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Cryptococcal meningitis accounts for 15% of all HIV-related deaths [1]. The overall number of cryptococcal meningitis cases has remained relatively stable in many low-to-middle income countries (LMICs) despite increasing roll-out of antiretroviral therapy (ART). Increasing numbers of patients are at risk of developing cryptococcal meningitis following ART failure or discontinuation, offsetting declines in those presenting for the first time with advanced HIV [2–4]. Over half of patients diagnosed with cryptococcal meningitis in recent studies in sub-Saharan Africa are ART-experienced (i.e. currently receiving or previously received ART) [5,6]. Although there is robust evidence from prospective randomized trials that ART initiation should be delayed until 4–6 weeks after starting antifungal therapy in ART-naive cryptococcal meningitis patients [7,8], the approach to ART management among ART-experienced cryptococcal meningitis patients lacks adequate evidence, with a paucity of published data.

The SARS-CoV-2 epidemic in southern Africa has been characterized by three distinct waves. The first was associated with a mix of SARS-CoV-2 lineages, while the second and third waves were driven by the Beta (B.1.351) and Delta (B.1.617.2) variants, respectively1–3. In November 2021, genomic surveillance teams in South Africa and Botswana detected a new SARS-CoV-2 variant associated with a rapid resurgence of infections in Gauteng province, South Africa. Within three days of the first genome being uploaded, it was designated a variant of concern (Omicron, B.1.1.529) by the World Health Organization and, within three weeks, had been identified in 87 countries. The Omicron variant is exceptional for carrying over 30 mutations in the spike glycoprotein, which are predicted to influence antibody neutralization and spike function4. Here we describe the genomic profile and early transmission dynamics of Omicron, highlighting the rapid spread in regions with high levels of population immunity.

Additional file 3: eTable 1. Sources of stroke information among respondents.

Additional file 4: eTable 2. Mann-Whitney U/ Kruskal-Wallis H - Association of awareness of calling EMS, and seeking immediate medical assistance with sociodemographic factors among respondents.

Additional file 2. Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) Checklist.

Additional file 1: eFigure 1. Awareness of calling EMS by acute stroke study.

Additional file 1. Protocol for scoping review.

SummaryThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in southern Africa has been characterised by three distinct waves. The first was associated with a mix of SARS-CoV-2 lineages, whilst the second and third waves were driven by the Beta and Delta variants respectively1–3. In November 2021, genomic surveillance teams in South Africa and Botswana detected a new SARS-CoV-2 variant associated with a rapid resurgence of infections in Gauteng Province, South Africa. Within three days of the first genome being uploaded, it was designated a variant of concern (Omicron) by the World Health Organization and, within three weeks, had been identified in 87 countries. The Omicron variant is exceptional for carrying over 30 mutations in the spike glycoprotein, predicted to influence antibody neutralization and spike function4. Here, we describe the genomic profile and early transmission dynamics of Omicron, highlighting the rapid spread in regions with high levels of population immunity.

Background Stroke remains the second leading cause of deaths and disability globally, with highest mortality in Africa (low- and middle-income countries). It is crucial for healthcare professionals to have sufficient stroke risk factors' knowledge in order to reduce the stroke burden. Aims We investigated healthcare professionals' knowledge of modifiable stroke risk factors, and identified demographic factors influencing this knowledge. Methods In this cross-sectional survey study from Botswana (upper middle-income country), structured questionnaires reflecting recent stroke guidelines were administered to a representative selection of healthcare workers in greater Gaborone. The response rate was 61.4%, comprising 84 doctors, 227 nurses and 33 paramedics. Categorical data were described using percentages and Chi-square tests. Associations between stroke risk factors' knowledge and demographic factors were analyzed with one-way ANOVA using SPSS 25 statistical software. Results Awareness rate of individual stroke risk factors was highest for hypertension (96.5%), followed by obesity (93.3%), smoking (91.9%), elevated total cholesterol (91.0%), physical inactivity (83.4%), elevated low-density lipoprotein (LDL) cholesterol (81.1%), excessive alcohol drinking (77.0%), and lowest for diabetes (73.3%). For all-8 risk factors, doctors had the highest knowledge, followed by nurses and paramedics lowest (7.11 vs 6.85 vs 6.06, P, Highlights • This is the first study in Africa assessing knowledge of stroke risk factors among the three healthcare professions concurrently • Understanding stroke risk factors is crucial for healthcare professionals as counsellors and managers of stroke • Doctors had highest stroke knowledge, followed by nurses and lowest paramedics. • Low knowledge was associated with paramedics, private sector, 0–1 year’ clinical experience and female gender. • Continuing education on ischemic stroke risk factors is needed

