Single-Dose Liposomal Amphotericin B Treatment for Cryptococcal Meningitis.

BACKGROUND: Cryptococcal meningitis is a leading cause of human immunodeficiency virus (HIV)-related death in sub-Saharan Africa. Whether a treatment regimen that includes a single high dose of liposomal amphotericin B would be efficacious is not known. METHODS: In this phase 3 randomized, controlled, noninferiority trial conducted in five African countries, we assigned HIV-positive adults with cryptococcal meningitis in a 1:1 ratio to receive either a single high dose of liposomal amphotericin B (10 mg per kilogram of body weight) on day 1 plus 14 days of flucytosine (100 mg per kilogram per day) and fluconazole (1200 mg per day) or the current World Health Organization-recommended treatment, which includes amphotericin B deoxycholate (1 mg per kilogram per day) plus flucytosine (100 mg per kilogram per day) for 7 days, followed by fluconazole (1200 mg per day) for 7 days (control). The primary end point was death from any cause at 10 weeks; the trial was powered to show noninferiority at a 10-percentage-point margin. RESULTS: A total of 844 participants underwent randomization; 814 were included in the intention-to-treat population. At 10 weeks, deaths were reported in 101 participants (24.8%; 95% confidence interval [CI], 20.7 to 29.3) in the liposomal amphotericin B group and 117 (28.7%; 95% CI, 24.4 to 33.4) in the control group (difference, -3.9 percentage points); the upper boundary of the one-sided 95% confidence interval was 1.2 percentage points (within the noninferiority margin; P<0.001 for noninferiority). Fungal clearance from cerebrospinal fluid was -0.40 log10 colony-forming units (CFU) per milliliter per day in the liposomal amphotericin B group and -0.42 log10 CFU per milliliter per day in the control group. Fewer participants had grade 3 or 4 adverse events in the liposomal amphotericin B group than in the control group (50.0% vs. 62.3%). CONCLUSIONS: Single-dose liposomal amphotericin B combined with flucytosine and fluconazole was noninferior to the WHO-recommended treatment for HIV-associated cryptococcal meningitis and was associated with fewer adverse events. (Funded by the European and Developing Countries Clinical Trials Partnership and others; Ambition ISRCTN number, ISRCTN72509687.).

Age and healthy lifestyle behavior's disparities and similarities on knowledge of myocardial infarction symptoms and risk factors among public and outpatients in a resource-limited setting, cross-sectional study in greater Gaborone, Botswana.

OBJECTIVES: In this cross-sectional study from Botswana, we investigated knowledge of myocardial infarction (MI) symptoms and risk factors among the general public and outpatients with MI risk factors based on age and lifestyle behaviors, in addition to assessing associations with sociodemographic and MI risk factors. METHOD: Open-ended questionnaires about 8 MI symptoms and 10 risk factors, were administered by research assistants to a representative selection of outpatients (n = 525) and the public (n = 2248). Weight and height were measured in all participants and BMI was calculated. Knowledge scores were compared between the two groups. We examined whether sociodemographic and MI risk factors had impact on the scores. Analyses were further adjusted for lifestyle behavior (smoking status, dietary status and physical activities). RESULTS: The valid response rate was 97.9% comprising 97.8% for the public (n = 2199) and 98.1% for outpatients (n = 515). Public respondents (35.2 ± 12.3 years) were younger than outpatients (38.5 ± 12.6 years). The public comprised 56.9% females while outpatients 54.6%. In general, outpatients had higher knowledge of MI symptoms than the public, with mean scores ± SD of 3.49 ± 2.84 vs 2.80 ± 2.54. Outpatients also had higher knowledge score of MI risk factors than the public, with mean scores, 5.33 ± 3.22 vs 3.82 ± 3.07. For MI symptoms, outpatients were more aware than the public for chest pains among all ages, for arm pain/ numbness, neck/ jaw pain radiating to/ from chest, and feeling sick or looking pallor on the skin among those aged 35-49 years. Among both the public and outpatients, lower knowledge of both MI symptoms and risk factors was associated with primary education, not residing/working together, history of hypertension, no history of heart disease/stroke, and obesity. There were similarities and disparities on MI knowledge among respondents with various numbers of healthy lifestyle behaviours. CONCLUSION: Results call for urgent educational campaigns on awareness and knowledge of MI and using strategies based on age and lifestyle behavior.

