Trajectory analyses of virologic outcomes reflecting community-based HIV treatment in Washington DC 1994-2012

Abstract

Background: Effective treatment of HIV since 1996 has reduced morbidity and mortality through virologic suppression. Combination antiretroviral therapy (cART) has been recognized as key to the prevention of drug resistance and the transmission of infection. We used eighteen years of virologic outcomes in a long-standing cohort of women to describe longitudinal viral load trajectories; and examine factors associated with sustained viremia and mortality. Methods: We analyzed data from DC WIHS women with > four semiannual visits using a group-based logistic trajectory analysis approach to identify patterns of HIV RNA detection (>80 copies/mL or lower assay limit, and >1000 copies/mL). We verified findings using cumulative viral load suppression-years, explored group characteristics using generalized linear modeling with generalized estimating equations for repeated measures, and examined survival using the Kaplan-Meier and Cox proportional hazard analyses. Results: 329 women contributed 6633 visits between 1994 and 2012 and demonstrated high, moderate, and low probability patterns of HIV RNA detection (>80 copies/mL) in 40.7, 35.6, and 23.7 % of participant visits, respectively. Analysis of cumulative years of viral load suppression supported these observations. Kaplan-Meier survival analysis demonstrated high mortality of 31.1 % with sustained viremia, but no significant difference in mortality between intermittent viremia and non-viremia patterns, 6.9 and 4.9 % respectively. Mortality was associated with higher age, lower CD4+ T lymphocyte count, and sustained viremia by Cox multivariate analysis. Conclusions: This ecologic study demonstrates the effectiveness of viral suppression, and conversely the association between viremia and mortality. In community delivery of cART for HIV care, distinct patterns of sustained viremia, intermittent viremia, and non-viremia were identified over nearly 18 years in the DC WIHS, capturing the dynamics and complexity of sustaining long-term HIV care. Persistent viremia was associated with lower CD4s and mortality, but surprisingly mortality was not different between continuous suppression and intermittent viremia. Classification of long-term virologic patterns such as these observed HIV treatment "careers" may provide a suitable framework to identify modifiable factors associated with treatment resilience and failure. Both individual and population interventions are needed to reduce transmission, prevent the emergence of drug resistance, and improve outcomes of community ART programs.