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AbstractIntroductionIn Botswana, where almost all pregnant women known to have HIV receive antiretroviral therapy, a large proportion of vertical HIV transmission may occur among women with incident undiagnosed HIV infection during pregnancy. Botswana guidelines recommend repeat HIV testing every 3 months in pregnancy, with at least one test in the third trimester. We evaluated the rate of repeat HIV testing, calculated HIV incidence during pregnancy and estimated missed seroconversions.MethodsIn the Botswana Tsepamo Study, we abstracted HIV test dates and results from obstetric records of all women who delivered at maternity wards in 18 communities between 7th May 2017 and 20th August 2021. We defined seroconversion as an initial negative/indeterminate HIV test in pregnancy followed by a positive test during pregnancy/at delivery. The incidence rate (IR) of seroconversion was calculated among women with > = 2 known test dates. Missed seroconversions were estimated among women without a test in the third trimester by applying the IR to the time after the last HIV test until delivery.ResultsAmong 103,529 women delivering in the study period testing negative at the first test and with known conception and HIV test dates, 29,085 (28%) were tested in one trimester of pregnancy, 73,156 (71%) were tested in ≥ 2 trimesters of pregnancy and 9628 (9%) had a test in all trimesters. A total of 78,162 (75%) women had a third‐trimester test. There were 223 seroconversions (2.58/1000 pregnancies, 0.26%) among those with ≥ 2 known HIV test dates, yielding an IR of 0.69/100 person‐years. Among 25,289 women who did not have a test in the third trimester, we estimate approximately 58 seroconversions may have been missed during pregnancy due to a lack of repeat testing. Factors associated with seroconversion during pregnancy included younger age, less education and not being married.ConclusionsMore than two‐thirds of women had repeat HIV testing in pregnancy and HIV incidence was low. However, an estimated 21% of seroconversions in pregnancy were likely missed due to a lack of re‐testing. To reach the goal of zero new paediatric HIV infections, Botswana will need to intensify repeat HIV testing in the third trimester of pregnancy.

AbstractIntroductionYoung women in sub‐Saharan Africa are at particularly high risk of HIV acquisition. Recent shifts towards "test and treat" strategies have potential to reduce transmission in this age group but have not been widely studied outside of clinical trials. Using data from nationwide surveillance among pregnant women in Botswana, where a "test and treat" program was implemented in 2016, we describe trends in HIV prevalence over time and highlight opportunities for targeted prevention.MethodsThe Tsepamo study abstracted data from obstetric records of all women delivering at eight government hospitals in Botswana between 2015 and 2019, accounting for 45% of all births in the country (n = 120,755). We used a stratified analysis to identify prevalence trends and evaluated decreases in HIV prevalence over time using the Cochrane–Armitage test for linear trend. A multivariable logistic regression analysis was also performed to identify factors associated with declines in HIV prevalence.ResultsOverall HIV prevalence was 24.1% among 120,755 women who delivered during the study period. Prevalence differed by site of delivery, ranging from 16.1% to 28.2%, and increased markedly with age. Lower educational attainment (adjusted odds ratio [aOR] = 3.28; 95% confidence interval [CI] 3.07–3.50) and being unmarried (aOR = 1.98; 95% CI 1.88–2.08) were associated with HIV infection. HIV prevalence was 10.0% with a first pregnancy, 21.0% with a second and 39.2% with a third or greater (aOR = 2.20; for any prior pregnancy; 95% CI 2.10–2.29). The same age‐adjusted trends were seen when data were limited to women aged 15–24, with a two‐ to three‐fold increase in HIV prevalence between a first and third pregnancy. Prevalence decreased linearly during the 5‐year study period from 25.8% to 22.7% (p <0.001). Among age‐specific strata, the greatest absolute decline occurred in those aged 35–39, with an 8.7% absolute decrease in HIV prevalence from 2015 to 2019. Minimal declines were seen in those 15–24, with a decrease of only 1.5% over the same period.ConclusionsWhile overall trends in Botswana show HIV prevalence declining among pregnant women, prevalence among the youngest age group has remained stagnant. Preventative interventions utilizing pre‐exposure prophylaxis should be prioritized during the high‐risk period surrounding a woman's first pregnancy.

