Assessing potential drug-drug interactions between clofazimine and other frequently used agents to treat drug-resistant tuberculosis.

Clofazimine is included in drug regimens to treat rifampicin/drug-resistant tuberculosis (DR-TB), but there is little information about its interaction with other drugs in DR-TB regimens. We evaluated the pharmacokinetic interaction between clofazimine and isoniazid, linezolid, levofloxacin, and cycloserine, dosed as terizidone. Newly diagnosed adults with DR-TB at Klerksdorp/Tshepong Hospital, South Africa, were started on the then-standard treatment with clofazimine temporarily excluded for the initial 2 weeks. Pharmacokinetic sampling was done immediately before and 3 weeks after starting clofazimine, and drug concentrations were determined using validated liquid chromatography-tandem mass spectrometry assays. The data were interpreted with population pharmacokinetics in NONMEM v7.5.1 to explore the impact of clofazimine co-administration and other relevant covariates on the pharmacokinetics of isoniazid, linezolid, levofloxacin, and cycloserine. Clofazimine, isoniazid, linezolid, levofloxacin, and cycloserine data were available for 16, 27, 21, 21, and 6 participants, respectively. The median age and weight for the full cohort were 39 years and 52 kg, respectively. Clofazimine exposures were in the expected range, and its addition to the regimen did not significantly affect the pharmacokinetics of the other drugs except levofloxacin, for which it caused a 15% reduction in clearance. A posteriori power size calculations predicted that our sample sizes had 97%, 90%, and 87% power at P < 0.05 to detect a 30% change in clearance of isoniazid, linezolid, and cycloserine, respectively. Although clofazimine increased the area under the curve of levofloxacin by 19%, this is unlikely to be of great clinical significance, and the lack of interaction with other drugs tested is reassuring.

The prevalence of multimorbidity in virally suppressed HIV-positive patients in Limpopo.

Background: Non-communicable diseases (NCDs) are an emerging global public health problem. Objectives: To assess the prevalence of NCDs and their risk factors among adults on antiretroviral therapy (ART). Method: This was a cross-sectional study (July 2019 - January 2020) in Limpopo, South Africa. Patients were enrolled if they were ≥ 40 years, HIV-positive, and virologically suppressed on ART. Data were analysed descriptively, and a binomial regression model was used to identify risk factors for NCDs. Results: The majority of participants (65%; 319/488) were women. Most (83%; 405/488) were aged 40-59 years; 60% (285/472) were overweight or obese. Based on self-report, 22% (107/488) were currently smokers. Almost half (44%) 213/488) reported daily consumption of vegetables and 65% (319/488) exercised regularly and 39% (190/488) reported treatment for another chronic disease. The leading comorbid conditions were hypertension (32%; 158/488) and diabetes mellitus (5%; 24/488). Risk factors for hypertension included age 60 years and older (relative risk [RR]: 1.72; 95% confidence interval [CI]: 1.29-2.30) diabetes (RR: 1.42; 95% CI: 1.08-1.87), overweight (RR: 1.32; 95% CI: 1.03-1.69) and obesity (RR: 1.69; 95% CI: 1.32-2.17). Conclusion: There is a high prevalence, both of risk factors for NCDs and multimorbidity (> 1 chronic disease) in patients who are ≥ 40 years and virologically suppressed on ART.

Coronavirus Host Genomics Study: South Africa (COVIGen-SA).

Host genetic factors are known to modify the susceptibility, severity, and outcomes of COVID-19 and vary across populations. However, continental Africans are yet to be adequately represented in such studies despite the importance of genetic factors in understanding Africa's response to the pandemic. We describe the development of a research resource for coronavirus host genomics studies in South Africa known as COVIGen-SA-a multicollaborator strategic partnership designed to provide harmonised demographic, clinical, and genetic information specific to Black South Africans with COVID-19. Over 2,000 participants have been recruited to date. Preliminary results on 1,354 SARS-CoV-2 positive participants from four participating studies showed that 64.7% were female, 333 had severe disease, and 329 were people living with HIV. Through this resource, we aim to provide insights into host genetic factors relevant to African-ancestry populations, using both genome-wide association testing and targeted sequencing of important genomic loci. This project will promote and enhance partnerships, build skills, and develop resources needed to address the COVID-19 burden and associated risk factors in South African communities.