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Cryptococcal meningitis is a major complication of HIV infection. In this phase 3, randomized, controlled trial in sub-Saharan Africa, a single dose of liposomal amphotericin B induction therapy combined with fluconazole and flucytosine for cryptococcal meningitis was shown to be noninferior to standard induction therapy with amphotericin B deoxycholate and was associated with fewer adverse events.

HIV prevalence among female sex workers (FSW) in sub-Saharan Africa is much higher than in the general population. HIV self-testing (HIVST) may be useful for increasing testing rates in FSW. We conducted semi-structured in-depth interviews among FSW, nurses and lay counsellors providing services to FSWs in Botswana. We aimed to gain understanding of perceived acceptability, anticipated barriers, and preferred approaches to HIVST among FSW. Interviews were audio-recorded, transcribed and translated. Transcripts were reviewed and coded independently by two investigators; high inter-coder agreement was achieved (Kappa = 0.80). We interviewed five care providers whose average age was 40 years (SD = 2,64, range = 37-43); three nurses and two counsellors. Thirty FSW were interviewed, with mean age 34 years (range = 20-52). Most (27; 90%) FSW expressed great interest in using HIVST kits. Facilitators of HIVST were: awareness of own risky sexual behaviours, desire to stay healthy, and perceived autonomy over one's healthcare decisions. Perceived advantages of HIVST included convenience, privacy, and perception of decreased stigma. Identified barriers to HIVST included lack of knowledge about the HIVST kit, fear of testing due to anticipated stigma, mistrust of the test's accuracy, doubt of self-competency to perform HIVST, and concerns about not linking to care. Assisting someone to test was noted as good for providing emotional support, but there were concerns about confidentiality breaches. Providers expressed concerns over low literacy among FSWs which could affect comprehension of testing instructions, and competency to perform testing and interpret results. Participants' recommendations for implementation of HIVST included: ensuring wide dissemination of information on HIVST, engaging peers in information-sharing and education, making test kits accessible in FSW-friendly centres, and having clear instructions for linkage to healthcare and support. HIVST shows high acceptability among FSWs in Gaborone Botswana, with providers expressing some concerns. Implementation should be peer-driven with healthcare provider oversight.

HIV-associated changes in intestinal microbiota are believed to be important drivers of disease progression. However, the majority of studies have focused on populations in high-income countries rather than in developing regions where HIV burden is greatest. To better understand the impact of HIV on fecal microbiota globally, we compare the fecal microbial community of individuals in the U.S., Uganda, and Botswana. We identify significant bacterial taxa alterations with both treated and untreated HIV infection with a high degree of uniqueness in each cohort. HIV-associated taxa alterations are also significantly different between populations that report men who have sex with men (MSM) behavior and non-MSM populations. Additionally, while we find that HIV infection is consistently associated with higher soluble markers of immune activation, most specific bacterial taxa associated with these markers in each region are not shared and none are shared across all three geographic locations in our study. Our findings demonstrate that HIV-associated changes in fecal microbiota are overall distinct among geographical locations and sexual behavior groups, although a small number of taxa shared between pairs of geographic locations warrant further investigation, highlighting the importance of considering host context to fully assess the impact of the gut microbiome on human health and disease. Here, the authors compare the fecal microbial community of individuals in the U.S., Uganda, and Botswana, and identify significant bacterial taxa alterations with both treated and untreated HIV infection although with a high degree of uniqueness in each cohort, and also significant differences between populations that report men who have sex with men (MSM) behavior and non-MSM populations.

