Background Cervical cancer is a major public health problem in resource-limited settings, particularly among HIV-infected women. Given the challenges of cytology-based approaches, the efficiency of new screening programs need to be assessed. Setting Community and hospital-based clinics in Gaborone, Botswana. Objective To determine the feasibility, and efficiency of the “See and Treat” approach using Visual Inspection Acetic Acid (VIA) and Enhanced Digital Imaging (EDI) for cervical cancer prevention in HIV-infected women. Methods A two-tier community-based cervical cancer prevention program was implemented. HIV-infected women were screened by nurses at the community using the VIA/EDI approach. Low-grade lesions were treated with cryotherapy on the same visit. Women with complex lesions were referred to our second tier, specialized clinic for evaluation. Weekly quality control assessments were performed by a specialist in collaboration with the nurses on all pictures taken. Results From March 2009 through January 2011, 2,175 patients were screened for cervical cancer at our community-based clinic. 253 (11.6%) were found to have low-grade lesions and received same-day cryotherapy. 1,347 (61.9%) women were considered to have a normal examination and 575 (27.3%) were referred for further evaluation and treatment. Of the 1,347 women initially considered to have normal exams, 267 (19.8%) were recalled based on weekly quality control assessments. 210 (78.6%) of the 267 recalled women and 499 (86.8%) of the 575 referred women were seen at the referral clinic. Of these 709 women, 506 (71.4%) required additional treatment. Overall, 264 CIN stage 2 or 3 were identified and treated, and six micro-invasive cancers identified were referred for further management. Conclusions Our “See and Treat” cervical cancer prevention program using the VIA/EDI approach is a feasible, high-output and high-efficiency program, worthy of considering as an additional cervical cancer screening method in Botswana, especially for women with limited access to the current cytology-based screening services.
ObjectivesSince vitamin D insufficiency is common worldwide in people with HIV, we explored safety and efficacy of high dose cholecalciferol (D₃) in Botswana, and evaluated potential modifiers of serum 25 hydroxy vitamin D change (Δ25D).DesignProspective randomized double-blind 12-week pilot trial of subjects ages 5.0–50.9 years.MethodsSixty subjects randomized within five age groups to either 4000 or 7000IU per day of D₃ and evaluated for vitamin D, parathyroid hormone, HIV, safety and growth status. Efficacy was defined as serum 25 hydroxy vitamin D (25D) ≥32ng/mL, and safety as no simultaneous elevation of serum calcium and 25D. Also assessed were HIV plasma viral RNA viral load (VL), CD4%, anti-retroviral therapy (ART) regime, and height-adjusted (HAZ), weight-adjusted (WAZ) and Body Mass Index (BMIZ) Z scores.ResultsSubjects were 50% male, age (mean±SD) 19.5±11.8 years, CD4% 31.8±10.4, with baseline VL log₁₀ range of <1.4 to 3.8 and VL detectable (>1.4) in 22%. From baseline to 12 weeks, 25D increased from 36±9ng/ml to 56±18ng/ml (p<0.0001) and 68% and 90% had 25D ≥32ng/ml, respectively (p = 0.02). Δ25D was similar by dose. No subjects had simultaneously increased serum calcium and 25D. WAZ and BMIZ improved by 12 weeks (p<0.04). HAZ and CD4% increased and VL decreased in the 7000IU/d group (p<0.04). Younger (5–13y) and older (30–50y) subjects had greater Δ25D than those 14–29y (26±17 and 28±12 vs. 11±11ng/ml, respectively, p≤0.001). Δ25D was higher with efavirenz or nevirapine compared to protease inhibitor based treatment (22±12, 27±17, vs. 13±10, respectively, p≤0.03).ConclusionsIn a pilot study in Botswana, 12-week high dose D₃ supplementation was safe and improved vitamin D, growth and HIV status; age and ART regimen were significant effect modifiers.Trial RegistrationClinicalTrials.gov NCT02189902
Objective(s) To determine the association between cytochrome p450 2B6 genotypes and efavirenz-based HIV treatment outcomes. Design Observational cohort study of HIV infected adults initiating efavirenz-based regimens in Botswana. Methods The primary endpoint was a composite of death or loss to care or HIV RNA>25 copies/ml at 6 months. CYP2B6 516G>T and 983T>C genotyping was done with Taqman Open Array platform. Adverse experiences were measured using the Subject Experience Questionnaire. Metabolism alleles were included in logistic regression models of the composite endpoint. Results 801 individuals included 406 (51%) males, median age 37 years, median baseline CD4 count 195 cells/mm3 and plasma HIV RNA 4·9 log10 copies/ml. 288 (36%) reached the endpoint including 34 (4%) deaths, 151 (19%) lost to care, 11 (1%) lost to the study, but alive and in care, and 92 (11%) with plasma HIV RNA>25 copies/ml. Metabolism variant alleles were common with 396 (49%) intermediate and 192 (24%) slow metabolizers. There were no statistically significant associations between metabolism and treatment endpoints. However, slower metabolism was associated with fewer adverse experiences. Conclusions Slow metabolism alleles were associated with lower efavirenz clearance but not any of the treatment endpoints. Slow efavirenz metabolism did not exacerbate CNS toxicity. These results should allay concern that slow efavirenz metabolism adversely impacts individuals in sub-Saharan African settings in which these alleles are common.
Background The prevalence of high-risk human papillomavirus (hrHPV) is poorly described overall and in women living with HIV (WLWH) and HIV-negative women living in Botswana, a high HIV and cervical cancer-burden country. We conducted a pilot study of self-collection and highrisk HPV testing for cervical screening, from which data on HPV prevalence was available. Methods From five health facilities in the Kweneng East District, 1,022 women aged 30-49 years were enrolled to self-collect their cervicovaginal specimen for hrHPV testing by the Xpert HPV Test (Cepheid, Sunnyvale, CA, USA). Crude and age group-adjusted hrHPV prevalence by HIV status were calculated, and the relationship of hrHPV risk groups HPV16>HPV18/45>other hrHPV types) to the presence and severity of visible lesions. Results Of the 1,022 women enrolled, 1,019 (99.7%), 570 WLWH and 449 HIV-negative women, had hrHPV testing results. Crude hrHPV prevalences were 25.2% (95%CI = 21.2-29.4%) for HIV-negative women and 40.4% (95%CI = 36.3-44.5%) for WLWH. Age group-adjusted hrHPV prevalences were 23.7% (95%CI = 19.9-27.9%) for HIV-negative women and 41.3% (95%CI = 37.2-45.4%) for WLWH. Age group-adjusted prevalences of HPV16 (p<0.001), HPV18/45 (p<0.001), HPV31/33/35/52/58 (p<0.001), and HPV39/56/66/68 (p = 0.011) were greater among WLWH than HIV-negative women. Riskier hrHPV groups were more likely to have visible abnormalities (p trend = 0.004) and visible abnormalities not eligible for cryotherapy (p trend = 0.030).
Inter-individual variability in efavirenz (EFV) pharmacokinetics and dynamics are 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 one 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.
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