OBJECTIVES:To determine the PK of the pro-drug colistimethate sodium (CMS) and colistin in adult patients admitted to a South African critical care unit and to compare the PK with historical data. MATERIALS AND METHODS:We conducted a prospective, observational, PK study in critically ill adult patients receiving intravenous colistin as part of standard of care. CMS was administered as a loading dose of either 9 million units (MU) or 12 MU followed by maintenance doses dependent on creatinine clearance (CrCl) at either 12- or 8-hourly. PK samples were collected at 1, 2, 4, 8, 12, 24 and 48 hours post-loading dose. CMS and colistin concentrations were analysed using liquid chromatography-tandem mass spectrometry. The PK of CMS and colistin were described using non-compartmental analysis in Phoenix WinNonlin. RESULTS:We enrolled 24 participants, 50% (12/24) were admitted with burns. Mean age was 42 years (SD ± 16.3) and mean CrCl was 140 mL/min (SD ± 58.7). The PK parameters following a loading dose of 9 MU were comparable to published data. Colistin AUC showed a negative correlation with white cell count (r = -0.63) and eGFR (r = -0.44). Probability of target attainment was acceptable at Acinetobacter baumannii minimum inhibitory concentrations <1 mg/L. CONCLUSION:Our results are comparable to previously published literature. Notably, increasing eGFR and WCC decreased colistin AUC. Future work will adopt a population pharmacokinetic modelling approach to quantify and account for sources of variability, with the aim of informing individualized dosing strategies for this South African population.

Background:Despite effective antiretroviral therapy (ART), serious non-AIDS events (SNAEs), including cardiovascular disease and death, remain prevalent among people with HIV (PWH). Imperfect ART adherence despite viral suppression may contribute to this risk, underscoring the need to clarify the relationship between adherence, viral load dynamics, and SNAE development. Methods:We performed an analysis of deidentified data of participants in the prospective observational Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections (ACTG) A5001 and A5322 studies. The baseline was defined as the time at the first viral suppression to <200 copies/mL after treatment initiation. Antiretroviral therapy adherence was assessed using the periodically administered ACTG self-report questionnaire and dichotomized as >90% versus ≤90% adherence. Data were primarily analyzed using inverse probability of censoring weights modeling. Results:Among 2940 participants followed for a median of 6.2 years, 237 SNAEs occurred, comprising 103 deaths and 134 cardiovascular events. Nearly all participants (95.9%) remained virally suppressed to <200 copies/mL over the full duration of follow-up. Adherence to ART >90% showed a protective effect on the development of all SNAEs: adjusted hazard ratio (aHR) 0.612 (95% confidence interval .390-.961). When only the development of the first SNAE was considered, the association remained substantially similar: aHR 0.641 (95% confidence interval .400-1.027). Conclusions:Adherence to ART >90% compared to ≤90% reduces SNAE risk even in virally suppressed PWH, underscoring the need for continued adherence support to improve long-term health outcomes for PWH.

OBJECTIVES:The glucose-lowering drug metformin has shown promise in non-diabetic conditions for improving endothelial dysfunction, but the literature of metformin's effect on endothelial dysfunction and the biomarkers used to measure endothelial dysfunction have not yet been synthesised.We aimed to map the extent and nature of the existing research related to metformin for endothelial dysfunction in non-diabetic non-communicable diseases (NCDs). This scoping review was conducted following the methodological framework by Arksey and O'Malley and the recommendations from the Joanna Briggs Institute, and was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. ELIGIBILITY CRITERIA:We considered any peer-reviewed studies in adult humans on the use of metformin for endothelial dysfunction in non-diabetic NCDs. Narrative reviews, expert opinion, preclinical studies and qualitative studies were excluded. SOURCES OF EVIDENCE:An unrestricted search was conducted on four electronic databases and three registries from inception to October 2024. CHARTING METHODS:Data charting was performed using predetermined data extraction headings. We used a systematic charting method and narrative synthesis to organise, synthesise and report the data. RESULTS:We identified 56 studies comprising 4620 participants (71.7% female). Polycystic ovarian syndrome was the most investigated NCD (57.1% of studies). 19 distinct biomarkers of endothelial dysfunction were identified, with flow-mediated dilation being the most frequently assessed (18 studies, 745 participants). Metformin showed a trend towards improvement for 7/19 (36.8%) biomarkers. Male participants were underrepresented in the literature and only five studies (9%) were conducted in the global south, potentially limiting the generalisability of repurposed metformin in diverse populations or settings. Studies with an active comparator reported a significant difference between the metformin and comparator groups in 20% (4/20), in contrast to studies without an active comparator (placebo or pre-post studies) reporting significant results favouring metformin in 83.3% (30/36). A knowledge gap also exists for metformin use in people with HIV, given that they are known to develop cardiovascular NCDs at a twofold higher rate than their HIV-negative counterparts. CONCLUSIONS:While there is a growing evidence base supporting metformin as treatment for endothelial dysfunction in non-diabetic NCDs, our scoping review highlighted knowledge gaps in optimal biomarker selection and dosing strategies, and applications in a broader range of NCDs, including in people with HIV. More primary and secondary research using robust methodologies and study designs is needed to determine the quantitative effect of metformin on endothelial dysfunction.