Self-reported cardiovascular disease risk factor screening among people living with HIV vs. members of the general population in Botswana: a community-based study.

BACKGROUND: Morbidity and mortality due to cardiovascular diseases (CVDs) are high and increasing in low- and middle-income countries. People living with HIV (PLWH) are more likely to experience CVD than members of the general population. Therefore, we aimed to assess whether PLWH were more likely to have previously been screened for cardiovascular disease risk factors (CVDRFs) than people without HIV. METHODS: A population-based, cross-sectional study was conducted among individuals aged 16 to 68 years across 22 communities in Botswana from February to August 2017 as part of a larger community-based cluster randomized HIV treatment-as-prevention trial. Participants were asked if they had been screened for and counselled on cardiovascular disease risk factors (history of hypertension or blood pressure check, blood glucose and cholesterol measurements, weight check and weight control, tobacco smoking and cessation, alcohol use and physical activity) in the preceding 3 years. HIV testing was offered to those with an unknown HIV status. Multiple logistic regression analysis controlling for age and sex was used to assess the relationship between CVDRF screening and HIV status. RESULTS: Of the 3981 participants enrolled, 2547 (64%) were female, and 1196 (30%) were PLWH (93% already on antiretroviral therapy [ART]). PLWH were more likely to report previous screening for diabetes (25% vs. 19%, p < 0.001), elevated cholesterol (17% vs. 12%, p < 0.001) and to have had their weight checked (76% vs. 55%, p < 0.001) than HIV-uninfected participants. PLWH were also more likely to have received counselling on salt intake (42% vs. 33%, p < 0.001), smoking cessation (66% vs. 46%, p < 0.001), weight control (38% vs. 29%, p < 0.001), physical activity (46% vs. 34%, p < 0.001) and alcohol consumption (35% vs. 23%, p < 0.001) than their HIV-uninfected counterparts. Overall, PLWH were more likely to have received screening for and/or counselling on CVDRFs (adjusted odds ratio 1.84, 95% CI: 1.46-2.32, p < 0.001). CONCLUSION: PLWH were almost two times more likely to have been previously screened for CVDRFs than those without HIV, indicating a need for universal scale-up of integrated management and prevention of CVDs in the HIV-uninfected population.

How Applicable Is the Single-Dose AMBITION Regimen for Human Immunodeficiency Virus-Associated Cryptococcal Meningitis to High-Income Settings?

The AmBisome Therapy Induction Optimization (AMBITION-cm) trial, conducted in eastern and southern Africa, showed that a single, high dose (10 mg/kg) of liposomal amphotericin B, given with an oral backbone of fluconazole and flucytosine, was noninferior to the World Health Organization (WHO)-recommended regimen of 7 days of amphotericin B deoxycholate plus flucytosine for treatment of human immunodeficiency virus (HIV)-associated cryptococcal meningitis and has been incorporated into WHO treatment guidelines. We believe that the trial also has important implications for the treatment of HIV-associated cryptococcal meningitis in high-income settings. We advance the arguments, supported by evidence where available, that the AMBITION-cm trial regimen is likely to be as fungicidal as the currently recommended 14-day liposomal amphotericin-based treatments, better tolerated with fewer adverse effects, and confer significant economic and practical benefits and, therefore, should be included as a treatment option in guidance for HIV-associated cryptococcal treatment in high-income settings.

Risk Factors for Community Colonization With Extended-Spectrum Cephalosporin-Resistant Enterobacterales (ESCrE) in Botswana: An Antibiotic Resistance in Communities and Hospitals (ARCH) Study.

