Archived HIV-1 Drug Resistance Mutations: Role of Proviral HIV-1 DNA Genotype for the Management of Virological Responder People Living with HIV

• Published in: Viruses Vol. 16; no. 11; p. 1697
• Main Authors: Campagna, Roberta, Nonne, Chiara, Antonelli, Guido, Turriziani, Ombretta
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.11.2024; MDPI
• Subjects: Anti-HIV Agents - pharmacology; Anti-HIV Agents - therapeutic use; Antiretroviral drugs; Antiretroviral therapy; Antiviral agents; APOBEC; Deoxyribonucleic acid; DNA; DNA GRT; DNA sequencing; DNA, Viral - genetics; Dosage and administration; Drug resistance; Drug Resistance, Viral - genetics; Drug therapy; Genetic aspects; Genotype; Genotype & phenotype; Genotypes; Genotyping; GLP-1 receptor agonists; HIV; HIV Infections - drug therapy; HIV Infections - virology; HIV patients; HIV-1; HIV-1 - drug effects; HIV-1 - genetics; Human immunodeficiency virus; Humans; Infections; Lymphocytes; Mutation; NGS; Patient outcomes; Plasma; Proviruses - drug effects; Proviruses - genetics; reservoir; Review; Sanger sequencing; Success; Viral Load - drug effects; Viremia; Italy; HIV-1; NGS; Sanger sequencing; reservoir; DNA GRT; APOBEC
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v16111697

Despite its effectiveness in controlling plasma viremia, antiretroviral therapy (ART) cannot target proviral DNA, which remains an obstacle to HIV-1 eradication. When treatment is interrupted, the reservoirs can act as a source of viral rebound, highlighting the value of proviral DNA as an additional source of information on an individual’s overall resistance burden. In cases where the viral load is too low for successful HIV-1 RNA genotyping, HIV-1 DNA can help identify resistance mutations in treated individuals. The absence of treatment history, the need to adjust ART despite undetectable viremia, or the presence of LLV further support the use of genotypic resistance tests (GRTs) on HIV-1 DNA. Conventionally, GRTs have been achieved through Sanger sequencing, but the advances in NGS are leading to an increase in its use, allowing the detection of minority variants present in less than 20% of the viral population. The clinical significance of these mutations remains under debate, with interpretations varying based on context. Additionally, proviral DNA is subject to APOBEC3-induced hypermutation, which can lead to defective, nonviable viral genomes, a factor that must be considered when performing GRTs on HIV-1 DNA.