Genetic Diversity and Drug Resistance Patterns among HIV-1 Positive Youths with Non-Suppressed Viral Load in South Rift Valley, Kenya

Abstract

Background: Globally, Human immunodeficiency virus (HIV) is a leading cause of morbidity and mortality. The fundamental Antiretroviral Therapy (ART) goal is to curb the spread of HIV and enhance the survival of HIV infected patients. Despite the tremendous benefits of ART, HIV treatment and management failures among the youth have been attributed to nonadherence to drug regimens and viral mutations leading to the emergence of drug resistance. Therefore, this study aimed to determine the genetic diversity and HIV-1 drug resistance patterns among the youth aged 15-24 years with non-suppressed viral load in the South Rift Valley Region (SRV), Kenya. Methods: A cross-sectional study design was adopted to select a total of 120 plasma samples from HIV-1-positive youth who had been on different ART regimens for over six months. Remnant plasma samples with >1000 copies/ml from real-time PCR using the Abbott RealTime HIV-1 m2000rt quantitative kit were sequenced using the HIV-1 genotyping kit with integrase between April 2024 and October 2024. The target genes were Reverse Transcriptase, Protease and Integrase of the pol gene. HIV-1 level of drug resistance was evaluated using the Exatype Sanger analysis tool. Mutation patterns were ascertained by analysing FASTA files using the drug resistance HIV Stanford database. The subtypes of HIV-1 were analysed by the REGA HIV subtyping tool, and Maximum-likelihood phylogenetic trees and annotations of the mutations were constructed using the integrated Tree of Life. Results: Sequencing was completed for 99 samples, and Tenofovir Disoproxil Fumarate + Lamivudine + Dolutegravir (TDF/3TC/DTG) was the most commonly prescribed antiretroviral regimen across all age groups. The predominant HIV subtype was A1 (83%). Drug resistance was attributed to mutation, M184V (31.4%) associated with resistance to Emtricitabine and Lamivudine, K103N (20.9%) and G190A (15.1%) resistance to efavirenz, nevirapine and rilpivirine, G118R (5.7%) to raltegravir, elvitegravir and bictegravir. Conclusion: There was high genetic diversity of HIV-1 among the youths aged between 15 and 24 years, and subtype A1 is the dominant circulating form of HIV-1 in the South Rift Valley region. Understanding the evolutionary relationships of these strains provides insights into their genetic diversity and transmission.