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


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.


CONCLUSIONS
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.
aThe Kirby Institute, UNSW Australia, Sydney bCentre for Applied Medical Research, St Vincent's Hospital Sydney, Sydney cSchool of Mathematics and Statistics, UNSW Australia, Sydney, Australia dLeidos Biomedical Research Inc, Frederick, Maryland, USA eSt Vincent's Hospital Sydney, Sydney, Australia. *Dr Anthony D. Kelleher and Dr Kersten K. Koelsch contributed equally to the writing of this article.
William J
WJ
Hey-Cunningham
John M
JM
Murray
Ven
V
Natarajan
Janaki
J
Amin
Cecilia L
CL
Moore
Sean
S
Emery
David A
DA
Cooper
John
J
Zaunders
Anthony D
AD
Kelleher
Kersten K
KK
Koelsch
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004279:DNA, Viral / Q000097:blood; D004359:Drug Therapy, Combination; D000069480:Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology*; D012367:RNA, Viral / Q000097:blood; D000068898:Raltegravir Potassium / Q000627:therapeutic use*; D019562:Viral Load
D019380:Anti-HIV Agents; D004279:DNA, Viral; D000069480:Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; D012367:RNA, Viral; D000068898:Raltegravir Potassium