Comprehensive Analysis of HIV-1 Integrase Resistance-Related Mutations in African Countries.

Area of Science:

• Virology
• Molecular Epidemiology
• Public Health

Background:

• Non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance in HIV has increased in sub-Saharan Africa (SSA).
• The World Health Organization (WHO) recommended dolutegravir (DTG) as a preferred first-line antiretroviral therapy (ART) in SSA in 2018.
• HIV-1 genetic diversity in SSA may influence DTG effectiveness and drug resistance mutation (DRM) patterns.

Purpose of the Study:

• To evaluate HIV-1 integrase (IN) DRMs and conserved regions in SSA over 40 years.
• To analyze DRM patterns during the transition to DTG-based ART.
• To understand the impact of HIV subtypes on INSTI resistance.

Main Methods:

• Analysis of published HIV-1 group M, N, O, and P sequences from 1983 to 2023.
• Evaluation of integrase (IN) drug resistance mutations (DRMs) and conserved regions.
• Comparison of DRM frequencies between pre-INSTI and INSTI eras.

Main Results:

• Overall low levels (<1%) of integrase strand transfer inhibitor (INSTI)-DRMs were detected between 1983 and 2023.
• DRMs were found at significantly higher frequencies in the pre-INSTI era (1983-2007) compared to the INSTI era (2008-2023).
• Variability in accessory INSTI-DRMs was associated with different HIV subtypes, impacting DTG susceptibility.

Conclusions:

• Findings offer new insights into INSTI molecular epidemiology and resistance profiles in SSA.
• Ongoing surveillance is crucial to monitor changing resistance patterns.
• Customized treatment strategies are needed to address diverse HIV subtypes and resistance in SSA.