BACKGROUND:Both efavirenz and dolutegravir have been associated with neuropsychiatric side-effects and cognitive impairment. Furthermore, cerebrospinal fluid (CSF) HIV RNA escape has not been comprehensively studied in African populations. We aimed to examine changes in cognition, neuropsychiatric symptoms, and CSF viral control associated with the widespread switch from efavirenz-based to dolutegravir-based antiretroviral therapy (ART). METHODS:This prospective cohort study of people with HIV and people without HIV recruited adults with HIV (aged 18-55 years) from the Gugulethu Community Health Centre in a low-income periurban area of Cape Town, South Africa. Eligible participants had been receiving efavirenz-based ART for at least 1 year and were identified by the clinic to switch to dolutegravir-based ART as part of the national programmatic switch. Participants were studied at baseline and followed up at 1 year after switch to dolutegravir. People without HIV were recruited from the same area, matched for age and gender, and followed up at the same time interval. People with HIV and people without HIV underwent comprehensive cognitive testing over seven domains and measures of functioning, mood, anxiety, and sleep. People with HIV had CSF sampling for HIV RNA quantification. FINDINGS:Between Aug 12, 2019, and Sept 16, 2022, we recruited 178 people with HIV and 95 people without HIV. 145 (81%) of 178 people with HIV and 40 (66%) of 60 people without HIV who were offered underwent follow-up. Global cognitive performance was 2·57 T score points lower in people with HIV than in people without HIV at baseline (p=0·0008). At follow-up, cognition in people with HIV improved more than practice effects observed in people without HIV (coefficient 1·40, 95% CI 0·48-2·32, p=0·0028) and no significant difference in cognitive performance between groups was apparent (51·43 vs 52·73; p=0·22). Sleep quality improved following the switch (risk ratio 0·90, 95% CI 0·84-0·95; p=0·0002), driven mainly by indicators of disturbed sleep. There were nine incident cases of depression, although baseline differences were present. There was one case (1%) of CSF escape at baseline and three cases (4%) at follow-up; all were at low levels or resolved with repeated sampling. INTERPRETATION:Improvements in cognition and sleep are probably related to switching from efavirenz. However, the possible increase in depression warrants further examination. Cognitive performance in virally supressed African people with HIV receiving dolutegravir-based therapy is similar to people without HIV. CSF escape is uncommon on both efavirenz-based and dolutegravir-based therapy. FUNDING:South African Medical Research Council and UK Medical Research Council, Newton Fund.

Background: Vancomycin is a glycopeptide antibiotic that has been used to treat hospital-acquired gram-positive infections for more than 5 decades. However, the literature is divided regarding the therapeutic advantages of vancomycin loading doses in neonates. Objectives: This study aimed to investigate the effect of vancomycin loading doses on therapeutic target attainment in neonates with sepsis. Methods: A retrospective cohort study was conducted to compare the vancomycin target attainment (area under the curve 0–24 hours/minimum inhibitory concentration ≥400) in neonates before and after the 2019 change in vancomycin prescription guidelines at a neonatal unit in Cape Town, South Africa. As the standard of care, Bayesian modelling software was used to compute the area under the curve from the trough concentrations. Results: Two hundred ten neonates were included. Multivariate regression analysis showed a 2-fold increase in the odds of target attainment among neonates receiving a loading dose of vancomycin. Early target attainment (within 8–12 hours of treatment initiation) was significantly higher in the loading dose group compared with the no loading dose group [97/105 (92.4%) versus 64/105 (61.0%); P < 0.001]. However, the overall proportion of neonates achieving target attainment at 24 hours was similar between groups [73/105 (69.5%) in the loading dose group versus 62/105 (59.0%) in the no loading dose group; P = 0.110]. The nephrotoxicity rates were low [2/105 (1.9%) in the loading dose group and 2/105 (1.9%) in the no loading dose group]. Conclusions: The addition of a vancomycin loading dose to neonates may facilitate early therapeutic target attainment.

