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- Title
HIV DNA Sequencing to Detect Archived Antiretroviral Drug Resistance.
- Authors
Geretti, Anna Maria; Blanco, Jose Luis; Marcelin, Anne Genevieve; Perno, Carlo Federico; Stellbrink, Hans Jurgen; Turner, Dan; Zengin, Tuba
- Abstract
Introduction: Proviral HIV DNA integrated within CD4 T-cells maintains an archive of viral variants that replicate during the course of the infection, including variants with reduced drug susceptibility. We considered studies that investigated archived drug resistance, with a focus on virologically suppressed patients and highlighted interpretative caveats and gaps in knowledge. Results: Either Sanger or deep sequencing can be used to investigate resistance-associated mutations (RAMs) in HIV DNA recovered from peripheral blood. Neither technique is free of limitations. Furthermore, evidence regarding the establishment, maintenance, expression and clinical significance of archived drug-resistant variants is conflicting. This in part reflects the complexity of the HIV proviral landscape and its dynamics during therapy. Clinically, detection of RAMs in cellular HIV DNA has a variable impact on treatment outcomes, modulated by the drugs affected, treatment duration and additional determinants of virological failure, including those leading to suboptimal drug exposure. Conclusions: Sequencing cellular HIV DNA can provide helpful complementary information in treatment-experienced patients with suppressed plasma HIV RNA who require a change of regimen. However, care should be taken when interpreting the results. Presence of RAMs is not necessarily a barrier to treatment success. Conversely, even the most sensitive sequencing techniques will fail to provide a comprehensive view of the HIV DNA archive. To inform treatment decisions appropriately, the overall clinical and treatment history of a patient must always be considered alongside the results of resistance testing. Prospective controlled studies are needed to validate the utility of drug resistance testing using cellular HIV DNA.
- Subjects
ANTIRETROVIRAL agents; DNA sequencing; DRUG resistance; HIV
- Publication
Infectious Diseases & Therapy, 2022, Vol 11, Issue 5, p1793
- ISSN
2193-8229
- Publication type
Article
- DOI
10.1007/s40121-022-00676-y