Urinary Eicosanoid Metabolites in HIV-Infected Women with Central Obesity Switching to Raltegravir: An Analysis from the Women, Integrase, and Fat Accumulation Trial

Abstract EN

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 F2-isoprostanes (F2-IsoPs), prostaglandin E2 (PGE-M), prostacyclin (PGI-M), and thromboxane B2 (TxB2) 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/m2 completed week 24.

TxB2 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 TxB2 ( 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 ( N = 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.