Effect of baseline- and treatment-related factors on immunologic recovery after initiation of antiretroviral therapy in HIV-1-positive subjects: Results from ACTG 384

Rajesh T. Gandhi, John Spritzler, Ellen Chan, David Asmuth, Benigno Rodriguez, Thomas C. Merigan, Martin S. Hirsch, Robert W. Shafer, Gregory K. Robbins, Richard B Pollard

Research output: Contribution to journalArticle

121 Citations (Scopus)

Abstract

OBJECTIVE: To assess the effect of baseline- and treatment-related factors on immunologic recovery after initiation of antiretroviral therapy (ART). METHODS: Nine hundred eighty antiretroviral-naive HIV-1+ subjects were randomized to start stavudine/didanosine or zidovudine/lamivudine with nelfinavir, efavirenz, or both nelfinavir and efavirenz. RESULTS: Greater CD4 cell recovery was associated with age of 40 years or younger, female sex, higher baseline naive/memory CD4 cell ratio, higher baseline virus load (VL), and virologic suppression (VS). Most subjects who maintained an undetectable VL had a substantial increase in CD4 cell count, but 13% of the subjects did not, even after 3 years of VS. Persistent T-cell activation was associated with lower CD4 cell recovery, even in subjects who achieved VS. Initial treatment assignment did not affect total CD4 cell recovery, naive/memory CD4 cell reconstitution, or decline in T-cell activation. In addition to CD4 cell recovery, B-cell counts rose substantially after ART initiation. CONCLUSIONS: In this large randomized trial, younger age, female sex, higher naive/memory CD4 cell ratio, higher baseline VL, and VS were associated with greater CD4 cell increase, whereas persistent T-cell activation was associated with impaired CD4 cell recovery after ART initiation. Initial treatment assignment did not affect CD4 cell reconstitution.

Original languageEnglish (US)
Pages (from-to)426-434
Number of pages9
JournalJournal of Acquired Immune Deficiency Syndromes
Volume42
Issue number4
DOIs
StatePublished - Aug 2006

Fingerprint

Immunologic Factors
HIV-1
efavirenz
Nelfinavir
Therapeutics
Viruses
T-Lymphocytes
Stavudine
Didanosine
Lamivudine
Zidovudine
CD4 Lymphocyte Count
B-Lymphocytes
Cell Count

Keywords

  • Antiretroviral therapy
  • CD4 cell recovery
  • HIV-1
  • Immunologic outcomes
  • Memory and naive CD4 cell subsets
  • T-cell activation

ASJC Scopus subject areas

  • Virology
  • Immunology

Cite this

Effect of baseline- and treatment-related factors on immunologic recovery after initiation of antiretroviral therapy in HIV-1-positive subjects : Results from ACTG 384. / Gandhi, Rajesh T.; Spritzler, John; Chan, Ellen; Asmuth, David; Rodriguez, Benigno; Merigan, Thomas C.; Hirsch, Martin S.; Shafer, Robert W.; Robbins, Gregory K.; Pollard, Richard B.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 42, No. 4, 08.2006, p. 426-434.

Research output: Contribution to journalArticle

Gandhi, Rajesh T. ; Spritzler, John ; Chan, Ellen ; Asmuth, David ; Rodriguez, Benigno ; Merigan, Thomas C. ; Hirsch, Martin S. ; Shafer, Robert W. ; Robbins, Gregory K. ; Pollard, Richard B. / Effect of baseline- and treatment-related factors on immunologic recovery after initiation of antiretroviral therapy in HIV-1-positive subjects : Results from ACTG 384. In: Journal of Acquired Immune Deficiency Syndromes. 2006 ; Vol. 42, No. 4. pp. 426-434.
@article{0baf7297d0374b369b5a10d1ddd2c6b4,
title = "Effect of baseline- and treatment-related factors on immunologic recovery after initiation of antiretroviral therapy in HIV-1-positive subjects: Results from ACTG 384",
abstract = "OBJECTIVE: To assess the effect of baseline- and treatment-related factors on immunologic recovery after initiation of antiretroviral therapy (ART). METHODS: Nine hundred eighty antiretroviral-naive HIV-1+ subjects were randomized to start stavudine/didanosine or zidovudine/lamivudine with nelfinavir, efavirenz, or both nelfinavir and efavirenz. RESULTS: Greater CD4 cell recovery was associated with age of 40 years or younger, female sex, higher baseline naive/memory CD4 cell ratio, higher baseline virus load (VL), and virologic suppression (VS). Most subjects who maintained an undetectable VL had a substantial increase in CD4 cell count, but 13{\%} of the subjects did not, even after 3 years of VS. Persistent T-cell activation was associated with lower CD4 cell recovery, even in subjects who achieved VS. Initial treatment assignment did not affect total CD4 cell recovery, naive/memory CD4 cell reconstitution, or decline in T-cell activation. In addition to CD4 cell recovery, B-cell counts rose substantially after ART initiation. CONCLUSIONS: In this large randomized trial, younger age, female sex, higher naive/memory CD4 cell ratio, higher baseline VL, and VS were associated with greater CD4 cell increase, whereas persistent T-cell activation was associated with impaired CD4 cell recovery after ART initiation. Initial treatment assignment did not affect CD4 cell reconstitution.",
keywords = "Antiretroviral therapy, CD4 cell recovery, HIV-1, Immunologic outcomes, Memory and naive CD4 cell subsets, T-cell activation",
author = "Gandhi, {Rajesh T.} and John Spritzler and Ellen Chan and David Asmuth and Benigno Rodriguez and Merigan, {Thomas C.} and Hirsch, {Martin S.} and Shafer, {Robert W.} and Robbins, {Gregory K.} and Pollard, {Richard B}",
year = "2006",
month = "8",
doi = "10.1097/01.qai.0000226789.51992.3f",
language = "English (US)",
volume = "42",
pages = "426--434",
journal = "Journal of acquired immune deficiency syndromes (1999)",
issn = "1525-4135",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - Effect of baseline- and treatment-related factors on immunologic recovery after initiation of antiretroviral therapy in HIV-1-positive subjects

