Rapid epidemic expansion of the SARS-CoV-2 Omicron variant in southern Africa.

The SARS-CoV-2 epidemic in southern Africa has been characterized by three distinct waves. The first was associated with a mix of SARS-CoV-2 lineages, while the second and third waves were driven by the Beta (B.1.351) and Delta (B.1.617.2) variants, respectively1-3. In November 2021, genomic surveillance teams in South Africa and Botswana detected a new SARS-CoV-2 variant associated with a rapid resurgence of infections in Gauteng province, South Africa. Within three days of the first genome being uploaded, it was designated a variant of concern (Omicron, B.1.1.529) by the World Health Organization and, within three weeks, had been identified in 87 countries. The Omicron variant is exceptional for carrying over 30 mutations in the spike glycoprotein, which are predicted to influence antibody neutralization and spike function4. Here we describe the genomic profile and early transmission dynamics of Omicron, highlighting the rapid spread in regions with high levels of population immunity.

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. Data were analyzed against a primary outcome of all-cause mortality with unadjusted Kaplan-Meier curves and Cox proportional hazard models. RESULTS: The study population included 774 CAHIV with variable intervals to ART initiation after starting TB treatment: <2 weeks (n = 266), 2 weeks to 2 months (n = 398), >2 months (n = 66), and no ART initiated (n = 44). Adjusted Cox proportional hazards models demonstrated increased mortality 1 year from TB treatment initiation in children never starting ART (adjusted HR [aHR]: 2.67; 95% CI: 1.03, 6.94) versus children initiating ART between 2 weeks and 2 months from TB treatment initiation. Mortality risk did not differ for the <2-weeks group (aHR: 1.02; 95% CI: .55, 1.89) versus the group initiating ART between 2 weeks and 2 months. CONCLUSIONS: This retrospective study demonstrated no increase in mortality among CAHIV initiating ART <2 weeks from TB treatment initiation. Given the broad health benefits of ART, this evidence supports the recent WHO recommendation for CAHIV to initiate ART within 2 weeks of initiating TB treatment.

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. Coded data was analyzed through an iterative process of analytic induction to document and interpret themes. RESULTS: Overall, respondents were of the view that feedback of actionable individual genomic results was an important outcome that could benefit participants. However, a number of themes surfaced that pointed to opportunities and challenges that exist in Botswana that could help in planning for feeding back of individual genomic results that were mapped. Some of the opportunities cited by the respondents included the existence of good governance; democracy and humanitarianism; universal healthcare system; national commitment to science; research and innovation to transform Botswana into a knowledge-based economy; and applicable standard of care which could promote actionability. On the other hand, contextual issues like the requirement for validation of genomic research results in accredited laboratories, high cost of validation of genomic results, and linkage to care, as well as lack of experts like genomic scientists and counselors were considered as challenges for return of individual results. CONCLUSION: We propose that decisions whether and which genomic results to return take into consideration contextual opportunities and challenges for actionability for return of results in a research setting. This is likely to avoid or minimize ethical issues of justice, equity and harm regarding actionability decisions.

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. Two independent coders carried out an inductive thematic analysis of the transcribed interviews with discrepancies discussed to consensus. Safe Haven was seen as largely acceptable among the youth. Youth felt Safe Haven was a place where they had freedom of expression and could receive practical advice from well-trained and approachable counsellors. Trained youth lay peer counsellors show promise to meet the mental health needs of mild and moderately symptomatic youth, where mental health professionals are in short supply.

Symptoms of depression, anxiety, and thoughts of suicide/self-injury in adolescents and young adults living with HIV in Botswana.

Globally, mental health problems have been reported to be more common in youth living with HIV (YLWH) than in the general population, but routine mental health screening is rarely done in high-volume HIV clinics. In 2019, YLWH in a large HIV clinic in Botswana were screened using the Generalized Anxiety Scale-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) in a pilot standard-of-care screening programme. Two-way ANOVA was used to describe the effects of age group (12-<16, 16-<20 and 20-25 years old) and sex on GAD-7 and PHQ-9 scores. Chi-square statistics were used to compare characteristics of YLWH with and without potential suicidality/self-harm symptoms based on question 9 in the PHQ-9. Among 1 469 YLWH, 33.1%, 44.3% and 15.0% had anxiety, depression and potential suicidality/self-harm symptoms respectively. YLWH of 20-25 years old and 16-<20 years old had higher GAD-7 scores compared to 12-<16-year-olds (p = 0.014 and p = <0.001 respectively). Female YLWH of 20-25 years old had higher PHQ-9 scores compared to 12-<16-year-olds (p = 0.002). There were no other sex-age dynamics that were statistically significant. Female YLWH endorsed more thoughts of suicidality/self-harm than males (17% versus 13%, p = 0.03 respectively). Given the proportion of YLWH with mental health symptoms, Botswana should enhance investments in mental health services for YLWH, especially for young female adults who bear a disproportionate burden.

