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

Cynthia Firnhaber, Livio Azzoni, Andrea S. Foulkes, Robert Gross, Xiangfan Yin, Desiree Van Amsterdam, Doreen Schulze, Deborah K. Glencross, Wendy Stevens, Gillian Hunt, Lynn Morris, Lawrence Fox (+3 others)
2011 PLoS ONE  
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
more » ... unt .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. Conclusion: 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.
doi:10.1371/journal.pone.0021450 pmid:21738668 pmcid:PMC3125169 fatcat:nizgz7j2xjcnpedeib7hrkxb3y