Predictors of Long-Term Increase in CD4 Cell Counts in Human Immunodeficiency Virus-Infected Patients Receiving a Protease Inhibitor-Containing Antiretroviral Regimen [Le Moing V et al. JID 2002;185:471]

This is a report from APROCO, which is a collaborative study involving 47 clinical centers in France. The study concerns 988 patients prospectively enrolled in a protease inhibitor-containing HAART regimen with analysis of the subsequent CD4 cell slope compared to virologic response. The short-term slope (baseline to month 4) showed a median increase in CD4 cell count of 21 cell/mm³/month, and the long term slope (month 4 through month 24) was a median increase of 5.5 cell/mm³/month. There was a direct correlation in long- term results with the virologic response that depended on the presence or absence of viral rebound (defined as an HIV RNA level exceeding 500 c/ml at any time during the 12 or 24 month follow-up) and the extent of this virologic rebound in terms of viral load measurements. These data are summarized in the table below:

Virologic Response	Change in CD4 (median, /mm3)
	Month 4-12	Month 4-24
Viral load < 500 at month 4    Viral rebound*    No viral rebound	+47 +60	+59 +124
Viral rebound**    <1000 c/mL    1000-5000 c/mL    5000-10,000 c/mL    >10,000 c/mL	+60 +47 +46 +16	+93 +68 0 -24
* VL > 500 c/mL within 12 or 24 months ** Results provided only for patients who had VL response to < 500 c/mL and then had rebound.

These results confirm clinical impressions that the long-term immunologic response is strongly correlated with virologic response. The early bump in the CD4 cell count is thought to reflect redistribution of cells, so the major point of analysis concerns values that are sustained. It is of interest to note that CD4 cell counts continued to increase until the VL increased to 5,000-10,000 c/ml, although the rate of increase (slope) was lower. The rate of decay in CD4 cell counts with viral loads >10,000 seemed to match those that were noted in the pre-HAART era. These results support the recommendation for intervention relatively early in virologic escape.
posted 3/05/2002

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