The Effect of a “Universal Antiretroviral Therapy” Recommendation on HIV RNA Levels Among HIV-Infected Patients Entering Care With a CD4 Count Greater Than 500/µL in a Public Health Setting

Over the past 10 years, the CD4 cell count threshold for antiretroviral therapy (ART) initiation has risen steadily. This trend stems from a growing consensus that a lower pretherapy CD4 cell count nadir predicts higher risk of end-organ disease (eg, cardiovascular disease, renal dysfunction, liver disease, and perhaps neurocognitive decline) and that viral replication independent of CD4 cell counts may increase morbidity [1–3] and possibly mortality [4, 5]. At the same time, ART has also become less demanding for patients: increasing potency has made treatment more forgiving of suboptimal adherence [6], diminished toxicities have eased the burden of adverse effects [7], and expanded drug selection allows more flexible assembly of regimens to suit individual patient needs. Earlier this decade, from 2000 through 2006, the Department of Health and Human Services (DHHS) expert panel had recommended against ART initiation in patients with a CD4 cell count of >500 cells/µL. In April 2007, the panel revised the recommendation to “optional” in this group [8], and in December 2009 the recommendation was further modified to an “optional/moderate” recommendation. In January 2010, the Division of HIV/AIDS at San Francisco General Hospital (SFGH) adopted a “universal ART” recommendation, based on assessment of individual patient benefits, to initiate ART in all untreated HIV-infected persons irrespective of CD4 cell count. This recommendation was subsequently endorsed by the San Francisco Department of Health in March 2010 [9]. Although guidance has increasingly advocated treatment at higher CD4 cell counts, the extent to which evolving standards have been translated into routine care is not completely understood. A recent study showed that the fraction of patients who suppress HIV RNA has increased over the past decade, but differences by CD4 cell count at clinic entry, which may differ significantly, were not presented [10]. In particular, results for ART uptake in patients with CD4 cell counts of >500 cells/µL is of interest because “test, link, and care plus” (TLC+) initiatives are expected to bring more patients with higher CD4 cell counts into the care system [11]. In addition, changes in HIV RNA suppression rates after clinic entry in relation to dates of benchmark guidelines are also unknown. Assessing the associations between guideline issuance and patient outcomes can shed light on the process of evidence translation and also yield practice-based evidence, both topics of growing attention in the implementation and dissemination sciences. Finally, in March 2012, the DHHS guideline committee formally recommended treatment for all HIV-infected persons with a BIII rating [12]. Analyses from a setting where local treatment guidance anticipated national guidance may therefore foreshadow wider changes in practice and patient outcomes. In this analysis, we describe changes in the HIV RNA levels among patients at a public health HIV clinic in San Francisco (the Ward 86 clinic at SFGH) over the course of a decade. We focus particular attention on untreated patients who enter care with CD4 cell counts of >500 cells/µL. Temporal thresholds of interest—against which changes in patient HIV RNA levels will be assessed—include publication dates of benchmark clinical practice guidelines from DHHS as well as 1 January 2010 (the date of the SFGH universal ART policy).