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Background: Retention in HIV treatment must be improved to advance the HIV response, but research to characterize gaps in retention has focused on estimates from single time points and population-level averages. These approaches do not assess the engagement patterns of individual patients over time and fail to account for both their dynamic nature and the heterogeneity between patients. We apply group-based trajectory analysis-a special application of latent class analysis to longitudinal data-among new antiretroviral therapy (ART) starters in Zambia to identify groups defined by engagement patterns over time and to assess their association with mortality., Methods and Findings: We analyzed a cohort of HIV-infected adults who newly started ART between August 1, 2013, and February 1, 2015, across 64 clinics in Zambia. We performed group-based multi-trajectory analysis to identify subgroups with distinct trajectories in medication possession ratio (MPR, a validated adherence metric based on pharmacy refill data) over the past 3 months and loss to follow-up (LTFU, >90 days late for last visit) among patients with at least 180 days of observation time. We used multinomial logistic regression to identify baseline factors associated with belonging to particular trajectory groups. We obtained Kaplan-Meier estimates with bootstrapped confidence intervals of the cumulative incidence of mortality stratified by trajectory group and performed adjusted Poisson regression to estimate adjusted incidence rate ratios (aIRRs) for mortality by trajectory group. Inverse probability weights were applied to all analyses to account for updated outcomes ascertained from tracing a random subset of patients lost to follow-up as of July 31, 2015. Overall, 38,879 patients (63.3% female, median age 35 years [IQR 29-41], median enrollment CD4 count 280 cells/μl [IQR 146-431]) were included in our cohort. Analyses revealed 6 trajectory groups among the new ART starters: (1) 28.5% of patients demonstrated consistently high adherence and retention; (2) 22.2% showed early nonadherence but consistent retention; (3) 21.6% showed gradually decreasing adherence and retention; (4) 8.6% showed early LTFU with later reengagement; (5) 8.7% had early LTFU without reengagement; and (6) 10.4% had late LTFU without reengagement. Identified groups exhibited large differences in survival: after adjustment, the "early LTFU with reengagement" group (aIRR 3.4 [95% CI 1.2-9.7], p = 0.019), the "early LTFU" group (aIRR 6.4 [95% CI 2.5-16.3], p < 0.001), and the "late LTFU" group (aIRR 4.7 [95% CI 2.0-11.3], p = 0.001) had higher rates of mortality as compared to the group with consistently high adherence/retention. Limitations of this study include using data observed after baseline to identify trajectory groups and to classify patients into these groups, excluding patients who died or transferred within the first 180 days, and the uncertain generalizability of the data to current care standards., Conclusions: Among new ART starters in Zambia, we observed 6 patient subgroups that demonstrated distinctive engagement trajectories over time and that were associated with marked differences in the subsequent risk of mortality. Further efforts to develop tailored intervention strategies for different types of engagement behaviors, monitor early engagement to identify higher-risk patients, and better understand the determinants of these heterogeneous behaviors can help improve care delivery and survival in this population., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: EHG is a member of the Editorial Board of PLOS Medicine. CBH has received grant funding from the Gates Foundation.

Background: Extending appointment intervals for stable HIV-infected patients in sub-Saharan Africa can reduce patient opportunity costs and decongest overcrowded facilities., Methods: We analyzed a cohort of stable HIV-infected adults (on treatment with CD4 >200 cells/μL for more than 6 months) who presented for clinic visits in Lusaka, Zambia. We used multilevel, mixed-effects logistic regression adjusting for patient characteristics, including prior retention, to assess the association between scheduled appointment intervals and subsequent missed visits (>14 days late to next visit), gaps in medication (>14 days late to next pharmacy refill), and loss to follow-up (LTFU; >90 days late to next visit)., Results: A total of 62084 patients (66.6% female, median age 38, median CD4 438 cells/μL) made 501281 visits while stable on antiretroviral therapy. Most visits were scheduled around 1-month (25.0% clinical, 44.4% pharmacy) or 3-month intervals (49.8% clinical, 35.2% pharmacy), with fewer patients scheduled at 6-month intervals (10.3% clinical, 0.4% pharmacy). After adjustment and compared to patients scheduled to return in 1 month, patients with six-month clinic return intervals were the least likely to miss visits (adjusted odds ratio [aOR], 0.20; 95% confidence interval [CI], 0.17-0.24); miss medication pickups (aOR, 0.47; 95% CI 0.39-0.57), and become LTFU prior to the next visit (aOR, 0.41; 95% CI, 0.31-0.54)., Conclusions: Six-month clinic return intervals were associated with decreased lateness, gaps in medication, and LTFU in stable HIV-infected patients and may represent a promising strategy to reduce patient burdens and decongest clinics., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)