Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya

Abstract

Introduction in Kenya, about 1.5 million people are living with the Human Immunodeficiency Virus (HIV). Antiretroviral therapy aids in viral suppression. However, drug-resistance threaten the gains of the HIV infection control program. To determine the prevalence of HIV-1 drug-resistant mutations among adults on ARV therapy attending Khunyangu sub-county hospital in Busia County, Kenya, 50 blood samples were analyzed. Methods the samples were collected from November 2019 to January 2020 and tested for HIV-1 viral load. HIV-1 drug-resistance was analyzed through the sequencing of the HIV-1 pol gene. Generated sequences were aligned using RECall (beta v3.05) software. HIV-1 drug-resistance was determined using the Stanford University HIV database. Results females were 34 and males 16. The general prevalence of HIV-1 drug-resistance was 68%. Out of 34 participants on first-line drugs, 59.9% had mutations against these drugs and 5.9% against the second-line drugs. Out of 16 participants on second-line drugs, 43.8% had mutations against these drugs and 50% against the first-line drugs. The prevalence of mutations encoding resistance to Nucleotide reverse transcriptase inhibitors (NRTIs) were 23(46%); Non-nucleotide Reverse transcriptase inhibitors (NNRTIs), 29(58%) and protease inhibitors (PIs), 7(14%). Dual and multi-class HIV-1 drug-resistance prevalence was as follows: NRTIs + NNRTIs 16(32%); NRTIs + NNRTs + PIs 4(8%); NRTIs + PIs 1(2%). A total of 126 mutations were identified. Predominant NNRTIs mutations were K103N (15), Y181C (9), G190A (7), and H221Y (6) NRTIs, M184V (17), Y115F (5) and PIs, I54V (4). Conclusion the study demonstrates a high prevalence of HIV-1 drug-resistance which calls for intervention for the strengthening of health programs.

High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort

“…LADRVs (frequency < 20%) have been associated with an increased risk of virological failure in a dose-dependent manner with respect to mutant load, regardless of medication adherence [34][35][36]. Our results highlight the importance and utility of NGS and high coverage sequencing techniques [34,37,38].…”

“…This is due to the finding that the M184I mutation decreases viral replication fitness and increases viral susceptibility to other ARV drugs TDF, dFT, and AZT [25]. M184 variants were identified in numerous studies within this region [23,37,38]. Interestingly, the M184V variant was not common (<1%, not shown) in this cohort.…”

“…A higher prevalence of IN-associated DRMs was seen in our study than in the others. The majority of studies in Kenya and surrounding countries have not yet included IN sequence data, and the ones that included IN sequence data did not find a high prevalence of INSTI DRMs [34,37,38]. In a recent study of a Congolese population, T97A, a variant conferring reduced susceptibility to INSTIs when acting synergistically with other INSTI mutations, was identified in 11% of the participants [25].…”

“…Each of these variants confers at least low-level resistance to one or more of the currently recommended ARV drugs, except D30N, which confers resistance to NFV, a discontinued PI [20]. Slightly divergent from the guidelines, commonly used medications in Kenya and surrounding countries, as of 2020, include the combined regimens AZT + 3TC + NVP, TDF + 3TC + EFV, and AZT + 3TC + EFV [38]. Twenty-four participants (9%) harbored HIV-1 variants conferring low to high-level resistance to both EFV and NVP, while 41% had resistant mutations to 3TC.…”

Magnitude and predictors of HIV-Drug resistance in Africa: A protocol for systematic review and meta-analysis

“…Some mutations like M184V, M184IV, and D67NS are found in NRTIs and NNRTIs resistant HIV [ 21 , 25 , 26 ]. Moreover, the frequent mutations affecting proteinase inhibitors (PIs) antiretroviral drugs are I54V, M46I, and V82A [ 21 , 28 , 29 , 31 , 32 ].…”