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

WJ Hey-Cunningham, JM Murray, V Natarajan, J Amin… - Aids, 2015 - journals.lww.com
WJ Hey-Cunningham, JM Murray, V Natarajan, J Amin, CL Moore, S Emery, DA Cooper…
Aids, 2015journals.lww.com
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 …
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 log 10 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: log 10 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.
Lippincott Williams & Wilkins