Background:  HIV infection causes dysfunction in humoral and cellular responses to recommended vaccines. These responses worsen with immunosuppression and improve with HAART. The effects of treatment interruption on these responses are unknown.

Methods:  We performed a single-center prospective, randomized, double-blind, placebo-controlled clinical trial to evaluate the effect of a vaccination program in successfully treated HIV-infected adults on HAART and after its interruption. We included 26 HIV⁺ adults with CD4 ³500/mm³ and plasma viral load <200 copies/mL, who were randomized to receive during 12 months either 10 commercial vaccines or placebo. Vaccination program included:  hepatitis B (months 0, 1, 2, and 6), influenza (month 1), pneumococcus (month 2), hepatitis A (months 4 and 10), chickenpox (months 4 and 6), measles-mumps-rubella (month 8), and diphtheria-tetanus (month 10). On month 12, HAART was interrupted during 6 months, and evolution of immune responses to vaccination agents were analyzed on the whole cohort and compared between groups. Humoral responses were evaluated with ELISA commercial assays (with quantitative and qualitative results) on months 12 and 18. Cellular responses were analysed with ELISpot and AmpliSpot assays on months 12, 15, and 18.

Results:  Effect of HAART interruption was evaluated in 25 patients (12 in the placebo group and 13 in the vaccination group). Although the vaccinated group presented higher levels of antibodies against the different agents on month 12, evolution of immune responses after HAART interruption was similar in both groups. Antibodies against rubella, S. pneumoniae, and tetanus presented a significant decrease (p ≤0.001), meanwhile titers against diphtheria decreased not significantly. In the qualitative analysis some patients presented a negativization of their serology:  1 of 24 for varicella, 3 of 24 for mumps, 2 of 7 for S. pneumoniae, 2 of 23 for tetanus, and 4 of 13 for diphtheria. Humoral responses against the other agents evaluated remained stable during the interruption period. By contrast, cellular responses presented a general trend (not significant) to increase after HAART interruption, except for hepatitis B.

Conclusions:  Interrupting HAART may cause dysfunction in acquired humoral responses to vaccines, even decreasing antibody titers to “unprotective” levels in some patients. The potential clinical risk of this dysfunction should be evaluated in larger randomized trials.