SARS-CoV-2 infection during pregnancy was associated with maternal mortality and adverse birth outcomes in the pre-Omicron era, including a stillbirth rate of 5.6% in Botswana. We re-evaluated these outcomes in the Tsepamo Study during the Omicron era. We assessed maternal mortality and adverse birth outcomes for all singleton pregnancies from mid-November 2021 (the start of the Omicron era) to mid-August 2022 at nine Tsepamo sites, among individuals with documented SARS-CoV-2 screening PCR or antigen tests and known HIV status. Of 9,705 women routinely screened for SARS-CoV-2 infection at delivery (64% of deliveries at these sites), 373 (3.8%) tested positive. Women with HIV were as likely to test positive for SARS-CoV-2 (77/1833, 4.2%) as women without HIV (293/6981, 4.2%) (p = 1.0). There were 5 recorded maternal deaths (0.03%), one occurring in a woman with a positive SARS-CoV-2 test result. In contrast, maternal mortality was 3.7% and 0.1% in those with and without SARS-CoV-2, respectively, during the pre-Omicron era. In the Omicron era, there were no differences among infants exposed or unexposed to SARS-CoV-2 in overall adverse birth outcomes (28.1% vs 29.6%; aRR 1.0, 95%CI 0.8–1.1), severe adverse birth outcomes (11.9 vs 10.6%; aRR 1.1, 95%CI 0.8–1.5), preterm delivery (15.1% vs 14.9%; aRR 1.0, 95%CI 0.8–1.3), or stillbirth (1.9% vs 2.3%; aRR 0.8, 95%CI 0.4–1.7). Adverse outcomes among those exposed to both HIV and SARS-CoV-2 were similar to those exposed to HIV alone (31.2% vs. 33.1%; aRR 0.9, 95%CI 0.6–1.3; p = 0.5). Maternal mortality was far lower in Botswana during the Omicron era than in the pre-Omicron era, and adverse birth outcomes were no longer significantly impacted by exposure to SARS-CoV-2 either overall or with HIV co-exposure. Increased population immunity to SARS-CoV-2, less stress on the hospital systems in the Omicron era, and possible differences in viral pathogenicity may combine to explain these findings.

Background Obesity is a growing public health concern, particularly in Sub-Saharan Africa, where undernutrition and obesity are in conjuction. In Botswana, the urban transition and environmental factors are likely influencing obesity risk. This study aimed to investigate the spatial distribution of central obesity across selected rural and peri-urban communities in Botswana and elucidate on likely demographics influencing the identified spatial variations. Methods Data were drawn from 2,039 individuals (aged 16–65 + years) who participated in the Botswana Combination Prevention Project (BCPP), a community-based ( n  = 22) cluster-randomized trial (NCT01965470). Central obesity was defined using waist-to-hip ratio > 0.90 in men, > 0.85 in women. Generalized linear mixed models (GLMM) were estimated to predict central obesity prevalence. A Global Moran’s I was used to evaluate if there was clustering of central obesity prevalence across communities. To further explore local patterns, Local Indicators of Spatial Association (LISA) was applied to identify specific communities where central obesity prevalence was not random. This analysis distinguished spatial clusters (high-high [HH] and low-low [LL]) as well as spatial outliers. Finally, bivariate local Moran’s I was performed to determine the spatial heterogeneity of central obesity and specific predictors (female and median age). Results Central obesity prevalence was estimated at 27.6% using GLMM (AoR 0.276 95% CI 0.131–0.582), ( n  = 887) and of these, 44.8% ( n  = 645) participants, resided in rural areas. Spatial analysis revealed significant clustering across rural and peri-urban communities (Moran’s I = 0.158, p  = 0.04;I = 0.171 p  = 0.05). The bivariate Local Moran’s I results showed significantly high clusters of central obesity and female (sex) (0.071 p  < .001) and central obesity and median age (I = 0.225 p  < .001) in both rural and peri-urban communities. Conclusions Central obesity in Botswana demonstrates spatial clustering and is significantly influenced by socio-demographic factors. These findings underscore the need for geographically targeted interventions to address central obesity, especially in peri-urban communities. Trial registration NCT01965470. Registered on October 2013. More information: https://www.clinicaltrials.gov/study/NCT01965470?tab=history&a=4 .