During the May Measurement Month 2018 (MMM18) campaign, we aimed to raise hypertension awareness and measure blood pressure (BP) across different communities in Botswana. Study sites included four large villages and Gaborone (capital city). Screening sites were shopping malls, train stations, churches, and workplaces. Individuals aged ≥18 years were recruited through fliers, word of mouth, and as volunteer walk-ins at the sites. Demographic and risk factor data were collected through a questionnaire prior to measuring three BP readings per participant. Weight was measured while height was usually estimated. Hypertension was defined as: systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg or taking antihypertensive medication. The mean of readings 2 and 3 was used and was estimated using multiple imputation where missing. Amongst 4599 participants whose BPs were measured, 54.5% were female, while mean age was 35.9 years. A total of 1510 (32.8%) participants were hypertensive and of those, 712 (47.1%) were aware of the hypertension. Only 35.2% of hypertensives were on antihypertensive treatment with 54.4% had controlled BP. Amongst all hypertensives, only 19.1% had controlled BP. Risk factors associated with higher BP included obesity, more than 1 unit of alcohol/week and BP measured on Sunday. Less than half (47.1%) of those identified as having hypertension during MMM18 were aware of their condition, despite the escalating prevalence of hypertension in the country. Regular BP awareness and opportunistic BP measurement campaigns like MMM are recommended to improve detection and control of hypertension and other cardiovascular risk factors.

Background Although CRE are a global threat, data in low- and middle-income countries are scarce. Colonization data are vital for informing antibiotic resistance strategies. We characterized the colonization prevalence of CRE in various settings in Botswana. Methods This study was conducted in 3 districts in Botswana (1 hospital and 2 clinics per district). Adult inpatients and clinic patients were randomly selected for enrollment. Community subjects were enrolled by inviting each enrolled clinic subject to refer up to 3 adults. Each adult clinic or community subject was also asked to refer their children. All subjects had rectal swabs obtained and inoculated on selective chromogenic media for preliminary identification of CRE. Final identification and susceptibility testing were performed using MALDI-TOF MS and VITEK-2, respectively. CRE underwent genotyping for carbapenemase genes. Results Subjects were enrolled from 1/15/20-9/4/20 with a pause from 4/2/20-5/21/20 due to a countrywide COVID lockdown. Of 5,088 subjects approached, 2,469 (49%) participated. Enrollment by subject type was: hospital – 469 (19%); clinic – 959 (39%); community adult – 477 (19%); and community child – 564 (23%). Of 2,469 subjects, the median (interquartile range) age was 32 years (19-44) and 1,783 (72%) were female. 42 (1.7%) subjects were colonized with at least one CRE; 10 subjects were colonized with multiple strains. E. coli (n=17), K. pneumoniae (n=20), and E. cloacae complex (n=11) were most common. CRE colonization prevalence was 6.8% for hospital subjects, 0.7% for clinic subjects, 0.2% for adult community subjects, and 0.5% for child community subjects (p< 0.001)). CRE prevalence varied across regions (Figure 1) and was significantly higher pre- vs post-lockdown (Figure 2). VIM and NDM were the most common carbapenemase genes (Figure 3). Figure 1. CRE Colonization - Study Sites Figure 2. CRE Colonization - Temporal Trends FIgure 3. CRE Genotypic Analyses Conclusion CRE colonization was significantly higher in hospital vs community settings in Botswana. CRE prevalence varied by region and decreased significantly following a countrywide lockdown. With CRE prevalence still modest, elucidating risk factors for CRE colonization holds promise in developing strategies to curb further emergence of CRE. Additional investigation of the CRE isolates without identified resistance genes is warranted. Disclosures Robert Gross, MD, MSCE, Pfizer (Other Financial or Material Support, Serve on DSMB for drug unrelated to HIV) Ebbing Lautenbach, MD, MPH, MSCE, Merck (Other Financial or Material Support, Member of Data and Safety Monitoring Board (DSMB))

