THE CHANGING HIV EPIDEMIC IN THE MODERN ANTI-RETROVIRAL THERAPY ERA
Embargo until
2015-05-01
Date
2014-03-14
Authors
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Journal ISSN
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Publisher
Johns Hopkins University
Abstract
During the early 21st century HIV underwent a transition from an invariably terminal illness to a manageable chronic condition. Much of this change is due to improvements in medication and management. Concurrently, treatment of HIV-infected individuals to prevent secondary transmission has emerged. As a result there has been an increasing interest in understanding each step from HIV infection to durable suppression of HIV replication. These stages are known as the HIV care cascade.
The first study is an analysis of how the time from HIV infection to diagnosis has changed in the time period following the 2006 the Centers for Disease Control and Prevention (CDC) HIV screening guidelines revision. We performed a retrospective cohort study analyzing newly presenting patients to the HIV Research Network (HIVRN). We used multiple linear regression to model the CD4+ T cell count (CD4) at enrollment over time. After adjusting for age, race/ethnicity, gender, HIV risk factor, and clinic site, the mean increase in CD4 at presentation per year was 13.3 cells/µl/year (95% confidence interval (CI) 6.4-20.1 cells/mm3/year) greater over the years 2008-11 than 2003-07, suggesting that the HIV testing practices changed following the CDC guideline change.
The second study is an analysis of the time from enrollment to ART initiation and HIV virologic suppression. We performed a time-to-event analysis using newly presenting patients to the HIVRN cohort. We used competing risks regression to estimate the subdistribution hazards ratio (SHR) for ART initiation and virologic suppression. The adjusted SHR for ART initiation and virologic suppression were increased for years 2007-08 (1.20 [1.13 - 1.27], and 1.25 [1.16 - 1.34], respectively) and 2009-10 (1.48 [1.40 - 1.58], and 1.43 [1.33 - 1.54], respectively) compared to 2003-04. We concluded that patients are being started on ART and achieving virologic suppression earlier after 2007.
The third study examines the incidence of and risk factors for Clostridium difficile infection (CDI) in the Johns Hopkins HIV Clinical Cohort. We determined incidence within the cohort and performed a nested case-control study using conditional logistic regression to ascertain CDI risk factors. We show an incidence of 8.3 cases/1000 patient years. In multivariate analysis, risk of CDI was independently increased for CD4+ cell count of 50 cells/µl or less [adjusted odds ratio (AOR) 20.7 [2.8-151.4]. We show that CDI risk is very high in HIV-infected patients and that severe immunosuppression is a risk factor.
These three studies make contributions to major questions in HIV diagnosis, treatment, and associated infections. We must re-evaluate these factors as HIV transitions to a chronic disease.
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Keywords
HIV, Antiretroviral therapy, CD4 count at presentation, Time to ART initiation, Time to virologic suppression, Clostridium difficile infection, HIV disparities