Botswana Harvard AIDS Institute Partnership

BackgroundAntimicrobial resistance is rampant in low- and middle-income countries. Recent data from Princess Marina Hospital (PMH), Botswana, revealed that 100% of pediatric surgical unit patients received antimicrobials inappropriately.MethodsWe implemented a quality improvement initiative to improve antimicrobial use in children admitted to PMH's pediatric surgical ward. With key stakeholders, we developed clinical pathways (CPs) to standardize antimicrobial use across common surgical diagnoses. A CP booklet, informed by the World Health Organization (WHO) Access, Watch, and Reserve (AWaRe) guideline, was distributed to prescribers. We conducted weekly prospective antimicrobial use audits over 1 year, from 3 months pre–CP implementation to 9 months post–CP implementation.ResultsA total of 1099 pediatric surgical patients were admitted and 374 (34.0%) required antimicrobials. The WHO Access group accounted for 360 antibiotic courses (72.4%) and the Watch group for 137 (27.6%), a total of 497. Overall, appropriate antimicrobial use improved significantly (pediatric surgery, 33 [50.8%] vs 99 [93.4%]; orthopedics, 3 [10.3%] vs 26 [89.7%]; neurosurgery, 5 [27.8%] vs 13 [72.2%]; and ear, nose, and throat, 4 [33.3%] vs 19 [95.0%]; each P < .001) in the postimplementation period except for maxillofacial-dental patients (1 [25.0%] vs 3 [75.0%]; P = .264). Improvements were observed across provider categories and years of experience: medical officers (28 [42.4%] vs 38 [91.0%]), interns (7 [33.3%] vs 20 [87.0%]), and specialists (11 [26.2%] vs 64 [97.0%]); years of experience: <2 years (9 [32.1%] vs 22 [91.7%]), 2–5 years (3 [25.0%] vs 50 [92.6%]), and >5 years (34 [38.2%] vs 154 [92.2%]) (P < .001 for each).ConclusionsAppropriate antimicrobial use improved post–CP implementation. Expanding CPs with ongoing antimicrobial stewardship education will ensure sustained improvement.

Broadly neutralizing antibodies (bnAbs) are evaluated as possible alternatives to standard antiretroviral treatment (ART) for maintaining control of HIV-1 replication and may enhance immune responses to reduce or control the viral reservoir. However, the immunological and virological effects of bnAbs in infants and children are unknown. We conducted a detailed analysis of proviral reservoir dynamics and antiviral immune responses in a unique group of young children from Botswana who started ART at birth and then stopped standard ART while receiving the bnAbs 10-1074 and VRC01-LS in a subsequent clinical trial. No quantitative changes in frequencies of proviral sequences were observed during bnAb treatment, but selection of genome-intact proviruses in transcriptionally repressive heterochromatin regions occurred in some study participants. Faster viral rebound following standard ART cessation was linked to elevated proportions of KIR2DL1-positive NK cells. In contrast, delayed viral rebound and more limited viral reservoir size were associated with elevated proportions of NKG2A-positive NK cells and with the HLA-B-21M signal peptide polymorphism. HIV-specific T cell responses were low in all study participants and unrelated to viral reservoir sizes or clinical outcomes following ART interruption. These results suggest that, in young children, specific NK cell subsets and KIR-HLA interactions might be linked to HIV-1 rebound kinetics after substitution of standard ART with bnAbs.

SUMMARYBACKGROUNDTobacco smoking remains a serious health threat, especially for patients with TB and HIV. Cessation services may be apt for integration into TB and HIV clinics, particularly in lower- and middle-income countries, where these services often have robust structures. We aimed to identify barriers and facilitators to the integration of smoking cessation within health care services for people with HIV on TB treatment in Botswana.METHODSUsing the Consolidated Framework for Implementation Research 2.0, we conducted a convergent parallel mixed-methods study collecting demographic data on current TB patients and semi-structured interviews with patients and providers.RESULTSWe identified four key themes on programme implementation: 1) Tobacco knowledge is necessary but insufficient to facilitate smoking cessation; 2) Providers lack skill to provide cessation services and are apprehensive about interactions with TB patients; 3) An intervention would be desirable but will require additional infrastructure and cannot exclude other non-TB populations; and 4) Leveraging non-governmental implementation partners would be an asset but may also impede programme longevity.CONCLUSIONNovel approaches are needed to overcome key barriers to the integration of smoking cessation treatments for this important subgroup of smokers, including developing a comprehensive tobacco treatment programme that can extend beyond education and provide critical skills for providers.

