Genetic diversity and drug resistance mutations of HIV-1 in Ghana: a systematic review of two decades

Background: Since the roll-out of antiretroviral therapy (ART), there has been a significant reduction in Human Immunodeficiency Virus 1 (HIV-1) related mortality and morbidity. Nonetheless, drug resistance has emerged significantly, affecting treatment outcomes, but there is limited surveillance of HIV-1 drug resistance and subtype diversity, which is critical for clinical decision-making on therapeutic choices as well as public health control measures. The goal of this systematic review was to analyze data from 2004 to 2024 on subtype diversity and drug resistance mutations (DRMs) among persons living with HIV-1 in Ghana. Methods: We searched PubMed, Scopus, Cochrane CENTRAL, CINAHL Complete, Web of Science, and Google Scholar for cross-sectional and longitudinal studies reporting on HIV-1 subtype diversity, drug resistance, or both among individuals in Ghana published from 2004 to 2024 and reviewed according to PRISMA guidelines. The protocol for this review was registered with PROSPERO (CRD42024529606). Results: A total of 2472 studies were screened, 28 were selected for full-text review, and 18 were included. The overall sample size was 2001 individuals. HIV-1 subtypes observed were CRF02_AG (68.9%), A (2.2%), A3 (1.7%), B (2.1%), C (0.6%), G (3.5%), CRF06_cpx (3.3%), CRF09_cpx (0.6%), and other recombinant forms (16.8%). Only one occurrence was observed each for Subtypes D and K. Key DRMs for NRTIs were documented, with M184V/I detected at 41.2%, followed by M41L (15.4%) and T215Y/F (11.8%). For NNRTIs, DRMs were in the set as K103N (28.4%), G190A/S (10.1%), and V106I/AT (10.7%). The DRMs for PI were primarily marked by M46I/L (25.0%), while I54V, L90M, and V82A were each identified in 12.5% of cases. The INSTIs accessory mutations observed were L74I/M (46.7%), E157Q (20.0%), G163R/K and T97A (13.3% each). Only two studies analyzed sequences for DRMs from the integrase gene; however, these were accessory DRMs and are not known to produce resistance to the current INSTI regimen. Also, mutational profiles varied notably by ART history, and key mutations in NRTIs, NNRTIs, and INSTIs were significantly associated with ART experience. Conclusion: The findings reveal CRF02_AG predominance and a considerable increase in NNRTI DRMs, highlighting the need for tailored therapies and continued surveillance to address emerging resistance in Ghana.