Real-world use and outcomes of dolutegravir-containing antiretroviral therapy in HIV and tuberculosis co-infection: a site survey and cohort study in sub-Saharan Africa.

INTRODUCTION: Dolutegravir is being scaled up globally as part of antiretroviral therapy (ART), but for people with HIV and tuberculosis co-infection, its use is complicated by a drug-drug interaction with rifampicin requiring an additional daily dose of dolutegravir. This represents a disadvantage over efavirenz, which does not have a major drug-drug interaction with rifampicin. We sought to describe HIV clinic practices for prescribing concomitant dolutegravir and rifampicin, and characterize virologic outcomes among patients with tuberculosis co-infection receiving dolutegravir or efavirenz. METHODS: Within the four sub-Saharan Africa regions of the International epidemiology Databases to Evaluate AIDS consortium, we conducted a site survey (2021) and a cohort study (2015-2021). The cohort study used routine clinical data and included patients newly initiating or already receiving dolutegravir or efavirenz at the time of tuberculosis diagnosis. Patients were followed from tuberculosis diagnosis until viral suppression (<1000 copies/ml), a competing event (switching ART regimen; loss to program/death) or administrative censoring at 12 months. RESULTS: In the survey, 86 of 90 (96%) HIV clinics in 18 countries reported prescribing dolutegravir to patients who were receiving rifampicin as part of tuberculosis treatment, with 77 (90%) reporting that they use twice-daily dosing of dolutegravir, of which 74 (96%) reported having 50 mg tablets available to accommodate twice-daily dosing. The cohort study included 3563 patients in 11 countries, with 67% newly or recently initiating ART. Among patients receiving dolutegravir (n = 465), the cumulative incidence of viral suppression was 58.9% (95% confidence interval [CI]: 54.3-63.3%), switching ART regimen was 4.1% (95% CI: 2.6-6.2%) and loss to program/death was 23.4% (95% CI: 19.7-27.4%). Patients receiving dolutegravir had improved viral suppression compared with patients receiving efavirenz who had a tuberculosis diagnosis before site dolutegravir availability (adjusted subdistribution hazard ratio [aSHR]: 1.47, 95% CI: 1.28-1.68) and after site dolutegravir availability (aSHR 1.28, 95% CI: 1.08-1.51). CONCLUSIONS: At a programmatic level, dolutegravir was being widely prescribed in sub-Saharan Africa for people with HIV and tuberculosis co-infection with a dose adjustment for the drug-drug interaction with rifampicin. Despite this more complex regimen, our cohort study revealed that dolutegravir did not negatively impact viral suppression.

[Low Body Mass Index and impact of antiretroviral therapy on nephrotoxicity, chronic renal disease among HIV-infected patients in Brazzaville, Congo]. / Faible indice de masse corporelle et impact des antirétroviraux sur la néphrotoxicité, la maladie rénale chronique chez les patients infectés par le VIH à Brazzaville, Congo.

OBJECTIVE: To describe the incidence and risks factors of ART induced nephrotoxicity and chronic kidney disease in HIV-1-infected adults with low body mass index (<18.5kg/m2). METHODS: A retrospective cohort study at the Ambulatory Treatment Center in Brazzaville, Congo. Patients with estimated glomerular filtration rate decrease by 25% compared to baseline or a 0.5mg/dL increase in serum creatinine above baseline were classified as having nephrotoxicity, and chronic kidney disease was defined as a value less than 60mL/min/1.73m2. We used Cox proportional hazards regression models to determine factors associated with nephrotoxicity and chronic kidney disease. RESULTS: Of 325 patients, 73.23% were women. Median values were an age 37.55 years (IQR: 33.51-44.96), weight 45kg (IQR: 41-49), CD4 count 137.5 cells/µL (42-245). In the first 24-months, follow-up on ART incidence rate of nephrotoxicity and chronic kidney disease was 27.95 and 7.44 per 100 persons-year respectively. Multivariate analysis identified as a risk factor of nephrotoxicity, baseline haemoglobin below or equal 8g/dL (aHR=2.25; 95%CI 1.28-3.98; P=0.005) and the use of tenofovir (aHR=1.51; 95%CI 1.01-2.27; P=0.04). DFG between 60-80 mL/min/1.73 m2 (aHR=0.35; 95%CI 0.21-0.59; P<0.001) and 45-59mL/min/1.73 m2 (aHR=0.10; 95%CI 0.01-0.72; P=0.02) was not a contraindication for initiating antiretroviral therapy. Each 10-year older age was associated with an increased risk of developing chronic kidney disease (aHR=1.95; 95%CI 1.2-3.17; P=0.007). CONCLUSION: Incidence of nephrotoxicity and chronic kidney disease were high. African HIV-positive patient with low body mass index at baseline need close monitoring of their renal function when treated with tenofovir.