BACKGROUND: The epidemiology of extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) in low- and middle-income countries (LMICs) is poorly described. Identifying risk factors for ESCrE colonization is critical to inform antibiotic resistance reduction strategies because colonization is typically a precursor to infection. METHODS: From 15 January 2020 to 4 September 2020, we surveyed a random sample of clinic patients at 6 sites in Botswana. We also invited each enrolled participant to refer up to 3 adults and children. All participants had rectal swabs collected that were inoculated onto chromogenic media followed by confirmatory testing. Data were collected on demographics, comorbidities, antibiotic use, healthcare exposures, travel, and farm and animal contact. Participants with ESCrE colonization (cases) were compared with noncolonized participants (controls) to identify risk factors for ESCrE colonization using bivariable, stratified, and multivariable analyses. RESULTS: A total of 2000 participants were enrolled. There were 959 (48.0%) clinic participants, 477 (23.9%) adult community participants, and 564 (28.2%) child community participants. The median (interquartile range) age was 30 (12-41) and 1463 (73%) were women. There were 555 cases and 1445 controls (ie, 27.8% of participants were ESCrE colonized). Independent risk factors (adjusted odds ratio [95% confidence interval]) for ESCrE included healthcare exposure (1.37 [1.08-1.73]), foreign travel [1.98 (1.04-3.77]), tending livestock (1.34 [1.03-1.73]), and presence of an ESCrE-colonized household member (1.57 [1.08-2.27]). CONCLUSIONS: Our results suggest healthcare exposure may be important in driving ESCrE. The strong links to livestock exposure and household member ESCrE colonization highlight the potential role of common exposure or household transmission. These findings are critical to inform strategies to curb further emergence of ESCrE in LMICs.

Stigma and Social Determinants of Health Associated With Fidelity to Guideline-Concordant Therapy in Patients With Breast Cancer Living With and Without HIV in Botswana.

BACKGROUND: Patients with breast cancer in sub-Saharan Africa (SSA) experience a disproportionate burden of mortality. Fidelity to treatment guidelines, defined as receiving optimal dose and frequency of prescribed treatments, improves survival. We sought to identify patient factors associated with treatment fidelity and how this may differ for people with HIV (PWH) and breast cancer. METHODS: We conducted a qualitative study of women who initiated outpatient treatment for stages I-III breast cancer in Botswana, with deviance sampling of high- and low-fidelity patients. One-on-one interviews were conducted using semi-structured guides informed by the Theory of Planned Behavior. The sample size was determined by thematic saturation. Transcribed interviews were double coded with an integrated analytic approach. RESULTS: We enrolled 15 high- and 15 low-fidelity participants from August 25, 2020 to December 15, 2020, including 10 PWH (4 high, 6 low fidelity). Ninety-three percent had stage III disease. Barriers to treatment fidelity included stigma, social determinants of health (SDOH), and health system barriers. Acceptance and de-stigmatization, peer and other social support, increased knowledge and self-efficacy were identified as facilitators. The COVID-19 pandemic amplified existing socioeconomic stressors. Unique barriers and facilitators identified by PWH included intersectional stigma, and HIV and cancer care integration, respectively. CONCLUSION: We identified multilevel modifiable patient and health system factors associated with fidelity. The facilitators provide opportunities for leveraging existing strengths within the Botswana context to design implementation strategies to increase treatment fidelity to guideline-concordant breast cancer therapy. However, PWH experienced unique barriers, suggesting that interventions to address fidelity may need to be tailored to specific comorbidities.

Standard of care in advanced HIV disease: review of HIV treatment guidelines in six sub-Saharan African countries.

