Pretreatment CD4 cell slope and progression to AIDS or death in HIV-infected patients initiating antiretroviral therapy--the CASCADE collaboration: a collaboration of 23 cohort studies

Marcel Wolbers ¹, Abdel Babiker , Caroline Sabin

⁰Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland. mwolbers@oucru.org

Plos Medicine +

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February 27, 2010

View abstract on PubMed

Summary

The rate of CD4 cell decline before combination antiretroviral therapy (cART) does not predict AIDS or death risk in HIV patients. Current CD4 cell count is sufficient for deciding when to start cART in asymptomatic individuals.

Area Of Science

Immunology
Virology
Clinical Medicine

Background

CD4 cell count is a key predictor of AIDS or death risk in HIV patients starting combination antiretroviral therapy (cART).
The prognostic value of the rate of CD4 cell decline before cART initiation remains unclear.
Understanding pre-therapy CD4 cell dynamics could inform optimal cART initiation strategies.

Purpose Of The Study

To investigate whether the rate of CD4 cell decline before cART initiation predicts clinical outcomes in HIV-infected patients.
To determine if pre-cART CD4 cell slope should influence the decision to initiate combination antiretroviral therapy.

Main Methods

Survival analyses were performed on 2,820 treatment-naïve patients from the CASCADE collaboration with known HIV seroconversion dates and pre-cART CD4 measurements.
Pre-cART CD4 slopes were estimated using linear mixed-effects models.
Primary outcome was time from cART initiation to the first AIDS event or death, with secondary analysis of CD4 cell slope in AIDS-free patients with >350 CD4 cells/microl.

Main Results

The median pre-cART CD4 cell decline was 61 cells/microl per year.
No significant association was found between pre-cART CD4 cell slope and the hazard of AIDS or death (HR 1.01, 95% CI 0.97-1.04 per 10 cells/microl/year reduction).
In AIDS-free patients with CD4 counts >350 cells/microl, CD4 cell decline rate was not significantly associated with progression to AIDS or death (HR 0.99, 95% CI 0.94-1.03 per 10 cells/microl/year reduction).

Conclusions

The rate of CD4 cell decline before cART does not improve the prediction of clinical outcomes in HIV-infected patients, particularly those with CD4 counts above 350 cells/microl.
Current CD4 cell count is sufficient for guiding cART initiation decisions in asymptomatic HIV patients.
Pre-therapy CD4 cell slope is not a necessary factor in determining the timing of cART initiation.

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