PURPOSE Breast cancer patients, including patients living with HIV (PLWH), in sub-Saharan Africa experience a disproportionate burden of mortality. Adherence to treatment guidelines improves quality of care and survival outcomes. We therefore sought to study patient socioeconomic and cultural factors associated with treatment fidelity and how this may differ for PLWH in Botswana. METHODS This was a qualitative study design with deviance sampling of high and low fidelity patients who initiated treatment for stage I-III breast cancer. One-on-one phone interviews were conducted using semi-structured interviews, guided by the Theory of Planned Behavior. The final sample size was determined by thematic saturation. Transcribed interviews were double-coded and analyzed in NVivo using an integrated analysis approach. We maintained a kappa statistic of 0.8 between coders. RESULTS Fifteen high and 15 low fidelity patients were enrolled from August 25-December 15, 2020. Ten out of 30 of the cohort were PLWH. Barriers to treatment adherence included concerns about safety and efficacy of chemotherapy, lack of trust in the care team, lack of psychosocial support, financial toxicity, geographical inaccessibility, and other health-system barriers. Drivers and manifestations of stigma, including intersectional stigma of cancer fatalism in PLWH were identified as prominent barriers. Conversely, self-acceptance and de-stigmatization were identified as facilitators of treatment initiation. Additional facilitators included knowledge of curative intent, anticipated management of side effects, self-motivation, social support, and peer support. COVID-19 pandemic amplified existing socioeconomic barriers especially for patients with food insecurity and geographic inaccessibility. CONCLUSION The study identified multi-level modifiable patient and related health-system factors associated with treatment initiation and adherence. PLWH experienced unique barriers including intersectional stigma, which is a critical finding and warrants further evaluation. The facilitators in this study provide opportunities for leveraging existing strengths within the specific context to design multilevel implementation strategies to increase treatment fidelity of guideline concordant breast cancer therapy.

Supplemental material, sj-pdf-1-qhr-10.1177_10497323211001361 for Identifying “What Matters Most” to Men in Botswana to Promote Resistance to HIV-Related Stigma by Supriya Misra, Haitisha T. Mehta, Evan L. Eschliman, Shathani Rampa, Ohemaa B. Poku, Wei-Qian Wang, Ari R. Ho-Foster, Mosepele Mosepele, Timothy D. Becker, Patlo Entaile, Tonya Arscott-Mills, Phillip R. Opondo, Michael B. Blank and Lawrence H. Yang in Qualitative Health Research