INTRODUCTION: Young women in sub‐Saharan Africa are at particularly high risk of HIV acquisition. Recent shifts towards "test and treat" strategies have potential to reduce transmission in this age group but have not been widely studied outside of clinical trials. Using data from nationwide surveillance among pregnant women in Botswana, where a "test and treat" program was implemented in 2016, we describe trends in HIV prevalence over time and highlight opportunities for targeted prevention. METHODS: The Tsepamo study abstracted data from obstetric records of all women delivering at eight government hospitals in Botswana between 2015 and 2019, accounting for 45% of all births in the country (n = 120,755). We used a stratified analysis to identify prevalence trends and evaluated decreases in HIV prevalence over time using the Cochrane–Armitage test for linear trend. A multivariable logistic regression analysis was also performed to identify factors associated with declines in HIV prevalence. RESULTS: Overall HIV prevalence was 24.1% among 120,755 women who delivered during the study period. Prevalence differed by site of delivery, ranging from 16.1% to 28.2%, and increased markedly with age. Lower educational attainment (adjusted odds ratio [aOR] = 3.28; 95% confidence interval [CI] 3.07–3.50) and being unmarried (aOR = 1.98; 95% CI 1.88–2.08) were associated with HIV infection. HIV prevalence was 10.0% with a first pregnancy, 21.0% with a second and 39.2% with a third or greater (aOR = 2.20; for any prior pregnancy; 95% CI 2.10–2.29). The same age‐adjusted trends were seen when data were limited to women aged 15–24, with a two‐ to three‐fold increase in HIV prevalence between a first and third pregnancy. Prevalence decreased linearly during the 5‐year study period from 25.8% to 22.7% (p <0.001). Among age‐specific strata, the greatest absolute decline occurred in those aged 35–39, with an 8.7% absolute decrease in HIV prevalence from 2015 to 2019. Minimal declines were seen in those 15–24, with a decrease of ...

BACKGROUND: Women with vertically acquired HIV (VHIV) may have a greater risk of adverse birth outcomes than women with horizontally acquired HIV (HHIV). METHODS: The Tsepamo study performed birth outcomes surveillance at 8 government delivery sites in Botswana from July 2014 through March 2019. Pregnant women diagnosed with HIV before their 11th birthday received VHIV status, and other women had HHIV. Small for gestational age (SGA), preterm delivery (PTD), stillbirth, and neonatal death were compared using χ2 and Fisher's exact tests. Log-binomial regression models determined risk ratios (RRs). RESULTS: VHIV women (n = 402) aged 15–27 years were identified over 4 years of surveillance and compared with HHIV women (n = 8465) of the same age. VHIV women were more likely to use nevirapine (NVP)-based antiretroviral treatment (ART) in pregnancy and to have SGA and very SGA infants, but less likely to have very PTD infants. In unadjusted analyses, VHIV women had a higher risk of any adverse birth outcome combined (RR = 1.21, 95% confidence interval [CI], 1.08–1.36). After adjusting for potential confounders, particularly use of NVP-based regimens, the risk of adverse birth outcomes among VHIV and HHIV women was similar. CONCLUSIONS: NVP-based ART is a primary and modifiable risk factor for adverse birth outcomes. Updating ART regimens could improve birth outcomes for women with HIV.

