Background: Here, we describe how the Collaborative African Genomics Network (CAfGEN) of the Human Heredity and Health in Africa (H3Africa) consortium is using genomics to probe host genetic factors important to the progression of HIV and HIV-tuberculosis (TB) coinfection in sub-Saharan Africa. The H3Africa was conceived to facilitate the application of genomics technologies to improve health across Africa.. Methods: CAfGEN is an H3Africa collaborative centre comprising expertise from the University of Botswana; Makerere University; Baylor College of Medicine Children’s Clinical Centers of Excellence (COEs) in Botswana, Uganda, and Swaziland; as well as Baylor College of Medicine, Texas. The COEs provide clinical expertise for community engagement, participant recruitment and sample collection while the three University settings facilitate processing and management of genomic samples and provide infrastructure and training opportunities to sustain genomics research. Results: The project has focused on utilizing whole-exome sequencing to identify genetic variants contributing to extreme HIV disease progression phenotypes in children, as well as RNA sequencing and integrated genomics to identify host genetic factors associated with TB disease progression among HIV-positive children. These cohorts, developed using the COEs’ electronic medical records, are exceptionally well-phenotyped and present an unprecedented opportunity to assess genetic factors in individuals whose HIV was acquired by a different route than their adult counterparts in the context of a unique clinical course and disease pathophysiology. Conclusions: Our approach offers the prospect of developing a critical mass of well-trained, highly-skilled, continent-based African genomic scientists. To ensure long term genomics research sustainability in Africa, CAfGEN contributes to a wide range of genomics capacity and infrastructure development on the continent, has laid a foundation for genomics graduate programs at its institutions, and continues to actively promote genomics research through innovative forms of community engagement brokered by partnerships with governments and academia to support genomics policy formulation.

Biorepositories in Africa need significant infrastructural support to meet International Society for Biological and Environmental Repositories (ISBER) Best Practices to support population-based genomics research. ISBER recommends a biorepository information management system which can manage workflows from biospecimen receipt to distribution. The H3Africa Initiative set out to develop regional African biorepositories where Uganda, Nigeria, and South Africa were successfully awarded grants to develop the state-of-the-art biorepositories. The biorepositories carried out an elaborate process to evaluate and choose a laboratory information management system (LIMS) with the aim of integrating the three geographically distinct sites. In this article, we review the processes, African experience, lessons learned, and make recommendations for choosing a biorepository LIMS in the African context.

Objective: A cross-sectional survey involving 134 pulmonary TB patients started on TB treatment at the TB Treatment Unit of the regional referral hospital was conducted to ascertain the prevalence of individual and health facility delays and associated factors. Prolonged health facility delay was taken as delay of more than 1 week and prolonged patient delay as delay of more than 3 weeks. A logistic regression model was done using STATA version 12 to determine the delays. Results: There was a median total delay of 13 weeks and 110 (82.1%) of the respondents had delay of more than 4 weeks. Patient delay was the most frequent and greatest contributor of total delay and exceeded 3 weeks in 95 (71.6%) respondents. At multivariate analysis, factors that influenced delay included poor patient knowledge on TB (adjOR 6.904, 95% CI 1.648–28.921; p = 0.04) and being unemployed (adjOR 3.947, 95% CI 1.382–11.274; p = 0.010) while being female was found protective of delay; adjOR 0.231, 95% CI 0.08–0.67; p = 0.007). Patient delay was the most significant, frequent and greatest contributor to total delay, and factors associated with delay included being unemployed, low knowledge on TB while being female was found protective of delay.

Human immunodeficiency virus (HIV) infection remains a significant public health burden globally. The role of viral co-infection in the rate of progression of HIV infection has been suggested but not empirically tested, particularly among children. We extracted and classified 42 viral species from whole-exome sequencing (WES) data of 813 HIV-infected children in Botswana and Uganda categorised as either long-term non-progressors (LTNPs) or rapid progressors (RPs). The Ugandan participants had a higher viral community diversity index compared to Batswana (p = 4.6 × 10⁻¹³), and viral sequences were more frequently detected among LTNPs than RPs (24% vs 16%;p = 0.008; OR, 1.9; 95% CI, 1.6–2.3), withAnelloviridaeshowing strong association with LTNP status (p = 3 × 10⁻⁴;q = 0.004, OR, 3.99; 95% CI, 1.74–10.25). This trend was still evident when stratified by country, sex, and sequencing platform, and after a logistic regression analysis adjusting for age, sex, country, and the sequencing platform (p = 0.02;q = 0.03; OR, 7.3; 95% CI, 1.6–40.5). Torque teno virus (TTV), which made up 95% of theAnelloviridaereads, has been associated with reduced immune activation. We identify an association between viral co-infection and prolonged AIDs-free survival status that may have utility as a biomarker of LTNP and could provide mechanistic insights to HIV progression in children, demonstrating the added value of interrogating off-target WES reads in cohort studies.

