Patients discontinuing HAART must be carefully monitored
By Brian Boyle MD, HIVandhepatitis.com
While “hit hard, hit early” was the approach taken by some physicians when highly active antiretroviral therapy (HAART) first became available, during the past six years this treatment algorithm has become significantly more conservative, with most guidelines advocating the initiation of HAART between 200 and 350 cells/mm3.
These more conservative guidelines are based upon studies that show that HAART has limited additional benefits in patients with CD4+ T cell counts >350 cells/mm3, and that there are significant issues regarding HAART toxicity and adherence.
One of the issues confronting patients and clinicians alike is how to manage the antiretroviral therapy of patients who were started on HAART when there CD4+ T cell count was >350 cells/mm3 or patients who have had their CD4+ T cell count rise to that level while on therapy.
To evaluate these issues researchers performed a retrospective study to evaluate the change in CD4+ T cell count among 72 patients (64% men; mean age 35 years) who maintained an undetectable viral load (<500 copies/mL) for at least three months and subsequently discontinued HAART.
The patients median CD4+ T cell count at the time of HAART interruption was 554 cells/mm3 and patients in the study were classified by their pre-HAART CD4+ T cell count nadir: <200 cells/mm3, 200-349 cells/mm3, and >350 cells/mm3.
The investigators found that the most frequent reasons for HAART discontinuation were patient preference and toxicity. The mean time of follow-up after HAART discontinuation was 45 weeks (range, 12-132 weeks). The median CD4+ T cell loss while off HAART was 16 cells/mm3/month, but while some patients lost few or no cells per month, other patients had very large losses, some higher than 100 cells/mm3/month.
The slope of the CD4+ T cell count decay was inversely correlated with the increase of CD4+ T cells while the patient was on HAART, the patient’s baseline viral load, the CD4+ T cell count at the time HAART was stopped, the patient’s age and the duration of the patient having an undetectable viral load; however, using a multivariate regression analysis, only the increase of CD4+ T cells while the patient was receiving HAART was found to be significant. Interestingly, and somewhat contrary to a prior study, the rate of the CD4+ T cell count decline did not correlate with the patient’s nadir CD4+ T cell count, nor did it correlate with the type of HAART the patient was receiving at the time of discontinuation or the patient’s sex.
Finally, four of the patients, all of whom had their CD4+ T cell count drop to <200 cells/mm3 while off HAART, developed an AIDS-defining event or a serious infection.
The authors conclude from these data that “Our study shows that discontinuation of antiretroviral therapy during successful virologic suppression is clinically safe for the majority of patients, provided that their CD4+ T cell counts remain >200 cells/mm3.
“The major predictor of the slope of CD4+ T cell decay is the number of CD4+ T cells gained while receiving therapy, suggesting that it may be possible in many patients to determine the interval during which therapy can be safely interrupted.”
Given the risk of a rapid loss of CD4+ T cells or an AIDS-defining event, patients and their CD4+ T cell counts should be monitored very carefully whenever HAART is discontinued.
P Tebas Henry K, Mondy K et al. Effect of Prolonged Discontinuation of Successful Antiretroviral Therapy on CD4+ T Cell Decline in Human Immunodeficiency Virus-Infected Patients: Implications for Intermittent Therapeutic Strategies. The Journal of Infectious Diseases. 2002; 186:851-854.
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