BACKGROUND: The World Health Organization (WHO) recommends an evidence-based package of care to reduce mortality and morbidity among people with advanced HIV disease (AHD). Adoption of these recommendations by national guidelines in sub-Saharan Africa is poorly documented. We aimed to review national guidelines for AHD management across six selected countries in sub-Saharan Africa for benchmarking against the 2021 WHO recommendations. METHODS: We reviewed national guidelines from six countries participating in an ongoing randomized controlled trial recruiting people with AHD. We extracted information addressing 18 items of AHD diagnosis and management across the following domains: [1] Definition of AHD, [2] Screening, [3] Prophylaxis, [4] Supportive care, and [5] HIV treatment. Data from national guideline documents were compared to the 2021 WHO consolidated guidelines on HIV and an agreement score was produced to evaluate extent of guideline adoption. RESULTS: The distribution of categories of agreement varied for the national documents. Four of the six countries addressed all 18 items (Malawi, Nigeria, Sierra Leone, Uganda). Overall agreement with the WHO 2021 guidelines ranged from 9 to 15.5 out of 18 possible points: Malawi 15.5 points, Nigeria, and Sierra Leone 14.5 points, South Africa 13.5 points, Uganda 13.0 points and Botswana with 9.0 points. Most inconsistencies were reported for the delay of antiretroviral therapy (ART) in presence of opportunistic diseases. None of the six national guidelines aligned with WHO recommendations around ART timing in patients with tuberculosis. Agreement correlated with the year of publication of the national guideline. CONCLUSION: National guidelines addressing the care of advanced HIV disease in sub-Saharan Africa are available. Besides optimal timing for start of ART in presence of tuberculosis, most national recommendations are in line with the 2021 WHO standards.

Pilot Test of Mopati, a Multi-Level Adherence Intervention for People Living with HIV and Their Treatment Partners in Botswana.

BACKGROUND: Low-cost, scalable strategies are necessary to reach the UNAIDS 2030 target of ending HIV as a public health threat. Use of treatment partners, informal caregivers selected by people living with HIV to support antiretroviral therapy adherence, is one such strategy that is included in many countries' HIV guidelines, including Botswana, a country with high HIV prevalence. METHOD: From June 2021 to June 2022, we pilot tested a clinic-based treatment partner intervention ("Mopati"), including standardized language for providers to guide patients on treatment partner selection and workshops to train treatment partners on providing non-directive support to patients using a non-confrontational, non-judgmental approach. Sixty unsuppressed patients (30 per clinic) and 45 treatment partners (17 intervention, 28 control) were recruited from an intervention-control clinic matched-pair in Gaborone, Botswana. RESULTS: Mopati had medium-to-large effects on increasing patients' adherence, adherence self-efficacy, intrinsic adherence motivation, and perceived non-directive support from treatment partners, and decreasing treatment partner caregiver burden. Aggregate viral suppression rates significantly increased in the intervention (vs. control) clinic. Qualitative data from 14 clinic staff, 21 patients, and 16 treatment partners indicated that Mopati was viewed as effective. Providers said the guidance empowered them to be proactive in communicating about adherence; most reported using the guidance. CONCLUSION: This study shows preliminary support for the use of treatment partners in HIV care, and further evidence for interventions that leverage patients' existing support. This research can inform ways to improve adherence to HIV treatment as well as the treatment of HIV-related comorbid conditions in lower-resource settings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04796610.

High concordance in plasma and CSF HIV-1 drug resistance mutations despite high cases of CSF viral escape in individuals with HIV-associated cryptococcal meningitis in Botswana.

OBJECTIVES: We compared the patterns of HIV-1 drug resistance mutations between the CSF and plasma of individuals with HIV-associated cryptococcal meningitis. METHODS: This is a cross-sectional study of archived CSF and plasma samples collected from ART-exposed participants recruited in the Phase 3 AmBisome Therapy Induction Optimisation randomized controlled trial (ISRCTN72509687) conducted in Botswana between 2018 and 2021. HIV-1 RT and protease genes were genotyped using next-generation sequencing and HIV-1 drug resistance mutations were compared between the CSF and plasma compartments stratified by thresholds of ≥20% and <20%. RESULTS: Overall, 66.7% (16/24) of participants had at least one HIV-1 drug resistance mutation in the CSF and/or plasma. A total of 15/22 (68.2%) participants had HIV-1 drug resistance mutations at ≥20% threshold in the plasma and of those, 11 (73.3%) had been on ART longer than 6 months. HIV-1 drug resistance mutations were highly concordant between the CSF and plasma at ≥20% threshold despite a substantial number of individuals experiencing CSF viral escape and with only 54.5% with CSF WBC count ≥20 cells/mm3. Minority HIV-1 drug resistance mutations were detected in 20.8% (5/24) of participants. There were no mutations in the CSF that were not detected in the plasma. CONCLUSIONS: There was high concordance in HIV-1 drug resistance mutations in the CSF and plasma, suggesting intercompartmental mixing and possibly a lack of compartmentalization. Some individuals harboured minority HIV-1 drug resistance mutations, demonstrating the need to employ more sensitive genotyping methods such as next-generation sequencing for the detection of low-abundance mutations.

