ABSTRACT
The World Health Organization (WHO) has put forth recommendations for the use of integrase (IN) strand transfer inhibitors (INSTIs) to be part of the first-line combination antiretroviral therapy regimen to treat HIV infections. The knowledge of pretreatment drug resistance against INSTIs is still scarce in resource-limited settings (RLS). We characterized the integrase gene to identify resistance-associated mutations (RAMs) in 56 INSTI-naive patient viral sequences from Cameroon. Study analysis used 37 sequences with fragment size ≥500 bp or of good quality .The majority of the sequences were identified as CRF02_AG 54.% (n = 20/37) and 45.9% (n = 17/37), other subtype viral sequences include (A, CRF36_cpx, F,G, and C). A total of 18.9% (n = 7/37) of the sequences had RAMs, with only 5.4% (n = 2/37) having major RAMs (Y143R/C/D/G and P145S), against INSTIs. Accessory RAMs were present in 8.1% (n = 3/37) of the sequences, of which one sequence contained solely E157Q, and another Q95K. One patient sequence had three accessory RAMs (G140E, E157Q, and G163R). We identified major RAMs to INSTIs, which might have a potential clinical impact to dolutegravir rollout in RLS, including Cameroon. This is the first study to describe RAMs among INSTI-naive people living with HIV-1 (PLHIV-1) infected with CRF02_AG and other subtypes in Cameroon.
Subject(s)
HIV Infections/virology , HIV Integrase/genetics , HIV-1/genetics , Mutation , Polymorphism, Genetic , Cameroon , Cohort Studies , Drug Resistance, Viral/genetics , Genotype , HIV Infections/drug therapy , HIV Integrase Inhibitors/therapeutic use , HIV-1/enzymology , Humans , Phylogeny , RNA, Viral/genetics , Sequence Analysis, DNAABSTRACT
INTRODUCTION: The emergence of drug resistance mutations (DRMs) has been a major threat for successful lifelong combination antiretroviral therapy (cART), especially for HIV-vertically infected children within the context of the prevention of mother-to-child transmission (PMTCT). This study aimed to evaluate DRMs amongst immune competent treatment-naïve children in Cameroon. METHODS: A cross-sectional study was conducted between 2015 and 2016 amongst 55 proxy consented HIV-1 positive children, aged 9 months to 6 years. They were all immune competent, cART naïve and with unknown history of PMTCT. CD4 cell counts and genotypic drug resistance testing were performed using standard methods. RESULTS: Levels of DRMs to protease (PR) inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs were 27.6%, 3.7% and 40.7%, respectively. Only minor DRMs were observed for PR. The observed mutations for NRTI were K65R, T215I and K219E (33.0% each) and for NNRTI: V106M, Y181C and Y188H (6.0% each). Only minor accessory mutations were found in the integrase (IN) region. CONCLUSION: Despite widely available cART we still observe naïve HIV children, especially from the rural communities. We observe that a proportion of study participants had HIV-1 drug resistance associated mutations (RAMs). Data generated could help strengthen the current PMTCT programmes within the country. There is a need to upscale approaches for drug resistance testing for children in Cameroon and many other resource-limited settings.