Purpose: Emerging data suggest that acetaminophen lowers intraocular pressure (IOP) and has the potential to be repurposed as pharmacotherapy to treat open-angle glaucoma. However, pharmacokinetic data are lacking. This study aims to describe the pharmacokinetics of topical acetaminophen and its metabolite [N-arachidonoylaminophenol (AM404)] when administered individually and in combination, and to determine its effect on IOP in the ocular normotensive adult New Zealand White Rabbit (NZWR). Methods: A randomized control trial was conducted using topical 1% acetaminophen and 1% AM404. The study was divided into two sub-studies using both paired-eye and two-eye designs. Results: The mean [95% confidence interval of the mean (95% CI)] concentration of acetaminophen detected in the aqueous humor (AH) was 4.09 ppm (3.18-5.00) at 2 h and 0.92 ppm (0.60-1.24) at 4 h after an immediate dose of topical acetaminophen. The integral IOP, defined as the integral of IOP change from baseline over time, was -5.1 mmHg⋅h (95% CI: -10 to 0.41) for control,-7.5 mmHg⋅h (95% CI: -14 to -1.1) for half-hourly acetaminophen, and -4.4 mmHg⋅h (95% CI: -14 to 5.5) for hourly acetaminophen over a 4-h period. When comparing topical acetaminophen with AM404 dosed half-hourly over a 4-h period, the integral IOP was -2.3 mmHg⋅h (95% CI: -5.9 to 1.3) for control,-2.0 mmHg⋅h (95% CI: -5.6 to 1.7) for AM404, -1.7 mmHg⋅h (95% CI: -4.5 to 1.2) for acetaminophen, and -3.2 mmHg⋅h (95% CI: -5.4 to -0.96) for acetaminophen/AM404 combined. Conclusions: Acetaminophen, but not its metabolite AM404, penetrated the multilayered cornea via passive diffusion in a dose-dependent fashion. There was a nonsignificant tendency to cause a lowering of IOP over the 4-h dosing period with higher AH concentrations of acetaminophen. Topical AM404 did not show a significant IOP-lowering effect.

Trained pharmacometricians remain scarce in Africa due to limited training opportunities, lack of a pharmaceutical product development ecosystem, and emigration to high-income countries. The Applied Pharmacometrics Training (APT) fellowship program was established to address these gaps and specifically foster job creation for talent retention. We review the APT program's progress over 3 years and encourage collaboration to enhance local clinical data analysis in Africa. Initiated in 2021 by Pharmacometrics Africa, a non-profit educational entity, with support from partners including the Bill & Melinda Gates Foundation and Certara, the APT program targets African doctoral-level scientists and clinicians. This 6-month program is jointly managed by partners, with Pharmacometrics Africa handling logistics and sponsor liaison. Job creation initiatives include inviting fellows to join consulting teams or local research centers. Over the 3 year reporting period, 177 applications were received, with 27 individuals (41% female, median age 35 years) from nine African countries selected into and completing the full program. The fellows worked on 13 data analysis projects, with six so far being presented at international conferences and/or submitted for publication in peer-reviewed journals. Nine fellows have joined consulting teams or research centers working from offices in Africa. Currently, in the 3rd year, the APT program has demonstrated success in skills development, job creation, and fostering a critical mass of African pharmacometricians. Collaboration is essential for the sustainable advancement of model-informed drug development in Africa.

