Long-term increase in CD4+ T-cell counts during combination antiretroviral therapy for HIV-1 infection.

TitleLong-term increase in CD4+ T-cell counts during combination antiretroviral therapy for HIV-1 infection.
Publication TypeJournal Article
Year of Publication2010
AuthorsLok JJ, Bosch RJ, Benson CA, Collier AC, Robbins GK, Shafer RW, Hughes MD
Corporate AuthorsALLRT team
JournalAIDS
Volume24
Issue12
Pagination1867-76
Date Published2010 Jul 31
ISSN1473-5571
KeywordsAdult, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes, Drug Therapy, Combination, Female, HIV Infections, HIV-1, Humans, Male, Practice Guidelines as Topic, Time Factors, United States, Viral Load
Abstract

OBJECTIVE: To inform guidelines concerning when to initiate combination antiretroviral therapy (ART), we investigated whether CD4(+) T-cell counts (CD4 cell counts) continue to increase over long periods of time on ART. Losses-to-follow-up and some patients discontinuing ART at higher CD4 cell counts hamper such evaluation, but novel statistical methods can help address these issues. We estimated the long-term CD4 cell count trajectory accounting for losses-to-follow-up and treatment discontinuations.

DESIGN: The study population included 898 US patients first initiating ART in a randomized trial (AIDS Clinical Trials Group 384); 575 were subsequently prospectively followed in an observational study (AIDS Clinical Trials Group Longitudinal Linked Randomized Trials).

METHODS: Inverse probability of censoring weighting statistical methods were used to estimate the CD4 cell count trajectory accounting for losses-to-follow-up and ART discontinuations, overall and for pretreatment CD4 cell count categories (500 cells/microl).

RESULTS: Median CD4 cell count increased from 270 cells/microl pre-ART to an estimated 556 cells/microl at 3 and 532 cells/microl at 7 years after starting ART in analyses ignoring treatment discontinuations, and to 570 and 640 cells/microl, respectively, had all patients continued ART. However, even had ART been continued, an estimated 25, 9, 3, and 2% of patients with pretreatment CD4 cell counts of 200 or less, 201-350, 351-500, and more than 500 cells/microl would have had CD4 cell counts of 350 cells/microl or less after 7 years.

CONCLUSION: If patients remain on ART, CD4 cell counts increase in most patients for at least 7 years. However, the substantial percentage of patients starting therapy at low CD4 cell counts who still had low CD4 cell counts after 7 years provides support for ART initiation at higher CD4 cell counts.

DOI10.1097/QAD.0b013e32833adbcf
Alternate JournalAIDS
PubMed ID20467286
PubMed Central IDPMC3018341
Grant List1U01-AI069484 / AI / NIAID NIH HHS / United States
5-MO1 RR00044 / RR / NCRR NIH HHS / United States
5-P30-AI-045008-09 / AI / NIAID NIH HHS / United States
5U01AI069472 / AI / NIAID NIH HHS / United States
AI 024643 / AI / NIAID NIH HHS / United States
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AL69415 / / PHS HHS / United States
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