DSMB stops boosted atazanavir monotherapy study due to virological failure
1 December 2013. Related: Conference reports, Antiretrovirals, EACS 14 Brussels 2013.
Simon Collins, HIV i-Base
Interim results from a study that switched virally suppressed patients to boosted atazanavir monotherapy, showed a significantly higher rate of failure compared to standard of care triple therapy.
This was a randomised, open label, non-inferiority study in 103 patients (84% males, 13% HCV-infected, median (IQR) age of 42 (36-48) years).
Enrolment criteria included viral suppression to <50 copies/mL for greater than 6 months on a combination that included atazanavir/ritonavir (300/100 mg) plus two NRTIs. Participants were randomised to switch to atazanavir/rintonavir monotherapy or continue with triple therapy.
In the 48-week interim analysis (ITT analysis), viral suppression was maintained by 73% (37/51 patients) in the monotherapy arm compared to 85% (44/52) in the triple-therapy arm (difference: -12.1%, 95% CI: -27.8 to 3.6).
This was sufficient for the Data and Safety Monitoring Board (DSMB) to recommended to stopping the study. Confirmed virological failure occurred in 11 vs 2 patients in the monotherapy vs triple-therapy groups and although this was reported as significantly more common in people with HCV coinfection (56% vs 17%; p=0.024), this was in very small numbers of patients.
Viral load was resuppressed in all patients with virological rebound by reintroducing previous NRTIs. Although drug resistant mutations were not detected, median HIV viral load was only 197 (IQR 134-510) copies/mL at the time of testing.
Although drug-related side effects were more common in the triple therapy group (n=0 vs 6, p=0.027), it is notable that these were mostly associated with atazanavir (5/6) rather than the NRTIs.
Comment
An earlier study already reported high rates of virological failure when atazanavir is used as boosted monotherapy. [2]
It therefore is unclear why Bristol-Myers Squibb supported this study other than from a marketing-driven interest.
References:
- Castagna A et al. 48 weeks outcomes of atazanavir/ritonavir monotherapy as maintenance strategy in HIV-1 treated subjects with viral suppression: interim analysis results of the MODAt Study. 14th European AIDS Conference (EACS), 16-19 October 2013, Brussels. Abstract PS 4/2.
http://www.abstractserver.com/eacsabstractarchive/absabstract.php?abid=4861 - Karlstrom et al. Early virologic rebound in a pilot trial of ritonavir-boosted atazanavir as maintenance monotherapy. J Acquir Immune Defic Syndr. 2007 Apr 1;44(4):417-22.
http://www.ncbi.nlm.nih.gov/pubmed/17159658
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http://www.medscape.com/viewarticle/554859