Background Sub-Saharan Africa (SSA) has confronted decades of the HIV epidemic with substantial improvements in access to life-saving antiretroviral therapy (ART). Now, with improved survival, people living with HIV (PLWH) are at increased risk for non-communicable diseases (NCDs), including atherosclerotic cardiovascular disease (CVD). We assessed the existing literature regarding the association of CVD outcomes and HIV in SSA. Methods We used the PRISMA guidelines to perform a systematic review of the published literature regarding the association of CVD and HIV in SSA with a focus on CVD surrogate and clinical outcomes in PLWH. Results From January 2000 until March 2017, 31 articles were published regarding CVD outcomes among PLWH in SSA. Data from surrogate CVD outcomes ( n  = 13) suggest an increased risk of CVD events among PLWH in SSA. Although acute coronary syndrome is reported infrequently in SSA among PLWH, limited data from five studies suggest extensive thrombus and hypercoagulability as contributing factors. Additional studies suggest an increased risk of stroke among PLWH ( n  = 13); however, most data are from immunosuppressed ART-naïve PLWH and thus are potentially confounded by the possibility of central nervous system infections. Conclusions Given ongoing gaps in our current understanding of CVD and other NCDs in PLWH in SSA, it is imperative to ascertain the burden of CVD outcomes, and to examine strategies for intervention and best practices to enhance the health of this vulnerable population.

The recognized burden of antimicrobial resistance (AR) is greatest in low- and middle-income countries (LMICs), but limitations in surveillance preclude accurate estimates of AR. We aimed to evaluate colonization in communities and hospitals across six LMICs for two clinically-important pathogens: extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) and carbapenem-resistant Enterobacterales (CRE). Participants in hospitals and communities provided rectal swabs or stool samples for ESCrE and CRE identification. Isolates recovered from selective agars underwent confirmatory identification and antibiotic susceptibility testing (AST) using Vitek ® 2, MALDI-TOF, and/or disc diffusion testing. ESCrE and CRE were defined based on established breakpoints of phenotypic resistance to third-generation cephalosporins and carbapenems, respectively, to calculate prevalence of colonization. Community prevalence estimates were weighted to account for sampling design differences. A total of 10,139 participants across the 6 countries provided samples; 63% were females with a median age of 35 years (range: 0–99). Colonization with ESCrE in hospitals was high in all sites (range 34–84%). In communities, ESCrE colonization ranged from 22 to 77%. Prevalence of CRE colonization in hospitals ranged from 7 to 36% and in communities ranged from < 1 to 14%. These findings reveal a high burden of AR colonization in LMICs in both communities and hospitals. Cost-effective strategies to reduce AR colonization burden are needed in LMICs.

Chronic HIV disease is associated with a fivefold increase in albuminuria outside of sub-Saharan Africa. However, very little is known about albuminuria risk among people living with HIV (PLWH) in sub-Saharan Africa. Therefore, we conducted a cross-sectional observational HIV clinic-based study of albuminuria among 1533 adults aged 21 years or older between January 2020 and January 2021 in Gaborone, Botswana. Clinical albuminuria was defined using a sex-based albumin‒creatinine ratio (ACR) of 25–355 mg/g for females and 17–250 mg/g for males. The study population mean age was 48.5 (SD 10.3) years, and 764/1533 (49.7%) were female. The overall prevalence of albuminuria was 20.7% (95% CI 18.7%, 22.8%). A higher proportion of males were more likely to be categorized as having albuminuria than females, 25% (95% CI 22.0, 28.2) versus 16.4% (95% CI 13.8,19.2), P value < 0.001. In the final multivariate models, predictors of albuminuria differed by sex group. Larger longitudinal studies are required to evaluate the impact of albuminuria among PLWH with particular emphasis on the effect of sex on the risk of albuminuria.

