Publications by Year: 2025

OBJECTIVE: To evaluate the impact of antiretroviral therapy (ART) duration and CD4 + cell count on risk for high grade cervical dysplasia in women with HIV (WWH) compared to women without HIV in the treat-all era with integrase strand inhibitors (INSTIs).

DESIGN: A prospective longitudinal cohort study in Botswana.

METHODS: From February 2021 to July 2022, baseline HPV self-sampling was offered to women with and without HIV. Those HPV+ underwent biopsy for histopathological diagnosis. Using women without HIV as reference, risk ratios were calculated for HPV, cervical intraepithelial neoplasia (CIN) 2 or worse (CIN2+), and CIN3+, stratified by ART duration and CD4 + cell counts.

RESULTS: Of 3000 women enrolled, 2953(98.4%) underwent HPV testing, which was positive in 823(55.7%) WWH and in 654(44.3%) women without HIV. Histopathology was available for analysis in 1291(87.4%) women (709 WWH, 582 women without HIV). Over 99% of WWH had an undetectable HIV viral load and 94.4% were on a dolutegravir-based ART regimen. WWH had a higher risk of HPV [risk ratio 1.27, 95% confidence interval (95% CI): 1.18-1.37], CIN2+ (risk ratio 1.52, 95% CI: 1.16-1.98), and CIN3+ (risk ratio 1.75, 95% CI: 1.25-2.45) compared to women without HIV. There was attenuation of risk for CIN2+ with higher recent CD4 + cell count, and those with higher nadir CD4 + cell count had similar risk to those without HIV (nadir CD4 + ≥500 CIN2+ risk ratio 1.15 [95% CI: 0.56-2.37], CIN3+ risk ratio 1.81 [95% CI: 0.86-3.79]; nadir CD4 + 350-499 CIN2+ risk ratio 1.23 [95% CI: 0.71-2.12], CIN3+ risk ratio 1.34 [95% CI: 0.68-2.64]).

CONCLUSION: Although some attenuation of risk for CIN2+ was observed with higher recent and nadir CD4 + cell counts, WWH continue to have a higher risk of CIN2+/CIN3+ compared to women without HIV. These findings support tailored cervical screening algorithms for WWH.

OBJECTIVE: The aim of this study was to evaluate the performance of HPV type restriction and cycle threshold (Ct)-limit setting to optimize detection of cervical intraepithelial neoplasia (CIN) with primary HPV testing.

METHODS: Baseline cervical screening at time of entry into a prospective longitudinal cohort of women with and without HIV was conducted from February 2021 to July 2022 in Botswana. All women underwent HPV testing of 15 individual types using the AmpFire assay; all HPV-positive and a random subset of HPV negative had histopathology collected. Performance parameters of HPV type restriction groupings were calculated, and sensitivity by individual HPV type Ct-value limits were plotted.

RESULTS: Among 2964 women who underwent primary HPV screening, 1293 (43.6%) tested HPV-positive. Among women with HIV (WWH), HPV types 16/18/33 were associated with the greatest burden of CIN2+/CIN3+ (53%/56%). In WWH, grouping by HPV types separately reported in commercial assays (16/18/45) had low sensitivity (44% [CI: 36%-52%]) but high specificity (86% [CI: 84%-88%]) for CIN2+; 8-type HPV restriction (16/18/31/33/35/45/52/58) improved sensitivity (79% [CI: 72%-86%]) and maintained reasonable specificity (67% [CI: 65%-70%]) for CIN2+. Similar results were seen in women without HIV. Ct-limit setting for medium oncogenic HPV types (31,33,35,52,58) maintained a sensitivity of 72% in WWH while reducing over-detection of non-pathogenic HPV.

CONCLUSION: Eight-type HPV restriction and Ct-limit setting are promising strategies for improving the performance of primary HPV screening. A potential strategy to improve 8-type HPV restriction would be to treat all with HPV 16/18/45; treat HPV 31/33/35/52/58 if below the type-specific Ct limit and repeat HPV testing in 1-year for other positive HPV results.

PURPOSE: In Botswana, a see-and-treat approach to cervical cancer screening is taken. Our objective was to determine the number of loop electrosurgical excision procedures (LEEPs) performed for cervical intraepithelial neoplasia (CIN) 2/3 in Botswana, and follow-up rates and outcomes, among women with positive cervical margins.

METHODS: Data (patient age, HIV status, margin status, follow-up, and recurrence) from women who underwent LEEP with histologically confirmed CIN 2/3 between January 2014 and December 2015 were analyzed retrospectively. Histopathologic reports were reviewed at a central laboratory in Gaborone, Botswana. Follow-up and recurrence rates were summarized descriptively and compared according to HIV and margin statuses using chi-squared tests.

RESULTS: In total, 779 women (median age, 39.2 years) underwent LEEP showing CIN2/3; 638 (81.9%) women had CIN3 and 390 (50.1%) had positive LEEP margins (ectocervical, 186 [47.7%]; endocervical [including with ectocervical], 204 [52.4%]). Margin positivity was not associated with HIV status. Of women with positive endocervical margins followed at ≤1 and >1 year, 9.6% and 48.3%, respectively, had persistent CIN2/3 on repeat LEEP. Forty percent (90 of 204) of women with positive endocervical margins had no re-excision documented.

CONCLUSION: Most women who underwent LEEP had CIN3 and positive margins. Almost half with positive margins followed at >1 year after initial LEEP had CIN2/3 recurrence warranting further treatment; two thirds were not followed. Resources are needed to improve post-LEEP follow-up for women with margin positivity who require additional ablative/excisional procedures to reduce the cervical cancer burden in Botswana.

OBJECTIVES: To improve the quality of intrapartum care at Princess Marina Hospital, Gaborone, Botswana, through a champion-led educational intervention, introduction of the World Health Organization's Labor Care Guide (LCG), which highlights four key measures to promote respectful maternal care (RMC).

METHODS: In August 2022, we engaged medical and nursing staff in interactive training on the WHO LCG and implemented a mnemonic-based checklist-"COPE" (Companions, Oral fluids, Pain relief, Eliminate the supine position). Motivational posters were displayed in the labor ward. Surveys to assess client labor experiences were conducted in November 2022 (n = 204) and October 2024 (n = 211). An anonymous staff survey assessed personal practice changes before and after the training.

RESULTS: Over 2 years, significant improvements in reported maternal experience were observed. Reports of a "very bad" experience decreased from 116/204 (56.9%) to 13/211 (6.2%) and dissatisfaction with care reduced from 22/204 (10.8%) to 3/211 (1.4%). Adequate fluid provision increased from 108/204 (52.9%) to 159/211 (75.4%) and pain relief from 41/204 (20.1%) to 108/211 (51.2%). The reported presence of a labor companion increased from 14/204 (6.9%) to 133/211 (63.0%). Patient reports of exclusive supine positioning during the second stage of labor decreased from 106/204 (52.0%) to 11/211(5.2%). Staff questionnaires showed a consistent improvement in reported adoption of "COPE" practices compared with recollected practices before the intervention.

CONCLUSIONS: Deeply entrenched labor care practices are difficult to change; however, sustained, champion-led quality improvement interventions using the LCG and with sustained supportive supervision can yield meaningful improvement in women's birth experiences.

OBJECTIVE: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSION: 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.

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.