Long-term non-progression and risk factors for disease progression among children living with HIV in Botswana and Uganda: A retrospective cohort study.

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.

Bibliometric analysis of cancer research outputs in Botswana between 2009 and 2021.

Introduction: Cancer research is critical for cancer control policies; however, the state of cancer research activities in Botswana is largely unknown. The goal of this review was to describe trends and patterns of cancer research outputs in Botswana.

Methods: PubMed, Web of Science, EBSCOhost, African Journals Online, and African Index Medicus databases were systematically searched for peer-reviewed, primary cancer-related research articles published on the Botswana population or by Botswana institutions between January 2009 and June 2021.

High concordance in plasma and CSF HIV-1 drug resistance mutations despite high cases of CSF viral escape in individuals with HIV-associated cryptococcal meningitis in Botswana.

Objectives: We compared the patterns of HIV-1 drug resistance mutations between the CSF and plasma of individuals with HIV-associated cryptococcal meningitis.

Methods: This is a cross-sectional study of archived CSF and plasma samples collected from ART-exposed participants recruited in the Phase 3 AmBisome Therapy Induction Optimisation randomized controlled trial (ISRCTN72509687) conducted in Botswana between 2018 and 2021. HIV-1 RT and protease genes were genotyped using next-generation sequencing and HIV-1 drug resistance mutations were compared between the CSF and plasma compartments stratified by thresholds of ≥20% and <20%.

Pharmacogenetics of Breast Cancer Treatments: A Sub-Saharan Africa Perspective.

Breast cancer is the most frequent cause of cancer death in low- and middle-income countries, in particular among sub-Saharan African women, where response to available anticancer treatment therapy is often limited by the recurrent breast tumours and metastasis, ultimately resulting in decreased overall survival rate. This can also be attributed to African genomes that contain more variation than those from other parts of the world. The purpose of this review is to summarize published evidence on pharmacogenetic and pharmacokinetic aspects related to specific available treatments and the known genetic variabilities associated with metabolism and/or transport of breast cancer drugs, and treatment outcomes when possible.

Reversal of CSF HIV-1 Escape during Treatment of HIV-Associated Cryptococcal Meningitis in Botswana.

Cerebrospinal fluid (CSF) viral escape has been poorly described among people with HIV-associated cryptococcal meningitis. We determined the prevalence of CSF viral escape and HIV-1 viral load (VL) trajectories in individuals treated for HIV-associated cryptococcal meningitis. A retrospective longitudinal study was performed using paired CSF and plasma collected prior to and during the antifungal treatment of 83 participants recruited at the Botswana site of the phase-3 AMBITION-cm trial (2018−2021).

The role of CYP2B6 516G>T polymorphism on efavirenz/nevirapine toxicity. Implications on treatment outcomes: Lessons from Botswana.

The two non-nucleoside reverse transcriptase inhibitors (NNRTIs), efavirenz (EFV) and nevirapine (NVP), are currently the core antiretroviral drugs for treatment of HIV in sub-Saharan Africa including Botswana. The drugs are metabolized by Cytochrome P450 2B6 (CYP2B6) liver enzyme. The CYP2B6 gene that encodes for metabolism of these drugs is known to be highly polymorphic.

Genetic diversity in L1 ORF of human papillomavirus in women with cervical cancer with and without human immunodeficiency virus in Botswana and Kenya.

Background: The variation of human papillomavirus (HPV) genotypes shapes the risks of cervical cancer and these variations are not well defined in Africa. Nucleotide changes within the L1 gene, nucleotide variability, and phylogeny were explored in relation to HIV in samples from Botswana and Kenya.

Methods: A total of 98 HPV-positive cervical samples were sequenced to identify different HPV variants.

Similar Ferroportin Q248H polymorphism prevalence in patients with Plasmodium falciparum malaria and control subjects in the low-endemic setting of Botswana.

Introduction: Recent evidence suggests that ferroportin (FPN) Q248H may confer a survival advantage against malaria by reducing erythrocytic intracellular iron in Africans. We investigated if FPN Q248H mutation, that is prevalent in Batswana, is a factor in limiting the susceptibility to Plasmodium falciparum malaria.

Methods: 264 archived dried blood spot samples (183 P.

Exome Sequencing Reveals a Putative Role for HLA-C*03:02 in Control of HIV-1 in African Pediatric Populations.

