Effect of obesity on dolutegravir exposure in Black Southern African adults living with HIV.

Background: Dolutegravir, a component of the preferred first-line antiretroviral therapy regimen, has been associated with increased weight gain. South Africa has a high prevalence of obesity, especially among women. Understanding dolutegravir exposure in patients with obesity is important for dose optimisation.

Pharmacogenetics of the Late-Onset Efavirenz Neurotoxicity Syndrome (LENS).

Background: The late-onset efavirenz neurotoxicity syndrome (LENS) presents as ataxia and/or encephalopathy with supratherapeutic efavirenz plasma concentrations (>4 µg/mL). Efavirenz is primarily metabolized by cytochrome P450 2B6 (CYP2B6), with CYP2A6 as an accessory pathway. We hypothesized that participants with LENS would predominantly be CYP2B6 slow metabolizers.

Pharmacokinetic interactions of modern antiretroviral therapy.

Drug--drug interactions (DDIs) have been a clinical challenge in HIV medicine for over two decades. The newer antiretroviral drugs (ARTs) have significantly fewer DDIs than protease inhibitors and boosted integrase inhibitors (INSTIs). The lower propensity of such newer antiretrovirals (e.

Pharmacogenetics of tenofovir and emtricitabine penetration into cerebrospinal fluid.

Background: Blood-cerebrospinal fluid (CSF) barrier transporters affect the influx and efflux of drugs. The antiretrovirals tenofovir and emtricitabine may be substrates of blood-brain barrier (BBB) and blood-CSF barrier transporters, but data are limited regarding the pharmacogenetics and pharmacokinetics of their central nervous system (CNS) penetration.

Objectives: We investigated genetic polymorphisms associated with CSF disposition of tenofovir and emtricitabine.

Low-dose ritonavir-boosted darunavir once daily versus ritonavir-boosted lopinavir for participants with less than 50 HIV RNA copies per mL (WRHI 052): a randomised, open-label, phase 3, non-inferiority trial.

Background: Pilot studies suggest that ritonavir-boosted darunavir could show high efficacy at doses below those currently approved. We investigated whether switch to 400 mg of darunavir boosted with 100 mg ritonavir once daily could show equivalent efficacy to continuation of ritonavir-boosted lopinavir (a protease inhibitor commonly used in low-income and middle-income countries) for individuals with HIV RNA suppression.

Methods: In the WRHI 052 study, a randomised, parallel-group, open-label, non-inferiority phase 3 trial, adults who were HIV-1 positive were enrolled in Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg, South Africa.

Pharmacogenetics and pharmacokinetics of CNS penetration of efavirenz and its metabolites.

Background: There are limited data on the pharmacogenetics and pharmacokinetics of the CNS penetration of efavirenz.

Objectives: We investigated genetic polymorphisms associated with CSF concentrations of efavirenz and its metabolites and explored the relationships with neurocognitive performance.

Methods: We included 47 HIV-infected South African black adults with and without HIV-associated neurocognitive disorder on efavirenz/tenofovir/emtricitabine and collected paired plasma-CSF samples.

Plasma Efavirenz Concentrations Are Associated With Lipid and Glucose Concentrations.

Efavirenz-based antiretroviral therapy (ART) has been associated with dyslipidemia and dysglycemia, risk factors for cardiovascular disease. However, the pathogenesis is not well understood. We characterized relationships between plasma efavirenz concentrations and lipid and glucose concentrations in HIV-infected South Africans.

Pharmacogenetics of plasma efavirenz exposure in HIV-infected adults and children in South Africa.

Aims: Genetic factors, notably CYP2B6 516G→T [rs3745274] and 983T→C [rs28399499], explain much of the interindividual variability in efavirenz pharmacokinetics, but data from Africa are limited. We characterized relationships between genetic polymorphisms and plasma efavirenz concentrations in HIV-infected Black South African adults and children.

Methods: Steady-state mid-dosing interval efavirenz concentrations were measured.

Mitochondrial genomics and antiretroviral therapy-associated metabolic complications in HIV-infected Black South Africans: a pilot study.

Studies suggest that mitochondrial DNA (mtDNA) haplogroups are associated with antiretroviral therapy (ART)-related metabolic complications and distal sensory polyneuropathy (DSP), but there have been few studies in persons of African descent. We explored such associations in South African adults. Clinical and laboratory data and DNA specimens from a cross-sectional study were used.

Association of lopinavir concentrations with plasma lipid or glucose concentrations in HIV-infected South Africans: a cross sectional study.

Background: Dyslipidaemia and dysglycaemia have been associated with exposure to ritonavir-boosted protease inhibitors. Lopinavir/ritonavir, the most commonly used protease inhibitor in resource-limited settings, often causes dyslipidaemia. There are contradictory data regarding the association between lopinavir concentrations and changes in lipids.

Lack of association between stavudine exposure and lipoatrophy, dysglycaemia, hyperlactataemia and hypertriglyceridaemia: a prospective cross sectional study.

Background: Stavudine continues to be widely used in resource poor settings despite its toxicity. Our objective was to determine association between plasma stavudine concentrations and lipoatrophy, concentrations of glucose, lactate and triglycerides.

Methods: Participants were enrolled in a cross-sectional study with lipoatrophy assessment, oral glucose tolerance test, fasting triglycerides, finger prick lactate, and stavudine concentrations.