Public and outpatients' awareness of calling emergency medical services immediately by acute stroke in an upper middle-income country: a cross-sectional questionnaire study in greater Gaborone, Botswana.

OBJECTIVES: In this cross-sectional study from Botswana, we investigated awareness of calling emergency medical services (EMS) and seeking immediate medical assistance by acute stroke among stroke risk outpatients and public. METHOD: Closed-ended questionnaires on awareness of calling EMS and seeking immediate medical assistance by acute stroke, were administered by research assistants to a representative selection of outpatients and public. RESULTS: The response rate was 96.0% (93.0% for public (2013) and 96.6% for outpatients (795)). Public respondents had mean age of 36.1 ± 14.5 years (age range 18-90 years) and 54.5% were females, while outpatients had mean age of 37.4 ± 12.7 years (age range 18-80 years) and 58.1% were females. Awareness of calling EMS (78.3%), and of seeking immediate medical assistance (93.1%) by stroke attack was adequate. For calling EMS by acute stroke, outpatients had higher awareness than the public (p < 0.05) among those with unhealthy diet (90.9% vs 71.1%), family history of both stroke and heart diseases (90.7% vs 61.2%), no history of psychiatric diseases (93.2% vs 76.0%) and sedentary lifestyle (87.5% vs 74.8%). Predictors of low awareness of both calling EMS and seeking immediate medical assistance were no medical insurance, residing/working together, history of psychiatric diseases, and normal weight. Male gender, ≥50 years age, primary education, family history of both stroke and heart diseases, current smoking, no history of HIV/AIDS, and light physical activity were predictors of low awareness of need for calling EMS. CONCLUSION: Results call for educational campaigns on awareness of calling EMS and seeking immediate medical assistance among those with high risk factor levels.

Prevalence of the metabolic syndrome and associated factors among inpatients with severe mental illness in Botswana: a cross-sectional study.

INTRODUCTION: The metabolic syndrome, a cluster of inter-related risk factors for cardiovascular diseases is highly prevalent among individuals with obesity and sedentary lifestyle. Chronic psychiatric disorders such as severe mental illness are associated with increased risk for cardiovascular diseases. We aimed to assess the prevalence and correlates of metabolic syndrome among inpatients with severe mental illness in a resource limited setting with high HIV prevalence. METHODS: This was a cross-sectional study among adult inpatients at a referral psychiatric hospital in Botswana. We used convenience sampling to enrol participants available at the time of the study. The National Cholesterol Education Program Adult Treatment Panel-III (NCEP-ATP III) criteria was used to define the metabolic syndrome. Data were analysed using descriptive statistics as well as multiple logistic regression modelling. RESULTS: A total of 137 participants were enrolled. Of these, 119 (87%) had complete data for the main analysis. The overall prevalence of metabolic syndrome was 22.6% (95% CI 15.9, 30.6) and did not differ significantly by gender or HIV status. Age was significantly associated with the risk of having the metabolic syndrome while gender, body mass index, HIV status, and days of moderate physical activity were not. CONCLUSION: There was a moderately high prevalence of metabolic syndrome. Thus, the management of individuals with severe mental illness in resource limited settings should include assessment of cardiovascular risk and target modifiable risk factors in this population. Consideration for the patient's age should be made when rationalizing the limited resources available for assessing metabolic syndrome among patients with severe mental illness.

Role of Support Reciprocity in HIV Viral Suppression Among People Living with HIV and Their Treatment Partners in Botswana.

