Short term adherence tool predicts failure on second line protease inhibitor-based antiretroviral therapy: an observational cohort study

BACKGROUND Most patients who experience virologic failure (VF) on second line antiretroviral therapy (ART) in low-middle income countries fail due to poor adherence rather than antiretroviral resistance. A simple adherence tool designed to detect VF would conserve resources by rationally limiting need for viral load (VL) testing and, in those countries with access to third line ART, the need for resistance testing. METHODS We conducted an observational cohort study of patients who initiated second line ART at a clinic in Kwazulu-Natal, South Africa. Using clinical and pharmacy refill data extracted from the clinic's electronic database, we determined risk factors for VF. Three different methods of calculating short term pharmacy refill adherence were evaluated and compared with long term adherence since second line initiation. We also explored the ability of differing durations of short term pharmacy refill to predict VF on second line ART. RESULTS We included 274 patients with a median follow up of 27 months on second line ART. VF ranged between 3% and 16% within each six month interval after initiating second line ART. 243 patients with at least one VL after 4 months on second line were analysed in the statistical analysis. Pharmacy refill adherence assessed over shorter periods (4 to 6 months) predicted virologic suppression as well as pharmacy refill assessed over longer periods. The risk of VF fell 73% with each 10% increase in adherence measured from pharmacy refills over a 4 month period. Low CD4 count at second line ART initiation was a significant independent risk factor for VF. CONCLUSION Patients identified as poorly adherent by short term pharmacy refill are at risk for VF on second line ART. This pragmatic adherence tool could assist in identifying patients who require adherence interventions, and help rationalize use of VL monitoring and resistance testing among patients on second line ART.