TEMPORAL TRENDS AND TRANSMISSION DYNAMICS OF PRE-TREATMENT HIV-1 DRUG RESISTANCE WITHIN AND BETWEEN RISK GROUPS IN KENYA, 1986-2020

Abstract

ABSTRACTBackgroundEvidence on the distribution of pre-treatment HIV-1 drug resistance (HIVDR) by risk groups is limited in Africa. We assessed prevalence, trends, and transmission dynamics of pre-treatment HIVDR within-and-between men who have sex with men (MSM), people who inject drugs (PWID), female sex workers (FSW), heterosexuals (HET), and children infected perinatally in Kenya.MethodsHIV-1 partialpolsequences from antiretroviral-naïve samples collected between 1986-2020 were used. Pre-treatment RTI, PI and INSTI mutations were assessed using the Stanford HIVDR database. Phylogenetics methods were used to determine and date transmission clusters.ResultsOf 3567 sequences analysed, 550 (15.4%, 95% CI: 14.2-16.6) had at least one pre-treatment HIVDR mutation, which was most prevalent amongst children (41.3%), followed by PWID (31.0%), MSM (19.9%), FSW (15.1%) and HET (13.9%). No INSTI resistance mutations were detected. Among HET, pre-treatment HIVDR increased from 6.6% in 1986-2005 to 20.2% in 2011-2015 but dropped to 6.5% in 2016-2020. Overall, 22 clusters with shared pre-treatment HIVDR mutations were identified. The largest was a K103N mutation cluster involving 16 MSM sequences sampled between 2010-2017, with an estimated tMRCA of 2005 (HPD, 2000-2008). This lineage had a growth rate=0.1/year and R0=1.1, indicating propagation over 12 years among ART-naïve MSM in Kenya.ConclusionsCompared to HET, children and key populations had higher levels of pre-treatment HIVDR. Introduction of INSTIs after 2016 may have reversed the increase in pre-treatment RTI mutations in Kenya. Continued surveillance of HIVDR, with a particular focus on children and key populations, is warranted to inform treatment strategies in Kenya.SummaryCompared to the heterosexual population, key populations had higher levels of pre-treatment HIV-1 drug resistance (HIVDR). Propagation of HIVDR was risk-group exclusive. Introduction of integrase inhibitors abrogated propagation of reverse transcriptase inhibitors mutations among the heterosexual, but not key populations.