Second-Line Switch to Dolutegravir for Treatment of HIV Infection.

BACKGROUND: Data to inform the switch from a ritonavir-boosted protease inhibitor (PI) to dolutegravir in patients living with human immunodeficiency virus (HIV) infection who do not have genotype information and who have viral suppression with second-line therapy containing a ritonavir-boosted PI have been limited. METHODS: In a prospective, multicenter, open-label trial conducted at four sites in Kenya, we randomly assigned, in a 1:1 ratio, previously treated patients without genotype information who had viral suppression while receiving treatment containing a ritonavir-boosted PI to either switch to dolutegravir or continue the current regimen. The primary end point was a plasma HIV type 1 RNA level of at least 50 copies per milliliter at week 48, assessed on the basis of the Food and Drug Administration snapshot algorithm. The noninferiority margin for the between-group difference in the percentage of participants who met the primary end point was 4 percentage points. Safety up to week 48 was assessed. RESULTS: A total of 795 participants were enrolled, with 398 assigned to switch to dolutegravir and 397 assigned to continue taking their ritonavir-boosted PI; 791 participants (397 in the dolutegravir group and 394 in the ritonavir-boosted PI group) were included in the intention-to-treat exposed population. At week 48, a total of 20 participants (5.0%) in the dolutegravir group and 20 (5.1%) in the ritonavir-boosted PI group met the primary end point (difference, -0.04 percentage points; 95% confidence interval, -3.1 to 3.0), a result that met the criterion for noninferiority. No mutations conferring resistance to dolutegravir or the ritonavir-boosted PI were detected at the time of treatment failure. The incidence of treatment-related grade 3 or 4 adverse events was similar in the dolutegravir group and the ritonavir-boosted PI group (5.7% and 6.9%, respectively). CONCLUSIONS: In previously treated patients with viral suppression for whom there were no data regarding the presence of drug-resistance mutations, dolutegravir treatment was noninferior to a regimen containing a ritonavir-boosted PI when the patients were switched from a ritonavir-boosted PI-based regimen. (Funded by ViiV Healthcare; 2SD ClinicalTrials.gov number, NCT04229290.).

High rates of kidney impairment among older people (≥ 60 years) living with HIV on first-line antiretroviral therapy at screening for a clinical trial in Kenya.

BACKGROUND: There is a paucity of data on kidney impairment among older people living with HIV (PLWH). We evaluated kidney function among PLWH age ≥ 60 years on first-line antiretroviral (ARV) therapy during screening for a clinical trial in Kenya. METHODS: The bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) Elderly Study is an open-label, randomized, active-controlled, non-inferiority trial conducted at two sites in Kenya. Potential participants were screened for study entry if they were at least 60 years old, had been on ARVs for at least 24 weeks and had no history of treatment failure. At screening, participants had samples collected for serum creatinine and estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration 2021 equation. RESULTS: Between January and April 2022, 714 participants were screened and had creatinine measured. All participants were black, 54.1% were female and the median age was 64 years (range 60 to 87 years). Most participants (666 [93.3%]) were on tenofovir disoproxil fumarate-containing regimens, 711 (99.6%) were on dolutegravir-containing regimens, and only 2 (0.3%) were on a regimen with a ritonavir-boosted protease inhibitor. Most participants (686 [96.6%]) were virally suppressed. Treatment for comorbidities was common, with 175 (24.5%) on treatment for hypertension and 39 (5.5%) on treatment for diabetes mellitus. The median eGFR was 64.7 mL/min/1.73m2, and 289 (40.5%) participants had an eGFR < 60 mL/min/1.73m2. In multivariate analysis, factors associated with lower eGFR were female gender (p<0.001), being on treatment for hypertension (p<0.001) and nadir CD4 count < 50 cells/µL (p = 0.008). CONCLUSIONS: Our study identified high rates of impaired kidney function among elderly PLHW in Kenya, which highlights the importance of routine assessment of kidney function and the need to address modifiable risk factors, use of appropriate ARVs, and management of kidney disease in this population.