AbstractIntroductionIn December 2019, the Botswana government expanded free antiretroviral therapy (ART) to include non‐citizens. We evaluated the impact of this policy change on antenatal care (ANC), antiretroviral therapy coverage and adverse birth outcomes.MethodsThe Tsepamo Surveillance study collects data at up to 18 delivery sites in Botswana. We compared outcomes in citizens and non‐citizens living with HIV before and after antiretroviral therapy expansion to non‐citizens. Adverse birth outcomes included preterm delivery (PTD) <37 weeks, very preterm delivery (VPTD) <32 weeks, small for gestational age (SGA) <10th percentile, very small for gestational age (VSGA) <3rd percentile, stillbirth and neonatal death. Log‐binomial regression models were constructed to generate risk ratios.ResultsFrom August 2014 to September 2021, 45,576 (96.5%) citizens and 1513 (3.2%) non‐citizens living with HIV delivered; 954 (62.9%) non‐citizen deliveries were before the antiretroviral therapy expansion, and 562 (37.1%) were after. Non‐citizen ANC attendance among pregnant people living with HIV increased from 79.2% pre‐expansion to 87.2% post‐expansion (p<0.001), and became more similar to citizens (96.0% post‐expansion). Non‐citizens receiving any antenatal antiretroviral therapy increased from 65.5% pre‐expansion to 89.9% post‐expansion (p < 0.001), also more similar to citizens (97.2% post‐expansion). Infants born to non‐citizens with singleton gestations in the pre‐expansion period had significantly greater risk of PTD (aRR = 1.28, 95% CI, 1.11, 1.46), VPTD (aRR = 1.89, 95% CI, 1.43, 2.44) and neonatal death (aRR = 1.69, 95% CI, 1.03, 2.60), but reduced SGA risk (aRR = 0.75; 95% CI, 0.62, 0.89) compared with citizens. Post‐expansion, greater declines in most adverse outcomes were observed in non‐citizens, with largely similar outcomes between non‐citizens and citizens. Non‐significant differences were observed for non‐citizenship in PTD (aRR = 0.84, 95% CI, 0.66, 1.06), VPTD (aRR = 0.57, 95% CI, 0.28, 1.01), SGA (aRR = 0.91, 95% CI, 0.72, 1.13), VSGA (aRR = 0.87, 95% CI, 0.58, 1.25), stillbirth (aRR = 0.71, 95% CI, 0.35, 1.27) and neonatal death (aRR = 1.35, 95% CI, 0.60, 2.62).ConclusionsFollowing the expansion of free antiretroviral therapy to non‐citizens, gaps narrowed in ANC and antiretroviral therapy use in pregnancy between citizens and non‐citizens living with HIV. Disparities in adverse birth outcomes were no longer observed.

OBJECTIVES: This study aims to evaluate the prevalence and outcome of twin pregnancies in Botswana. SETTING: The Tsepamo Study conducted birth outcomes surveillance at 8 government-run hospitals (~45% of all births in Botswana) from August 2014 to June 2018 and expanded to 18 hospitals (~70% of all births in Botswana) from July 2018 to March 2019. PARTICIPANTS: Data were collected for all live-born and stillborn in-hospital deliveries with a gestational age (GA) greater than 24 weeks. This analysis included 117 593 singleton and 3718 twin infants (1859 sets (1.6%)) born to 119 477 women between August 2014 and March 2019 and excluded 73 higher order multiples (23 sets of triplets and 1 set of quadruplets). OUTCOMES MEASURED: Our primary outcomes were preterm delivery (<37 weeks GA), very preterm delivery (<32 weeks GA) and stillbirth (APGAR (Appearance, Pulse, Grimace, Activity, Respiration) score of 0, 0, 0). RESULTS: Women with twin pregnancies had a similar median number of antenatal care visits (9 vs 10), but were more likely to deliver in a tertiary centre (54.8% vs 45.1%, p<0.001) and more likely to have a cesarean-section (54.6% vs 22.0%, p<0.001) than women with singletons. Compared with singletons, twin pregnancies had a higher risk of preterm delivery (<37 weeks GA) (47.6% vs 16.7%, adjusted risk ratio (aRR) 2.8, 95% CI 2.7 to 2.9) and very preterm delivery (<32 weeks) (11.8% vs 4.0%, aRR 3.0 95% CI 2.6 to 3.4). Among all twin pregnancies, 128 (6.9%) had at least one stillborn infant compared with 2845 (2.4%) stillbirths among singletons (aRR 2.8, 95% CI 2.3 to 3.3). CONCLUSION: Adverse birth outcomes are common among twins in Botswana, and are often severe. Interventions that allow for earlier identification of twin gestation and improved antenatal management of twin pregnancies may improve infant and child survival.