BACKGROUND: Social support reciprocity (the extent to which people exchange mutual support) is associated with long-term health. METHOD: We examined whether overall social support and reciprocity of support between people living with HIV and their treatment partners (informal caregivers selected from patients' social networks to support adherence) are associated with HIV viral suppression. A total of 130 patients living with HIV and their treatment partners were recruited from a clinic in Gaborone, Botswana, from May 2016 to April 2017. Participants completed surveys assessing sociodemographic and social network characteristics. Patients and treatment partners rated their emotional closeness to each other (not at all close = 0, somewhat close = 1, very close = 2). RESULTS: Multivariable logistic regressions indicated a significantly higher likelihood of viral suppression among patients who reported greater average emotional closeness to social network members. The likelihood of viral suppression was lower in asymmetric relationships in which patients felt closer to treatment partners than treatment partners felt to them (compared to when treatment partners felt closer to patients); this negative effect was strongest in dyads with female treatment partners and male patients. Follow-up analyses additionally indicated that asymmetric relationships in which treatment partners felt closer to patients were as protective as symmetric relationships, in which patients and treatment partners felt equally close. CONCLUSION: Perceptions around reciprocity may matter as much as overall relationship closeness in patients' health outcomes. Interventions to improve the support of informal caregivers could help to improve relationship quality and health outcomes among people with HIV.

Modest reduction in adverse birth outcomes following the COVID-19 lockdown.

BACKGROUND: Widespread lockdowns imposed during the coronavirus disease 2019 crisis may impact birth outcomes. OBJECTIVE: This study aimed to evaluate the association between the COVID-19 lockdown and the risk of adverse birth outcomes in Botswana. STUDY DESIGN: In response to the coronavirus disease 2019 crisis, Botswana enforced a lockdown that restricted movement within the country. We used data from an ongoing nationwide birth outcomes surveillance study to evaluate adverse outcomes (stillbirth, preterm birth, small-for-gestational-age fetuses, and neonatal death) and severe adverse outcomes (stillbirth, very preterm birth, very-small-for-gestational-age fetuses, and neonatal death) recorded prelockdown (January 1, 2020-April 2, 2020), during lockdown (April 3, 2020-May 7, 2020), and postlockdown (May 8, 2020-July 20, 2020). Using difference-in-differences analyses, we compared the net change in each outcome from the prelockdown to lockdown periods in 2020 relative to the same 2 periods in 2017-2019 with the net change in each outcome from the prelockdown to postlockdown periods in 2020 relative to the same 2 periods in 2017-2019. RESULTS: In this study, 68,448 women delivered a singleton infant in 2017-2020 between January 1 and July 20 and were included in our analysis (mean [interquartile range] age of mothers, 26 [22-32] years). Across the included calendar years and periods, the risk of any adverse outcome ranged from 27.92% to 31.70%, and the risk of any severe adverse outcome ranged from 8.40% to 11.38%. The lockdown period was associated with a 0.81 percentage point reduction (95% confidence interval, -2.95% to 1.30%) in the risk of any adverse outcome (3% relative reduction) and a 0.02 percentage point reduction (95% confidence interval, -0.79% to 0.75%) in the risk of any severe adverse outcome (0% relative reduction). The postlockdown period was associated with a 1.72 percentage point reduction (95% confidence, -3.42% to 0.02%) in the risk of any adverse outcome (5% relative reduction) and a 1.62 percentage point reduction (95% confidence interval, -2.69% to -0.55%) in the risk of any severe adverse outcome (14% relative reduction). Reductions in adverse outcomes were largest among women with human immunodeficiency virus and among women delivering at urban delivery sites, driven primarily by reductions in preterm birth and small-for-gestational-age fetuses. CONCLUSION: Adverse birth outcomes decreased from the prelockdown to postlockdown periods in 2020, relative to the change during the same periods in 2017-2019. Our findings may provide insights into associations between mobility and birth outcomes in Botswana and other low- and middle-income countries.

Identifying "What Matters Most" to Men in Botswana to Promote Resistance to HIV-Related Stigma.

