Background:
Patients failing protease inhibitor (PI)-based 2nd-line antiretroviral therapy (ART) in the South African ART programme qualify for genotypic antiretroviral resistance testing (GART) – those with PI resistance receive a darunavir (DRV/r)-based 3rd-line regimen; those without PI resistance continue their regimen with adherence support. In the Western Cape Province from September 2020, an adaption to the national guideline allowed switching to tenofovir-lamivudine-dolutegravir (TLD) in such patients who had no tenofovir resistance irrespective of PI resistance.
Methods:
We conducted a prospective cohort study to evaluate virologic outcomes on TLD amongst consecutive adults who had virologic failure on a PI (lopinavir or atazanavir) 2nd-line regimen in whom GART was performed. We compared outcomes in patients switched to TLD between August 2019 and March 2022, and those continuing the same PI regimens or switched to DRV/r-based regimens. Patients were followed up until the primary outcome (time to HIV-1 RNA <400 copies/mL), or censored at death, loss to follow-up, or July 2023.
Results:
355 patients were enrolled: 133 switched to TLD, 101 switched to DRV/r-based regimens (84% switched to DRV/r with dolutegravir), and 121 continued the same PI regimens. Median age was 40 years (IQR 34–46), 69% female, median duration on PI regimens was 65 months (IQR 34–91), median HIV-1 RNA was 4.7 log10 copies/mL (IQR 4.1–5.2) at the time of PI regimen failure. 36% and 38% had resistance to lopinavir and atazanavir, respectively. Baseline characteristics were similar between the 3 groups. In patients with PI resistance, 44/47 (94%) in the TLD group suppressed to HIV-1 RNA <400 copies/mL compared to 89/99 (90%) in the DRV/r group (HR 1.25, 95% CI 0.86–1.82, Figure A). In patients without PI resistance, 66/86 (77%) in the TLD group suppressed to HIV-1 RNA <400 copies/mL compared to 43/120 (36%) in the continue PI group (HR 4.35, 95% CI 2.78–7.14, Figure B). Death occurred in 1/128 (0.8%) in the TLD group, 3/95 (3.2%) in the DRV/r group, and 8/114 (7.0%) in the continue PI group at 6 months. Two (2%) patients in the TLD group were known to have developed virologic failure with dolutegravir resistance at 1-3 years.
Conclusions:
Among patients with virologic failure on PI-based 2nd-line ART, switching to TLD when there was no PI resistance was associated with higher virologic suppression likely due to improved adherence. Virologic outcomes were similar in patients with PI resistance switched to DRV/r or TLD.
