothers within the context of Sub-Saharan Africa.Medicine, Faculty ofOther UBCNon UBCObstetrics and Gynaecology, Department ofPathology and Laboratory Medicine, Department ofReviewedFacult

Healthcare worker perspectives on mother’s insufficient milk supply in Malawi

Background Human milk insufficiency is a significant barrier to implementing breastfeeding, and it is identified as a prevalent concern in 60–90% of mothers in low-and-middle-income countries. Breastmilk insufficiency can lead to hypoglycemia, hypernatremia, nutritional deficiencies, and failure to thrive in newborns and infants. Studies investigating the impact of breastfeeding interventions to improve milk production highlight inconsistencies between healthcare workers and mothers perceived support, as well as gaps in practical knowledge and training. The aim of this study was to determine perceptions surrounding human milk insufficiency from Malawian healthcare workers. Methods This study is a secondary analysis of 39 interviews with healthcare workers from one tertiary and three district hospitals in Malawi employing content analysis. Interviewed healthcare workers included nurses, clinical officers, midwives, and medical doctors. An inclusive coding framework was developed to identify themes related to human milk insufficiency, which were analyzed using an iterative process with NVivo12 software. Researchers focused on themes emerging from perceptions and reasons given by healthcare workers for human milk insufficiency. Results Inability to produce adequate breastmilk was identified as a prevalent obstacle mothers face in the early postpartum period in both district and tertiary facilities in Malawi. The main reasons given by participants for human milk insufficiency were mothers’ perceived normalcy of milk insufficiency, maternal stress, maternal malnutrition, and traditional beliefs around food and eating. Three focused solutions were offered by participants to improve mother’s milk production – improving education for mothers and training for healthcare providers on interventions to improve mother’s milk production, increasing breastfeeding frequency, and ensuring adequate maternal nutrition pre- and post-partum. Conclusion Health care workers perspectives shed light on the complexity of causes and solutions for human milk insufficiency in Malawi. This research highlights that a respectful professional relationship between health care workers and mothers is an essential bridge to improving communication, detecting human milk insufficiency early, and implementing appropriate interventions. The results of this study may help to inform research, clinical practice, and education in Malawi to improve human milk production.Medicine, Faculty ofOther UBCNon UBCObstetrics and Gynaecology, Department ofPathology and Laboratory Medicine, Department ofReviewedFacultyResearche