Background: The smallest dolutegravir (DTG) dose approved is 5 mg once-daily in infants ≥4 weeks and weighing ≥3 to <6 kg using a dispersible tablet (DT). Neonates (<28 days of life) may require a lower dose due to immature organ development. We evaluated the aqueous dispersibility of the generic DTG-DT 10-mg scored tablets (Viatris Inc.) to determine the possibility of uniform concentrations that could allow for lower daily doses in neonates. Methods: Each 5-mL polypropylene tube had DTG-DT 5 mg dissolved in 5-mL ultrapure water. Tubes were labeled with 3 “zones” (bottom: 0–1 mL; middle: 1–3 mL; top: 3–5 mL). Suspensions were mixed by swirling or swirling with a syringe pump, vortexing, or sonication. DTG concentration in each zone was determined using high-performance liquid chromatography. Tubes were rinsed with 1-mL acetonitrile to determine the residual drug. Acceptable criterion for percentage difference was set at ≤20% according to the European Medicines Agency guidelines. Results: Dispersion of DTG-DT in water did not remain homogeneous, resulting in DTG concentrations that varied by over 50% across the 3 zones within the tubes. Rapid sedimentation was observed shortly after mixing. Furthermore, it was found that 24%–35% of the DTG residue remained adhered to the tube after the aqueous dispersion had been eluted, highlighting the importance of the rinse step. Conclusions: Aqueous dispersion of the DTG-DT is not uniform and displays a high degree of sedimentation. It is therefore not possible to administer a fraction of the dispersion (lower DTG dose) to neonates by using this formulation.

Intramuscular injection of long-acting cabotegravir and rilpivirine is a novel, long-acting antiretroviral therapy (ART) combination approved for use as a fully suppressive regimen for people living with HIV. Long-acting cabotegravir with rilpivirine ART has reduced required dosing frequency from once daily to once every month or every 2 months injections. This new era of long-acting ART, which includes other antiretrovirals and formulations in various stages of clinical development, holds tremendous promise to change the standard of HIV treatment. Although long-acting ART has high potential to be revolutionary in the landscape of HIV care, prevention, and treatment cascade, more data are needed to substantiate its efficacy and cost-effectiveness among patients at risk of non-adherence and across age groups, pregnancy, and post partum. Advocacy efforts and policy changes to optimise a sustained, high-quality, equitable reach of long-acting ART, especially in low-income and middle-income countries where most people living with HIV reside, are needed to realise the full benefits of long-acting ART.

ABSTRACT In low-resource settings, access to intravenous formulations of antituberculosis drugs is lacking or absent. Thus, critically ill patients with tuberculosis (TB) are often treated with readily available tablets which are crushed, mixed with water, and administered via a nasogastric tube (NGT). This has been associated with plasma concentrations below the recommended target, particularly of rifampicin (RIF) and isoniazid (INH), leading to clinical failure and development of drug resistance. We aimed to identify physiochemical factors contributing to lower plasma concentrations of antituberculosis drugs when administered in this manner using laboratory-based techniques, including the addition of ascorbic acid (AA) for optimum administration. Aqueous solubility of crushed medication using the inversion mixing method was evaluated against easily implementable mixing methods (sonication/vortexing) with or without AA. Stability of crushed medication in simulated-gastrointestinal fluids was evaluated with or without AA. Drug loss via NGT surface adsorption was quantitatively determined. RIF demonstrated poor aqueous solubility of 5.2%. Incorporation of AA improved the solubility to 29.7%, and with the addition of mixing techniques, solubility improved to 86.3%. Mixing methods with AA further improved the solubilities of both INH (80%) and pyrazinamide (PZA, 64%) to over 90%. AA also showed protective effects against unstable RIF in simulated-gastric fluid. Conventional flushing of NGT after drug administration with 10 mL of water resulted in drug losses of 1.5%, 0.13%, and 1.4% for RIF, INH, and PZA, respectively. An additional flushing step halved this amount. These interventions may improve the poor plasma concentrations of crushed antituberculosis drugs in critically ill patients. IMPORTANCE The incidence of tuberculosis (TB) in intensive care units (ICUs) can be as high as 3% in high-burden settings, translating to more than 7,500 patients admitted to the ICU annually. In resource-limited settings, the lack or absence of intravenous formulations of drug-sensitive antituberculosis medications necessitates healthcare practitioners to crush, dissolve, and administer the drugs to critically ill patients via a nasogastric tube (NGT). This off-label practice has been linked to plasma concentrations below the recommended target concentrations, particularly of rifampicin and isoniazid, leading to clinical failure and the development of drug resistance. Optimizing the delivery of crushed drug-sensitive antituberculosis medication via the NGT to critically ill patients is of utmost importance.