Predictive Validity of a Computerized Battery for Identifying Neurocognitive Impairments Among Children Living with HIV in Botswana.

Children living with HIV (HIV+) experience increased risk of neurocognitive deficits, but standardized cognitive testing is limited in low-resource, high-prevalence settings. The Penn Computerized Neurocognitive Battery (PennCNB) was adapted for use in Botswana. This study evaluated the criterion validity of a locally adapted version of the PennCNB among a cohort of HIV+ individuals aged 10-17 years in Botswana. Participants completed the PennCNB and a comprehensive professional consensus assessment consisting of pencil-and-paper psychological assessments, clinical interview, and review of academic performance. Seventy-two participants were classified as cases (i.e., with cognitive impairment; N = 48) or controls (i.e., without cognitive impairment; N = 24). Sensitivity, specificity, positive predictive value, negative predictive value, and the area under receiver operating characteristic curves were calculated. Discrimination was acceptable, and prediction improved as the threshold for PennCNB impairment was less conservative. This research contributes to the validation of the PennCNB for use among children affected by HIV in Botswana.

Medical stakeholder perspectives on implementing a computerized battery to identify neurocognitive impairments among youth in Botswana.

HIV infection and in utero exposure, common in Sub-Saharan Africa, are associated with pediatric neurocognitive impairment. Cognitive screening can identify impairments, but it is rarely used in this setting. The Penn Computerized Neurocognitive Battery (PennCNB), an evidence-based cognitive screening tool, was adapted for use in Botswana. To facilitate future implementation, 20 semi-structured interviews were conducted to elicit key stakeholders' perspectives on factors likely to be related to successful uptake of the PennCNB in clinical settings. An integrated analytic approach combining constructs from the Consolidated Framework for Implementation Research and modified grounded theory was used. Results underscore the need for cognitive screening in Botswana and the acceptability of the PennCNB. Implementation barriers include limited time and resources, whereas facilitators include standard procedures for introducing new tools into medical settings and for training implementers. Recommended implementation strategies include integrating screening into the existing workflow, implementing the tool in the medical and educational sectors, and targeting selection of children for assessment. This research addresses the research-to-practice gap by engaging in pre-implementation inquiry and designing for implementation. Results will inform the development of strategies to maximize the likelihood of successful implementation of the PennCNB to identify neurocognitive impairment in children in this high-need setting.

Building a Community Based Mental Health Program for Adolescents in Botswana: Stakeholder Feedback.

BACKGROUND: When planning interventions for adolescents, adult interventions should not be used 'as is' in youth settings. Stakeholder engagement can help understand the overall adolescent mental health ecosystem and adapt existing evidence-based interventions for the youth. OBJECTIVE: To understand the overall mental health needs of adolescents in Botswana and the necessary adaptations required for an adolescent lay counselor based intervention in the country. METHODS: We used the theory of change model and the nominal group technique in five stakeholder meetings. Meetings were held to discuss the mental health needs of youth in Botswana and identify priorities for a lay counsellor based intervention modelled after the Friendship Bench intervention, an existing mental health intervention for adults. RESULTS: The root causes of mental health problems among Botswana's youth identified by stakeholders included limited mental health knowledge among the youth and the community, family problems, poor communication, low self-esteem, the rapid growth of technology, and biological/genetic predisposition. Structurally barriers included: mental illness-related stigma, lack of psychosocial support, incomplete follow up for health services, cultural beliefs about mental illness, and fragmented mental health services. The stakeholders envisage a program that could empower adolescents and youth counselors to address mental health concerns for a healthier community. The group identified and prioritized several key elements of an effective lay counselor intervention. CONCLUSIONS: A diverse group of community stakeholders can illustrate critical mental health needs and elements that countries could use to adapt and contextualize a lay counsellor based mental health intervention for new populations such as the youth.

