Associations Between Multiple Measures of HIV-1 Persistence in Persons on Suppressive Antiretroviral Therapy

Abstract

Clinical research to achieve antiretroviral therapy-free remission requires quantitative assays of the HIV-1 reservoir. Intact proviral DNA (IPD) measurement has greater throughput than the quantitative viral outgrowth assay (QVOA). In 25 individuals with well-documented long-term viral suppression, IPD levels and infectious units per million CD4+ T cells by QVOA strongly correlated (r = 0.59, P = .002), and IPD correlated with total cell-associated HIV-1 DNA and cell-associated HIV-1 RNA (r = 0.62 and r = 0.59, P ≤ .002). IPD may provide an accessible marker of inducible replication-competent virus, total numbers of infected cells, and cellular expression of HIV-1 RNA.

Keywords: HIV-1 cure; HIV-1 expression; HIV-1 reservoir; QVOA; intact proviruses.

Figure 1.

Cell-associated HIV-1 measurements in people with HIV-1 on long-term ART. Boxes display median, quartile 1, and quartile 3 levels. Total DNA is the sum of intact, 5ʹ defective, and hypermutated/3ʹ defective HIV-1 proviruses from the intact proviral DNA assay. Total HIV-1 DNA was also estimated by measuring integrase DNA. Circles represent participants who had initiated ART in chronic HIV-1 infection, squares represent ART initiation in acute HIV-1 infection, and triangles represent participants who had initiated ART as HIV-1 controllers. Abbreviations: ART, antiretroviral therapy; HIV-1, human immunodeficiency virus-1; IUPM, infectious units per million CD4⁺ T cells by the quantitative viral outgrowth assay; nd, not detected.

Figure 2.

Spearman correlations between IPD levels and the other cell-associated HIV-1 measurements. Total DNA is the sum of intact, 5ʹ defective, and hypermutated/3ʹ defective HIV-1 proviruses from the intact proviral DNA assay. Total HIV-1 DNA was also estimated by measuring integrase DNA. Abbreviations: HIV-1, human immunodeficiency virus-1; IPD, intact proviral DNA; IUPM, infectious units per million CD4⁺ T cells by the quantitative viral outgrowth assay; nd, not detected by the intact proviral DNA assay.