Human leucocyte antigen (HLA) class I molecules present endogenously processed antigens to T-cells and have been linked to differences in HIV-1 disease progression. HLA allelotypes show considerable geographical and inter-individual variation, as does the rate of progression of HIV-1 disease, with long-term non-progression (LTNP) of disease having most evidence of an underlying genetic contribution. However, most genetic analyses of LTNP have occurred in adults of European ancestry, limiting the potential transferability of observed associations to diverse populations who carry the burden of disease.

Limited HIV-1 Subtype C 3'PPT Variation in Combination Antiretroviral Therapy Naïve and Experienced People Living with HIV in Botswana.

Dolutegravir (DTG) is a potent anti-HIV drug that is used to treat HIV globally. There have been reports of mutations in the HIV-1 3'-polypurine tract (3'PPT) of the gene, contributing to DTG failure; however, there are limited 'real-world' data on this. In addition, there is a knowledge gap on the variability of 3'PPT residues in patients receiving combination antiretroviral therapy (cART) with and without viral load (VL) suppression.

Improving laboratory quality and capacity through leadership and management training: Lessons from Zambia 2016-2018.

Background: Competent leadership and management are imperative for delivering quality laboratory services; however, few laboratory managers receive job-specific training in organisational management and leadership.

Objective: To develop and evaluate participants' competencies in organisational leadership and management as measured through learner and laboratory quality improvement assessments.

Methods: This professional development programme employed a mentored, blended learning approach, utilising in-person didactic and online training, with the practical application of a capstone project in the laboratories.

HIV-1 Subtype C Drug Resistance Mutations in Heavily Treated Patients Failing Integrase Strand Transfer Inhibitor-Based Regimens in Botswana.

There are limited real-world mutational and virological outcomes data of treatment-experienced persons diagnosed with HIV-1 subtype C (HIV-1 C) who are failing Integrase Strand Transfer Inhibitor-based regimens. Requisition forms sent for HIV-1 genotypic resistance testing (GRT) between May 2015 and September 2019 were reviewed and participants experiencing virologic failure while on dolutegravir (DTG) or raltegravir (RAL) cART at sampling recruited. Sanger sequencing of the HIV-1 Pol gene was performed from residual plasma samples and drug resistance mutational (DRM) analysis performed using the Stanford University HIV drug resistance database.

Association of Genetic Variation with Efavirenz and Nevirapine Drug Resistance in HIV-1 Patients from Botswana.

Purpose: CYP2B6 liver enzyme metabolizes the two non-nucleoside reverse transcriptase inhibitors Efavirenz (EFV) and Nevirapine (NVP) used in the antiretroviral therapy (ART) regimens for HIV-infected individuals. Polymorphisms of the gene influence drug levels in plasma and possibly virological outcomes. The aim of this study was to explore the potential impact of genotype and haplotype variation on the risk of developing EFV/NVP drug resistance mutations (DRMs) in HIV-1 patients receiving EFV-/NVP-containing regimens in Botswana.

Unmapped exome reads implicate a role for Anelloviridae in childhood HIV-1 long-term non-progression.

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).

Promoter Hypermethylation Analysis of Host Genes in Cervical Cancer Patients With and Without Human Immunodeficiency Virus in Botswana.

Epidemics of human immunodeficiency virus (HIV) and cervical cancer are interconnected. DNA hypermethylation of host genes' promoter in cervical lesions has also been recognized as a contributor to cervical cancer progression. For this purpose we analyzed promoter methylation of four tumor suppressor genes ( and ) and explored their possible association with cervical cancer in Botswana among women of known HIV status.

Lack of RH2 gene expression may have influenced the HIV pandemic in sub-Saharan Africa.

Objective: To evaluate the association between the Rhesus system RH2-blood group expression and susceptibility to HIV infection, viral load, CD4+ cell count and rate of CD4+ decline. We also aimed to determine if a country's HIV prevalence may be predicted from its RH2 relative frequency.

Design: Our previous studies did not find any HIV-infected RH2 homozygotes.

HIV-1C and Variation in the Cerebrospinal Fluid and Plasma of Patients with HIV-Associated Cryptococcal Meningitis in Botswana.

HIV-1 compartmentalization in reservoir sites remains a barrier to complete HIV eradication. It is unclear whether there is variation in HIV-1 and between cerebrospinal fluid (CSF) and plasma of individuals with HIV-associated cryptococcal meningitis (CM). We compared HIV-1 characteristics and the cytotoxic T-lymphocyte (CTL) escape mutations from CSF and plasma samples.

