Longitudinal engagement trajectories and risk of death among new ART starters in Zambia: A group-based multi-trajectory analysis

Autoři: Aaloke Mody aff001;  Ingrid Eshun-Wilson aff001;  Kombatende Sikombe aff002;  Sheree R. Schwartz aff003;  Laura K. Beres aff003;  Sandra Simbeza aff002;  Njekwa Mukamba aff002;  Paul Somwe aff002;  Carolyn Bolton-Moore aff002;  Nancy Padian aff005;  Charles B. Holmes aff006;  Izukanji Sikazwe aff002;  Elvin H. Geng aff001
Působiště autorů: Division of HIV, ID and Global Medicine, University of California, San Francisco, Zuckerberg San Francisco General Hospital, San Francisco, California, United States of America aff001;  Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia aff002;  Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America aff003;  Division of Infectious Diseases, University of Alabama at Birmingham, Alabama, United States of America aff004;  Division of Epidemiology, University of California, Berkeley, California, United States of America aff005;  Department of Medicine, Georgetown University, Washington, District of Columbia, United States of America aff006
Vyšlo v časopise: Longitudinal engagement trajectories and risk of death among new ART starters in Zambia: A group-based multi-trajectory analysis. PLoS Med 16(10): e32767. doi:10.1371/journal.pmed.1002959
Kategorie: Research Article
doi: 10.1371/journal.pmed.1002959



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.


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.

Klíčová slova:

Death rates – Patients – Probability distribution – Public and occupational health – Tuberculosis – Zambia


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