While modern antiretroviral therapy (ART) effectively suppresses HIV replication, it has been associated with neuropsychiatric adverse events including depression. We examined the combined effect of ART regimens on somatic (e.g. sleep/appetite disturbances) and non-somatic (e.g. sadness) depressive symptoms in women with HIV.
Women’s Interagency HIV Study (WIHS) participants with ≥2 study visits after January 1st, 2014, receiving common contemporary ART regimens were divided into three groups using longitudinal Center of Epidemiology Studies Depression (CES-D) scale scores: high (CES-D >16 on >50% of WIHS visits since study enrollment), low (CES-D >16 on < 50% of WIHS visits), and no (CES-D < 16 for all WIHS visits) depressive symptoms. Novel Bayesian machine learning methods building upon a subset-tree kernel approach were developed to estimate the combined effects of ART regimen on somatic and non-somatic depressive symptoms in each group after controlling for relevant covariates.
Among 1,538 women who participated in 12,924 (mean 8.4) visits, the mean age was 49.9 years; 72.4% were Black, 14.3% were Hispanic, and 72.5% had HIV RNA < 50 copies/mL at study entry. Tenofovir disoproxil fumarate (TDF) (54%) followed by tenofovir alafenamide (TAF) (20%) were the most common ART agents used; 49% received integrase inhibitors (INSTI); 33% non-nucleoside reverse transcriptase inhibitors (NNRTI); and 31%, protease inhibitors (PI). In the high-depression group, the combination of TAF with either a cobicistat-boosted INSTI or PI was associated with greater somatic symptoms (worse concentration, sleep, and motivation) while no difference was observed with TDF in these combinations (Figure 1). Moreover, in the same group, TDF combined with an NNRTI was associated with fewer somatic symptoms. ART regimens were not associated with somatic symptoms in the low- or no-depression groups, and no relationship was found between ART and non-somatic symptoms in any group.
Somatic depressive symptoms were observed more frequently among women who received TAF with a cobicistat-boosted INSTI or PI, but no relationship was found between depressive symptoms and TDF or un-boosted INSTIs or PIs. Our findings suggest complex associations between ART and depression, such that ART combinations rather than individual agents are associated with depressive symptoms. Future studies should consider complete drug regimens when assessing the risk of long-term neuropsychiatric complications of ART.
Combined effects of different ART regimens according to frequency on somatic depressive symptoms by group