BackgroundAbacavir (ABC) may be associated with a small, increased risk of myocardial infarction in HIV‐infected adults, possibly related to cytokine‐mediated inflammation.MethodsTo evaluate the induction of inflammatory cytokine transcription by ABC, we used samples from women randomized to receive zidovudine/lamivudine/ABC (Trizivir) or lopinavir/ritonavir and zidovudine/lamividine (Kaletra/Combivir) from the third trimester through six‐months postpartum for the prevention of mother‐to‐child transmission (PMTCT). Women were matched by CD4 count and baseline HIV RNA. All women attained viral suppression (<50 copies/ml) by the time of sampling.ResultsFour cytokines showed a difference in expression between the treatment arms, all in a proinflammatory direction for the ABC arm: CD40LG 1.82‐fold, (p=.027); IL‐8 3.16‐fold (p=.020); LTA 2.82‐fold, (p=.008); and CCL5 −1.67‐fold, (p=.035). At 12‐months postpartum, 6‐months after antiretroviral discontinuation, cytokine expression was similar by treatment arm.ConclusionsWe conclude that ABC may upregulate proinflammatory cytokines at the transcriptional level in this population.

Abstract Background The contribution of HIV-exposure to childhood mortality in a setting with widespread antiretroviral treatment (ART) availability has not been determined. Methods From January 2012 to March 2013, mothers were enrolled within 48 h of delivery at 5 government postpartum wards in Botswana. Participants were followed by phone 1–3 monthly for 24 months. Risk factors for 24-month survival were assessed by Cox proportional hazards modeling. Results Three thousand mothers (1499 HIV-infected) and their 3033 children (1515 HIV-exposed) were enrolled. During pregnancy 58 % received three-drug ART, 23 % received zidovudine alone, 11 % received no antiretrovirals (8 % unknown); 2.1 % of children were HIV-infected by 24 months. Vital status at 24 months was known for 3018 (99.5 %) children; 106 (3.5 %) died including 12 (38 %) HIV-infected, 70 (4.7 %) HIV-exposed uninfected, and 24 (1.6 %) HIV-unexposed. Risk factors for mortality were child HIV-infection (aHR 22.6, 95 % CI 10.7, 47.5 %), child HIV-exposure (aHR 2.7, 95 % CI 1.7, 4.5) and maternal death (aHR 8.9, 95 % CI 2.1, 37.1). Replacement feeding predicted mortality when modeled separately from HIV-exposure (aHR 2.3, 95 % CI 1.5, 3.6), but colinearity with HIV-exposure status precluded investigation of its independent effect. Applied at the population level (26 % maternal HIV prevalence), an estimated 52 % of child mortality occurs among HIV-exposed or HIV-infected children. Conclusions In a programmatic setting with high maternal HIV prevalence and widespread maternal and child ART availability, HIV-exposed and HIV-infected children still account for most deaths at 24 months. Lack of breastfeeding was a likely contributor to excess mortality among HIV-exposed children.

BACKGROUND: Adolescent girls are three times more likely to be living with HIV than boys of the same age. Prior studies have found associations between adolescent pregnancies and increased maternal morbidity and infant mortality, but few studies have assessed the impact of HIV infection on maternal and infant outcomes in adolescents. METHODS: The Tsepamo Study abstracts maternal and infant data from obstetric records in government maternity wards in Botswana. We assessed maternal complications and adverse birth outcomes for all singleton pregnancies from August 2014 to August 2020 at eighteen Tsepamo sites among adolescents (defined as 10–19 years of age) and adults (defined as 20–35 years of age), by HIV status. Univariate and multivariate logistic regression using a complete case analysis method were used to evaluate differences in outcomes. RESULTS: This analysis included 142,258 singleton births, 21,133 (14.9%) to adolescents and 121,125 (85.1%) to adults. The proportion of adults living with HIV (N = 22,114, 22.5%) was higher than adolescents (N = 1593, 7.6%). The proportion of most adverse birth outcomes was higher in adolescents. Among adolescents, those with HIV had increased likelihoods of anemia (aOR = 1.89, 95%CI 1.66, 2.15) and cesarean sections (aOR = 1.49, 95%CI 1.3,1.72), and infants with preterm birth (aOR = 1.15, 95%CI 1.0, 1.32), very preterm birth (aOR = 1.35, 95%CI 1.0,1.8), small for gestational age (aOR = 1.37, 95%CI 1.20,1.58), and very small for gestational age (aOR = 1.46, 95%CI 1.20, 1.79). CONCLUSIONS: Adolescent pregnancy and adolescent HIV infection remain high in Botswana. Adolescents have higher risk of adverse maternal and infant birth outcomes than adults, with the worst outcomes among adolescents living with HIV. Linking HIV prevention and family planning strategies for this age group may help minimize the number of infants with poor birth outcomes among this already vulnerable population.

