Background: According to current guidelines HAART approaches should be maintained for life. Because HAART regimens produce substantial toxicities it is important to explore whether intermittent treatment guided by CD4 and VL is safe and minimizes the ART-associated toxicity.

Objective: To compare the safety of continuous vs intermittent HAART in chronically HIV-infected patients (pts) with a successful virus suppression. In addition, we assessed the virological and immunological changes.

Study Design: Multi-center, open label clinical trial with blinded and centralized randomization.

Methods:  Pts on HAART with VL < 80 c/ml for ³ 1 yr, CD4 counts ³ 500 cells/mm3 for ³ 6 mo. before the study entry and nadir CD4 count >100 cells/mm3 were eligible. Pts were randomised to interrupt therapy (Group A) or continue with the same prior treatment (Group B). The criteria for restarting therapy in pts assigned to Group A were: a VL increase of  ³ 100,000 c/ml or a drop of CD4 below 350 cells/mm3 or the appearance of any opportunistic infection (OI). Pts were planned to stop therapy again when: CD4 ³ 500 cells/mm3 and VL< 80 c/ml. In pts who discontinued HAART, CD4 counts and VL levels were determined monthly whereas in those continuing therapy these parameters were controlled every 3 mo.

Results at 48 weeks: A total of 122 pts were enrolled (Group A, n = 61; Group B, n = 61).  At baseline, median CD4 count was 850 cells/mm3 in Group A and 800 cells/mm3 in Group B. Subjects from Group B maintained undetectable VL except 2 pts, and the median CD4 counts remained stable (804 cells/mm3). In Group A, 35/61 (57%) pts had to reinitiate HAART (96% due to a VL increase >100,000 c/ml, 4% due to CD4 < 350 cells/mm3 and 23% due to both reasons). A median CD4 decrease of 96 cells/mm3/mo. (-29 to -239) was observed in Group A. Median time off therapy was 8 wks (range: 6–40) in those pts who resumed HAART. In the 26 (43%) pts that remained without therapy at wk 48, the median VL was 4.1 log10 c/ml (2.7– 4.9). CD4 count decreased 335 cells/mm3 (+384 to -1341), (33 cells/mm3/mo.; +16 to -140) in this group. Acute retroviral syndrome was observed in 6 (10%) of the pts discontinuing therapy.  OI or tumors did not appear during the study.

Conclusions: Treatment discontinuation controlled by CD4 and viral load was safe in our study cohort. Our results show that 43% of the patients could remain without therapy for at least 48 wks.