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American Journal of Epidemiology Vol. 153, No. 4 : 386-393
Copyright © 2001 by The Johns Hopkins University School of Hygiene and Public Health

ORIGINAL CONTRIBUTIONS

Modeling Changes in CD4-positive T-Lymphocyte Counts after the Start of Highly Active Antiretroviral Therapy and the Relation with Risk of Opportunistic Infections The Aquitaine Cohort, 1996–1997

C. Binquet1, G. Chêne1, H. Jacqmin-Gadda1, V. Journot1, M. Savès1, D. Lacoste2, F. Dabis1 and the Groupe d'Epidémiologie Clinique du SIDA en Aquitaine

1 Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 330, Université Victor Segalen Bordeaux 2, 146 rue Léo-Saignat, 33076 Bordeaux Cedex, France.
2 Centre d'Information et de Soins sur l'Immunodéficience Humaine, Hopital Pellegrin-Tondu, Place Amélie Raba-Léon, 33076 Bordeaux Cedex, France.
Members of the Groupe d'Epidémiologie Clinique du SIDA en Aquitaine are listed in the Acknowledgments.

After initiation of a treatment for human immunodeficiency virus type 1 infection containing a protease inhibitor, immune restoration associated with increases in CD4-positive (CD4+) T lymphocyte count may be delayed. In a sample of patients who had been prescribed protease inhibitors for the first time, the authors tested to see whether there was a minimal duration of CD4+ cell count increase before the increase had an impact on the occurrence of opportunistic infections. The evolution (difference between time t and baseline) of CD4+ cell count was modeled using a mixed effects linear model. Changes in CD4+ count estimated by this model were then included as time-dependent covariates in a proportional hazards model. Finally, the authors tested for the existence of a CD4+ change x time interaction. The authors used a sample of 553 French patients first prescribed protease inhibitors in 1996 and followed for a median of 16 months. During the first 120 days, there was no association between CD4+ change and the rate of opportunistic infections. After 120 days, each 50-cell/mm3 increase in CD4+ count was associated with a 60% (95% confidence interval: 45, 72) reduction in the incidence of opportunistic infections. These results, based on modeling of CD4+ cell response, at least indirectly reinforce the concept of a delayed but possible immune recovery with the use of protease inhibitors. The findings support the potential for interruption of certain types of prophylaxis against opportunistic infections under reasonable conditions of duration of antiretroviral therapy and sustained CD4+ cell response.

acquired immunodeficiency syndrome; antiviral agents; CD4-positive T-lymphocytes; cell count; immune system; immunity; opportunistic infections; protease inhibitors

Abbreviations: AIC, Akaike Information Criterion; AIDS, acquired immunodeficiency syndrome; CI, confidence interval; HAART, highly active antiretroviral therapy; HIV, human immunodeficiency virus


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