Dolutegravir-associated resistance gene mutations among people living with human immunodeficiency virus in Malawi.
Date
2024
Authors
Hussein, Felistus Zumazuma Kanjira
Journal Title
Journal ISSN
Volume Title
Publisher
The University of Zambia
Abstract
The emergence of drug resistance among Human Immunodeficiency Virus (HIV) patients poses a significant challenge to the success of antiretroviral therapy (ART) programs globally. In Malawi, where HIV prevalence remains a major public health concern, the incorporation of Dolutegravir (DTG) into first-line ART regimens has demonstrated significant promise in improving treatment outcomes. However, the development of resistance to DTG threatens these advancements, necessitating continuous monitoring and adjustments in treatment strategies. This retrospective study identified HIV drug resistance mutations associated with DTG use among individuals living with HIV in Malawi. Data from HIV-positive individuals aged 15 to 60 years, undergoing routine ART monitoring, were evaluated. Patients with high viral loads (≥ 1000 copies/ml) were included, and HIV-1 pol gene sequences were examined to identify mutations linked to DTG resistance. Phylogenetic analysis was performed to assess the relatedness of samples
with resistance mutations. A total of 91 sequences from various districts in Malawi were reviewed, comprising 60.4% females and 39.6% males. DTG resistance mutations were found 15.4% of samples, with females accounting for 57.1% and males for 42.9% of those affected. G118R/R, G140A, Q148H/R, and R263K mutations associated DTG resistance, to varying levels, were identified. Among the 14 cases, 50% exhibited high-level
resistance, 28% intermediate resistance, and 14.3% low resistance potential. The findings indicate a widespread distribution of DTG resistance mutations across Malawi, with evidence of both isolated and clustered patterns of resistance mutation from different districts emergence suggesting transmission of resistance within the communities. These DTG resistance mutations impact treatment outcomes by reducing the drug's binding
efficiency to the integrase enzyme, which is essential for HIV replication inhibition. Mutations such as G118R and Q148H/R significantly impair DTG’s potency, potentially leading to treatment failure, virological rebound, and an increased risk of onward transmission of drug-resistant HIV strains. Additionally, these mutations can limit future ART options by conferring cross-resistance to other Integrase Strand Transfer Inhibitors (InSTIs), complicating treatment regimens and increasing healthcare costs.
Description
Thesis of Master in One Health Laboratory Diagnostic.