Whole-Exome Sequencing Reveals Uncaptured Variation and Distinct Ancestry in the Southern African Population of Botswana.

Large-scale, population-based genomic studies have provided a context for modern medical genetics. Among such studies, however, African populations have remained relatively underrepresented. The breadth of genetic diversity across the African continent argues for an exploration of local genomic context to facilitate burgeoning disease mapping studies in Africa. We sought to characterize genetic variation and to assess population substructure within a cohort of HIV-positive children from Botswana-a Southern African country that is regionally underrepresented in genomic databases. Using whole-exome sequencing data from 164 Batswana and comparisons with 150 similarly sequenced HIV-positive Ugandan children, we found that 13%-25% of variation observed among Batswana was not captured by public databases. Uncaptured variants were significantly enriched (p = 2.2 × 10-16) for coding variants with minor allele frequencies between 1% and 5% and included predicted-damaging non-synonymous variants. Among variants found in public databases, corresponding allele frequencies varied widely, with Botswana having significantly higher allele frequencies among rare (<1%) pathogenic and damaging variants. Batswana clustered with other Southern African populations, but distinctly from 1000 Genomes African populations, and had limited evidence for admixture with extra-continental ancestries. We also observed a surprising lack of genetic substructure in Botswana, despite multiple tribal ethnicities and language groups, alongside a higher degree of relatedness than purported founder populations from the 1000 Genomes project. Our observations reveal a complex, but distinct, ancestral history and genomic architecture among Batswana and suggest that disease mapping within similar Southern African populations will require a deeper repository of genetic variation and allelic dependencies than presently exists.

G6PD distribution in sub-Saharan Africa and potential risks of using chloroquine/hydroxychloroquine based treatments for COVID-19.

Chloroquine/hydroxychloroquine have been proposed as potential treatments for COVID-19. These drugs have warning labels for use in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Analysis of whole genome sequence data of 458 individuals from sub-Saharan Africa showed significant G6PD variation across the continent. We identified nine variants, of which four are potentially deleterious to G6PD function, and one (rs1050828) that is known to cause G6PD deficiency. We supplemented data for the rs1050828 variant with genotype array data from over 11,000 Africans. Although this variant is common in Africans overall, large allele frequency differences exist between sub-populations. African sub-populations in the same country can show significant differences in allele frequency (e.g. 16.0% in Tsonga vs 0.8% in Xhosa, both in South Africa, p = 2.4 × 10-3). The high prevalence of variants in the G6PD gene found in this analysis suggests that it may be a significant interaction factor in clinical trials of chloroquine and hydroxychloroquine for treatment of COVID-19 in Africans.

Psychological Reactance is a Novel Risk Factor for Adolescent Antiretroviral Treatment Failure.

Psychological reactance is an aversive response to perceived threats against personal agency. For adolescents receiving HIV treatment in Botswana, we utilized a two-question, medication-specific reactance tool to assess whether: (1) verbal reminders to take medicines made adolescents want to avoid taking them, and, (2) whether adolescents felt anger when reminded to take medicines. Reactant adolescents had 2.05-fold (95% CI 1.23, 3.41) greater odds of treatment failure than non-reactant adolescents (p = 0.03). Adjusted risk of treatment failure was 14% (95% CI 3%, 28%) greater for each point elevation in reactance score (p = 0.016). Autonomy over medication-taking did not modify the association between reactance and treatment failure. Psychological reactance may be a useful interventional target for improving adolescent adherence.

Do solidarity and reciprocity obligations compel African researchers to feedback individual genetic results in genomics research?

BACKGROUND: A key ethical question in genomics research relates to whether individual genetic research results should be disclosed to research participants and if so, which results are to be disclosed, by whom and when. Whilst this issue has received only scarce attention in African bioethics discourse, the extension of genomics research to the African continent has brought it into sharp focus. METHODS: In this qualitative study, we examined the views of adolescents, parents and caregivers participating in a paediatric and adolescent HIV-TB genomic study in Botswana on how solidarity and reciprocity obligations could guide decisions about feedback of individual genetic research results. Data were collected using deliberative focus group discussions and in-depth interviews. RESULTS: Findings from 93 participants (44 adolescents and 49 parents and caregivers) demonstrated the importance of considering solidarity and reciprocity obligations in decisions about the return of individual genetic research results to participants. Participants viewed research participation as a mutual relationship and expressed that return of research results would be one way in which research participation could be reciprocated. They noted that when reciprocity obligations are respected, participants feel valued and not respecting reciprocity expectations could undermine participant trust and participation in future studies. CONCLUSIONS: We conclude that expectations of solidarity and reciprocity could translate into an obligation to feedback selected individual genetic research results in African genomics research.

