Urinary eicosanoid metabolites in HIV-infected women with central obesity switching to raltegravir: an analysis from the women, integrase, and fat accumulation trial.

Chronic inflammation is a hallmark of HIV infection. Eicosanoids reflect inflammation, oxidant stress, and vascular health and vary by sex and metabolic parameters. Raltegravir (RAL) is an HIV-1 integrase inhibitor that may have limited metabolic effects. We assessed urinary F-2-isoprostanes (F-2 -IsoPs), prostaglandin E-2 (PGE-M), prostacyclin (PGI-M), and thromboxane B-2 (TxB(2)) in HIV-infected women switching to RAL-containing antiretroviral therapy (ART). Thirty-seven women (RAL = 17; PI/NNRTI = 20) with a median age of 43 years and BMI 32 kg/m(2) completed week 24. TxB(2) increased in the RAL versus PI/NNRTI arm (+0.09 versus -0.02;P = 0.06). Baseline PGI-M was lower in the RAL arm (P = 0.005); no other between-arm cross-sectional differences were observed. In the PI/NNRTI arm, 24-week visceral adipose tissue change correlated with PGI-M (rho = 0.45;P = 0.04) and TxB 2 (rho = 0.44;P = 0.005) changes, with a trend seen for PGE-M (rho = 0.41;P = 0.07). In an adjusted model, age >= 50 years (P = 8) was associated with increased PGE-M (P = 0.04). In this randomized trial, a switch to RAL did not significantly affect urinary eicosanoids over 24 weeks. In women continuing PI/NNRTI, increased visceral adipose tissue correlated with increased PGI-M and PGE-M. Older age (>= 50) was associated with increased PGE-M. Relationships between aging, adiposity, ART, and eicosanoids during HIV-infection require further study.