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

Abstract

BackgroundEffective 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.MethodsWe 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.Results329 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.ConclusionsThis 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.

HIV viral load trajectories of women living with HIV in Metro Vancouver, Canada

“…This study offers insight into the dynamic and heterogeneous nature of the longitudinal VL trajectories of WLWH, not captured by cross-sectional study designs. 22 We identified three distinct group-based VL trajectory patterns, comparable in number and shape to those described in Ocampo et al.’s 2015 study 20 : (1) ‘ sustained low probability of detectable VL’ (similar to Ocampo’s ‘non-viremia’ trajectory 20 ) ; (2) ‘ high probability of delayed viral undetectability’ (comparable to Ocampo’s ‘intermittent viremia’ trajectory 20 ); and (3) ‘ high the probability of detectable VL’ (similar to Ocampo’s ‘viremia’ trajectory 20 ) . We also found that lifetime incarceration, younger age at baseline, and lower baseline CD4 levels predicted a ‘ high probability of delayed viral undetectability’ compared to a ‘ sustained low probability of detectable VL’ .…”

“…While we hypothesized that there would be three VL trajectory groups, 20 we tested for the possibility of between 2-6 latent trajectory groups. Up to a cubic polynomial function was considered for each group to allow for maximum flexibility in trajectory forms, and backward selection of time-related parameters (e.g., linear, quadratic, cubic) was employed, based on statistical significance (at p ≤0.10).…”

“…While women’s VL suppression rates continue to lag behind men’s, there remains a gap in research surrounding temporal trends in women’s VL suppression and the individual, social, and structural drivers of VL trends over time. 20 This research is critical to help identify individuals who may experience heightened barriers to retention in treatment and care, and in developing improved public health policy, programming, and strategies to address barriers. Using trajectory analysis, 20–22 this study aimed to: (1) identify longitudinal trajectories of detectable VL; and (2) identify predictors of the resulting VL trajectories among a cohort of WLWH in Metro Vancouver.…”

Viremia Trajectories of HIV in HIV-Positive Women in the United States, 1994-2017

“…Identification of this phenomenon mirrors previous findings among the Washington, DC, WIHS participants. 12 This phenomenon supports the need for regionally representative viral load and drug resistance surveillance. Conversely, analysis of our most recent data demonstrates that women without previous viral suppression can achieve and maintain viral suppression.…”

“… 12 Using a group-based trajectory analysis we identified 3 distinct longitudinal viremia trajectory patterns: high, intermediate, and low probability of viral suppression. 12 This initial study was limited to the mid-Atlantic WIHS participants. We expanded this analysis to the national WIHS cohort that has representation from across the United States to determine whether similar longitudinal patterns of viremia emerge.…”