183 research outputs found

    Effect of co-trimoxazole on mortality in HIV-exposed but uninfected children in Botswana (the Mpepu Study): a double-blind, randomised, placebo-controlled trial

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    Background Co-trimoxazole prophylaxis reduces mortality among HIV-infected children, but efficacy in HIV-exposed but uninfected (HEU) children in a non-malarial, low-breastfeeding setting with a low risk of mother-to-child transmission of HIV is unclear. Methods HEU children in Botswana were randomly assigned to receive co-trimoxazole (100 mg/20 mg once daily until age 6 months and 200 mg/40 mg once daily thereafter) or placebo from age 14–34 days to age 15 months. Mothers chose whether to breastfeed or formula feed their children. Breastfed children were randomly assigned to breastfeeding for 6 months (Botswana guidelines) or 12 months (WHO guidelines). The primary outcome, analysed by a modified intention-to-treat approach, was cumulative child mortality from treatment assignment to age 18 months. We also assessed HIV-free survival by duration of breastfeeding. This trial is registered with ClinicalTrials.gov, number NCT01229761. Findings From June 7, 2011, to April 2, 2015, 2848 HEU children were randomly assigned to receive co-trimoxazole (n=1423) or placebo (n=1425). The data and safety monitoring board stopped the study early because of a low likelihood of benefit with co-trimoxazole. Only 153 (5%) children were lost to follow-up (76 in the co-trimoxazole group and 77 in the placebo group), and 2053 (72%) received treatment continuously to age 15 months, death, or study closure. Mortality after the start of study treatment was similar in the two study groups: 30 children died in the co-trimoxazole group, compared with 34 in the placebo group (estimated mortality at 18 months 2·4% vs 2·6%; difference –0·2%, 95% CI –1·5 to 1·0, p=0·70). We saw no difference in hospital admissions between groups (12·5% in the cotrimoxazole group vs 17·4% in the placebo group, p=0·19) or grade 3–4 clinical adverse events (16·5% vs 18·4%, p=0·18). Grade 3–4 anaemia did not differ between groups (8·1% vs 8·3%, p=0·93), but grade 3–4 neutropenia was more frequent in the co-trimoxazole group than in the placebo group (8·1% vs 5·8%, p=0·03). More co-trimoxazole resistance in commensal Escherichia coli isolated from stool samples was seen in children aged 3 or 6 months in the co-trimoxazole group than in the placebo group (p=0·001 and p=0·01, respectively). 572 (20%) children were breastfed. HIV infection and mortality did not differ significantly by duration of breastfeeding (3·9% for 6 months vs 1·9% for 12 months, p=0·21). Interpretation Prophylactic co-trimoxazole seems to offer no survival benefit among HEU children in non-malarial, low-breastfeeding areas with a low risk of mother-to-child transmission of HIV

    High Prevalence of Hypertension and Placental Insufficiency, but No In Utero HIV Transmission, among Women on HAART with Stillbirths in Botswana

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    Background: Increased stillbirth rates occur among HIV-infected women, but no studies have evaluated the pathological basis for this increase, or whether highly active antiretroviral therapy (HAART) influences the etiology of stillbirths. It is also unknown whether HIV infection of the fetus is associated with stillbirth. Methods: HIV-infected women and a comparator group of HIV-uninfected women who delivered stillbirths were enrolled at the largest referral hospital in Botswana between January and November 2010. Obstetrical records, including antiretroviral use in pregnancy, were extracted at enrollment. Verbal autopsies; maternal HIV, CD4 and HIV RNA testing; stillbirth HIV PCR testing; and placental pathology (blinded to HIV and treatment status) were performed. Results: Ninety-nine stillbirths were evaluated, including 62 from HIV-infected women (34% on HAART from conception, 8% on HAART started in pregnancy, 23% on zidovudine started in pregnancy, and 35% on no antiretrovirals) and 37 from a comparator group of HIV-uninfected women. Only 2 (3.7%) of 53 tested stillbirths from HIV-infected women were HIV PCR positive, and both were born to women not receiving HAART. Placental insufficiency associated with hypertension accounted for most stillbirths. Placental findings consistent with chronic hypertension were common among HIV-infected women who received HAART and among HIV-uninfected women (65% vs. 54%, p = 0.37), but less common among HIV-infected women not receiving HAART (28%, p = 0.003 vs. women on HAART). Conclusions: In utero HIV infection was rarely associated with stillbirths, and did not occur among women receiving HAART. Hypertension and placental insufficiency were associated with most stillbirths in this tertiary care setting

    Rapid antiretroviral therapy initiation in the Botswana Combination Prevention Project: a quasi-experimental before and after study.

