Comparison of HIV Virologic Failure Rates Between Patients with Variable Adherence to Three Antiretroviral Regimen Types

Abstract

Medication adherence is a major determinant of antiretroviral (ARV) treatment success and a significant challenge for HIV-positive patients, yet a well-defined adherence threshold to maintain virologic suppression on current ARV regimens remains unclear. The present study evaluated 1915 Kaiser Permanente Southern California HIV-positive patients on one of three regimen types: (1) emtricitabine-tenofovir-efavirenz (FTC-TDF-EFV); (2) emtricitabine-tenofovir (FTC-TDF) and raltegravir (RAL); and (3) FTC-TDF and a boosted protease inhibitor, either darunavir (DRV) or atazanavir (ATV), to compare virologic failure rates between patients with varying levels of adherence to the regimens. Medication possession ratios (MPRs) were calculated to determine adherence, and HIV RNA PCR levels drawn 12-18 months after the initial pharmacy claim for the measured drug were used to determine virologic failure, which was defined as two consecutive HIV RNA PCR measurements ≥200 copies/mL. Adherence was inversely related to virologic failure, with an 80-90% MPR threshold resulting in no more than 3.5% virologic failure rate. In comparison, ≥90% MPR yielded no more that 1.1% virologic failure rate. Although the gold-standard adherence threshold for older ARV regimens has been 95%, an 80-90% MPR appears sufficient to maintain virologic suppression in patients treated with these three ARV regimen types.

Predictors and Profiles of Antiretroviral Therapy Adherence Among African American Adolescents and Young Adult Males Living with HIV

“…An 80-90% medication progression ratio to each of the three regimens was found to be associated with a virologic failure rate of just 3.5%, significantly below the 20% accepted virologic failure rate used to define adherence threshold requirements in older studies. 20 Despite the notable improved potency of newer first-line ARVs compared with ARVs of the 2000s, the goal for ART adherence remains 100% given the complexity of some ART regimens, the risk of developing resistance to ARVs, the effect of inflammatory processes, and increased mortality with suboptimal adherence. 20,21 Adherence to ART regimens for adolescents and young adults living with HIV (YLH) is often less than optimal.…”

“…20 Despite the notable improved potency of newer first-line ARVs compared with ARVs of the 2000s, the goal for ART adherence remains 100% given the complexity of some ART regimens, the risk of developing resistance to ARVs, the effect of inflammatory processes, and increased mortality with suboptimal adherence. 20,21 Adherence to ART regimens for adolescents and young adults living with HIV (YLH) is often less than optimal. A 2014 systematic review and meta-analysis of adherence to ART among YLH (ages of [12][13][14][15][16][17][18][19][20][21][22][23][24] across the globe identified that overall only 62.3% were adherent to their therapy regimens.…”

A Mathematical Model to Predict HIV Virological Failure and Elucidate the Role of Lymph Node Drug Penetration

“…In comparison, two out of three macaques having plasma drug concentrations similar to those of simulated patients had high viral loads and significant resistance within the first 42 weeks of therapy 5. For the treatment combination, predictions of virological failure (green bars) are displayed along a regression curve that is based on clinical data 9. Compared to the regression curve, more virtual patients having an adherence level between 20% and 60% experienced virological success.…”

“…This choice was driven by the availability of virological failure data5, 9, 10 and the required parameters for the model (lymph node drug penetration,8 see below).…”

“…Virological failure could occur without resistance mutations or with resistance‐associated mutations when at least 20% of the viral load has major resistance mutations. For the combination therapy, HIV patients were followed for a period of 12–18 months, with blood samples taken approximately every 3 months 9. Patients differed in their level of drug adherence, measured using pharmacy refill records.…”