Background:
People living with HIV (PLHIV) who switch to a dolutegravir (DTG)-based regimen with HIV-1 viremia and possibly NRTI resistance may be at a higher risk of virologic failure and integrase strand transfer inhibitor (INSTI) resistance. We report viral load (VL) and drug resistance from the 2-year follow-up of the DTG SWITCH study in Malawi and Zambia. In Malawi, PLHIV were switched irrespective of their VL value whereas in Zambia, only patients with the last routine VL <1000 copies/mL were switched.
Methods:
We present proportions of patients with viremia (VL >400 copies/mL) 2 years after switching (+/-90 days) to DTG-based first-line ART between Nov/2019 and Dec/2020, by country and VL at switch. We calculated relative risks (RR) of viremia at 2 years, with exact 95% confidence intervals (CI). We also report major integrase drug resistance mutations (DRM) detected in 2-year samples among participants with VL >1000 copies/mL.
Results:
Of PLHIV switched during the study period, 1422/1458 (97.5%) in Malawi and 1410/1417 (99.5%) in Zambia had a viral load measurement available at switch and were eligible. Most participants were women; 1409 (91%) in Malawi and 1169 (83%) in Zambia; median time on ART was 6.1 years. Seventy-seven PLHIV were viremic at baseline in Malawi (5.4%), compared to 42 (3.0%) in Zambia. In Malawi, 1149/1422 (81%) participants had a 2-year VL available: among those viremic at switch, 27.8% were viremic at 2 years compared to 3.7% among those suppressed at switch, RR=7.8 (4.2-13.4). In Zambia, 1248/1410 (89%) participants had a 2-year VL; the corresponding percentages were 5.1% and 1.7%, RR=3.1 (0.4-12.0). Viremia at switch was strongly associated with an increased risk of viremia at 2 years in Malawi but not in Zambia (Table). Integrase sequencing was successful for 45 of 62 samples with VL ≥1000 c/mL at 2 years. Two had major INSTI DRM: G118R, E138K, T66A (Malawi); G118R, E138K (Zambia); and both were viremic at switch and/or 1 year. The sample from Malawi also contained NRTI mutations (D67N, K70R, M184V, K219Q).
Conclusions:
Viremia was uncommon two years after the programmatic switch to DTG-based first-line ART, and only two cases of emergent DTG drug resistance were detected. Still, PLHIV switching to DTG with viremia had a substantially higher risk of viremia at 2 years than PLHIV with viral suppression at switch. The Zambian policy of only switching virologically suppressed patients may have reduced the risk of developing viremia and virologic failure on DTG.