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    BACKGROUND: Ensuring that individuals who are living with HIV rapidly initiate antiretroviral therapy (ART) is an essential step in meeting the 90-90-90 targets. We evaluated the feasibility and outcomes of rapid ART initiation in the Botswana Combination Prevention Project (BCPP). We aimed to establish whether simplified ART initiation with the offer of same-day treatment could increase uptake and reduce time from clinic linkage to treatment initiation, while maintaining rates of retention in care and viral suppression. METHODS: We did a quasi-experimental before and after study with use of data from the BCPP. The BCPP was a community-randomised HIV-prevention trial done in 30 communities across Botswana from Oct 1, 2013, to June 30, 2018. Participants in the 15 intervention clusters, who were HIV-positive and not already taking ART were offered universal HIV-treatment and same-day ART with a dolutegravir-based regimen at first clinic visit. This rapid ART intervention was implemented mid-way through the trial on June 1, 2016, enabling us to determine the effect of rapid ART guidelines on time to ART initiation and rates of retention in care and viral suppression at 1 year in the BCPP intervention group. FINDINGS: We assessed 1717 adults linked to study clinics before rapid ART introduction and 800 after rapid ART introduction. During the rapid ART period, 457 (57·1%, 95% CI 53·7-60·6) individuals initiated ART within 1 day of linkage, 589 (73·7%, 70·6-76·7) of 799 within 1 week, 678 (84·9%, 82·4-87·3) of 799 within 1 month, and 744 (93·5%, 91·6-95·1) of 796 within 1 year. Before the introduction of rapid ART, 163 (9·5%, 95% CI 8·2-11·0) individuals initiated ART within 1 day of linkage, 276 (16·1%, 14·4-17·9) within 1 week, 839 (48·9%, 46·5-51·3) within 1 month, and 1532 (89·2%, 87·7-90·6) within 1 year. 1 year after ART initiation, 1472 (90·5%, 87·4-92·8) of 1627 individuals who linked in the standard ART period were in care and had a viral load of less than 400 copies per mL, compared with 578 (91·6%, 88·1-94·1) of 631 in the rapid ART period (risk ratio 1·01, 95% CI 0·92-1·11). INTERPRETATION: Our findings provide support for the WHO recommendations for rapid ART initiation, and add to the accumulating evidence showing the feasibility, acceptability, and safety of rapid ART initiation in low-income and middle-income country settings. FUNDING: US President's Emergency Plan for AIDS Relief

    Atypical hepatitis B virus serology profile—hepatitis B surface antigen-positive/hepatitis B core antibody-negative—in hepatitis B virus/HIV coinfected individuals in Botswana

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    DATA AVAILABILITY : The data presented in this study are available upon request from the corresponding author. The data are not publicly available as the sequences are currently being analyzed for other objectives of the bigger project.BACKGROUND : Hepatitis B core antibodies (anti-HBc) are a marker of hepatitis B virus (HBV) exposure; hence, a normal HBV serology profile is characterized by HBV surface antigen (HBsAg) and anti-HBc positivity. However, atypical HBV serologies occur, and we aimed to determine the prevalence of an atypical profile (HBsAg+/anti-HBc-) in a cohort of people with HIV-1 (PWH) in Botswana. METHODS : Plasma samples from an HIV-1 cohort in Botswana (2013–2018) were used. The samples were screened for HBsAg and anti-HBc. Next-generation sequencing was performed using the GridION platform. The Wilcoxon rank-sum test and Chi-squared tests were used for the comparison of continuous and categorical variables, respectively. RESULTS : HBsAg+/anti-HBc- prevalence was 13.7% (95% CI 10.1–18.4) (36/263). HBsAg+/anti-HBc- participants were significantly younger (p < 0.001), female (p = 0.02) and ART-naïve (p = 0.04) and had a detectable HIV viral load (p = 0.02). There was no statistically significant difference in the number of mutations observed in participants with HBsAg+/anti-HBc- vs. those with HBsAg+/anti-HBc+ serology. CONCLUSIONS : We report a high HBsAg+/anti-HBc- atypical serology profile prevalence among PWH in Botswana. We caution against HBV-testing algorithms that consider only anti-HBc+ samples for HBsAg testing, as they are likely to underestimate HBV prevalence. Studies to elucidate the mechanisms and implications of this profile are warranted.Wellcome Trust and the National Institutes of Health (NIH) Common Fund.https://www.mdpi.com/journal/virusesSchool of Public Management and Administration (SPMA

    Advanced HIV disease in the Botswana combination prevention project: prevalence, risk factors, and outcomes.