T2 - Results from ACTG 384

AU - Gandhi, Rajesh T.

AU - Spritzler, John

AU - Chan, Ellen

AU - Asmuth, David

AU - Rodriguez, Benigno

AU - Merigan, Thomas C.

AU - Hirsch, Martin S.

AU - Shafer, Robert W.

AU - Robbins, Gregory K.

AU - Pollard, Richard B

PY - 2006/8

Y1 - 2006/8

N2 - OBJECTIVE: To assess the effect of baseline- and treatment-related factors on immunologic recovery after initiation of antiretroviral therapy (ART). METHODS: Nine hundred eighty antiretroviral-naive HIV-1+ subjects were randomized to start stavudine/didanosine or zidovudine/lamivudine with nelfinavir, efavirenz, or both nelfinavir and efavirenz. RESULTS: Greater CD4 cell recovery was associated with age of 40 years or younger, female sex, higher baseline naive/memory CD4 cell ratio, higher baseline virus load (VL), and virologic suppression (VS). Most subjects who maintained an undetectable VL had a substantial increase in CD4 cell count, but 13% of the subjects did not, even after 3 years of VS. Persistent T-cell activation was associated with lower CD4 cell recovery, even in subjects who achieved VS. Initial treatment assignment did not affect total CD4 cell recovery, naive/memory CD4 cell reconstitution, or decline in T-cell activation. In addition to CD4 cell recovery, B-cell counts rose substantially after ART initiation. CONCLUSIONS: In this large randomized trial, younger age, female sex, higher naive/memory CD4 cell ratio, higher baseline VL, and VS were associated with greater CD4 cell increase, whereas persistent T-cell activation was associated with impaired CD4 cell recovery after ART initiation. Initial treatment assignment did not affect CD4 cell reconstitution.

AB - OBJECTIVE: To assess the effect of baseline- and treatment-related factors on immunologic recovery after initiation of antiretroviral therapy (ART). METHODS: Nine hundred eighty antiretroviral-naive HIV-1+ subjects were randomized to start stavudine/didanosine or zidovudine/lamivudine with nelfinavir, efavirenz, or both nelfinavir and efavirenz. RESULTS: Greater CD4 cell recovery was associated with age of 40 years or younger, female sex, higher baseline naive/memory CD4 cell ratio, higher baseline virus load (VL), and virologic suppression (VS). Most subjects who maintained an undetectable VL had a substantial increase in CD4 cell count, but 13% of the subjects did not, even after 3 years of VS. Persistent T-cell activation was associated with lower CD4 cell recovery, even in subjects who achieved VS. Initial treatment assignment did not affect total CD4 cell recovery, naive/memory CD4 cell reconstitution, or decline in T-cell activation. In addition to CD4 cell recovery, B-cell counts rose substantially after ART initiation. CONCLUSIONS: In this large randomized trial, younger age, female sex, higher naive/memory CD4 cell ratio, higher baseline VL, and VS were associated with greater CD4 cell increase, whereas persistent T-cell activation was associated with impaired CD4 cell recovery after ART initiation. Initial treatment assignment did not affect CD4 cell reconstitution.

KW - Antiretroviral therapy

KW - CD4 cell recovery

KW - HIV-1

KW - Immunologic outcomes

KW - Memory and naive CD4 cell subsets

KW - T-cell activation

UR - http://www.scopus.com/inward/record.url?scp=33745891216&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33745891216&partnerID=8YFLogxK

U2 - 10.1097/01.qai.0000226789.51992.3f

DO - 10.1097/01.qai.0000226789.51992.3f

M3 - Article

C2 - 16810109

AN - SCOPUS:33745891216

VL - 42

SP - 426

EP - 434

JO - Journal of acquired immune deficiency syndromes (1999)

JF - Journal of acquired immune deficiency syndromes (1999)

SN - 1525-4135

IS - 4

ER -