Background Oral HIV self-testing (HIVST) may be useful for increasing testing in persons at elevated risk of acquiring HIV. Methods We conducted a pilot study to evaluate the feasibility (defined by uptake) of HIVST among FSW in Gaborone, Botswana. FSW age 18 years and above were recruited through a non-governmental organization serving FSW. FSW with unknown or negative HIV status at screening performed HIVST in the study clinic following brief training. FSW testing HIV-negative were each given two test kits to take home: one kit to perform unassisted HIVST and another to share with others. Feasibility (use) of HIVST (and sharing of test kits with others) was assessed in these women at a study visit four months later. Results Two hundred FSW were screened. Their average age was 34 years (range 18–59), and 115 (58%) were HIV-positive. Eighty-five (42%) tested HIV-negative at entry and were eligible to take part in the HIVST pilot study. All 85 (100%) agreed to take home HIVST kits. Sixty-nine (81%) of these 85 participants had a follow-up visit, 56 (81%) of whom reported performing HIVST at a mean of three and half months after the initial visit. All 56 participants who performed HIVST reported negative HIVST results. Fifty (73%) of the 69 participants who took HIVST kits home shared them with others. Of the 50 women sharing HIVST kits, 25 (50%) shared with their non-client partners, 15 with a family member, 8 with friends, and 3 with a client. One participant did not test herself but shared both her test kits. Most participants 53/56 (95%) found oral HIVST very easy to use whilst 3/56 (5%) felt it was fairly easy. Conclusion Oral HIVST is feasible among FSW in Gaborone, Botswana. The majority of FSW used the HIVST kits themselves and also shared extra HIVST kits with other individuals.

Background With funding from the United States Health Resources Service Administration (HRSA), a consortium of health professional training institutions from Africa developed HIV-specific, interprofessional, team-based educational resources to better support trainees during the transition period between pre-service training and professional practice. Methods Ten faculty members representing nine medical and nursing schools in sub-Saharan Africa (SSA) developed a training package of modules focused on core clinical, public health, interprofessional education (IPE), and quality improvement (QI) domains related to HIV service delivery. Curriculum development was informed by a rapid needs assessment of existing tools and future needs for HIV education across 27 SSA health professions training institutions. A total of 17 modules were developed, targeted at newly qualified health care professionals to be taught in a series of two-day workshops meant to complement existing institution specific HIV-curricula. Results Between April and July 2019, a comprehensive case-based HIV training package was developed to support trainees in transition from pre-service training to independent professional practice. Each module, addressing different elements of interprofessional practice, was intended to be delivered in an interprofessional format. Thus far, 70 health professions training institutions in 14 countries have implemented the program; 547 educators facilitated STRIPE workshops, with a total of 5027 learners trained between September 2019 and September 2020. Conclusions To our knowledge this is the first IPE HIV-specific curriculum explicitly focused on enhancing the quality of training provided to graduating health care professionals working in SSA. The collaborative, cross-institutional, interprofessional approach to curriculum development provides a benchmark for how best-practice approaches to education can be disseminated in SSA.

BackgroundChronic kidney disease is a common comorbid condition among persons living with human immunodeficiency virus (PWH). We characterized baseline kidney function in the REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) trial cohort.MethodsREPRIEVE enrolled PWH with low to moderate cardiovascular risk based on traditional risk factors to evaluate the effect of statin therapy on cardiovascular events. We determined baseline estimated glomerular filtration rate (eGFR) with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Modification of Diet in Renal Disease, and Cockcroft-Gault equations, and we evaluated baseline factors associated with eGFR ResultsAmong 7770 participants enrolled, the median age was 50 years, 31% were female (natal sex), 43% black or African American and 15% Asian, the median body mass index (calculated as calculated as weight in kilograms divided by height in meters squared) was 25.8, and the median CD4 cell count 620/µL. The median CKD-EPI eGFR was 97 mL/min/1.73 m2, and 38% had an eGFR ConclusionsREPRIEVE enrolled a diverse cohort including a substantial number of PWH with reduced kidney function. Factors associated with reduced eGFR included traditional risk factors and tenofovir disoproxil fumarate exposure. Three commonly used equations have only fair agreement, with potential implications for both clinical care and epidemiologic studies.Clinical Trials RegistrationNCT02344290.

