BACKGROUND: In 2021, pediatric Dolutegravir 10 mg tablets (pDTG) became available to children living with HIV in Eswatini. Selection of nucleoside reverse transcriptase inhibitor (NRTI) backbone was genotype guided in clients with a detectable viral load (DVL) on a first-line Protease Inhibitor (PI) regimen.
METHODS: This is a retrospective review of routine data for pediatric clients with VL >1,000 copies/mL on first-line, PI-based antiretroviral therapy (ART) that accessed genotypes before optimization. The National Reference Laboratory performed genotypes in Johannesburg and the Stanford HIVdb Program was used to calculate predicted activity of NRTIs. This abstract will share the most recent VL during the 18 months after optimization.
RESULTS: Thirty clients on first line ABC-3TC-LPV/r (abacavir, lamivudine, lopinavir/ritonavir) with viral loads > 1,000 copies/mL were genotyped. Average age was 2.6 years (50% male, 50% female). Half (50%; 15/30) demonstrated drug pressure (through the presence of M184V(14) or T215S(1) alone) with no or low-level ABC resistance and were optimized to ABC-3TC-DTG. Follow-up VL=400 copies/mL in this cohort was 85% (11/13; 2 LTFU). Wild-type virus was observed in 37% (11/30). These clients were optimized to ABC-3TC-DTG, and subsequent VL =400 copies/mL was observed in 67% (6/9; 1 LTFU, 1 remains on PI). The final 4 clients (13%; 4/30) had high level ABC resistance on genotype and were optimized to AZT-3TC-DTG. VL =400 copies/mL was observed in 75% (3/4), with the remaining 1 viral load <1000 copies/mL. Overall VL suppression (=400 copies/mL) was 77% (20/26) at an average of 5 months after pDTG initiation (1-13 months). No PI mutations were present in this cohort.
CONCLUSIONS: Our cohort demonstrates high re-suppression rates with the introduction of pDTG despite still struggling to reach national suppression targets. However, high level ABC resistance does exist in this young cohort, confirming that in resource limited settings without genotype guidance, some children are being placed on regimens that are not fully active. It is unknown if this is a safe and durable strategy. Protease inhibitor mutations were not routinely identified, suggesting this class of drugs may still be useful in the future should they fail a DTG based regimen.