Certain ART combinations carry some risk of depression among women with HIV

Women with HIV who use antiretroviral therapy (ART) combinations such as tenofovir alafenamide (TAF) with a cobicistat-boosted integrase inhibitor (INSTI) or protease inhibitor (PI) appear to frequently show somatic depressive symptoms, according to data from the Women’s Interagency HIV Study (WIHS) presented at CROI 2023.

Among women with high depressive symptoms, the combination of TAF with either a cobicistat-boosted INSTI or PI was associated with greater somatic symptoms, as reflected by worse concentration, sleep, and motivation. Conversely, tenofovir disoproxil fumarate (TDF) in the same combinations had no association with depressive symptoms. [CROI 2023, abstract 469]

Of note, TDF combined with a non-nucleoside reverse transcriptase inhibitors (NNRTIs) even showed some protective effect on somatic symptoms, reported lead study investigator Dr Luis Parra-Rodriguez of Washington University in Saint Louis, Missouri, US.

Meanwhile, ART combination regimens were not associated with somatic depressive symptoms among women with low or no depression and with nonsomatic depressive symptoms overall.

“We all know that modern ART has become progressively effective and safe, [and they] have changed the life course of people living with HIV,” according to Parra-Rodriguez.

He acknowledged, however, that some ARTs have been implicated in depression, particularly INSTIs. The present study, he added, was conducted to address the lack of evidence for complete ART combinations.

“Our findings, and I think this is a very important point, suggest complex associations between ART and depression, such that ART combinations rather than individual agents are associated with depressive symptoms,” Parra-Rodriguez stated.

WIHS included 1,538 women (mean age was 49.9 years, 72.4 percent Black, 14.3 percent Hispanic) receiving common contemporary ART regimens who contributed 12,924 (mean 8.4) visits worth of data. Most of these women (72.5 percent) had HIV RNA <50 copies/mL at study entry.

In the cohort, TDF (54 percent) was the most common ART used, followed by TAF (20 percent). A total of 49 percent of women also received INSTIs, 33 percent received NNRTIs, and 31 percent received PIs.

The women were grouped according to their Center of Epidemiology Studies Depression (CES-D) scale scores: high depressive symptoms (CES-D >16 on >50 percent of WIHS visits), low symptoms (CES-D >16 on <50 percent of WIHS visits), and no symptoms (CES-D <16 for all WIHS visits). Somatic depressive symptoms were defined as sleep or appetite disturbances, while nonsomatic symptoms were characterized by sadness.

“Future studies should consider complete drug regimens when assessing the risk of long-term neuropsychiatric complications of ART,” Parra-Rodriguez said.