Purpose: This study was conducted to investigate the drug resistance mutations and genetic diversity of HIV-1 in ART experienced patients in South Omo, Ethiopia. Patients and Methods: A cross-sectional study conducted on 253 adult patients attending ART clinics for ≥ 6 months in South Omo. Samples with VL ≥ 1000 copies/mL were considered as virological failures (VF) and their reverse transcriptase gene codons 90– 234 were sequenced using Illumina MiSeq. MinVar was used for the identification of the subtypes and drug resistance mutations. Phylogenetic tree was constructed by neighbor-joining method using the maximum likelihood model. Results: The median duration of ART was 51 months and 18.6% (47/253) of the patients exhibited VF. Of 47 viraemic patients, the genome of 41 were sequenced and subtype C was dominant (87.8%) followed by recombinant subtype BC (4.9%), M-09-CPX (4.9) and BF1 (2.4%). Of 41 genotyped subjects, 85.4% (35/41) had at least one ADR mutation. Eighty-one percent (33/41) of viraemic patients harbored NRTI resistance mutations, and 48.8% (20/41) were positive for NNRTI resistance mutations, with 43.9% dual resistance mutations. Among NRTI resistance mutations, M184V (73.2%), K219Q (63.4%) and T215 (56.1%) complex were the most mutated positions, while the most common NNRTI resistance mutations were K103N (24.4%), K101E, P225H and V108I 7.5% each. Active tuberculosis (aOR=13, 95% CI= 3.46– 29.69), immunological failure (aOR=3.61, 95% CI=1.26– 10.39), opportunistic infections (aOR=8.39, 95% CI= 1.75– 40.19), and poor adherence were significantly associated with virological failure, while rural residence (aOR 2.37; 95% CI: 1.62– 9.10, P= 0.05), immunological failures (aOR 2.37; 95% CI: 1.62– 9.10, P= 0.05) and high viral load (aOR 16; 95% CI: 5.35 51.59, P < 0.001) were predictors of ADR mutation among the ART experienced and viraemic study subjects. Conclusion: The study revealed considerable prevalence of VF and ADR mutation with the associated risk indicators. Regular virological monitoring and drug resistance genotyping methods should be implemented for better ART treatment outcomes of the nation.

Objectives: We utilize a large retrospective study cohort derived from electronic medical records to estimate the prevalence of long-term non-progression (LTNP) and determine the factors associated with progression among children infected with HIV in Botswana and Uganda. Methods: Electronic medical records from large tertiary HIV clinical centers in Botswana and Uganda were queried to identify LTNP children 0-18 years enrolled between June 2003 and May 2014 and extract demographic and nutritional parameters. Multivariate subdistribution hazard analyses were used to examine demographic factors and nutritional status in progression in the pre-antiretroviral therapy era. Results: Between the two countries, 14,246 antiretroviral therapy-naive children infected with HIV were enrolled into clinical care. The overall proportion of LTNP was 6.3% (9.5% in Botswana vs 5.9% in Uganda). The median progression-free survival for the cohort was 6.3 years, although this was lower in Botswana than in Uganda (6.6 vs 8.8 years; P < 0.001). At baseline, the adjusted subdistribution hazard ratio (aHR(sd)) of progression was increased among underweight children (aHR(sd) 1.42; 95% confidence interval [CI]: 1.321.53), enrolled after 2010 (aHR(sd) 1.32; 95% CI 1.22-1.42), and those from Botswana (aHR(sd)2; 95% CI 1.912.10). Conclusions: In our study, the prevalence of pediatric LTNP was lower than that observed among adult populations, but progression-free survival was higher than expected. Underweight, year of enrollment into care, and country of origin are independent predictors of progression among children. (c) 2023 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.