Early antiretroviral therapy with raltegravir generates sustained reductions in HIV reservoirs but not lower T-cell activation levels
Autor: | David A. Cooper, John Zaunders, William J. Hey-Cunningham, Anthony D. Kelleher, Sean Emery, Cecilia L. Moore, Ven Natarajan, Kersten K. Koelsch, John M. Murray, Janaki Amin |
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Rok vydání: | 2015 |
Předmět: |
CD4-Positive T-Lymphocytes
Anti-HIV Agents T cell Immunology HIV Infections CD8-Positive T-Lymphocytes CD38 Lymphocyte Activation Emtricitabine Immunophenotyping Cohort Studies Pharmacotherapy Antiretroviral Therapy Highly Active Raltegravir Potassium medicine Humans Immunology and Allergy business.industry Emtricitabine Tenofovir Disoproxil Fumarate Drug Combination Viral Load Raltegravir CD4 Lymphocyte Count Cross-Sectional Studies Infectious Diseases medicine.anatomical_structure DNA Viral Cohort HIV-1 RNA Viral Drug Therapy Combination business Viral load CD8 medicine.drug |
Zdroj: | AIDS. 29:911-919 |
ISSN: | 0269-9370 |
Popis: | OBJECTIVE: The initiation of antiretroviral therapy (ART) during primary infection may offer clinical benefits for HIV-infected individuals by reducing HIV DNA reservoir size and chronic T-cell activation. Current evidence for the advantages of early ART, however, are mostly derived from cross-sectional studies, with the long-term benefits yet to be ascertained.DESIGN/METHODS: We conducted an open-label, nonrandomized study, monitoring for 3 years: plasma viral load (pVL), T-cell phenotypes, and peripheral CD4(+) T-cell associated total, integrated and 2-long terminal repeat HIV DNA species. The study included 16 treatment-naive individuals initiating ART with raltegravir and Truvada during either primary (PHI, n = 8) or chronic (CHI, n = 8) HIV infection.RESULTS: ART initiated during PHI compared with CHI generated significant reductions of peripheral CD4(+) T-cell HIV DNA reservoirs that were sustained for 3 years of therapy. Median log10 HIV DNA copies/10(6) CD4(+) T cells at the final visit: total; CHI = 3.23 > PHI = 2.72, P PHI = 1.77, P < 0.01. Similar trends were observed for pVL, however, did not reach significance: log10 HIV RNA copies/ml plasma at the final visit: CHI = 1.3 ≥ PHI = 0.39, P = 0.08. Both cohorts displayed similar and elevated levels of CD38/HLA-DR coexpression on CD4(+) and CD8(+) T cells relative to uninfected healthy controls.CONCLUSION: The reduction in HIV DNA reservoirs generated by the early initiation of ART was sustained for 3 years of therapy. Although the PHI cohort trended to lower levels of pVL, and pVL was associated with CD8(+) T-cell activation, no differences in T-cell activation were observed between the PHI and CHI groups. |
Databáze: | OpenAIRE |
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