High Adherence Key to Success with Raltegravir-Based Regimens
Treatment interruptions and decreased adherence raised the risk for virologic failure with twice-daily raltegravir-based regimens.
The relationship between treatment adherence and risk for virologic failure has been well studied for nonnucleosidse reverse transcriptase inhibitor (NNRTI)-based and boosted protease inhibitor (PI)-based antiretroviral regimens but not for the more recently available integrase inhibitor–based ones. In a recent prospective cohort study, researchers examined patterns of adherence among HIV-infected patients receiving twice-daily raltegravir and the effect of these patterns on the development of drug resistance.
The 81 study participants had a mean age of 48, and 72% were men. At baseline, 12% were treatment naive, and 74% had viral loads <40 copies/mL; the median CD4 count was 468 cells/mm3. All the regimens being used had genotypic sensitivity scores 3 (including raltegravir). Electronic bottle caps, raltegravir plasma levels, and self-report questionnaires were used to monitor drug adherence.
During a median follow-up of 6 months, virologic failure occurred in 15% of the cohort. In multivariate analysis, longer treatment interruption was associated with an increased risk for virologic failure (adjusted odds ratio per 24-hour increase, 2.4), whereas better adherence was associated with a reduced risk (aOR per 5% increase in adherence, 0.68). Raltegravir plasma levels were not associated with risk for virologic failure, but plasma levels were not systematically measured at the time of failure. Genotypic resistance testing, conducted on samples from 10 patients with virologic failure, showed new major raltegravir-resistance mutations in 2 patients.
Comment: This study involved a modest-sized, heterogeneous patient population followed for a relatively short time. Nonetheless, the results underscore the observation that success with raltegravir-based regimens is highly dependent on adherence, in part because of the short half-life of the drug in plasma (compared with that of efavirenz) and because of the drug's low genetic barrier to resistance (similar to that of NNRTIs and distinctly lower than that of boosted PIs).
Published in Journal Watch HIV/AIDS Clinical Care November 9, 2012
Gras G et al. Patterns of adherence to raltegravir-based regimens and the risk of virological failure among HIV-infected patients: The RALTECAPS Cohort Study. J Acquir Immune Defic Syndr 2012 Nov 1; 61:265.
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