Longitudinal Dynamics of Intact HIV Proviral DNA and Outgrowth Virus Frequencies in a Cohort of Individuals Receiving Antiretroviral Therapy.

The Journal of Infectious Diseases
Shane D FalcinelliNancie M Archin

Abstract

The replication-competent human immunodeficiency virus (HIV) reservoir is the major barrier to cure. The quantitative viral outgrowth assay (QVOA), the gold-standard method to quantify replication-competent HIV, is resource intensive, which limits its application in large clinical trials. The intact proviral DNA assay (IPDA) requires minimal cell input relative to QVOA and quantifies both defective and intact proviral HIV DNA, the latter potentially serving as a surrogate marker for replication-competent provirus. However, there are limited cross-sectional and longitudinal data on the relationship between IPDA and QVOA measurements. QVOA and IPDA measurements were performed on 156 resting CD4 T-cell (rCD4) samples from 83 antiretroviral therapy-suppressed HIV-positive participants. Longitudinal QVOA and IPDA measurements were performed on rCD4 from 29 of these participants. Frequencies of intact, defective, and total proviruses were positively associated with frequencies of replication-competent HIV. Longitudinally, decreases in intact proviral frequencies were strikingly similar to that of replication-competent virus in most participants. In contrast, defective proviral DNA frequencies appeared relatively stable over time in m...Continue Reading

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Citations

Dec 29, 2020·Journal of Virology·Christian GaeblerMichel C Nussenzweig
May 6, 2021·Cell Reports Medicine·Claire N LevyFlorian Hladik
May 17, 2021·Current Opinion in HIV and AIDS·Aurelija CicilionytėAlexander O Pasternak
Jul 3, 2021·Frontiers in Microbiology·Cynthia LunguFrancesco A Procopio
Jun 29, 2021·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Sherazaan D IsmailWendy A Burgers

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