Modeling the time course of CD4 T-lymphocyte counts according to the level of virologic rebound in HIV-1-infected patients on highly active antiretroviral therapy

Kousignian, I.; Abgrall, S.; Duval, X.; Descamps, D.; Matheron, S.; Costagliola, D.

Journal of Acquired Immune Deficiency Syndromes 34(1): 50-57


ISSN/ISBN: 1525-4135
PMID: 14501793
DOI: 10.1097/00126334-200309010-00007
Accession: 012313546

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Objective: To study the influence of the level of virologic rebound during combination antiretroviral therapy on the time course of the CD4 count. Methods: Between January 1997 and December 1999, we enrolled 3736 patients from the French Hospital HIV Database who had an undetectable viral load on a first course of highly active antiretroviral therapy (HAART). Four levels of virologic rebound were defined on the basis of viral load values during the year following initial undetectability on HAART: group 1, all viral loads <500 copies/mL; group 2, all viral loads <5000 copies/mL: group 3, all viral loads <10,000 copies/mL; and group 4, at least 1 viral load >10,000 copies/mL. We developed a continuous time-homogeneous Markov process with 5 reversible stages defined by CD4 count intervals. Results: CD4 counts increased continuously over time in each group. The smaller the virologic rebound, the stronger was the increase in the CD4 count (P < 0.0001). The mean CD4 cell count increments between months 2 and 6 were 26, 20, 11, and 2 cells/mm3 in groups 1, 2, 3, and 4, respectively. The rate of gain fell after month 6 and was almost nil in group 4. Conclusion: After achieving an undetectable viral load on HAART, immunologic reconstitution is possible whatever the subsequent level of viral replication, except among patients with high-level rebound, meaning that in patients with a long history of antiretroviral therapy and a reduced choice of antiretroviral drugs due to acquisition of resistances, delay in antiretroviral therapy switch can be possible in patients with low or intermediate rebound.