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AIDS. 2010 Jul 31;24(12):1867-76. doi: 10.1097/QAD.0b013e32833adbcf.

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

Author information

1
Center for Biostatistics in AIDS Research, Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts 02115, USA. jlok@hsph.harvard.edu

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 (<or=200, 201-350, 351-500, and >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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00000919 NCT00001137.

PMID:
20467286
PMCID:
PMC3018341
DOI:
10.1097/QAD.0b013e32833adbcf
[Indexed for MEDLINE]
Free PMC Article

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