Differences in human immunodeficiency virus-1C viral load and drug resistance mutation between plasma and cerebrospinal fluid in patients with human immunodeficiency virus-associated cryptococcal meningitis in Botswana.

To determine effects of cryptococcal meningitis (CM) on human immunodeficiency virus (HIV)-1C cerebrospinal fluid (CSF) viral escape, CSF/plasma viral discordance, and drug resistance mutation (DRM) discordance between CSF and plasma compartments, we compared CSF and plasma viral load (VL) and DRMs in individuals with HIV-associated CM in Botswana.This cross-sectional study utilized 45 paired CSF/plasma samples from participants in a CM treatment trial (2014-2016). HIV-1 VL was determined and HIV-1 protease and reverse transcriptase genotyping performed.

Immune Phenotype and Functionality of Specific T-Cells in HIV/TB Co-Infected Patients on Antiretroviral Treatment.

The performance of host blood-based biomarkers for tuberculosis (TB) in HIV-infected patients on antiretroviral therapy (ART) has not been fully assessed. We evaluated the immune phenotype and functionality of antigen-specific T-cell responses in HIV positive (+) participants with TB (n = 12) compared to HIV negative (-) participants with either TB (n = 9) or latent TB infection (LTBI) (n = 9). We show that the cytokine profile of Mtb-specific CD4+ T-cells in participants with TB, regardless of HIV status, was predominantly single IFN-γ or dual IFN-γ/ TNFα.

High incidence of tuberculosis in the first year of antiretroviral therapy in the Botswana National antiretroviral therapy programme between 2011 and 2015.

Objective: Tuberculosis (TB) remains one of the leading causes of mortality and morbidity among people living with HIV. We sought to estimate the incidence of TB in a national database of HIV-infected patients receiving antiretroviral therapy (ART) in Botswana.

Design: A retrospective analysis of HIV-infected adult patients (≥18years) who initiated ART between 2011 and 2015 in the Botswana ART program.

Comparison of an in-house 'home-brew' and commercial ViroSeq integrase genotyping assays on HIV-1 subtype C samples.

Background: Roll-out of Integrase Strand Transfer Inhibitors (INSTIs) such as dolutegravir for HIV combination antiretroviral therapy (cART) in sub-Saharan Africa necessitates the development of affordable HIV drug resistance (HIVDR) assays targeting the Integrase gene. We optimised and evaluated an in-house integrase HIV-1 drug resistance assay (IH-Int) and compared it to a commercially available assay, ViroSeq™ Integrase Genotyping kit (VS-Int) amongst HIV-1 clade C infected individuals.

Methods: We used 54 plasma samples from treatment naïve participants and one plasma sample from a patient failing INSTI based cART.

Hyperuricaemia is associated with dyslipidemia but not HbA1c among type 2 diabetes mellitus patients in Botswana.

Medical records and residual samples from 334 type 2 diabetes mellitus patients attending a clinic in Gaborone, Botswana, during the period September-December 2016 were analysed for the effects of hyperuricaemia on biochemical markers of adverse outcomes. The patients were stratified as having hyperuricaemia (> 400 mol/L) or normal serum uric acid (≤ 400 mol/L). We compared glycated haemoglobin, triglycerides, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, total cholesterol and serum creatinine between the two serum uric acid categories.

Detection of Second Line Drug Resistance among Drug Resistant Mycobacterium Tuberculosis Isolates in Botswana.

The emergence and transmission of multidrug resistant (MDR) and extensively drug resistant (XDR) strains is a threat to global tuberculosis (TB) control. The early detection of drug resistance is critical for patient management. The aim of this study was to determine the proportion of isolates with additional second-line resistance among rifampicin and isoniazid resistant and MDR-TB isolates.

Potential role of Lu/BCAM in HIV-related atherosclerosis.

Atheromatous lesions are formed by macrophages and low-density lipoprotein cholesterol invading the vascular intima. Here we show that increasing cholesterol levels are associated with peripheral monocyte depletion and this imbalance is aggravated by carriage of Lu/BCAM leukocyte adhesion molecules. This is true only in HIV infection and probably explains the risk of atherosclerosis observed in HIV-positive patients.