OBJECTIVES National guidelines in Botswana recommend baseline CD4 count measurement and both CD4 and HIV viral load (VL) monitoring post-antiretroviral therapy (ART) initiation. We evaluated the utility of CD4 count measurement in Botswana in the era of universal ART. METHODS CD4 and VL data were analysed for HIV-infected adults undergoing CD4 count measurement in 2015-2017 at the Botswana Harvard HIV-Reference Laboratory. We determined (1) the proportion of individuals with advanced HIV disease (CD4 count

There are limited data on the effectiveness of dolutegravir (DTG)-based combination antiretroviral therapy (ART) in real-life settings in southern Africa where HIV-1 subtype C predominates. We report a patient infected with HIV-1 subtype C on DTG-based ART previously exposed to raltegravir who developed multidrug resistance mutations to four antiretroviral classes. There is need for drug resistance monitoring and clinical vigilance to ensure effectiveness of HIV treatment programs even in the era of DTG-based ART.

Summary Background Untreated HIV infection is associated with increased biomarkers of endothelial dysfunction. However, the predictors and degree of endothelial dysfunction among virally suppressed HIV–infected adults on long–term antiretroviral therapy (ART) have not been well studied in sub– Saharan Africa (SSA). Methods We enrolled 112 HIV–infected adults with virological suppression on long–term ART and 84 HIV–uninfected controls in Botswana. We measured plasma levels of markers of endothelial injury [soluble vascular adhesion molecule 1 (VCAM–1), intercellular adhesion molecule 1 (ICAM–1) and E–selectin] and plasma levels of biomarkers of inflammation [interleukin 6 (IL–6)] and monocyte activation (sCD163). Baseline traditional cardiovascular disease (CVD) risk factors and bilateral common carotid intima–media thickness (cIMT) were also available for all participants. We assessed whether HIV status (despite virological suppression on ART) was associated with biomarkers of endothelial dysfunction after controlling for traditional CVD risk factors in linear regression models. We additionally assessed the association between IL–6, sCD163 and cIMT with endothelial dysfunction in separate multivariate linear regression models, controlling for cIMT, among virally suppressed HIV–infected participants only. Results In multivariate analysis, HIV infection was significantly associated with increased VCAM–1 (p < 0.01) and ICAM–1 (p = 0.03) but not E–selectin (p = 0.74) levels. Within the HIV–positive group, higher sCD163 levels were associated with decreased ICAM–1 and E–selectin (p < 0.01 and p = 0.01, respectively) but not VCAM–1 (p = 0.13) levels. IL–6 was not associated with any of the biomarkers of endothelial dysfunction. Conclusion HIV disease was associated with biomarkers of endothelial dysfunction among virally suppressed adults in Botswana on long–term ART after controlling for traditional CVD risk factors. Future work should explore the clinical impact of persistent endothelial dysfunction following longterm HIV viral suppression on the risk of CVD clinical endpoints among HIV–infected patients in this setting.

Inter-individual variability in efavirenz (EFV) pharmacokinetics and dynamics are dominantly driven by the polymorphism in cytochrome P450 (CYP) isoenzyme 2B6 516G>T. We hypothesized that additional CYP polymorphisms mediate the relationship between CYP2B6 516G>T, EFV metabolism, and clinical events. We investigated 21 SNPs in 814 HIV-infected adults initiating EFV-based therapy in Botswana for population pharmacokinetics, CNS toxicities, and treatment outcomes. Two SNPs (rs28399499 and rs28399433) showed reduced apparent oral EFV clearance. Four SNPs (rs2279345, rs4803417, rs4802101, and rs61663607) showed extensive clearance. Composite CYP2B-mediated EFV metabolism was significantly associated with CNS toxicity (p=0.04), with extensive metabolizers reporting more and slow and very slow metabolizers reporting less toxicity after one month compared to intermediate metabolizers. Composite CYP2B6 metabolism was not associated with composite early treatment failure. In conclusion, our data suggest that CNS-related toxicities might not be solely the result of super-therapeutic parent EFV concentrations in HIV-infected individuals in patients of African ancestry.