Revealing a safer sex option to reduce HIV risk: a cluster-randomized trial in Botswana.

BACKGROUND: 1.8 million new HIV infections occur every year, disproportionately affecting adolescent girls and young women. Abstinence-only risk avoidance approaches have had limited impact on reducing new infections. This cluster-randomized trial examines a risk reduction approach to curbing risky sex for school-going girls in Botswana. METHODS: The unit of randomization was the school (n = 229). Intervention participants received a 1-h intervention revealing a safer sex option: dating same-age partners which have 5-9x lower HIV prevalence than older partners. Primary outcomes were pregnancy as a proxy for unprotected sex and HIV. Secondary outcomes included self-reported sexual behavior. Generalized linear multilevel models with school-level robust variance for adjusted relative risk ratios were used in an intention-to-treat analysis. RESULTS: At a 12-month follow up, the intervention reduced pregnancy with an adjusted Relative Risk Ratio (aRRR) of .657 [95% CI .433-.997] significant at the 5% level. Effects were largest at junior school (aRRR = .575 [95% CI .394-.841]) and in rural areas (aRRR = .518 [95% CI .323-.831]), significant at the 1% level. There were no significant effects for primary school students, suggesting age of sexual debut and related mechanisms are critical factors in the intervention's effectiveness. Moreover, baseline beliefs of which partner is riskiest mediate the magnitude of effects. CONCLUSIONS: Information on safe sex options can change sexual behavior. The success of the intervention working across contexts will depend on various factors, such as age of sexual debut and baseline beliefs. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR201901837047199 . Registered 31 December 2018. Retrospectively registered. This study adheres to CONSORT guidelines.

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. The 5-year overall-survival was 48.9% [95% confidence interval (CI) 33.0-72.2 and 51.1% (95% CI 34.0-76.8)] in the efavirenz and nonefavirenz groups, respectively suggesting efavirenz is unlikely driving poorer survival in women living with HIV and estrogen-receptor positive breast cancer.

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. We called star alleles from 961 high-depth full genomes using StellarPGx, Aldy, and PyPGx. In addition, we performed CYP2B6 and CYP2A6 star allele frequency comparisons between SSA and other global biogeographical groups represented in the new 1000 Genomes Project high-coverage dataset (n = 2,000). This study presents frequency information for star alleles in CYP2B6 (e.g., *6 and *18; frequency of 21-47% and 2-19%, respectively) and CYP2A6 (e.g., *4, *9, and *17; frequency of 0-6%, 3-10%, and 6-20%, respectively), and predicted phenotypes (for CYP2B6), across various African populations. In addition, 50 potentially novel African-ancestry star alleles were computationally predicted by StellarPGx in CYP2B6 and CYP2A6 combined. For each of these genes, over 4% of the study participants had predicted novel star alleles. Three novel star alleles in CYP2A6 (*54, *55, and *56) and CYP2B6 apiece, and several suballeles were further validated via targeted Single-Molecule Real-Time resequencing. Our findings are important for informing the design of comprehensive pharmacogenetic testing platforms, and are highly relevant for personalized medicine strategies, especially relating to antiretroviral medication and smoking cessation treatment in Africa and the African diaspora. More broadly, this study highlights the importance of sampling diverse African ethnolinguistic groups for accurate characterization of the pharmacogene variation landscape across the continent.

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. RESULTS: Between the two countries, 14,246 antiretroviral therapy-naïve 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 (aHRsd) of progression was increased among underweight children (aHRsd 1.42; 95% confidence interval [CI]: 1.32-1.53), enrolled after 2010 (aHRsd 1.32; 95% CI 1.22-1.42), and those from Botswana (aHRsd 2; 95% CI 1.91-2.10). 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.

