<p><strong>BACKGROUND: </strong>Poor vitamin D status is a global health problem and common in patients with human immunodeficiency virus (HIV) in high-income countries. There is less evidence on prevalence of vitamin D deficiency and nutrition and growth in HIV-infected and -exposed children in low- and middle-income countries.</p>

<p><strong>OBJECTIVES: </strong>To determine the vitamin D status in Batswana HIV-infected mothers and their children, differences among HIV-infected mothers and between HIV-exposed and -infected infants and children, and associations between vitamin D and disease-related outcomes, nutrition, and growth.</p>

<p><strong>METHODS: </strong>This was a cross-sectional study of HIV+ mothers and HIV-exposed infants and unrelated children (1-7.9 years). Serum 25-hydroxyvitamin D (25(OH)D) was measured, among other nutritional indicators, for mothers, infants and children. Vitamin D status for HIV-infected mothers and children, and an immune panel was assessed. History of HIV anti-retroviral medications and breastfeeding were obtained. Data were collected prior to universal combination antiretroviral therapy in pregnancy.</p>

<p><strong>RESULTS: </strong>Mothers (n = 36) had a mean serum 25(OH)D of 37.2±12.4ng/mL; 11% had insufficient (&lt;20ng/mL), 17% moderately low (20.0-29.9ng/mL) and 72% sufficient (≥30ng/mL) concentrations. No infants (n = 36) or children (n = 48) were vitamin D insufficient; 22% of HIV- and no HIV+ infants had moderately low concentrations and 78% of HIV- and 100% of HIV+ infants had sufficient status, 8% of HIV- and no HIV+ children had moderately low concentrations and 92% of HIV- and 100% HIV+ children had sufficient concentrations. HIV+ children had significantly lower length/height Z scores compared to HIV- children. Length/height Z score was positively correlated with serum 25(OH)D in all children (r = 0.33, p = 0.023), with a stronger correlation in the HIV+ children (r = 0.47 p = 0.021). In mothers, serum 25(OH)D was positively associated with CD4% (r = 0.40, p = 0.016).</p>

<p><strong>CONCLUSIONS: </strong>Results showed a low prevalence of vitamin D insufficiency in Botswana. Growth was positively correlated with vitamin D status in HIV-exposed children, and HIV+ children had poorer linear growth than HIV- children.</p>

<p>Inter-individual variability in efavirenz (EFV) pharmacokinetics and dynamics is dominantly driven by the polymorphism in cytochrome P450 (CYP) isoenzyme 2B6 516G&gt;T. We hypothesized that additional CYP polymorphisms mediate the relationship between CYP2B6 516G&gt;T, EFV metabolism, and clinical events. We investigated 21 SNPs in 814 HIV-infected adults initiating EFV-based therapy in Botswana for population pharmacokinetics, CNS toxicities, and treatment outcomes. Two SNPs (rs28399499 and rs28399433) showed reduced apparent oral EFV clearance. Four SNPs (rs2279345, rs4803417, rs4802101, and rs61663607) showed extensive clearance. Composite CYP2B-mediated EFV metabolism was significantly associated with CNS toxicity (p = 0.04), with extensive metabolizers reporting more and slow and very slow metabolizers reporting less toxicity after 1 month compared to intermediate metabolizers. Composite CYP2B6 metabolism was not associated with composite early treatment failure. In conclusion, our data suggest that CNS-related toxicities might not be solely the result of super-therapeutic parent EFV concentrations in HIV-infected individuals in patients of African ancestry.</p>

<p><strong>AIMS: </strong>To determine alcohol use effect on HIV treatment success and whether alcohol use mediates the relation between male sex and treatment failure.</p>

<p><strong>DESIGN: </strong>Longitudinal cohort study.</p>

<p><strong>SETTING: </strong>Eight HIV clinics in and near Gaborone, Botswana.</p>

<p><strong>PARTICIPANTS: </strong>A total of 938 HIV-infected treatment-naive adults initiating regimens containing the antiretroviral medication efavirenz between June 2009 and February 2013, including 478 (51%) males, median age 38&nbsp;years, and plasma HIV RNA 4.9 logcopies/ml.</p>

<p><strong>MEASUREMENTS: </strong>Primary outcome was a composite of treatment failure over 6&nbsp;months including death, lost to care or plasma HIV RNA &gt; 25 copies/ml. Exposures included alcohol use and gender.</p>

