Oxidant Stress Is Increased during Treatment of Human Immunodeficiency Virus Infection

Abstract

Some diseases and environmental exposures, including those that are risk factors for atherosclerosis, are associated with increased oxidant stress. The objective of this cross-sectional, observational study was to determine whether oxidant stress is increased during human immunodeficiency virus type 1 (HIV-1) infection or its therapy. To quantify oxidant stress, plasma F2 isoprostane (F2-IsoP) concentrations were determined by gas chromatography/mass spectroscopy. A total of 120 subjects were enrolled during routine primary care visits. The median CD4+ T cell count was 341 cells/mm3, the median HIV-1 RNA level was 3.4 log10 copies/mL, and 74% of patients were receiving antiretroviral therapy. Plasma F2-IsoP concentrations were 12-149 pg/mL (median, 31 pg/mL). In univariate analysis, higher F2-IsoP concentrations were associated with lower log10 plasma HIV-1 RNA levels (P=.009) and with efavirenz use (P=.02). Both factors remained associated with plasma F2-IsoP concentrations in multivariate analysis. Oxidant stress associated with therapeutic control of viral replication may have important implications for long-term complications of antiretroviral therapy.

Investigation of the levels of oxidative stress parameters in HIV and HIV-TB co-infected patients

“…This observation may indicate the chronic inflammatory state of HIV naive patients which will definitely enhance their state of oxidative stress. Although there was a reduced level of plasma protein in HIV patients on HAART, antiretroviral therapy has also been known to increase chemically reactive species in circulation, possibly by producing more oxidized metabolites deriving from the interaction between ROS and infected-cell biomolecules as reported by Martín et al, [21], Hulgan et al, [22], and Lizette et al, [23]. This argument may be substantiated by the report of FriisMoller et al [14], which showed that HIV-infected patients are in oxidative imbalance early in the disease; serum and tissue anti-oxidants levels are low and peroxidation products elevated.…”

“…Highly active anti-retroviral therapy (HAART) may increase chemically reactive species in circulation, possibly by producing more oxidized metabolites deriving from the interaction between ROS and infected-cell biomolecules [21][22][23]. This is supported by several biochemical mechanisms, such as mitochondrial interference, following treatment with HAART-NRTI (nucleoside reverse transcriptase inhibitors) [22], and activation of the P 450 hepatic system by HAART, which are protease inhibitors (PI) [21].…”

“…This is supported by several biochemical mechanisms, such as mitochondrial interference, following treatment with HAART-NRTI (nucleoside reverse transcriptase inhibitors) [22], and activation of the P 450 hepatic system by HAART, which are protease inhibitors (PI) [21]. A putative mechanism of these toxicities includes inhibition of mitochondrial DNA polymerase-γ, with resultant mitochondrial DNA depletion and tissue-specific mitochondrial dysfunction [24].…”

Altered Redox Regulation as Cofactor in Comorbidities and Accelerated Aging in HIV Infection Evolution and Antiretroviral Treatment

“…Hepatic toxicity from ART was reported early in epidemic, and recent reports continue to point out the mitochondria as toxic target and OS as a consequence of therapy [61][62][63][64][65][66]. Since HAART does not completely eliminate HIV, it is likely that the final outcome of treatment will depend not only on the effective reduction of viral load (VL), but also on recover ability of immune system and residual virus control [60].…”

“…Virus control with HAART may not, as one might expect, reduce OS levels, on the contrary [61][62][63].…”