BACKGROUND: Botswana updated its antiretroviral treatment (ART) guidelines in May 2016 to support breastfeeding for women living with HIV (WLHIV) on ART who have documented HIV RNA suppression during pregnancy. METHODS: From September 2016 to March 2019, we evaluated feeding method at discharge among WLHIV at eight government maternity wards in Botswana within the Tsepamo Study. We validated the recorded feeding method on the obstetric record using the prevention of mother-to-child transmission of HIV (PMTCT) counsellor report, infant formula dispensing log or through direct observation. Available HIV RNA results were recorded from the obstetric record, and from outpatient HIV records (starting February 2018). In a subset of participants, we used electronic laboratory records to verify whether an HIV RNA test had occurred. Univariable and multivariable logistic regression analyses were performed to identify factors associated with infant feeding choice. RESULTS: Among 13,354 WLHIV who had a validated feeding method at discharge, 5303 (39.7%) chose to breastfeed and 8051 (60.3%) chose to formula feed. Women who had a documented HIV RNA result in the obstetric record available to healthcare providers at delivery were more likely to breastfeed (50.8%) compared to women who did not have a documented HIV RNA result (35.4%) (aOR 0.59; 95% CI 0.54, 0.65). Among women with documented HIV RNA, 2711 (94.6%) were virally suppressed ( 400 copies/mL, and 134 (27.4%) of 489 women with no reported ART use. A sub-analysis of electronic laboratory records among 150 women without a recorded result on the obstetric record revealed that 93 (62%) women had an HIV RNA test during pregnancy. CONCLUSIONS: In a setting of long-standing use of suppressive ART, with majority of WLHIV on ART from the time of conception, requiring documentation of HIV RNA suppression in the obstetric ...

BACKGROUND: Vaginal discharge syndrome (VDS) is a common clinical diagnosis during pregnancy in Botswana; it is treated with broad-spectrum antibiotics using a syndromic approach. We evaluated associations between the syndromic management of VDS and adverse birth outcomes. METHODS: The Tsepamo Study performs birth outcomes surveillance at government hospitals throughout Botswana. Obstetric record data collected from August 2014 to March 2019 were analyzed. Chi-square tests were conducted to compare proportions of maternal characteristics and infant outcomes. To avoid immortal time bias, all analyses were conducted among women who presented to care before 24 weeks gestation, with VDS categorized as present or absent by 24 weeks gestation. Log-binomial regression models were generated to determine associations between treated VDS and infant outcomes. RESULTS: VDS was diagnosed in 36 731 (30.7%) pregnant women, of whom 33 328 (90.7%) received antibiotics. Adjusted analyses yielded a harmful association between treated VDS and very preterm delivery (adjusted risk ratio, 1.11; 95% CI, 1.02–1.21). This association remained when restricting to women with VDS who received the recommended antibiotic treatment regimen. Sensitivity analyses produced nonsignificant associations when women with treated VDS were compared with women without VDS who received antibiotics for other indications. CONCLUSIONS: A clinical diagnosis of VDS is common among pregnant women in Botswana, and the majority receive antibiotics in pregnancy. Although analyses of VDS occurring later in pregnancy are precluded by immortal time bias, a modest association between treated VDS and very preterm delivery was observed among women diagnosed with VDS by 24 weeks gestation.

