Background:  Oxidant stress, or free radical-induced cell damage, may mediate ART toxicities. Elevated plasma F₂-isoprostane (F₂-IsoP) levels reflect lipid peroxidation and in vivo oxidant stress, and have been described in ART-associated lipoatrophy, hyperlactatemia, and during therapeutic control of plasma HIV-1 viremia. We explored factors associated with F₂-IsoP in HIV-infected adults.

Methods:  This cross-sectional observational study enrolled ambulatory HIV-infected adults from the Comprehensive Care Center in Nashville, Tennessee, from 2003 to 2005. Eligible participants were assigned to 1 of 3 categories:  on ART that included a thymidine analogue (zidovudine [AZT] or stavudine [d4T]) but no non-nucleoside reverse transcriptase inhibitor (NNRTI); on ART that included an NNRTI (efavirenz [EFV] or nevirapine [NVP]) for >30 days; or not on ART for >3 months. Laboratory and clinical data were collected prospectively. Plasma F₂-IsoP was quantified by gas chromatography/mass spectroscopy (GC/MS), and plasma NNRTI concentrations by high-performance liquid chromatography (HPLC). Factors associated with F₂-IsoP were assessed by Wilcoxon rank-sum, Fisher’s exact and χ² tests, and multivariable linear regression.

Results:  Among 285 participants with F₂-IsoP levels, the median age was 41 years, 24% were female, 37% were African American, and 68% were receiving ART. Of these, 89 (46%) were on a NNRTI (44 EFV, 45 NVP) and 85 (44%) were on a protease inhibitor. Median F₂-IsoP was 37 pg/mL (IQR 27 to 48) and did not differ among the 3 participant categories. By univariate analysis, higher plasma F₂-IsoP was associated with female sex (p = 0.006), heavy cigarette smoking (p = 0.003), and higher body mass index (p = 0.03). Lower F₂-IsoP levels were associated with NVP use (p = 0.04) and antioxidant use (p = 0.04). F₂-IsoP levels were not associated with other ART, CD4 count, HIV-1 RNA level, or total cholesterol. In a multivariable model adjusting for demographic and clinical factors, ART use and type, and NNRTI concentrations, factors independently associated with increased F₂-IsoP levels were female sex (p = 0.001), higher body mass index (p = 0.007), and heavy smoking (p = 0.003), while NNRTI use was associated with decreased F₂-IsoP levels (p = 0.036).

Conclusions:  Among HIV-infected adults, increased oxidant stress was associated with female sex, higher body mass index, and heavy smoking. NNRTI use may be associated with decreased oxidant stress when adjusted for plasma NNRTI concentrations. Prospective studies should better define the importance of ART and environmental exposures for oxidant stress and complications during HIV infection and its therapy.