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

Author:

Nduva George M12,Otieno Frederick3,Kimani Joshua45,Sein Yiakon2,Arimide Dawit A1,Mckinnon Lyle R456,Cholette Francois57,Lawrence Morris K8,Majiwa Maxwell9,Masika Moses10,Mutua Gaudensia10,Anzala Omu10,Graham Susan M211ORCID,Gelmon Larry45,Price Matt A1213,Smith Adrian D14,Bailey Robert C315,Medstrand Patrik1,Sanders Eduard J214,Esbjörnsson Joakim114ORCID,Hassan Amin S12ORCID

Affiliation:

1. Department of Translational Medicine, Lund University , Lund , Sweden

2. Department of HIV/STI, KEMRI/Wellcome Trust Research Programme , PO Box 230-80108 Kilifi , Kenya

3. Nyanza Reproductive Health Society , Kisumu , Kenya

4. Department of Medical Microbiology, University of Nairobi , Nairobi , Kenya

5. Department of Medical Microbiology and Infectious Diseases, University of Manitoba , Winnipeg , Canada

6. Centre for the AIDS Programme of Research in South Africa (CAPRISA) , Durban , South Africa

7. National Microbiology Laboratory at the JC Wilt Infectious Diseases Research Centre, Public Health Agency of Canada , Winnipeg , Canada

8. Department of Biochemistry and Biotechnology, Pwani University , Kilifi , Kenya

9. Kenya Medical Research Institute/Centre for Global Health Research , Kisumu , Kenya

10. KAVI Institute of Clinical Research, University of Nairobi , Nairobi , Kenya

11. Department of Medicine, Global Health and Epidemiology, University of Washington , Seattle , USA

12. IAVI , NewYork , USA

13. Department of Epidemiology and Biostatistics, University of California San Francisco , San Francisco, CA , USA

14. Nuffield Department of Medicine, University of Oxford , Oxford , UK

15. Division of Epidemiology & Biostatistics, University of Illinois at Chicago , Chicago, IL , USA

Abstract

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.

Funder

New Partnership for Africa’s Development (NEPAD) Planning

Wellcome Trust

UK government

Swedish Research Council

Swedish Society for Medical Research

IAVI

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology,Microbiology (medical)

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