Randomized Trial of Time-Limited Interruptions of Protease Inhibitor-Based Antiretroviral Therapy (ART) vs. Continuous Therapy for HIV-1 Infection

Background: The clinical outcomes of short interruptions of PI-based ART regimens remains undefined. Methods: A 2-arm non-inferiority trial was conducted on 53 HIV-1 infected South African participants with viral load,50 copies/ml and CD4 T cell count.450 cells/ml on stavudine (or zidovudine), lamivudine and lopinavir/ritonavir. Subjects were randomized to a) sequential 2, 4 and 8-week ART interruptions or b) continuous ART (cART). Primary analysis was based on the proportion of CD4 count.350 cells(c)/ml over 72 weeks. Adherence, HIV-1 drug resistance, and CD4 count rise over time were analyzed as secondary endpoints. Results: The proportions of CD4 counts.350 cells/ml were 82.12 % for the intermittent arm and 93.73 for the cART arm; the difference of 11.95 % was above the defined 10 % threshold for non-inferiority (upper limit of 97.5 % CI, 24.1%; 2-sided CI: 20.16, 23.1). No clinically significant differences in opportunistic infections, adverse events, adherence or viral resistance were noted; after randomization, long-term CD4 rise was observed only in the cART arm