Date of this Version
The clinical outcomes of short interruptions of PI-based ART regimens remains undefined.
A 2-arm non-inferiority trial was conducted on 53 HIV-1 infected South African participants with viral load/ml and CD4 T cell count >450 cells/µl 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.
The proportions of CD4 counts >350 cells/µl 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: −0.16, 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.
We are unable to conclude that short PI-based ART interruptions are non-inferior to cART in retention of immune reconstitution; however, short interruptions did not lead to a greater rate of resistance mutations or adverse events than cART suggesting that this regimen may be more forgiving than NNRTIs if interruptions in therapy occur.
© 2011 Firnhaber et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PI-based ART regimens, antiretroviral therapy, Sub-Saharan, Africa, STI
Firnhaber, Cynthia; Azzoni, Livio; Foulkes, Andrea S.; Gross, Robert; Yin, Xiangan; Van Amsterdam, Desiree; Schulze, Doreen; Glencross, Deborah K.; Stevens, Wendy; Hunt, Gillian; Morris, Lynn; Fox, Lawerence; Sanne, Ian; and Montaner, Luis J., "Randomized Trial of Time-Limited Interruptions of Protease Inhibitor-Based Antiretroviral Therapy (ART) vs. Continuous Therapy for HIV-1 Infection" (2011). Botswana-UPenn Scholarly Publications. 39.
Date Posted: 02 December 2014
This document has been peer reviewed.