Early antiretroviral therapy with raltegravir generates sustained reductions in HIV reservoirs but not lower T-cell activation levels.

Abstract

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 < 0.01; integrated; CHI = 2.64 > 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.

• Authors: William J Hey-Cunningham, John M Murray, Ven Natarajan, Janaki Amin, Cecilia L Moore, Sean Emery, David A Cooper, John Zaunders, Anthony D Kelleher, Kersten K Koelsch, PINT study team
• Journal: AIDS (London, England) (AIDS) Vol. 29 Issue 8 Pg. 911-9 (May 15 2015) ISSN: 1473-5571 [Electronic] England
• PMID: 25730509 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-HIV Agents
• DNA, Viral
• Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
• RNA, Viral
• Raltegravir Potassium

Topics

• Anti-HIV Agents (therapeutic use)
• Antiretroviral Therapy, Highly Active
• CD4 Lymphocyte Count
• CD4-Positive T-Lymphocytes (immunology, virology)
• CD8-Positive T-Lymphocytes (immunology)
• Cohort Studies
• Cross-Sectional Studies
• DNA, Viral (blood)
• Drug Therapy, Combination
• Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination (therapeutic use)
• HIV Infections (drug therapy)
• HIV-1
• Humans
• Immunophenotyping
• Lymphocyte Activation (immunology)
• RNA, Viral (blood)
• Raltegravir Potassium (therapeutic use)
• Viral Load