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. FL.2 is a sub-lineage of XBB.1.9.1. The repertoire of mutations and minority variants in the Spike protein differed between the two time points. Notably, we also observed deletions within the ORF1a and Membrane proteins; both regions are associated with high T-cell epitope density. The internal milieu of immune-suppressed individuals may accelerate SARS-CoV-2 evolution; hence, close monitoring is warranted.

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. Objectives: To compare the prevalence of cervical abnormalities in young women with perinatally acquired HIV with women aged 30-49 years, regardless of HIV status. Method: We conducted a cross-sectional study of 30-49-year-old women who had visual inspection with acetic acid screening through the Botswana public sector programme, and youth (aged 15-24 years) with perinatally acquired HIV, at a single referral site between 2016 and 2018. We describe the prevalence of cervical abnormalities in each group as well as the crude prevalence ratio. Results: The prevalence of cervical abnormalities in women 30-49 years of age was 10.9% (95% confidence interval [CI]: 10.4, 11.4), and 10.1% (95% CI: 4.7, 18.3) for youth. The crude prevalence ratio was 1.07 (95% CI: 0.58, 2.01). Conclusion: Inclusion of youth living with HIV in cervical cancer screening services should be considered in settings with a high prevalence of HIV and cervical cancer.

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. Therefore, this study explores the challenges and coping strategies of YALPH in order to inform health policies and programming in Botswana. METHODS: In-depth interviews were conducted with 45 YALPH (ages 18-27 years) who were enrolled on antiretroviral therapy at the Botswana-Baylor Children's Clinical Centre of Excellence (Botswana-Baylor Clinic). The Botswana-Baylor Clinic is the largest centre for pediatric, adolescent, and young adult HIV treatment and care in Botswana. The maximum variation sampling method was used to select information-rich participants. The questions focused on the challenges YALPH faced and how they coped with HIV. The data was analyzed using content analysis. RESULTS: The results showed that the majority of YALPH had suppressed HIV viral load and perceived themselves to be in good physical health and functioning. They did, however, face numerous challenges, including occasional or longstanding poor antiretroviral therapy adherence, disabilities and impairments, poor school performance and attainment, unemployment, financial stressors, fear of stigma, disclosure worries and concerns, and limited social support. The most vulnerable YALPH included those with disabilities and impairments, those transitioning out of residential care, young parents, the unemployed, and those with maladaptive coping strategies. The YALPH mainly used adaptive coping strategies. The most commonly used maladaptive coping strategies were self-distraction and venting. CONCLUSION: Interventions to prevent, screen for, assess, and manage the challenges identified by this study are critical to improving the health and well-being of YALPH. In addition, diverse interventions that can contribute to the development of adaptive coping mechanisms and reduce the likelihood of maladaptive coping in YALPH should be sought.

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. SETTING: Botswana-Baylor Children's Clinical Centre of Excellence, Gaborone. METHODS: This study examined dyslipidemia in 18- to 24-year olds with perinatally-acquired HIV with and without linear growth retardation ("stunting"). Anthropometry and lipid profiles were measured following a minimum 8-hour fast. Stunting was defined by a height-for-age z-score of <2 SDs below the mean. Dyslipidemia was defined by non-high-density lipoprotein cholesterol (HDL-C) of ≥130 mg/dL, low-density lipoprotein cholesterol (LDL-C) of ≥100 mg/dL, or HDL of <40 mg/dL for male subjects and <50 mg/dL for female subjects. We used logistic regression to determine whether dyslipidemia was associated with stunting while adjusting for demographic and HIV treatment variables. RESULTS: Of 107 young adults (46 males; 61 females) enrolled, 36 (33.6%) were stunted. Prevalence of dyslipidemia was 11.2%, 24.3%, and 65.4% for high non-HDL-C, high LDL-C, and low HDL-C, respectively. In univariable analysis, being stunted was associated with elevated LDL-C (odds ratio [OR], 2.52; 95% confidence interval [CI] =1.02 to 6.25) but not with elevated non-HDL-C (OR = 2.17; 95% CI: = 0.65 to 7.28) or with low HDL-C (OR = 0.75; 95% CI: = 0.33 to 1.73). The association between stunting and elevated LDL-C (OR = 4.40; 95% CI: = 1.49 to 12.98) remained significant after controlling for measured confounders. CONCLUSION: Dyslipidemia was common among perinatally HIV-infected youth and those with evidence of early nutritional deprivation who were more likely to have elevated LDL-C.