<p><strong>FINDINGS: </strong>Failure in 339 (36%) participants included 40 (4%) deaths, 194 (21%) lost to care and 105 (11%) with HIV RNA&nbsp;&gt;&nbsp;25 copies/ml. Both hazardous alcohol use in the past year [adjusted odds ratio (aOR)&nbsp;=&nbsp;1.4, 95% confidence interval (CI)&nbsp;=&nbsp;1.0, 1.9] and male sex (aOR&nbsp;=&nbsp;2.1, 95% CI&nbsp;=&nbsp;1.5, 2.9) were associated with failure. Hazardous alcohol use in the year prior to enrollment was more common in men (57%) than women (24%), P&nbsp;&lt;&nbsp;0.001. There was no difference in alcohol use effect on failure between sexes (P for interaction&nbsp;&gt;&nbsp;0.5). Controlling for hazardous alcohol use did not change the relation between sex and failure.</p>

<p><strong>CONCLUSION: </strong>Alcohol use among HIV-infected adults in Botswana appears to worsen HIV treatment outcomes. Alcohol use does not appear to have either a mediating or a moderating effect on the relation between gender and HIV treatment outcome failure.</p>

<p><strong>Background: </strong>Human immunodeficiency virus-exposed but uninfected (HIV-EU) children have a higher mortality rate than the children of HIV-negative mothers (HIV-unexposed). Causal mediators of the poor health outcomes of HIV-EU children remain poorly defined.</p>

<p><strong>Methods: </strong>We conducted a hospital-based prospective cohort study of children aged 1 to 23 months with clinically defined pneumonia. The children were recruited at a referral hospital in Gaborone, Botswana, between April 2012 and June 2016. The primary outcome, treatment failure at 48 hours, was assessed by an investigator blinded to the children's HIV-exposure status. We examined associations between HIV exposure and pneumonia outcomes in HIV-uninfected children. We next determined whether the effect of HIV exposure on outcomes was mediated by low-birth-weight status, nonbreastfeeding, malnutrition, in utero exposure to combination antiretroviral therapy, or pneumonia severity.</p>

<p><strong>Results: </strong>A total of 352 HIV-uninfected children were included in these analyses, including 245 (70%) HIV-unexposed and 107 (30%) HIV-EU children. Their median age was 7.4 months, and 57% were male. Treatment failure occurred in 111 (32%) children, and 19 (5.4%) children died. HIV-EU children were more likely to fail treatment (risk ratio [RR], 1.57 [95% confidence interval (CI), 1.19-2.07]; P = .002) and had a higher in-hospital mortality rate (RR, 4.50 [95% CI, 1.86-10.85]; P = .001) than HIV-unexposed children. Nonbreastfeeding mediated 47% of the effect of HIV exposure on the risk of in-hospital death.</p>

<p><strong>Conclusions: </strong>HIV-EU children have worse pneumonia outcomes than HIV-unexposed children. Nonbreastfeeding mediates nearly half of the effect of HIV exposure on pneumonia mortality. Our findings provide additional evidence for a mortality benefit of breastfeeding by HIV-EU children.</p>

<p><strong>OBJECTIVES: </strong>To determine the association between cytochrome p450 2B6 genotypes and efavirenz-based HIV treatment outcomes.</p>

<p><strong>DESIGN: </strong>Observational cohort study of HIV infected adults initiating efavirenz-based regimens in Botswana.</p>

<p><strong>METHODS: </strong>The primary endpoint was a composite of death or loss to care or HIV RNA&gt;25 copies/ml at 6 months. CYP2B6 516G&gt;T and 983T&gt;C genotyping was done with Taqman Open Array platform. Adverse experiences were measured using the Subject Experience Questionnaire. Metabolism alleles were included in logistic regression models of the composite endpoint.</p>

<p><strong>RESULTS: </strong>801 individuals included 406 (51%) males, median age 37 years, median baseline CD4 count 195 cells/mm and plasma HIV RNA 4·9 log10 copies/ml. 277 (35%) reached the endpoint including 34 (4%) deaths, 151 (19%) lost to care, and 92 (11%) with plasma HIV RNA&gt;25 copies/ml. Metabolism variant alleles were common with 396 (49%) intermediate and 192 (24%) slow metabolizers. There were no statistically significant associations between metabolism and treatment endpoints. However, slower metabolism was associated with fewer adverse experiences.</p>

<p><strong>CONCLUSIONS: </strong>Slow metabolism alleles were associated with lower efavirenz clearance but not any of the treatment endpoints. Slow efavirenz metabolism did not exacerbate CNS toxicity. These results should allay concern that slow efavirenz metabolism adversely impacts individuals in sub-Saharan African settings in which these alleles are common.</p>