BackgroundHIV, cancer, and their respective treatments are independently associated with cardiovascular risk, but limited data exist on the intersection of these conditions. The purpose of this study was to gain insights into the cardiovascular risk factor burden and cardiac function in people with HIV (PWH) treated for breast cancer.MethodsIn a cohort of PWH and breast cancer treated with anthracyclines and/or trastuzumab (2017–2022) in Botswana, we assessed pre-treatment (baseline) left ventricular ejection fraction (LVEF), and prospectively obtained an echocardiogram at least one year after cancer treatment initiation. Wilcoxon signed rank sum test was used to test the differences between baseline and follow-up LVEF.ResultsThirty-three women were enrolled at a median of 2.1 years (Quartile (Q)1-Q3 1.8–3.1) from their cancer treatment initiation. The median age was 48.0 years (Q1-Q3 44.0–54.0). All but one patient was on antiretroviral therapy (ART); the median ART duration was 11.6 years (Q1-Q3 6.3–15 years) with a median viral load of 30 (Q1-Q3 0–30) and CD4 count of 874 (Q1-Q3 361–1131). At baseline, 70% were obese or overweight, and 24.2% reported hypertension; this increased to 30.3% at follow-up. The median LVEF at baseline was 65% (Q1-Q3 60–68%), and decreased to 62% (Q1-Q3 59–65%) at follow-up; an absolute difference of 2.9%, 95%CI: -5.3 to -0.2% (p = 0.038). There was no report of clinical heart failure.ConclusionsObesity and hypertension are highly prevalent amongst PWH and breast cancer. We also noted a statistically significant, but modest decline in LVEF after cancer therapy initiation. Further studies are needed to prospectively characterize the cardiovascular risk factor burden and changes in cardiac structure and function following cardiotoxic cancer treatment in this population.Supplementary InformationThe online version contains supplementary material available at 10.1186/s40959-025-00417-3.

Perinatal depression is an important cause of maternal and infant morbidity. Rates of perinatal depression amongst pregnant and postpartum women in Botswana are not well-documented. We examined the prevalence of symptoms of depression and potential associated factors among pregnant and postpartum women participating in a sexually transmitted infection screening study. We conducted a repeated time-point cross-sectional analysis of the Maduo study, a non-randomized clinic-controlled trial evaluating the benefit of antenatal Chlamydia trachomatis and Neisseria gonorrhoeae screening in Gaborone, Botswana. The Edinburgh Postnatal Depression Scale (EPDS) was used to screen for symptoms of depression at the first antenatal care and 6–8 week postnatal care visit. Prevalence of depression was assessed using EPDS cut-off scores of ≥11 and ≥13. Participants with an EPDS score of ≥13 were referred to local mental health services. We used multivariate logistic regression to identify potential associations with symptoms of perinatal depression (EPDS score ≥13) at first antenatal care visit, 6–8 week postnatal visit and overall, including socioeconomic, pregnancy-related and relationship factors. We also conducted a sensitivity analysis with EPDS score specified as a continuous variable. All 500 enrolled women completed at least one EPDS questionnaire during the study: 495 (99%) at first antenatal care and 428 (86%) at the postnatal visit. Median EPDS score was 3 (IQR 1–6) at the first antenatal visit and 2 (IQR 0–5) at the postnatal visit. Similar proportions of women had EPDS scores suggestive of depression at first antenatal (EPDS ≥13, 5% (95% CI 3–7%); EPDS ≥11, 7% (95% CI 5–10%)) and postnatal visits (EPDS ≥13, 3% (95% CI 1–5%); EPDS ≥11, 7% (95% CI 5–10%)), however there was minimal overlap in women with antenatal and postnatal symptoms of depression. Symptoms of depression were strongly associated with experience of intimate partner violence both antenatally (aOR 5.41, 95% CI 1.94–15.10, p = 0.001) and postnatally (aOR 5.18, 95% CI 3.35–8.02, p = < 0.001); whilst symptoms of depression at the first antenatal care visit were also associated with unintended pregnancy (aOR 29.44, 95% CI 2.75–314.6, p = 0.005). Rates of perinatal depression in this study were lower than estimated rates in Southern Africa. Nonetheless, screening pregnant women for depression as part of routine antenatal care in Botswana provides an opportunity to identify those most in need of support and specialist services.

