When patients fail (high virus load) their initial (first line) antiretroviral therapy, we are often confronted with the question: was the failure due to poor choice of medication (weak combo? did we miss a mutation although the resistance testing shows no resistance?) or was it because the patient did not take the medications as often as they were prescribed?

In a retrospective cohort analysis conducted in South Africa, investigators used stored specimens from patients with treatment failure on first-line ART to determine the contributions of resistance and nonadherence to failure or success with second-line regimens. From among 417 patients switching to second-line ART with viral loads >400 copies/mL, 122 had samples for genotyping, drug-concentration measurement, or both (73 had both, 42 had genotyping only, and 7 had drug-concentration measurements only). Overall, 83 of the 122 (68%) achieved viral suppression on second-line ART. Patients with ≥1 nucleoside reverse transcriptase inhibitor drug-resistance mutation (DRM) before switching regimens were more likely to achieve viral suppression than those with no DRMs. Moreover, patients with subtherapeutic first-line ART drug concentrations who had no major DRMs were less likely to achieve suppression than those with major DRMs or those with therapeutic first-line drug concentrations. Overall, patients with subtherapeutic first-line ART and no major DRMs were the least likely to achieve viral suppression with second-line ART, followed by those with subtherapeutic first-line ART and major DRMs, and, finally, those on therapeutic first-line ART.

Citation(s):Johnston V et al. Viral suppression following switch to second-line antiretroviral therapy: Associations with nucleoside reverse transcriptase inhibitor resistance and subtherapeutic drug concentrations prior to switch. J Infect Dis 2013 Sep 13;

Appeared in NEJM Journal watch on 9/23/2013.

Comment: Although this is a retrospective study, it points to adherence, or lack of it, as the main cause for failure of first regimen; it also predicts the success of the second regimen!  Medicine in bottles do not work_BA