Dataset Information

Randomized trial of time-limited interruptions of protease inhibitor-based antiretroviral therapy (ART) vs. continuous therapy for HIV-1 infection.

ABSTRACT:

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/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.

Results

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.

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.

Trial registration

ClinicalTrials.gov NCT00100646.

SUBMITTER: Firnhaber C

PROVIDER: S-EPMC3125169 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Randomized trial of time-limited interruptions of protease inhibitor-based antiretroviral therapy (ART) vs. continuous therapy for HIV-1 infection.

Firnhaber Cynthia C Azzoni Livio L Foulkes Andrea S AS Gross Robert R Yin Xiangfan X Van Amsterdam Desiree D Schulze Doreen D Glencross Deborah K DK Stevens Wendy W Hunt Gillian G Morris Lynn L Fox Lawrence L Sanne Ian I Montaner Luis J LJ

PloS one 20110628 6

<h4>Background</h4>The clinical outcomes of short interruptions of PI-based ART regimens remains undefined.<h4>Methods</h4>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/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 C ...[more]

PMID: 21738668

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Project description:IntroductionEarly antiretroviral therapy (ART) has improved neurodevelopmental outcomes of HIV-infected (HIV-positive) children; however, little is known about the longer term outcomes in infants commencing early ART or whether temporary ART interruption might have long-term consequences. In the children with HIV early antiretroviral treatment (CHER) trial, HIV-infected infants ≤12 weeks of age with CD4 ≥25% were randomized to deferred ART (ART-Def); immediate time-limited ART for 40 weeks (ART-40W) or 96 weeks (ART-96W). ART was restarted in the time-limited arms for immunologic/clinical progression. Our objective was to compare the neurodevelopmental profiles in all three arms of Cape Town CHER participants.MethodsA prospective, longitudinal observational study was used. The Griffiths mental development scales (GMDS), which includes six subscales and a global score, were performed at 11, 20, 30, 42 and 60 months, and the Beery-Buktenica developmental tests for visual motor integration at 60 months. HIV-exposed uninfected (HEU) and HIV-unexposed (HU) children were enrolled for comparison. Mixed model repeated measures were used to compare groups over time, using quotients derived from standardized British norms.ResultsIn this study, 28 ART-Def, 35 ART-40W, 33 ART-96W CHER children, and 34 HEU and 39 HU controls were enrolled. GMDS scores over five years were similar between the five groups in all subscales except locomotor and general Griffiths (interaction p < 0.001 and p = 0.02 respectively), driven by early lower scores in the ART-Def arm. At 60 months, scores for all groups were similar in each GMDS scale. However, Beery visual perception scores were significantly lower in HIV-infected children (mean standard scores: 75.8 ART-Def, 79.8 ART-40W, 75.9 ART-96W) versus 84.4 in HEU and 90.5 in HU (p < 0.01)).ConclusionsEarly locomotor delay in the ART-Def arm resolved by five years. Neurodevelopmental outcomes at five years in HIV-infected children on early time-limited ART were similar to uninfected controls, apart from visual perception where HIV-infected children scored lower. Poorer visual perception performance warrants further investigation.

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Dataset Information

Randomized trial of time-limited interruptions of protease inhibitor-based antiretroviral therapy (ART) vs. continuous therapy for HIV-1 infection.

Background

Methods

Results

Conclusion

Trial registration

Publications

Randomized trial of time-limited interruptions of protease inhibitor-based antiretroviral therapy (ART) vs. continuous therapy for HIV-1 infection.

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