Genetic Diversity in the Capsid Protein-Coding Region of HIV-1 Circulating in Benguela, Angola: Implications for Primary Resistance to the Novel Capsid Inhibitor Lenacapavir

In 2023, the HIV-1 pandemic claimed around 630,000 lives worldwide due to AIDS-related complications. Its burden is significantly heavier in Sub-Saharan Africa, where an increased HIV-1 genetic diversity is common, which increases the risk of resistance to antiretroviral (ARV) drugs. This study aims to update the molecular epidemiology of HIV-1 in Angola, focusing specifically on the gag gene, which is often overlooked, and to assess the potential viability of lenacapavir (LEN)-based ARV therapy in the region. A total of 243 blood samples were collected from ARV-naïve, HIV-infected patients at the General Hospital of Benguela, city of Benguela, Angola. The capsid-encoding region of HIV-1 proviral DNA was amplified by PCR and sequenced. Phylogenetic analysis was performed using the maximum likelihood method, and genome recombinant forms were characterised through bootscanning analysis. Primary resistance mutations to LEN were identified using Stanford University’s HIVdb algorithm. Among the 80 successfully sequenced samples, 13 different genetic forms/subtypes were identified, with unique recombinant forms (URFs) (37.5%, 30/80) and subtype C (31.25%, 25/80) being the most prevalent. Regarding resistance mutations, none were detected, apart from four polymorphic mutations. These findings reinforce Angola’s position as a transitional HIV-1 hotspot between the genetically highly diverse Central Africa and the subtype C-dominated Southern Africa, while also supporting the potential effectiveness of LEN-based regimens for treatment and prevention of HIV-1 infections in the future.