1016. Global trends in Integrase Strand Transfer Inhibitor resistance among HIV-1B Infected Patients

Abstract

BackgroundIntegrase strand transfer inhibitors (INSTIs), a new class of antiretroviral (ART) therapy for HIV, have quickly become a cornerstone of ART regimens globally. Here, we present the prevalence of INSTI resistance globally and over time among people living with HIV/AIDS (PLWHA), clade B.MethodsTo characterize trends in INSTI resistance, we conducted a literature search of articles published after 2010 via Pubmed and posters/abstracts from the Conference on Retroviruses and Opportunistic Infections (CROI) from 2016-2020. Included in our analysis are studies that include more than 100 individuals with INSTI resistance testing, who are infected with HIV clade B. We stratified the studies by country and by time period. We defined two time periods, 2008-2015 during which primarily first generation of INSTI were used (raltegravir and elvitegravir), and 2015-2020 during which second generation INSTIs (dolutegravir and bictegravir) use became widespread. We considered drug-resistance associated mutations (DRAM) in both ART-naive and in ART-experienced PLWHA.ResultsOverall, we reviewed 31 papers and 11 CROI abstracts that met the inclusion criteria. We observed that prevalence of DRAM in naïve patients is low globally and has remained low over time, ranging from 0%-8%. Meanwhile, we observed a downward trend in DRAM among INSTI-experienced patients from the 2008-2015 period to the 2015-2020 period from 11%-47.6% to 8%- 32.1%, reflecting higher barrier to resistance described in vivo among the 2nd generation INSTIs. See table below.INSTI Resistance Summary Results Table ConclusionHere, we have analyzed the trends in INSTI prevalence over time and in different countries for HIV1 clade B. We demonstrate that globally, INSTI DRAM among INSTI-naïve patients are rare and incidence does not increase significantly over time despite increased usage. In addition, published studies showed a downward trend in INSTI DRAM among INSTI-experienced patients after 2015, reflecting the higher barrier to resistance in the second generation INSTIs. The most commonly occurring INSTI DRAMs observed were N155H (more common in the era of f1st generation INSTI), Q148H/K/R, and G140S. As INSTI usage continues to increase globally, continued vigilance and surveillance is needed to monitor continued INSTI resistance over time.Disclosures All Authors: No reported disclosures