Long-term treatment outcome and mutational analysis of patients on third-line antiretroviral therapy in programmatic conditions

Background: In low- and middle-income countries where most patients receive standardized third-line ART through national programmes, real-world data are scarce. This study was done to assess the long-term survival, and virological and mutational outcomes of people living with HIV receiving third-line ART between July 2016 and December 2019 in an ART centre in India. Methods: Eighty-five patients were started on third-line ART. Genotypic resistance testing to identify drug resistance mutations in the integrase, reverse transcriptase and protease genes was done at the start of third-line therapy, as well as in those who did not attain virological suppression after 12 months of therapy. Results: Survival was 85% (72/85) at 12 months and 72% (61/85) at the end of follow-up in March 2022. Virological suppression was present in 82% (59/72) and 88% (59/67) at 12 months and at the end of follow-up, respectively. Five out of 13 patients who had virological failure at 12 months showed virological suppression at the end of the study. At the start of third-line therapy, 35% (14/40) and 45% (17/38) of patients had major integrase- and protease-associated mutations, respectively, even though they had never been on integrase inhibitor-based regimens. At 1 year follow-up, among those failing third-line therapy, 33% (4/12) of patients had major integrase mutations, but none had major protease mutations. Conclusions: This study demonstrates good long-term outcome in patients on standardized third-line ART in programmatic conditions with very few mutations in those failing the therapy.