Dynamics of immune reconstitution and activation markers in HIV+ treatment-naïve patients treated with raltegravir, tenofovir disoproxil fumarate and emtricitabine.

TitleDynamics of immune reconstitution and activation markers in HIV+ treatment-naïve patients treated with raltegravir, tenofovir disoproxil fumarate and emtricitabine.
Publication TypeJournal Article
Year of Publication2013
AuthorsFunderburg NT, Andrade A, Chan ES, Rosenkranz SL, Lu D, Clagett B, Pilch-Cooper HA, Rodriguez B, Feinberg J, Daar E, Mellors J, Kuritzkes D, Jacobson JM, Lederman MM
JournalPLoS One
Volume8
Issue12
Paginatione83514
Date Published2013
ISSN1932-6203
KeywordsAdenine, Adult, Anti-HIV Agents, Biomarkers, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes, Deoxycytidine, Emtricitabine, Female, HIV Infections, HIV-1, Humans, Lymphocyte Activation, Male, Middle Aged, Organophosphonates, Pyrrolidinones, Raltegravir Potassium, Tenofovir, Young Adult
Abstract

BACKGROUND: The dynamics of CD4+ T cell reconstitution and changes in immune activation and inflammation in HIV-1 disease following initiation of antiretroviral therapy (ART) are incompletely defined and their underlying mechanisms poorly understood.

METHODS: Thirty-nine treatment-naïve patients were treated with raltegravir, tenofovir DF and emtricitabine. Immunologic and inflammatory indices were examined in persons with sustained virologic control during 48 weeks of therapy.

RESULTS: Initiation of ART increased CD4+ T cell numbers and decreased activation and cell cycle entry among CD4+ and CD8+ T cell subsets, and attenuated markers of coagulation (D-dimer levels) and inflammation (IL-6 and TNFr1). These indices decayed at different rates and almost all remained elevated above levels measured in HIV-seronegatives through 48 weeks of viral control. Greater first and second phase CD4+ T cell restoration was related to lower T cell activation and cell cycling at baseline, to their decay with treatment, and to baseline levels of selected inflammatory indices, but less so to their changes on therapy.

CONCLUSIONS: ART initiation results in dynamic changes in viral replication, T cell restoration, and indices of immune activation, inflammation, and coagulation. These findings suggest that determinants of T cell activation/cycling and inflammation/coagulation may have distinguishable impact on immune homeostasis.

TRIAL REGISTRATION: Clinicaltrials.gov NCT00660972.

DOI10.1371/journal.pone.0083514
Alternate JournalPLoS ONE
PubMed ID24367599
PubMed Central IDPMC3867440
Grant ListAI 36219 / AI / NIAID NIH HHS / United States
AI-068636 / AI / NIAID NIH HHS / United States
AI-69501 / AI / NIAID NIH HHS / United States
AI060354 / AI / NIAID NIH HHS / United States
AI069424 / AI / NIAID NIH HHS / United States
AI069472 / AI / NIAID NIH HHS / United States
K99 HL108743 / HL / NHLBI NIH HHS / United States
UL1 TR000170 / TR / NCATS NIH HHS / United States
UL1 TR000170 / TR / NCATS NIH HHS / United States
UL1TR000124 / TR / NCATS NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI069412 / AI / NIAID NIH HHS / United States
UM1 AI069424 / AI / NIAID NIH HHS / United States
UM1 AI069494 / AI / NIAID NIH HHS / United States
UM1 AI069534 / AI / NIAID NIH HHS / United States
UM1 AI106701 / AI / NIAID NIH HHS / United States