Trends in antiretroviral therapy prescription,durability and modification: new drugs, more changes, but less failure

Currently, HIV treatment is recommended for all persons living with HIV (PLWH) regardless of their immune status in order to prevent HIV-related morbidity, mortality and reduce transmission to others[1, 2]. There are multiple first line antiretroviral therapy (ART) regimens recommended for treatment-naive PLWH based on efficacy and tolerability data obtained in randomized controlled trials[3, 4]. Each contains 3 or more antiretroviral agents, and most contain an Integrase Strand Transfer Inhibitor (InSTI). A majority of these ART regimens contain an antiretroviral agent that was approved by the Food and Drug Administration (FDA) in the last 3 years based on short-term surrogate endpoints including achieving viral suppression[5–7]. Further, these first line regimens have demonstrated relatively little toxicity, like neurologic disturbances, in select samples and controlled settings[8, 9]. Due to their novelty, many of these contemporary ART regimens have not been studied in observational cohorts. Because participants in a randomized control trial (RCT) may vary greatly from real world populations (race/ethnicity, comorbidities, and adherence rates), and additional supports are afforded by the RCT environment, it is important to study ART outcomes as a part of routine care to demonstrate the comparative effectiveness of novel ART[10, 11]. Real world ART durability may reflect more subjective treatment outcomes like quality of life or mild side effects that affect adherence in routine care and are likely of greater importance in clinic-based samples consisting of more diverse and heterogeneous PLWH in routine HIV care[12]. Provider and patient decisions also contribute to real world durability[13]. Recently, two national multi-site cohorts have demonstrated improved durability of ART [14, 15]. Notably, these studies extended to 2009 and 2011, respectively, precluding the study of novel antiretroviral agents, like elvitegravir, and dolutegravir, which are now included in first line treatment guidelines[3]. In our single-site clinic population we found that, in treatment naive individuals, ART durability was decreasing in recent years (2010–2012 vs. 2007–2009); largely due to the availability of newer ART regimens, which afford improved tolerability and dosing convenience[13, 16]. This trend emerged when patients and providers selected novel ART to replace older ART, abbreviating the durability of older regimens in the current treatment era. Yet, these findings are already dated by the dynamic ART treatment landscape in which several novel regimens have been FDA-approved and increasingly adopted as first-line ART since the conclusion of this study. The objective of this study was to evaluate the durability, defined as time to regimen modification (including discontinuation), of novel ART regimens, including those released since 2012, as part of routine care in a multi-site cohort in the U.S. We examined various socio-demographic and clinical characteristics associated with the initial regimen modification. We hypothesized that novel InSTI-based regimens would be more durable than older regimens and that overall durability would decrease in more recent years, reflective of a treatment landscape that now includes multiple well tolerated co-formulated and single tablet ART regimens, based on prior research in our clinic cohort and elsewhere[13, 16].