Improvement in depressive symptoms after antiretroviral therapy initiation in people with HIV in Rakai, Uganda

Abstract

Depression is common following HIV infection and often improves after ART initiation. We aimed to identify distinct dimensions of depression that change following ART initiation in persons with HIV (PWH) with minimal comorbidities (e.g., illicit substance use) and no psychiatric medication use. We expected that dimensional changes in improvements in depression would differ across PWH. In an observational cohort in Rakai, Uganda, 312 PWH (51% male; mean age = 35.6 years) completed the Center for Epidemiologic Studies-Depression (CES-D) scale before and up to 2 years after ART initiation. Twenty-two percent were depressed (CES-D scores ≥ 16) pre-ART that decreased to 8% after ART. All CES-D items were used in a latent class analysis to identify subgroups with similar change phenotypes. Two improvement phenotypes were identified: affective-symptom improvement (n = 58, 19%) and mixed-symptom improvement (effort, appetite, irritability; n = 41, 13%). The affect-improvement subgroup improved on the greatest proportion of symptoms (76%). A third subgroup was classified as no-symptom changes (n = 213, 68%) as they showed no difference is symptom manifestation from baseline (93% did not meet depression criteria) to post-ART. Factors associated with subgroup membership in the adjusted regression analysis included pre-ART self-reported functional capacity, CD4 count, underweight BMI, hypertension, female sex(P's < 0.05). In a subset of PWH with CSF, subgroup differences were seen on Aβ-42, IL-13, and IL-12. Findings support that depression generally improves following ART initiation; however, when improvement is seen the patterns of symptom improvement differ across PWH. Further exploration of this heterogeneity and its biological underpinning is needed to evaluate potential therapeutic implications of these differences.

Keywords: Antiretroviral; Depression; Global health; HIV; Heterogeneity.

Fig. 1.

Patterns of changes in depression in the overall sample and by subgroup.

Fig. 2.

Three-latent-class model of antiretroviral (ART)-related depressive symptom improvement. Probability of Center for Epidemiologic Studies Depression Scale (CES-D) item level symptom improvement for each subgroup.

Fig. 3.

Average CES-D item scores for each subgroup pre- and post-antiretroviral (ART). Green corresponds to symptom improvement with ART and magenta with symptom exacerbation with ART.

Fig. 4.

Pre-antiretroviral CSF estimated mean (standard error) biomarker levels (log-transformed and z-scored) showing significant differences between the subgroups demonstrating affect or somatic symptom improvement compared to the no-change subgroup. Note. Shaded regions meet statistical significance following a false discovery rate correction.