High KIR diversity in Uganda and Botswana children living with HIV.

Killer-cell immunoglobulin-like receptors (s) are essential components of the innate immune system found on the surfaces of natural killer (NK) cells. The s encoding genes are located on chromosome 19q13.4 and are genetically diverse across populations.

Identification of a Clade-Specific HLA-C*03:02 CTL Epitope GY9 Derived from the HIV-1 p17 Matrix Protein.

Efforts towards an effective HIV-1 vaccine have remained mainly unsuccessful. There is increasing evidence for a potential role of HLA-C-restricted CD8 T cell responses in HIV-1 control, including our recent report of HLA-C*03:02 among African children. However, there are no documented optimal HIV-1 CD8 T cell epitopes restricted by HLA-C*03:02; additionally, the structural influence of HLA-C*03:02 on epitope binding is undetermined.

Mapping Epigenetic Gene Variant Dynamics: Comparative Analysis of Frequency, Functional Impact and Trait Associations in African and European Populations.

Epigenetic modifications influence gene expression levels, impact organismal traits, and play a role in the development of diseases. Therefore, variants in genes involved in epigenetic processes are likely to be important in disease susceptibility, and the frequency of variants may vary between populations with African and European ancestries. Here, we analyse an integrated dataset to define the frequencies, associated traits, and functional impact of epigenetic gene variants among individuals of African and European ancestry represented in the UK Biobank.

An assessment of the genomic structural variation landscape in Sub-Saharan African populations.

Structural variants are responsible for a large part of genomic variation between individuals and play a role in both common and rare diseases. Databases cataloguing structural variants notably do not represent the full spectrum of global diversity, particularly missing information from most African populations. To address this representation gap, we analysed 1,091 high-coverage African genomes, 545 of which are public data sets, and 546 which have been analysed for structural variants for the first time.

Low Prevalence of Nirmatrelvir-Ritonavir Resistance-Associated Mutations in SARS-CoV-2 Lineages From Botswana.

Background: We evaluated naturally occurring nirmatrelvir-ritonavir (NTV/r) resistance-associated mutations (RAMs) among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains from Botswana, a country with no NTV/r use to date, in order to recommend the usage of the agent for high-risk patients with coronavirus disease 2019 (COVID-19).

Methods: We conducted a retrospective analysis using 5254 complete SARS-CoV-2 sequences from Botswana (September 2020-September 2023). We evaluated the mutational landscape of SARS-CoV-2 3-Chymotrypsin-like protease (3CLpro) relative to the highlighted list of RAMs granted Food and Drug Administration Emergency Use Authorization in 2023.

Impact of efavirenz on hormone-positive breast cancer survival in women living with HIV.

Women living with HIV and breast cancer have poorer survival than HIV-negative women. Efavirenz-estrogen interactions are documented; however, the survival impact is unknown. Survival between women with estrogen-receptor positive breast cancer taking efavirenz (n = 38) and nonefavirenz regimens (n = 51) were compared.

Characterization of CYP2B6 and CYP2A6 Pharmacogenetic Variation in Sub-Saharan African Populations.

Genetic variation in CYP2B6 and CYP2A6 is known to impact interindividual response to antiretrovirals, nicotine, and bupropion, among other drugs. However, the full catalogue of clinically relevant pharmacogenetic variants in these genes is yet to be established, especially across African populations. This study therefore aimed to characterize the star allele (haplotype) distribution in CYP2B6 and CYP2A6 across diverse and understudied sub-Saharan African (SSA) populations.

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.

Rapid dynamic changes of FL.2 variant: A case report of COVID-19 breakthrough infection.

We investigated intra-host genetic evolution using two SARS-CoV-2 isolates from a fully vaccinated (primary schedule x2 doses of AstraZeneca plus a booster of Pfizer), >70-year-old woman with a history of lymphoma and hypertension who presented a SARS-CoV-2 infection for 3 weeks prior to death due to COVID-19. Two full genome sequences were determined from samples taken 13 days apart with both belonging to Pango lineage FL.2: the first detection of this Omicron sub-variant in Botswana.

