Early and prolonged antiretroviral therapy is associated with an HIV-1-specific T-cell profile comparable to that of long-term non-progressors

• Published in: PloS one 2011-04, Vol.6 (4), p.e18164
• Main Authors: Cellerai, Cristina, Harari, Alexandre, Stauss, Hans, Yerly, Sabine, Geretti, Anna-Maria, Carroll, Anne, Yee, Thynn, Ainsworth, Jonathan, Williams, Ian, Sweeney, John, Freedman, Andrew, Johnson, Margaret, Pantaleo, Giuseppe, Kinloch-de Loes, Sabine
• Format: Article
• Language: English
• Subjects: Adult; Aged; Anti-HIV Agents - pharmacology; Anti-HIV Agents - therapeutic use; Antiretroviral agents; Antiretroviral drugs; Antiretroviral therapy; Biology; CD4 antigen; CD4 Antigens - metabolism; CD8 antigen; CD8 Antigens - metabolism; Cohort Studies; Comparative analysis; Cytometry; Cytotoxicity; Deoxyribonucleic acid; DNA; Epitopes - immunology; Female; Flow cytometry; gag Gene Products, Human Immunodeficiency Virus - immunology; Gene Expression Regulation - drug effects; Genotype; Highly active antiretroviral therapy; Histocompatibility Antigens Class I - genetics; HIV; HIV Infections - blood; HIV Infections - drug therapy; HIV Infections - genetics; HIV Infections - immunology; HIV Long-Term Survivors; HIV-1 - drug effects; HIV-1 - immunology; HIV-1 - physiology; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; Immunology; Interferon; Interleukin 2; Leishmania major; Lymphocytes T; Male; Medicine; Middle Aged; Perforin; Perforin - metabolism; Peripheral blood; Replication; Ribonucleic acid; RNA; Seroconversion; Species Specificity; T cell receptors; T cells; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; T-Lymphocytes - virology; Time Factors; Tumor necrosis factor-α; Viral infections; Virus Replication - drug effects; γ-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0018164

Intervention with antiretroviral treatment (ART) and control of viral replication at the time of HIV-1 seroconversion may curtail cumulative immunological damage. We have therefore hypothesized that ART maintenance over a very prolonged period in HIV-1 seroconverters could induce an immuno-virological status similar to that of HIV-1 long-term non-progressors (LTNPs). We have investigated a cohort of 20 HIV-1 seroconverters on long-term ART (LTTS) and compared it to one of 15 LTNPs. Residual viral replication and reservoirs in peripheral blood, as measured by cell-associated HIV-1 RNA and DNA, respectively, were demonstrated to be similarly low in both cohorts. These two virologically matched cohorts were then comprehensively analysed by polychromatic flow cytometry for HIV-1-specific CD4(+) and CD8(+) T-cell functional profile in terms of cytokine production and cytotoxic capacity using IFN-γ, IL-2, TNF-α production and perforin expression, respectively. Comparable levels of highly polyfunctional HIV-1-specific CD4(+) and CD8(+) T-cells were found in LTTS and LTNPs, with low perforin expression on HIV-1-specific CD8(+) T-cells, consistent with a polyfunctional/non-cytotoxic profile in a context of low viral burden. Our results indicate that prolonged ART initiated at the time of HIV-1 seroconversion is associated with immuno-virological features which resemble those of LTNPs, strengthening the recent emphasis on the positive impact of early treatment initiation and paving the way for further interventions to promote virological control after treatment interruption.