Non-adherence, not resistance, major factor in NRTI failure
Non-adherence to antiretroviral therapy was a major contributor to treatment failure, rather than resistance to nucleoside reverse transcriptase inhibitors, or NRTIs, researchers from the London School of Hygiene and Tropical Medicine have found.
“Whilst resistance patterns on identification of virological failure are well described, few data exist on resistance patterns on switching regimens and the influence of non-adherence on such patterns,” the researchers wrote in the Journal of Infectious Diseases. “Also, few studies have explored how NRTI mutations and the resultant loss of regimen activity, impacts on empirically prescribed second-line ART.”
The researchers used prospective data collected from patients in South Africa to create a cohort of patients who switched to second-line ART from 2003 to 2008. They conducted genotyping on the samples and also determined the drug concentrations of lamivudine, nevirapine and efavirenz on samples before the patients switched medication.
The study included 115 patients who had samples that were successfully genotyped and 80 patients who had samples sufficient enough to measure drug concentrations. Before switching therapy, 55% of the patients had sub-therapeutic drug concentrations. More patients who had therapeutic drug concentrations were more likely to have resistance and major drug-resistance mutations.
After switching to second-line ART, 68% of the patients achieved viral suppression. Patients who had sub-therapeutic drug concentrations and no major mutations were less likely to achieve viral suppression with second-line therapy. NRTI resistance was associated with achieving viral suppression with the second-line ART.
“Patients need intensified adherence support when switching regimens if successful outcomes are to be realized,” the researchers wrote. “However, the optimal strategy for achieving this is unclear.”
Disclosure: The researchers report no relevant financial disclosures.