IntroductionIt would be useful to understand which populations are not reached by home‐based HIV‐1 testing and counselling (HTC) to improve strategies aimed at linking these individuals to care and reducing rates of onward HIV transmission.MethodsWe present the results of a baseline home‐based HTC (HBHTC) campaign aimed at counselling and testing residents aged 16 to 64 for HIV in the north‐eastern sector of Mochudi, a community in Botswana with about 44,000 inhabitants. Collected data were compared with population references for Botswana, the United Nations (UN) estimates based on the National Census data and the Botswana AIDS Impact Survey IV (BAIS‐IV). Analyzed data and references were stratified by age and gender.ResultsA total of 6238 age‐eligible residents were tested for HIV‐1; 1247 (20.0%; 95% CI 19.0 to 21.0%) were found to be HIV positive (23.7% of women vs. 13.4% of men). HIV‐1 prevalence peaked at 44% in 35‐ to 39‐year‐old women and 32% in 40‐ to 44‐year‐old men. A lower HIV prevalence rate, 10.9% (95% CI 9.5 to 12.5%), was found among individuals tested for the first time. A significant gender gap was evident in all analyzed subsets. The existing HIV transmission network was analyzed by combining phylogenetic mapping and household structure. Between 62.4 and 71.8% of all HIV‐positive individuals had detectable virus. When compared with the UN and BAIS‐IV estimates, the proportion of men missed by the testing campaign (48.5%; 95% CI 47.0 to 50.0%) was significantly higher than the proportion of missed women (14.2%; 95% CI 13.2 to 15.3%; p<0.0001). The estimated proportion of missed men peaked at about 60% in the age group 30 to 39 years old. The proportions of missed women were substantially smaller, at approximately 28% within the age groups 30 to 34 and 45 to 49 years old.ConclusionsThe HBHTC campaign seems to be an efficient tool for reaching individuals who have never been tested previously in southern African communities. However, about half of men from 16 to 64 years old were not reached by the HBHTC, including about 60% of men between 30 and 40 years old. Alternative HTC strategies should be developed to bring these men to care, which will contribute to reduction of HIV incidence in communities.

There is a global cancer crisis, and it is disproportionately affecting resource-constrained settings, especially in low- and middle-income countries (LMICs). Radiotherapy is a critical and cost-effective component of a comprehensive cancer control plan that offers the potential for cure, control, and palliation of disease in greater than 50% of patients with cancer. Globally, LMICs do not have adequate access to quality radiation therapy and this gap is particularly pronounced in sub-Saharan Africa. Although there are numerous challenges in implementing a radiation therapy program in a low-resource setting, providing more equitable global access to radiotherapy is a responsibility and investment worth prioritizing. We outline a systems approach and a series of key questions to direct strategy toward establishing quality radiation services in LMICs, and highlight the story of private-public investment in Botswana from the late 1990s to the present. After assessing the need and defining the value of radiation, we explore core investments required, barriers that need to be overcome, and assets that can be leveraged to establish a radiation program. Considerations addressed include infrastructure; machine choice; quality assurance and patient safety; acquisition, development, and retention of human capital; governmental engagement; public–private partnerships; international collaborations; and the need to critically evaluate the program to foster further growth and sustainability.

AbstractIntroductionStudies have reported a higher risk of suboptimal neurodevelopment among children who are HIV‐exposed uninfected (HEU) compared to children HIV‐unexposed uninfected (HUU). Actual academic performance among school‐aged children by HIV exposure status has not been studied.MethodsAcademic performance in Mathematics, Science, English, Setswana and overall among children enrolled in the Botswana‐based FLOURISH study who were attending public primary school and ranging in age from 7.1 to 14.6 years were compared by HIV exposure status using a Cochran‐Mantel‐Haenszel test. Lower academic performance was defined as a grade of "C" or lower (≤60%). Unadjusted and adjusted logistic regression models were fit to assess for an association between HIV exposure and lower academic performance.ResultsBetween April 2021 and December 2022, 398 children attending public primary school enrolled in the FLOURSH study, 307 (77%) were HEU. Median age was 9.4 years (IQR 8.9–10.2). Only 17.9% of children HEU were breastfeed versus 100% of children HUU. Among children HEU, 80.3% had foetal exposure to three‐drug antiretroviral treatment, 18.7% to zidovudine only and 1.0% had no antiretroviral exposure. Caregivers of children HEU were older compared to caregivers of children HUU (median 42 vs. 36 years) and more likely to have no or primary education only (15.0% vs. 1.1%). In unadjusted analyses, children HEU were more likely to have lower overall academic performance compared to their children HUU (odds ratio [OR]: 1.96 [95% confidence interval (CI): 1.16, 3.30]), and lower performance in Mathematics, Science and English. The association was attenuated after adjustment for maternal education, caregiver income, breastfeeding, low birth weight and child sex (aOR: 1.86 [95% CI: 0.78, 4.43]).ConclusionsIn this Botswana‐based cohort, primary school academic performance was lower among children HEU compared to children HUU. Biological and socio‐demographic factors, including child sex, appear to contribute to this difference. Further research is needed to identify modifiable contributors, develop screening tools to identify the risk of poor academic performance and design interventions to mitigate risk.