Phenotypic and genotypic analyses to guide selection of reverse transcriptase inhibitors in second-line HIV therapy following extended virological failure in Uganda

Objectives We investigated phenotypic and genotypic resistance after 2 years of first-line therapy with two HIV treatment regimens in the absence of virological monitoring. Methods NORA [Nevirapine OR Abacavir study, a sub-study of the Development of AntiRetroviral Therapy in Africa (DART) trial] randomized 600 symptomatic HIV-infected Ugandan adults (CD4 cell count <200 cells/mm3) to receive zidovudine/lamivudine plus abacavir (cABC arm) or nevirapine (cNVP arm). All virological tests were performed retrospectively, including resistance tests on week 96 plasma samples with HIV RNA levels ≥1000 copies/mL. Phenotypic resistance was expressed as fold-change in IC50 (FC) relative to wild-type virus. Results HIV-1 RNA viral load ≥1000 copies/mL at week 96 was seen in 58/204 (28.4%) cABC participants and 21/159 (13.2%) cNVP participants. Resistance results were available in 35 cABC and 17 cNVP participants; 31 (89%) cABC and 16 (94%) cNVP isolates had a week 96 FC below the biological cut-off for tenofovir (2.2). In the cNVP arm, 16/17 participants had resistance mutations synonymous with high-level resistance to nevirapine and efavirenz; FC values for etravirine were above the biological cut-off in 9 (53%) isolates. In multivariate regression models, K65R, Y115F and the presence of thymidine analogue-associated mutations were associated with increased susceptibility to etravirine in the cABC arm. Conclusions Our data support the use of tenofovir following failure of a first-line zidovudine-containing regimen and shed further light on non-nucleoside reverse transcriptase inhibitor hypersusceptibility

Towards equitable and sustainable availability of blood products in Zimbabwe : an analysis of strengths, weaknesses, opportunities and challenges

Blood transfusion can be a lifesaving intervention in a number of medical emergencies. To attain sustainable and equitable availability of blood products, it is important to understand the strengths, weaknesses, opportunities, and challenges of the national blood services programme. We, therefore, with this letter to the editor, discuss some of the strengths, weaknesses, opportunities and threats to the Zimbabwean programme since its inception. Despite several strengths and opportunities that the national blood services of Zimbabwe (NBSZ) leverages on, we argue that among other challenges, donor shortages and an upsurge of transfusion transmittable infections in the eligible donor population continue to be the biggest threats to the achievement of the programme objectives. These can be addressed through expanding the blood donor base and the catchment area. Additionally, improving the level of knowledge and attitude towards blood donation in the communities is critical for driving the sustainable and equitable distribution of safe blood products to the population.https://www.journals.elsevier.com/transfusion-clinique-et-biologique2023-08-17hj2022School of Health Systems and Public Health (SHSPH

Human papillomavirus genotype distribution in genital warts among women in Harare-Zimbabwe

This study aimed to determine the prevalence of HPV genotypes in genital warts among women in Harare, Zimbabwe. Women aged 18–45 years attending gynaecology and genitourinary clinics with a clinical diagnosis of genital-warts were recruited. HPV-DNA was extracted from tissue biopsies. HPV-DNA testing and typing was done by Southern Dot Blot Hybridisation. A hundred samples from 100 women were analysed. Median age of participants was 30.3 years (range 18–45 years). Seventy-eight percent of participants were HIV infected. HPV prevalence was 98%. Low risk genotypes predominated at 86% prevalence. The most prevalent genotypes were 11 (47%), 6 (42%) and 16 (14%). This is the first study on HPV genotype distribution among women with genital warts in Zimbabwe. The high prevalence of HR-HPV 16 in clinically benign lesions shows that warts should have histological analysis to exclude pre-malignancy and malignancy.Impact statement What is already known on this subject? Genital warts (GWs), also known as condylomata acuminata (EAC), are a clinical manifestation of persistent infection with ‘low risk’ or non-oncogenic HPV genotypes. HPV 6 and 11 are examples of low risk genotypes, and both are associated with 90% of GWs. Data on HPV genotypes causing genital warts in the population under study are scarce. What do the results of this study add? A high prevalence (98%) of HPV DNA in genital warts, confirms that the biopsied lesions were HPV related. Over and above the high prevalence of low risk HPV 11 (47%) and HPV 6 (42%), the women had 14% prevalence of HPV 16, an oncogenic genotype, in genital warts. Seventy-eight percent of the participants were HIV infected. The HIV infected women had a 33.3% prevalence of HR-HPV as compared to the 15.8% prevalence in the HIV uninfected women. What are the implications of these findings for clinical practice and/or further research? The population under study will benefit more if an HPV vaccine that includes anti-HPV 6 and 11 is used. The high prevalence of the HR-HPV in apparently benign lesions shows that warts should have histological analysis to exclude vulvar cancer and vulvar intraepithelial neoplasia. All women presenting with genital warts should be offered an HIV test

The virological durability of first-line ART among HIV-positive adult patients in resource limited settings without virological monitoring: a retrospective analysis of DART trial data

Few low-income countries have virological monitoring widely available. We estimated the virological durability of first-line antiretroviral therapy (ART) after five years of follow-up among adult Ugandan and Zimbabwean patients in the DART study, in which virological assays were conducted retrospectively