Despite a comprehensive national program of free HIV services, men living with HIV in Botswana participate at lower rates and have worse outcomes than women. Directed content analysis of five focus groups (n = 38) and 50 in-depth interviews with men and women with known and unknown HIV status in Gaborone, Botswana in 2017 used the "what matters most" (WMM) and "structural vulnerability" frameworks to examine how the most valued cultural aspects of manhood interact with HIV-related stigma. WMM for manhood in Botswana included fulfilling male responsibilities by being a capable provider and maintaining social status. Being identified with HIV threatened WMM, which fear of employment discrimination could further exacerbate. Our findings indicate how cultural and structural forces interact to worsen or mitigate HIV-related stigma for urban men in Botswana. These threats to manhood deter HIV testing and treatment, but interventions could capitalize on cultural capabilities for manhood to promote stigma resistance.

HIV self-testing may overcome stigma and other barriers to HIV testing among higher-socioeconomic status men in Botswana: A qualitative study.

In Botswana, HIV prevalence is 20.3% among those between 15 and 49 years old, and in sub-Saharan Africa, higher income has been associated with increased HIV risk. We qualitatively explored barriers to HIV testing and acceptability of HIV self-testing (HIVST) among higher socio-economic status (SES) men in Botswana. Twenty higher SES men (10 tested, 10 not tested recently) participated in semi-structured interviews and 10 men participated in asynchronous online focus groups (FGs) about HIV testing barriers and HIVST acceptability. Results indicated that stigma, inconvenience and perceived lack of confidentiality were barriers to HIV testing, as were masculinity-related concerns (e.g. fear of losing status if they accessed testing or were found to be HIV positive). Men said that HIVST reduced barriers to testing and that test kits could be placed in public spaces for pick-up and used in private. Overall, HIVST was seen as acceptable and feasible among higher SES men in Botswana.

An Evaluation of Baseline Kidney Function in the REPRIEVE Trial of Pitavastatin in Human Immunodeficiency Virus.

BACKGROUND: Chronic 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. METHODS: REPRIEVE 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 <90 mL/min/1.73 m2 by logistic regression. We performed Bland-Altman plots and scatterplots to assess agreement between equations. RESULTS: Among 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 <90 mL/min/1.73 m2. In the adjusted model, factors associated with eGFR <90 mL/min/1.73 m2 included white race, older age, higher body mass index, high-income region of enrollment, hypertension, and tenofovir disoproxil fumarate. The CKD-EPI and Modification of Diet in Renal Disease equations demonstrated strong agreement, particularly at lower eGFR values. Overall, there was 56% concordance between the 3 equations (categories <60, 60 to <90, ≥90 mL/min), improving to 73% after accounting for individual body surface area. CONCLUSIONS: REPRIEVE 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 REGISTRATION: NCT02344290.

May Measurement Month 2018: an analysis of blood pressure screening results from Botswana.

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.

Polymorphisms in cytochrome P450 are associated with extensive efavirenz pharmacokinetics and CNS toxicities in an HIV cohort in Botswana.

Inter-individual variability in efavirenz (EFV) pharmacokinetics and dynamics is 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 1 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.

Role of Noncommunicable Diseases (NCDs) in Resource-Limited Settings (RLS).

PURPOSE OF REVIEW: As access to effective antiretroviral therapy (ART) expands globally, a decline in AIDS-related morbidity and mortality has been complicated by rising rates of noncommunicable diseases (NCDs). This review provides a brief description of NCDs and existing gaps on knowledge about NCDs among HIV-infected adults mostly in Africa. RECENT FINDINGS: Recent reports show that one in every five persons living with HIV has a chronic illness, predominantly diabetes and/or hypertension, depression, and most of these conditions are either not diagnosed or not being managed. Human papilloma virus-associated anal dysplasia occurs among 70% of HIV-infected women in RLS. Recognizing risk factors for NCDs and providing effective screening and optimal care remains challenging. Research is urgently needed to carefully characterize HIV-associated NCDs in RLS. Such studies should provide a framework for high-priority NCDs that the limited resources can be focused on in these settings.