Background:  The dynamics of CD4⁺ T cells recovery during the periods on treatment during 2 years of structured therapy interruption  strategy or the long-term immune reconstitution with HAART after completion of structured therapy interruption  were analyzed.

Methods:  We randomized 120 HIV-1-infected patients on successful HAART with CD4⁺ T cell count >450/mm³ to receive continuous HAART (Control Arm [CA], n = 37) or 2 different strategies of structured therapy interruption:  interruption of HAART until viral load increased >30000 copies/mL in the Virologic Arm (VA, n = 45) or CD4⁺ drop to <350/mm³ in the Inmunologic Arm (IA, n = 38) and then resumption of HAART until viral load dropped to <200 copies/mL and CD4⁺ increased to >450/mm³ for ≥3 months in both arms for 2 years. After conclusion of structured therapy interruption period, 99 of 120 (82.5%) received HAART for a median of 25 months (IQR 12 to 34).  

Results:  At baseline of the structured therapy interruption period, CD4⁺ T cells were not different between arms:  46% of patients of structured therapy interruption arms did not reinitiate HAART during the 2 years of structured therapy interruption cycles (31% in VA and 65% in IA). Of 45 patients 25 (55.5%) in VA vs 3 of 38 patients (8%) in IA performed ≥2 cycles of structured therapy interruption. The median drop in CD4⁺ T cells after the first 3 to 6 months of interruption was –246 cells/mm³. During the structured therapy interruption period, the rate of recovery of CD4⁺ T cells was decreasing progressively from the first to the last resumption of HAART (Δ of increase: 232, 116, 87, and –26.5 cells/mm³ after 3 months on HAART after the first, second, third, and fourth structured therapy interruption, respectively). After 25 months of HAART after conclusion of 2 years of structured therapy interruption, CD4⁺ T cells remained significantly lower than at baseline before the structured therapy interruption period both in VA (618 vs 797 cells/mm³, p <0.0001) and IA (656 vs 832 cells/mm³, p <0.0001), but not in CA (862 vs 830 cells/mm³, p = 0.68). In a multivariate analysis, the nadir of CD4⁺ T cells during the structured therapy interruption period and the baseline value of CD4⁺ before the structured therapy interruption period independently predicted the level of CD4⁺ T cells after 25 months of HAART after conclusion of structured therapy interruption.

Conclusions:  The drop in CD4⁺ T cells after a first period of 3 to 6 months of interruption of HAART was recovered completely after 3 months of first HAART resumption. Conversely, repeated interruptions of HAART were progressively deleterious for the recovery of CD4⁺ T cells. CD4⁺ T cells did not recover completely in patients who received 2 years of HAART after 2 years of a structured therapy interruption regimen. These data are useful to decide how long an analytical treatment interruption should last.