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    OBJECTIVE(S): To determine the proportion of individuals linking to HIV-care with advanced HIV-disease (CD4 cell counts ≤200 cells/μl) in the Botswana Combination Prevention Project, describe the characteristics of these individuals, and examine treatment outcomes. DESIGN: A subanalysis of a cluster-randomized HIV-prevention trial. HIV status was assessed in 16-64-year-olds through home and mobile testing. All HIV-positive persons not on antiretroviral therapy were referred to local Ministry of Health and Wellness clinics for treatment. METHODS: Analysis was restricted to the 15 intervention clusters. The proportion of individuals with advanced HIV disease was determined; associations between advanced HIV disease and sex and age explored; and rates of viral suppression determined at 1-year. Mortality and retention in care were compared between CD4 strata (CD4 cell counts ≤200 vs. >200 cells/μl). RESULTS: Overall, 17.2% [430/2499; 95% confidence interval (CI) 15.7-18.8%] of study participants had advanced HIV disease (CD4 cell counts ≤200 cells/μl) at time of clinic linkage. Men were significantly more likely to present with CD4 cell counts 200 cells/μl or less than women [23.7 vs. 13.4%, adjusted odds ratio 1.9, 95% CI 1.5-2.3]. The risk of advanced HIV disease increased with increasing age (adjusted odds ratio 2.2, 95% CI 1.4-3.2 >35 vs. <25 years). Patients with CD4 cell counts 200 cells/μl or less had significantly higher rates of attrition from care during follow-up (hazards ratio 1.47, 95% CI 1.1-2.1). CONCLUSION: Advanced HIV disease due to late presentation to or disengagement from antiretroviral therapy care remains common in the Treat All era in Botswana, calling for innovative testing, linkage, and treatment strategies to engage and retain harder-to-reach populations in care

    HIV-1 Subtype C-Infected Individuals Maintaining High Viral Load as Potential Targets for the “Test-and-Treat” Approach to Reduce HIV Transmission

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    The first aim of the study is to assess the distribution of HIV-1 RNA levels in subtype C infection. Among 4,348 drug-naïve HIV-positive individuals participating in clinical studies in Botswana, the median baseline plasma HIV-1 RNA levels differed between the general population cohorts (4.1–4.2 log10) and cART-initiating cohorts (5.1–5.3 log10) by about one log10. The proportion of individuals with high (≥50,000 (4.7 log10) copies/ml) HIV-1 RNA levels ranged from 24%–28% in the general HIV-positive population cohorts to 65%–83% in cART-initiating cohorts. The second aim is to estimate the proportion of individuals who maintain high HIV-1 RNA levels for an extended time and the duration of this period. For this analysis, we estimate the proportion of individuals who could be identified by repeated 6- vs. 12-month-interval HIV testing, as well as the potential reduction of HIV transmission time that can be achieved by testing and ARV treating. Longitudinal analysis of 42 seroconverters revealed that 33% (95% CI: 20%–50%) of individuals maintain high HIV-1 RNA levels for at least 180 days post seroconversion (p/s) and the median duration of high viral load period was 350 (269; 428) days p/s. We found that it would be possible to identify all HIV-infected individuals with viral load ≥50,000 (4.7 log10) copies/ml using repeated six-month-interval HIV testing. Assuming individuals with high viral load initiate cART after being identified, the period of high transmissibility due to high viral load can potentially be reduced by 77% (95% CI: 71%–82%). Therefore, if HIV-infected individuals maintaining high levels of plasma HIV-1 RNA for extended period of time contribute disproportionally to HIV transmission, a modified “test-and-treat” strategy targeting such individuals by repeated HIV testing (followed by initiation of cART) might be a useful public health strategy for mitigating the HIV epidemic in some communities
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