We investigated how randomness may have contributed to the apparent decline in observed risk of neural tube defects (NTDs) following in-utero dolutegravir (DTG) exposure. We aimed to describe statistical approaches to uncertainty using accessible language for nonstatistical audiences. We reanalyzed Tsepamo Study data using frequentist confidence intervals, repeated intervals accounting for group sequential monitoring, and Bayesian posterior and posterior predictive distributions. We estimated the probability of decision reversal using simulation. The initial Tsepamo analysis reported a large difference in NTD risk between DTG and non-DTG exposures, with point estimates of 0.94 and 0.12%, respectively. This difference diminished with subsequent data, with updated estimates of 0.10% for DTG and 0.11% for non-DTG exposures. Our analyses showed the early finding was statistically compatible with a wide range of effect sizes, including no difference. Due to the large uncertainty in the first analysis, the probability of decision reversal was high under repeated testing frameworks. Early safety signals may reflect statistical noise. Evaluating the range of confidence intervals and estimating decision reversal probabilities provide meaningful insight into early results. Formal frameworks for uncertainty should guide decisions about interim data reporting, especially when findings may influence clinical or regulatory action.

We assessed whether children/adolescents ages 9-11 years with in-utero HIV exposure but uninfected (CAHEU) had a lower chance of pubertal onset compared to children/adolescents who were HIV-unexposed (CAHU) during gestation. Among CAHEU, we assessed the association of in-utero combination antiretroviral therapy (ART) vs. zidovudine monotherapy exposure with pubertal onset. An observational cross-sectional study. Pubertal onset (Tanner stage ≥2) was classified by sex and by in-utero HIV exposure status for each puberty indicator (pubic hair, breast development in girls, and male genitalia in boys) among adolescents aged 9-11 years from the Botswana-based FLOURISH study. Logistic regression models were fit to assess the association of in-utero HIV/ARV exposure with pubertal onset, adjusting for age at assessment and potential confounders. Among CAHEU, we compared the occurrence of pubertal onset for ART-exposed vs. zidovudine-exposed. We evaluated 325 children/adolescents (228 CAHEU) at median age (IQR) 10.0 years (9.5, 10.6 years). CAHEU had lower mean BMI Z -scores at Tanner assessment (-0.36 vs. 0.19) than CAHU. While female CAHEU had higher odds of pubertal onset by pubic hair compared with female CAHU (adjusted odds ratio=2.75, 95% confidence interval: 1.04-7.30), no other differences in pubertal onset were observed by in-utero HIV exposure. Among CAHEU, no differences in pubertal onset by in-utero exposure to ART vs. zidovudine were observed. In this small Botswana cohort, we observed no consistent differences in pubertal onset by in-utero HIV exposure status or by in-utero antiretroviral exposure. Longitudinal studies are needed to confirm these findings.

Clinical Decision Support Systems (CDSSs) are software tools which support routine clinical practice through data processing, including clinical decision making, efficient data retrieval, and generating visualisations. Despite a substantial increase in the development of evidence-based CDSSs for asthma in recent years, no tools have been widely implemented as part of routine care in the United Kingdom. Previous pilot studies have highlighted barriers to implementation, including tools failing to fit into existing workflows, and requiring extensive deviation from current practice to succeed. The lack of collaboration with intended clinical users in early development has been a recurring concern. Particularly, available studies have sought non-specific feedback on the value of features that aimed to improve certain outcomes (such as “enhanced patient–provider relationships”) rather than specifically focussing using on integral components such as functionality. This study aimed to identify workflows in routine asthma care which could benefit from CDSS support by interviewing 19 primary and specialist health care providers (HCPs). Transcripts were analysed using inductive content analysis. Key opportunities for improving routine care using CDSSs identified included: the possibility of retrieving patients’ medical history, the availability of best practice reminders and alerts, and the capacity of triaging patients for referral to secondary care. This will inform future CDSS development, maximizing their desirability and usefulness in routine clinical practice. Engaging stakeholders from idea conception through to implementation is key to optimising resources in a sustainable manner.