Youth perspectives of working with near peer youth lay counsellors: The Safe Haven Pilot.

Youth living with HIV (YLWH) have higher rates of common mental disorders (CMDs) when compared with HIV-negative youth. We adapted the Friendship Bench to create a problem solving-based counselling intervention in Botswana delivered by near peer youth lay counsellors for YLWH called Safe Haven. In August 2020, and from June to August 2021, we conducted 22 semistructured interviews with youth aged 13-25 years with mild-to-moderate symptoms of CMDs.

Feeding back of individual genetic results in Botswana: mapping opportunities and challenges.

Purpose: We explored the views of Botswana stakeholders involved in developing, implementing and applying ethical standards for return of individual study results from genomic research. This allowed for mapping opportunities and challenges regarding actionability requirements that determine whether individual genomic research results should be fed back.

Methods: Using in-depth interviews, this study explored the views of sixteen (16) stakeholders about the extent, nature and timing of feedback of individual genomic research findings, including incidental findings that arise in the context of African genomics research.

Near-complete genome of SARS-CoV-2 Delta variant of concern identified in a symptomatic dog (Canis lupus familiaris) in Botswana.

We sought to investigate whether SARS-CoV-2 was present, and to perform full-length genomic sequencing, in a 5-year-old male crossbreed dog from Gaborone, Botswana that presented overt clinical signs (flu-like symptoms, dry hacking cough and mild dyspnoea). It was only sampled a posteriori, because three adult owners were diagnosed with SARS-CoV-2 infection. Next-generation sequencing based on Oxford Nanopore Technology (ONT) was performed on amplicons that were generated using a reverse transcriptase real-time polymerase chain reaction (RT-qPCR) of confirmed positive SARS-CoV-2 nasopharyngeal and buccal swabs, as well as a bronchoalveolar lavage with mean real cycle threshold (qCt) value of 36 based on the Nucleocapsid (N) gene.

Challenges and coping strategies among young adults living with perinatally acquired HIV infection in Botswana. A qualitative study.

Background: Due to antiretroviral therapy, many people with perinatally acquired HIV are surviving into young adulthood which is a critical period of human development. Research conducted in various settings globally has shown that young adults living with perinatally acquired HIV (YALPH) face multiple challenges related to HIV infection while also confronting the same challenges of young adulthood faced by other HIV-negative youth. However, there is a paucity of information on YALPH in Botswana and what needs to be done to improve their health and wellbeing.

Stunted Growth Is Associated With Dyslipidemia in Young Adults With Perinatal HIV Infection.

Background: HIV increases the risk of atherosclerosis and cardiovascular diseases (CVD). This risk maybe even higher in adult survivors of perinatal HIV infection because of prolonged exposure to HIV and its treatments. Nutritional deprivation in early life may further increase CVD risk.

The prevalence of cervical abnormalities: Comparison of youth with perinatally acquired HIV and older women in Botswana.

Background: Cervical cancer burden and prevalence of precursor lesions is unknown among young women living with HIV in high prevalence settings. Current cervical cancer screening guidelines in resource-limited settings with high HIV prevalence typically exclude adolescents and young women. After observing two cases of advanced cervical cancer among young women with perinatally acquired HIV, a pilot screening programme was established in Botswana.

Participant views on practical considerations for feedback of individual genetic research results: a case study from Botswana.

Key to discussions around feedback of individual results from genomics research are practical questions on how such results should be fed back, by who and when. However, there has been virtually no work investigating these practical considerations for feedback of individual genetic results in the context of low-and middle-income countries (LMICs), especially in Africa. Consequently, we conducted deliberative focus group discussions with 6 groups of adolescents ( = 44) who previously participated in a genomics study in Botswana as well as 6 groups of parents and caregivers ( = 49) of children who participated in the same study.

Association of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection With Maternal Mortality and Neonatal Birth Outcomes in Botswana by Human Immunodeficiency Virus Status.

