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

Abstract

BackgroundMost 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.MethodsWe 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.ResultsWe 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.ConclusionPatients 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-014-0664-3) contains supplementary material, which is available to authorized users.

Predictors of treatment failure on second-line antiretroviral therapy among adults in northwest Ethiopia: a multicentre retrospective follow-up study

“…This finding is consistent with studies done in Thailand, Malawi, and South Africa 1336 38 This might be due to the fact that patients with a very low CD4 count are more likely to have different opportunistic infections and the added burden of these diseases further complicates their response. This likely increases the possibility of treatment failure and/or death.…”

Comparison of six methods to estimate adherence in an ART-naïve cohort in a resource-poor setting: which best predicts virological and resistance outcomes?

“…The number of medication-free days are subtracted from the number of days in the period, and the result divided by the number of days in the period (up to week 16 or up to week 48) to give an adherence percentage [10]. This method identifies days when it was not possible for a patient to have taken medication; and might be expected to yield lower but potentially more accurate median adherence values than the average method.…”

“…Self-report is the most frequently used method, but is often imprecise and overestimates adherence, similar to clinic-based pill count [4–7]. Pharmacy refill data also overestimate adherence, but have been consistently associated with virological failure and mortality [8–10]. Electronic drug monitoring methods have been closely associated with virologic failure, despite underestimating adherence due to storage and ingestion of medications outside of the device (pocket-doses) [6, 11, 12].…”

Random lopinavir concentrations predict resistance on lopinavir-based antiretroviral therapy

“…Unfortunately, measurement of lopinavir hair concentrations is not widely available and this remains a research tool. We recently showed that adherence assessed by pharmacy refills, which is an inexpensive and easily implementable adherence measure, is strongly associated with the presence of VF on second-line ART [17]. Our group has also shown that adherence assessed by pharmacy refills predicted PI resistance [18].…”