Cervical cancer remains the leading cause of cancer death among women in sub-Saharan Africa and is more severe in high HIV-burdened countries due to persistent high-risk human papillomavirus (hrHPV). In 2021, the World Health Organization recommended primary hrHPV testing for cervical cancer screening; however, optimal triage strategies following positive hrHPV tests remain unclear. We conducted a prospective cost analysis of triage methods for positive hrHPV results among women living with and without HIV in Gaborone, Botswana. We used a micro-costing approach from the perspective of the healthcare provider. The main outcomes were the implementation costs associated with three triage strategies following hrHPV testing: 8-type HPV genotype restriction, visual inspection with acetic acid (VIA), and colposcopy. We also compared the strategies by measuring the change in costs divided by the change in number of true cases of cervical intraepithelial neoplasia (CIN) 2 or worse (CIN2+) identified, based on the results of a prospective cohort study. Results indicated that the 8-type HPV genotype restriction strategy was the most cost-efficient, requiring no additional costs beyond hrHPV testing and identifying the highest number of true CIN2 + cases. VIA and colposcopy triage identified fewer true cases of CIN2+ and incurred additional costs, with colposcopy being the most expensive. Results were consistent in women with and without HIV. Sensitivity analysis highlighted personnel and hrHPV test kit cartridge costs as significant drivers of overall costs. Post-hoc analysis incorporating average treatment costs for precancer demonstrated that genotyping remained dominant at lower treatment costs but became less favorable as treatment costs increased. We found that 8-type genotype restriction was optimal compared to hrHPV screening combined with VIA or colposcopy. Cost estimates can inform future studies that examine the long-term costs and health outcomes of HPV-based two-stage screening algorithms.

This study aimed to evaluate maternal outcomes in a large cohort with high prevalence of human immunodeficiency virus (HIV) infection in Botswana after implementation of a treat-all policy. In this retrospective cohort study, data were collected from the medical record at the time of discharge from November 2021 to December 2023. Outcomes were recorded in the Tsepamo Birth Outcomes Surveillance and Safe Birth studies at Princess Marina Hospital in Botswana. We evaluated maternal mortality and obstetric morbidities by HIV status, including preeclampsia, eclampsia, hemorrhage, infection, and acute pulmonary or cardiac conditions at the time of hospital discharge. We included 11,754 participants; 2,201 (18.7%) were pregnant people with HIV infection. Ninety-seven percent (2,135) were on antiretroviral therapy (ART) at time of delivery; 1,996 (93.5%) of those with a known ART regimen were on dolutegravir, tenofovir disoproxil fumarate, and lamivudine. Of the 1,090 people with HIV infection with known CD4 counts, 757 (69.4%) had more than 500 cells/microliter, and only 42 (3.9%) had fewer than 200 cells/microliter. Of 1,524 people with HIV infection with known viral loads, 1,436 (94.2%) were undetectable on initial testing. There were no statistically significant differences in incidence of hemorrhage (90 [4.1%] vs 370 [3.9%], adjusted risk ratio [RR] 0.93, 95% CI, 0.73-1.17), infection (38 [1.7%] vs 126 [1.3%], adjusted RR 1.56, 95% CI, 0.97-2.51), eclampsia (6 [0.3%] vs 28 [0.3%], adjusted RR 1.12, 95% CI, 0.50-2.53), acute pulmonary or cardiac conditions (15 [0.7%] vs 43 [0.4%], adjusted RR 1.22, 95% CI, 0.65-2.27), transfusion of 2 or more units of packed red blood cells (33 [36.7%] vs 110 [29.8%], P= .21), additional uterotonics (48 [53.3%] vs 173 [47.1%], P= .29), use of tranexamic acid (31 [ 34.4%] vs 106 [29.0%], P= .31), intensive care unit admission (4 [0.2%] vs 10 [0.1%], P= .31), mechanical ventilation (3 [0.1%] vs 6 [0.1%], P= .38), pressor support (2 [0.1%] vs 2 [0.0%], P= .16), or mortality (5 [0.2%] vs 11 [0.1%], adjusted RR 1.44, 95% CI, 0.46-4.57) in people with HIV infection compared with those without HIV infection. There were few notable differences, including a slightly reduced risk of preeclampsia (184 [8.4%] vs 818 [8.6%], adjusted RR 0.84, 95% CI, 0.71-0.98) and, although rare, an increased risk of uterine rupture (12 [0.5%] vs 8 [0.1%], adjusted RR 6.54, 95% CI, 2.33-18.33) in people with HIV infection compared with those without HIV infection. There was little difference in adverse maternal obstetric outcomes between people with and those without HIV infection in the treat-all era with integrase strand inhibitors (primarily dolutegravir); notable exceptions included a slightly reduced risk of preeclampsia and, although rare, an increased risk of uterine rupture in those with HIV infection.