Sulfasalazine has been identified as a candidate molecule to be investigated as an intervention to treat preterm pre-eclampsia during pregnancy. However, placental exposure of sulfasalazine and its systemically absorbed metabolite, sulfapyridine, is unknown. A robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to simultaneously quantitate these analytes in human placenta with an application to a pilot clinical trial. The placental tissue was homogenised using a water:methanol (1:1, v/v) mixture, followed by sample extraction using both protein precipitation and solid phase extraction. Sulfasalazine-d4 and sulfapyridine-d4 were used as internal standards. An Agilent Poroshell EC-C18 (3.0 x100 mm, 2.7 & mu;m) column was used for chromatographic separation, with gradient elution employed at a flow rate of 0.450 mL/min over a total run time of seven minutes. The mobile phases consisted of water with 0.1% formic acid (mobile phase A) and acetonitrile:methanol (90:10, v/v) with 0.1% formic acid (mobile phase B). A Shimadzu-8040 mass spectrometer was operated in multiple reaction monitoring (MRM) mode using positive electrospray ionisation (ESI). For both analytes, the assay was validated over the range 30-30,000 ng/mL, or 150-150,000 ng/g. During inter-day validations (n = 18), the average accuracies of quality controls ranged from 101.6% to 112.7% with corresponding precisions of 4.4-6.7% for sulfasalazine, and from 97.4% to 108.4%, with corresponding precisions of 3.7-10.0% for sulfapyridine. No significant matrix effects were observed, and the method proved to be sensitive and specific for both analytes. This study presents the first validated analytical method for quantifying sulfasalazine and sulfapyridine in human placenta as part of a pilot clinical trial to generate preliminary data on its pharmacokinetics and efficacy as in intervention for preterm pre-eclampsia.

Current antiretroviral therapy (ART) adherence monitoring is premised on patients' self-reported adherence behaviour (prone to recall error) and verified by blood viral load measurement (which can delay results). A newly developed Urine Tenofovir Rapid Assay (UTRA) assesses tenofovir in urine at point-of-care and is a novel tool to test and immediately respond to adherence levels of people living with HIV (PLHIV). We explored PLHIV and health workers' initial perceptions about integrating the UTRA into routine medical care for adherence support. We conducted a series of once-off in-depth qualitative interviews with PLHIV (n = 25) and health workers (n = 5) at a primary care health facility in Cape Town, South Africa. Data analysis involved descriptive summaries of key emergent themes with illustrative case examples. We applied a deductive, outcomes-driven analytic approach to the summaries using the Implementation Outcomes Framework proffered by Proctor et al. (2011). The three relevant concepts from this framework that guided our evaluation were: acceptability, appropriateness, and feasibility. We found positive perceptions about the UTRA from many PLHIV and health worker participants. Many PLHIV reported that the immediate results offered by the UTRA could enable them to have constructive discussions with health workers on how to resolve adherence challenges in real-time. Few PLHIV reported concerns that drinking alcohol could affect their UTRA results. Many health workers reported that the UTRA could help them identify patients at risk of treatment failure and immediately intervene through counselling, though some relayed that they would support the UTRA's implementation if more staff members could be added in their busy facility. Overall, these findings show that the UTRA was widely perceived to be acceptable and actionable by many PLHIV and health workers in the study.

HIV-associated neurocognitive disorders (HAND) persist in the era of antiretroviral therapy (ART). Thus, ART does not completely halt or reverse the pathological processes behind HAND. Adjuvant mitigating treatments are, therefore, prudent. Lithium treatment is known to promote neuronal brain–derived neurotrophic factors (BDNF). Lithium is also an inhibitor of glycogen synthase kinase-3 beta (GSK-3-β). We analyzed biomarkers obtained from participants in a randomized placebo-controlled trial of lithium in ART-treated individuals with moderate or severe HAND. We assayed markers at baseline and 24 weeks across several pathways hypothesized to be affected by HIV, inflammation, or degeneration. Investigated biomarkers included dopamine, BDNF, neurofilament light chain, and CD8 + lymphocyte activation (CD38 + HLADR +). Alzheimer’s Disease (AD) biomarkers included soluble amyloid precursor protein alpha and beta (sAPPα/β), Aβ38, 40, 42, and ten other biomarkers validated as predictors of mild cognitive impairment and progression in previous studies. These include apolipoprotein C3, pre-albumin, α1-acid glycoprotein, α1-antitrypsin, PEDF, CC4, ICAM-1, RANTES, clusterin, and cystatin c. We recruited 61 participants (placebo = 31; lithium = 30). The age baseline mean was 40 (± 8.35) years and the median CD4 + T-cell count was 498 (IQR: 389–651) cells/μL. Biomarker concentrations between groups did not differ at baseline. However, both groups’ blood dopamine levels decreased significantly after 24 weeks (adj. p < 002). No other marker was significantly different between groups, and we concluded that lithium did not confer neuroprotection following 24 weeks of treatment. However, the study was limited in duration and sample size.

