Replication capacity in relation to immunologic and virologic outcomes in HIV-1-infected treatment-naive subjects.

TitleReplication capacity in relation to immunologic and virologic outcomes in HIV-1-infected treatment-naive subjects.
Publication TypeJournal Article
Year of Publication2009
AuthorsSkowron G, Spritzler JG, Weidler J, Robbins GK, Johnson VA, Chan ES, Asmuth DM, Gandhi RT, Lie Y, Bates M, Pollard RB
Corporate AuthorsNIH/NIAID ACTG 384 Protocol Team and Monogram Biosciences
JournalJ Acquir Immune Defic Syndr
Volume50
Issue3
Pagination250-8
Date Published2009 Mar 1
ISSN1525-4135
KeywordsAdult, Aged, CD4 Lymphocyte Count, Female, HIV Infections, HIV-1, Humans, Male, Middle Aged, Viral Load, Virus Replication
Abstract

OBJECTIVES: To evaluate the association between baseline (BL) replication capacity (RC) (RCBL) and immunologic/virologic parameters (at BL and after 48 weeks on therapy) in HIV-1-infected subjects initiating antiretroviral therapy.

METHODS: RCBL was determined using a modified Monogram PhenoSense HIV drug susceptibility assay on plasma HIV-1 from 321 treatment-naive subjects from AIDS Clinical Trials Group 384. Univariate and multivariable analyses were performed to determine the association of RCBL with BL and on-therapy virologic and immunologic outcomes.

RESULTS: Higher RCBL was associated with lower baseline CD4 (CD4BL) (r = -0.23, P < 0.0001), higher baseline HIV-1 RNA (r = 0.25, P < 0.0001), higher CD4BL activation percent (r = 0.23, P < 0.0001), and lower CD4BL memory count (r = -0.21, P = 0.0002). In a multivariable model, week 48 CD4 increase (DeltaCD448) was associated with lower CD4BL memory count and higher CD4BL-naive percent (P = 0.004, P = 0.015, respectively). The interaction between CD4BL and RCBL was significant (P = 0.018), with a positive association between RCBL and DeltaCD448 in subjects with higher CD4BL and a negative association at lower absCD4BL.

CONCLUSIONS: At baseline, higher RC was significantly associated with higher HIV-1 RNA, higher CD4 cell activation, lower CD4 cell count, and lower CD4 memory cell count. These factors may interact, directly or indirectly, to modify the extent to which CD4 recovery occurs in patients starting antiretroviral therapy at different CD4BL counts.

DOI10.1097/QAI.0b013e3181938faf
Alternate JournalJ. Acquir. Immune Defic. Syndr.
PubMed ID19194319
PubMed Central IDPMC3482469
Grant List1P30AI060354 / AI / NIAID NIH HHS / United States
AI46381 / AI / NIAID NIH HHS / United States
K01 AI062435 / AI / NIAID NIH HHS / United States
K01 AI062435-02 / AI / NIAID NIH HHS / United States
K01AI062435 / AI / NIAID NIH HHS / United States
P30 AI050410 / AI / NIAID NIH HHS / United States
P30 AI050410-04 / AI / NIAID NIH HHS / United States
P30 AI060354 / AI / NIAID NIH HHS / United States
P30 AI060354-01 / AI / NIAID NIH HHS / United States
R01 AI066992 / AI / NIAID NIH HHS / United States
R01 AI066992-01A1 / AI / NIAID NIH HHS / United States
R01 DK056593 / DK / NIDDK NIH HHS / United States
R01AI066992 / AI / NIAID NIH HHS / United States
R44 AI050321-04 / AI / NIAID NIH HHS / United States
R44AI050321 / AI / NIAID NIH HHS / United States
U01 AI025859-13 / AI / NIAID NIH HHS / United States
U01 AI025868 / AI / NIAID NIH HHS / United States
U01 AI025868-16 / AI / NIAID NIH HHS / United States
U01 AI025879 / AI / NIAID NIH HHS / United States
U01 AI025879-13 / AI / NIAID NIH HHS / United States
U01 AI025897 / AI / NIAID NIH HHS / United States
U01 AI025897-12 / AI / NIAID NIH HHS / United States
U01 AI025903-13 / AI / NIAID NIH HHS / United States
U01 AI025915 / AI / NIAID NIH HHS / United States
U01 AI025915-13 / AI / NIAID NIH HHS / United States
U01 AI025924-13 / AI / NIAID NIH HHS / United States
U01 AI027659-13 / AI / NIAID NIH HHS / United States
U01 AI027661-14 / AI / NIAID NIH HHS / United States
U01 AI027665-13 / AI / NIAID NIH HHS / United States
U01 AI027666-13 / AI / NIAID NIH HHS / United States
U01 AI027670 / AI / NIAID NIH HHS / United States
U01 AI027670-13 / AI / NIAID NIH HHS / United States
U01 AI027673-13 / AI / NIAID NIH HHS / United States
U01 AI027675 / AI / NIAID NIH HHS / United States
U01 AI027675-13 / AI / NIAID NIH HHS / United States
U01 AI032770 / AI / NIAID NIH HHS / United States
U01 AI032770-13 / AI / NIAID NIH HHS / United States
U01 AI032775 / AI / NIAID NIH HHS / United States
U01 AI032775-08 / AI / NIAID NIH HHS / United States
U01 AI032782 / AI / NIAID NIH HHS / United States
U01 AI032782-12 / AI / NIAID NIH HHS / United States
U01 AI032783 / AI / NIAID NIH HHS / United States
U01 AI032783-12 / AI / NIAID NIH HHS / United States
U01 AI034832-11 / AI / NIAID NIH HHS / United States
U01 AI038858 / AI / NIAID NIH HHS / United States
U01 AI038858-029001 / AI / NIAID NIH HHS / United States
U01 AI038858-04 / AI / NIAID NIH HHS / United States
U01 AI039156 / AI / NIAID NIH HHS / United States
U01 AI039156-08 / AI / NIAID NIH HHS / United States
U01 AI046381 / AI / NIAID NIH HHS / United States
U01 AI046381-01 / AI / NIAID NIH HHS / United States
U01 AI068634 / AI / NIAID NIH HHS / United States
U01 AI068634-01 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
U01 AI068636-01 / AI / NIAID NIH HHS / United States
U01 AI38858 / AI / NIAID NIH HHS / United States
U01 AI68634 / AI / NIAID NIH HHS / United States
U01 AI68636 / AI / NIAID NIH HHS / United States
UM1 AI069477 / AI / NIAID NIH HHS / United States