Factors predicting the time for CD4 T‐cell count to return to nadir in the course of CD4‐guided therapy interruption in chronic HIV infection^*

Abstract

ObjectiveOur previous studies on CD4-guided therapy interruption (TI) showed that the durations of the first and second TIs were similar if antiretroviral therapy (ART) was resumed at a level of the CD4 cell count similar to or higher than the nadir CD4 T-cell count. Therefore, in a strategy of repeated CD4-guided TI, it is important to know which factors predict the time for the CD4 T-cell count to return to nadir (TRN). MethodsFrom a cohort of 125 patients who interrupted ART, 92 patients who reached a CD4 T-cell count similar to the nadir count were included in the study. ResultsThe median TRN was 12.3 months. In the multivariate analysis, younger age (P 5 0.011), lower pre-ART HIV RNA (P 5 0.022) and female gender (P 5 0.045) were associated with a longer TRN. After TI there were 11 clinical events in the group of patients whose nadir CD4 count was 4200 cells/mL. Most of these events occurred when the TI was prolonged beyond the TRN. ConclusionsThe factors predicting the TRN were age, HIV RNA pre-ART and gender. Resumption of therapy at a CD4 cell count similar to the nadir CD4 count appears to protect against the development of clinical events. Given the observational nature of this study, no conclusions can be drawn regarding the possible application of TI in clinical practice.Keywords: age, antiretroviral therapy, CD4 lymphocyte count, sex Received: 31 May 2007, accepted 9 October 2007 Introduction At present, HIV infection cannot be eradicated and its control requires life-long treatment with antiretroviral therapy (ART).The need to find a balance between the efficacy and toxicity of ART has led to numerous studies evaluating the possible use of strategies based on therapy interruptions (TIs) guided by the number of CD4 lymphocytes. Recent randomised trials comparing a strategy of TI guided by CD4 cell counts and continuous treatment have produced discordant results.In both the SMART [1] and TRIVACAN [2] trials, the patients managed with CD4-guided TI had a higher risk of disease progression or death compared with those managed with continuous therapy. In contrast, in the STACCATO [3], BASTA [4] and TIBET [5] trials the results of the two strategies were equivalent in terms of clinical events.The results of SMART, the study on TI that has enrolled the largest number of patients, profoundly altered the recommendations of the Department of Health and Human Services (DHHS) concerning CD4-guided TI, which was previously indicated as a possibility to offer to patients with immune reconstitution (October 2005) [6] and is now stated to be an approach that should be avoided in clinical practice (May 2006) 19In the SMART study [1], the risk of clinical events was independent of the nadir CD4 cell count and always higher in the ''drug conservation'' arm. The risk was also higher in patients who were not taking any medication at the time of enrolment, suggesting that at least part of the increased risk was not dependent on the TI but rather on the criteria for resuming treatment. There is, in fact, no doubt that...