Women living with HIV-1 (WLHIV) are at higher risk of having an adverse birth outcome, but the underlying mechanism(s) are unknown. We hypothesized that HIV-associated endothelial activation could adversely impact placental function and lead to impaired fetal growth or stillbirth. We used stored samples from WLHIV and HIV-negative women who had enrolled during pregnancy in the observational Botswana Tshipidi cohort. Written informed consent was obtained from the participants. We measured plasma levels of markers of endothelial activation (soluble vascular adhesion molecule 1 [VCAM-1], intercellular adhesion molecule 1 [ICAM-1] and E-selectin) from samples taken during pregnancy. We compared log10 biomarker levels by maternal HIV status and by the timing of ART initiation (ART prior to conception vs. during pregnancy; ART prior to sample collection vs. no ART prior to sampling) using t-tests and the Kruskal-Wallis rank test. We evaluated the association between these biomarkers and adverse birth outcomes (composite of stillbirth or small for gestational age [SGA]) using univariate and multivariate log-binomial regression controlling for maternal age (continuous) and timing of ART start. We also used generalized linear models (GLM) to evaluate the association between continuous birthweight (in grams) and gestational age (in weeks) and markers of endothelial dysfunction, adjusting for maternal age (continuous) and timing of ART relative to sample collection. Specimens collected before delivery were available for 414 women (372 WLHIV and 42 HIV-negative women), with a median age of 28 years and median gestational age at sample collection of 30 weeks (range 26, 35 weeks). WLHIV had significantly higher median VCAM1 (p = 0.002) than HIV-negative women, but HIV-negative women had higher median ICAM1 (p = 0.01); e-Selectin levels did not differ by maternal HIV status. Women starting ART during pregnancy had higher log10 VCAM1 levels than those on ART before conception, regardless of whether the sample was collected before (p = 0.02) or after (p = 0.03) ART initiation. However, ICAM1 and e-Selectin did not differ significantly by ART status or ART timing. Ninety-eight women (91 WLHIV and 7 HIV-negative), or 9 (2%) and 89 (22%) included in this study, had a stillborn or SGA baby respectively. Univariate and adjusted analyses did not show significant associations between levels of any of the biomarkers with these adverse birth outcomes. However, lower birthweight (p = 0.03) and lower gestational age at delivery were associated e-Selectin and ICAM (p = 0.008), respectively. Maternal HIV infection and lack of ART (or recent ART initiation) were associated with one marker of greater endothelial activation (VCAM-1), but not with other markers (ICAM-1 nor E-selectin) in pregnancy. e-Selectin was associated with lower birthweight and every unit increase in log ICAM-1 at delivery was associated with lower gestation age at delivery.

Objectives In this cross-sectional study from Botswana, we investigated awareness of acute stroke treatment and prevention among stroke-risk outpatients and the public based on age and sources of information, in addition to association of stroke risk factors with this awareness. Method Questionnaires on awareness of acute stroke treatment and prevention were administered by research assistants to a representative selection of outpatients and the public. Results The response rate was 93.0% for the public and 96.6% for outpatients. Public respondents had a mean age of 36.1 ± 14.5 years (age range 18–90 years) and 54.5% were females, while outpatients had a mean age of 37.4 ± 12.7 years (age range 18–80 years) and 58.1% were females. Awareness of medical therapy as acute stroke treatment was inadequate among outpatients (75.5% for public vs 43.4% for outpatients among all-age, p  < 0.001), due to awareness differences among all ages. Awareness of stroke prevention was adequate (81.5% of outpatients vs 71.6% of public among all-age, p  = 0.601%), and similar trend was observed also among individual age groups. For awareness of medical therapy as an acute stroke treatment among all ages, the public was more likely than outpatients to get stroke information ( p  < 0.001) from almost all sources of information, while for awareness of stroke prevention among all-age, outpatients were more likely than the public to get stroke information from family/ friends (83.9% vs 70.5%, p  = 0.042). History of HIV/AIDS and having a healthy diet were associated with lower awareness of both acute stroke treatment and prevention ( p  < 0.05). Conclusion Results call for strategic educational stroke campaigns using best information relaying tool for each age and respondents’ group. Highlights • This is the first study comparing awareness of acute stroke treatment and prevention among outpatients and the public based on age and sources of information in sub-Saharan Africa • Awareness of medical therapy as acute stroke treatment was lower among outpatients while higher among the public among all ages • Almost all sources of stroke information were associated with higher awareness of acute stroke treatment among the public • History of HIV/AIDS and having a healthy diet were associated with both poor awareness of acute stroke treatment and prevention • Results call for educational stroke campaigns based on age and using almost all sources of information