355   CD4 Decay after Discontinuation of Virologically Successful Antiretroviral Therapy.

P .Tebas*¹, K. Henry², K. Mondy¹, S. Deeks³, J. Barbour³, C. Cohen⁴, and W. Powderly¹.
¹Washington Univ. Sch. of Med., St. Louis, MO;²Regions Hosp., St. Paul, MN;³Univ. of California, San Francisco; and Harvard Med. Sch., Boston, MA.

Background:CD4-driven "pulse" therapy (initiation and discontinuation of antiretroviral therapy at specific CD4⁺cell thresholds) has been proposed as an alternative strategy to the current virologically driven paradigm of HIV treatment. There is little available data about rate of decline of CD4 cells after discontinuation of therapy in patients who stop therapy with an undetectable viral load.

Methods:We looked at the rate of decay of the CD4 cell count in patients who discontinued antiretroviral therapy for at least 20 weeks after being fully suppressed with potent antiretroviral therapy, in two clinical practices.

Results:31 subjects were identified (43% males, 40% white, 32+2 yr of age). The most frequent reasons for discontinuation of therapy were patient preference in 56% (most frequently in females in the post-partum), and drug toxicity (43%). The median nadir CD4 (before therapy) was 383 cells/mm³(interquartile range, IQR 244— 588) and the baseline VL was 29,845 HIV RNA copies/ml. Patients gained on therapy an average 202+32 CD4 cells. The median time with an undetectable VL before stopping therapy was 19 weeks (IQR, 9—38 weeks). The median CD4 cell count at stop was 635 cells/mm³(IQR 355—832). The mean follow-up after discontinuation of therapy was 50 weeks (range 20 to 119 weeks). Mean CD4 decay was 16+4 cells/month. The slope of the CD4 decay inversely correlated with the magnitude of change of CD4 on therapy (r = -0.527, p = 0.008) but did not correlate with nadir CD4 cell count, baseline viral load, type of potent antiretroviral regimen (PI based vs others), CD4 at the time of stop or gender. No patient developed an AIDS-defining event during follow-up. Two patients restarted therapy and reached an undetectable viral load again.

Conclusions:In this retrospective cohort of patients, discontinuation of therapy while fully suppressed was clinically safe. The predicted average time to reach a CD4 count of 250 cells/mm³in our cohort is 24 months (95% CI 18—30 months). Patients who gained more CD4 cells on therapy tended to lose them faster. Pulse therapy strategies deserve further evaluation in the setting of prospective clinical trials.