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Temporal trends and transmission dynamics of pre-treatment HIV-1 drug resistance within and between risk groups in Kenya, 1986-2020

Temporal trends and transmission dynamics of pre-treatment HIV-1 drug resistance within and between risk groups in Kenya, 1986-2020

George M Nduva 1 2Frederick Otieno 3Joshua Kimani 4 5Yiakon Sein 2Dawit A Arimide 1Lyle R Mckinnon 4 5 6Francois Cholette 5 7Morris K Lawrence 8Maxwell Majiwa 9Moses Masika 10Gaudensia Mutua 10Omu Anzala 10Susan M Graham 2 11Larry Gelmon 4 5Matt A Price 12 13Adrian D Smith 14Robert C Bailey 3 15Patrik Medstrand 1Eduard J Sanders 2 14Joakim Esbjörnsson 1 14Amin S Hassan 1 2

Affiliations
  • 1Department of Translational Medicine, Lund University, Lund, Sweden.
  • 2Department of HIV/STI, KEMRI/Wellcome Trust Research Programme, PO Box 230-80108 Kilifi, Kenya.
  • 3Nyanza Reproductive Health Society, Kisumu, Kenya.
  • 4Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya.
  • 5Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Canada.
  • 6Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa.
  • 7National Microbiology Laboratory at the JC Wilt Infectious Diseases Research Centre, Public Health Agency of Canada, Winnipeg, Canada.
  • 8Department of Biochemistry and Biotechnology, Pwani University, Kilifi, Kenya.
  • 9Kenya Medical Research Institute/Centre for Global Health Research, Kisumu, Kenya.
  • 10KAVI Institute of Clinical Research, University of Nairobi, Nairobi, Kenya.
  • 11Department of Medicine, Global Health and Epidemiology, University of Washington, Seattle, USA.
  • 12IAVI, NewYork, USA.
  • 13Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA.
  • 14Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • 15Division of Epidemiology & Biostatistics, University of Illinois at Chicago, Chicago, IL, USA.
  • PMID: 38091580
  • DOI: 10.1093/jac/dkad375
Abstract

Background: Evidence on the distribution of pre-treatment HIV-1 drug resistance (HIVDR) among risk groups is limited in Africa. We assessed the prevalence, trends and transmission dynamics of pre-treatment HIVDR within and between MSM, people who inject drugs (PWID), female sex workers (FSWs), heterosexuals (HETs) and perinatally infected children in Kenya.

Methods: HIV-1 partial pol sequences from antiretroviral-naive individuals collected from multiple sources between 1986 and 2020 were used. Pre-treatment reverse transcriptase inhibitor (RTI), PI and integrase inhibitor (INSTI) mutations were assessed using the Stanford HIVDR database. Phylogenetic methods were used to determine and date transmission clusters.

Results: Of 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%), FSWs (15.1%) and HETs (13.9%). Overall, pre-treatment HIVDR increased consistently, from 6.9% (before 2005) to 24.2% (2016-20). Among HETs, pre-treatment HIVDR increased from 6.6% (before 2005) to 20.2% (2011-15), but dropped to 6.5% (2016-20). Additionally, 32 clusters with shared pre-treatment HIVDR mutations were identified. The majority of clusters had R0 ≥ 1.0, indicating ongoing transmissions. The largest was a K103N cluster involving 16 MSM sequences sampled between 2010 and 2017, with an estimated time to the most recent common ancestor (tMRCA) of 2005 [95% higher posterior density (HPD), 2000-08], indicating propagation over 12 years.

Conclusions: Compared to HETs, children and key populations had higher levels of pre-treatment HIVDR. Introduction of INSTIs after 2017 may have abrogated the increase in pre-treatment RTI mutations, albeit in the HET population only. Taken together, our findings underscore the need for targeted efforts towards equitable access to ART for children and key populations in Kenya.

© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.