Objective: To evaluate the combined association of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human immunodeficiency virus (HIV) infection on adverse birth outcomes in an HIV-endemic region.

Methods: The Tsepamo Study abstracts data from antenatal and obstetric records in government maternity wards across Botswana. We assessed maternal mortality and adverse birth outcomes for all singleton pregnancies from September 2020 to mid-November 2021 at 13 Tsepamo sites among individuals with documented SARS-CoV-2 screening tests and known HIV status.

Risk factors and prognostic significance of platelet count abnormalities in children with HIV infection on antiretroviral therapy.

Objectives: To establish the incidence, risk factors and correlation with survival of thrombocytopenia and thrombocytosis (T/T) among children with HIV infection (CWH).

Design: A retrospective nested case control study of patients 0-18 years in five Baylor International Pediatric AIDS Initiative (BIPAI) centers in sub-Sahara Africa, 2004-2014.

Methods: Clinical and laboratory variables including complete blood counts (CBC) were extracted from the BIPAI electronic medical record system.

Characterization of CYP2D6 Pharmacogenetic Variation in Sub-Saharan African Populations.

Cytochrome P450 2D6 (CYP2D6) is a key enzyme in drug response owing to its involvement in the metabolism of ~ 25% of clinically prescribed medications. The encoding CYP2D6 gene is highly polymorphic, and many pharmacogenetics studies have been performed worldwide to investigate the distribution of CYP2D6 star alleles (haplotypes); however, African populations have been relatively understudied to date. In this study, the distributions of CYP2D6 star alleles and predicted drug metabolizer phenotypes-derived from activity scores-were examined across multiple sub-Saharan African populations based on bioinformatics analysis of 961 high-depth whole genome sequences.

Optimal Timing of Antiretroviral Therapy Initiation in Children and Adolescents With Human Immunodeficiency Virus-Associated Pulmonary Tuberculosis.

Background: There is insufficient evidence in children and adolescents with human immunodeficiency virus (CAHIV) to guide the timing of antiretroviral treatment (ART) initiation after starting treatment for pulmonary tuberculosis (pTB). To address this knowledge gap, we evaluated the risk of mortality associated with timing of ART initiation in ART-naive CAHIV treated for pTB.

Methods: Data were extracted from electronic medical records of ART-naive patients, aged 0-19 years, who were treated for HIV-associated pTB at Baylor Centers of Excellence in Botswana, Eswatini, Malawi, Lesotho, Tanzania, or Uganda between 2013 and 2020.

Risk factors and prognostic significance of anemia in children with HIV infection on antiretroviral therapy.

Objectives: To establish the incidence, risk factors and prognostic effect of anemia in children living with HIV (CLWH).

Design: Retrospective nested case-control study of patients 0-18 years in five centers in sub-Saharan Africa, 2004-2014.

Methods: Incident cases of anemia were identified from electronic records and matched with CLWH without anemia.

The barriers and facilitators of HIV-exposed infant testing as perceived by HIV-positive mothers in Botswana: A qualitative study.

Background: Despite high rates of HIV testing and enrolment of HIV-positive pregnant women on antiretroviral therapy in Botswana, coverage for HIV-exposed infant (HEI) testing remains suboptimal. Many factors can contribute to suboptimal HEI testing rates, but they have seldom been thoroughly investigated in Botswana. Therefore, the aim of this study was to explore the experiences and perspectives of HIV-positive mothers on the barriers and facilitators of HEI testing to inform interventions to promote HEI testing in Botswana.

Test-Retest Reliability of a Computerized Neurocognitive Battery in School-Age Children with HIV in Botswana.

Human immunodeficiency virus (HIV) infection is prevalent among children and adolescents in Botswana, but standardized neurocognitive testing is limited. The Penn Computerized Neurocognitive Battery (PennCNB) attempts to streamline evaluation of neurocognitive functioning and has been culturally adapted for use among youth in this high-burden, low-resource setting. However, its reliability across measurements (i.