Unraveling clinical outcomes of long-term cART treatment in HIV-1 patients with or without the Brazilian GWGR motif in the V3 loop

• Published in: Revista do Instituto de Medicina Tropical de São Paulo Vol. 66; p. e38
• Main Authors: Folgosi, Victor Ângelo, Komninakis, Shirley Vasconcelos, Lopes, Luciano, Monteiro, Mariana Amélia, Assone, Tatiane, Fonseca, Luiz Augusto Marcondes, Domingues, Wilson, Leite Junior, Pedro Domingos, Victor, Jefferson Russo, Casseb, Jorge
• Format: Journal Article
• Language: English
• Published: Brazil Instituto de Medicina Tropical de São Paulo 2024
• Subjects: Adult; Amino Acid Motifs; Anti-HIV Agents - therapeutic use; Antiretroviral Therapy, Highly Active; Brazil; CD4 Lymphocyte Count; Cohort Studies; Disease Progression; Female; HIV Envelope Protein gp120 - genetics; HIV Infections - drug therapy; HIV Infections - virology; HIV-1 - drug effects; HIV-1 - genetics; Humans; Male; Middle Aged; Mutation; Original; Treatment Outcome; TROPICAL MEDICINE; Viral Load; Brazil; HIV-1; GWGR signature; Brazil; ART; Subtype B
• ISSN: 1678-9946; 0036-4665; 1678-9946
• DOI: 10.1590/S1678-9946202466038

The presence of genetic mutations in HIV poses a significant challenge, potentially leading to antiretroviral resistance and hampering therapeutic development. The Brazilian population has presented variations in the HIV envelope V3 loop gene, especially the GWGR motif. This motif has been linked to reduced transmission potential and slower CD4+ T cell decline. This study aimed to assess clinical outcomes in patients with HIV-1 infected with strains containing the GWGR motif compared with those without it during long-term cART. A cohort of 295 patients with HIV was examined for the GWGR motif presence in the V3 loop. A total of 58 samples showed the GWGR signature, while 237 had other signatures. Multifactorial analyses showed no significant differences in demographic characteristics, CD4+ cell count, AIDS progression, or mortality between GWGR carriers and others. However, the mean interval between the first positive HIV test and the initial AIDS-defining event was more than two times longer for women carrying the GWGR signature (p = 0.0231). We emphasize the positive impact of cART on HIV/AIDS treatment, including viral suppression, CD4+ cell preservation, and immune function maintenance. Although no significant differences were found during cART, residual outcomes reflecting adherence challenges were observed between diagnosis and the first AIDS-defining event. The previously described outcomes, highlighting statistically significant differences between individuals carrying the GPGR motif compared with those with the Brazilian GWGR motif, may be directly linked to the natural progression of infection before advancements in cART. Presently, these physicochemical aspects may no longer hold the same relevance.