ABSTRACT Physiological changes during pregnancy may alter the pharmacokinetics (PK) of antituberculosis drugs. The International Maternal Pediatric Adolescent AIDS Clinical Trials Network P1026s was a multicenter, phase IV, observational, prospective PK and safety study of antiretroviral and antituberculosis drugs administered as part of clinical care in pregnant persons living with and without HIV. We assessed the effects of pregnancy on rifampin, isoniazid, ethambutol, and pyrazinamide PK in pregnant and postpartum (PP) persons without HIV treated for drug-susceptible tuberculosis disease. Daily antituberculosis treatment was prescribed following World Health Organization-recommended weight-band dosing guidelines. Steady-state 12-hour PK profiles of rifampin, isoniazid, ethambutol, and pyrazinamide were performed during second trimester (2T), third trimester (3T), and 2–8 of weeks PP. PK parameters were characterized using noncompartmental analysis, and comparisons were made using geometric mean ratios (GMRs) with 90% confidence intervals (CI). Twenty-seven participants were included: 11 African, 9 Asian, 3 Hispanic, and 4 mixed descent. PK data were available for 17, 21, and 14 participants in 2T, 3T, and PP, respectively. Rifampin and pyrazinamide AUC 0–24 and C max in pregnancy were comparable to PP with the GMR between 0.80 and 1.25. Compared to PP, isoniazid AUC 0–24 was 25% lower and C max was 23% lower in 3T. Ethambutol AUC 0–24 was 39% lower in 3T but limited by a low PP sample size. In summary, isoniazid and ethambutol concentrations were lower during pregnancy compared to PP concentrations, while rifampin and pyrazinamide concentrations were similar. However, the median AUC 0–24 for rifampin, isoniazid, and pyrazinamide met the therapeutic targets. The clinical impact of lower isoniazid and ethambutol exposure during pregnancy needs to be determined.

Background: Obesity is increasing worldwide including in people living with HIV (PLWH). Antiretroviral pharmacokinetic data in obesity are limited. Objectives: To measure antiretroviral drug concentrations in obese and nonobese PLWH treated with the fixed-dose combination of efavirenz–tenofovir–emtricitabine. To determine pharmacokinetic differences across indicators of obesity and their associated immunovirological outcomes. Methods: We conducted a cross-sectional sample analysis of 2 cohort studies. We measured mid-dose efavirenz, 8-hydroxy-efavirenz, tenofovir, and emtricitabine concentrations. Antiretroviral drug concentrations were analyzed by body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR). Results: We performed a study of 213 participants: General obesity was detected in 20.4% using BMI and abdominal obesity in 53.6% using WC and 62.4% using WHR, respectively. The median concentrations of all antiretroviral drugs were lower among obese participants determined by BMI and WC, with efavirenz showing greater differences than tenofovir or emtricitabine. For BMI, results were most striking for efavirenz (1752.3 vs 2342.9 ng/mL, P = 0.002) with lower concentrations in obese participants. Using WC, efavirenz (1845.8 vs 2571.2 ng/mL, P < 0.001), tenofovir (65.8 vs 73.2 ng/mL, P = 0.036), and emtricitabine (159.5 vs 221.0 ng/mL, P = 0.005) concentrations were lower in obese participants. Eight-hydroxyefavirenz concentrations were similar in nonobese and obese participants for WC. Using WHR, the concentrations of all antiretroviral drugs were lower in the obese population, most strikingly for emtricitabine (173.5 vs 229.0 ng/mL, P = 0.015). There were no immunovirological associations. Conclusion: We found lower antiretroviral concentrations in all obese groups, most strikingly in participants with abdominal obesity determined by WC. Lower drug concentrations had no immunovirological associations.