Effects of docosahexanoic acid supplementation on inflammatory and subcutaneous adipose tissue gene expression in HIV-infected patients on combination antiretroviral therapy (cART). A sub-study of a randomized, double-blind, placebo-controlled study.

BACKGROUND: Omega-3 fatty acids have the potential to decrease inflammation and modify gene transcription. Whether docosahexanoic acid (DHA) supplementation can modify systemic inflammatory and subcutaneous adipose tissue (SAT) gene expression in HIV-infected patients is unknown. METHODS: A randomized, double-blind, placebo-controlled trial that enrolled 84 antiretroviral-treated patients who had fasting TG levels from 2.26 to 5.65 mmol/l and received DHA or placebo for 48 weeks was performed (ClinicalTrials.gov, NCT02005900). Systemic inflammatory and SAT gene expression was assessed at baseline and at week 48 in 39 patients. RESULTS: Patients receiving DHA had a 43.9% median decline in fasting TG levels at week 4 (IQR: -31% to -56%), compared with -2.9% (-18.6% to 16.5%) in the placebo group (P < 0.0001). High sensitivity C reactive protein (hsCRP) and arachidonic acid levels significantly decreased in the DHA group. Adipogenesis-related and mitochondrial-related gene expression did not experience significant changes. Mitochondrial DNA (mtDNA) significantly decreased in the placebo group. SAT inflammation-related gene expression (Tumor necrosis factor alpha [TNF-α], and monocyte chemoattractant protein-1 [MCP-1]) significantly decreased in the DHA group. CONCLUSIONS: DHA supplementation down-regulated inflammatory gene expression in SAT. DHA impact on markers of systemic inflammation was restricted to hsCRP and arachidonic acid.

Effects of docosahexanoic acid on metabolic and fat parameters in HIV-infected patients on cART: A randomized, double-blind, placebo-controlled study.

BACKGROUND: Hypertriglyceridemia is common in HIV-infected patients. Polyunsaturated fatty acids reduce fasting serum triglyceride (TG) levels in HIV-infected patients. It is not known whether docosahexanoic acid (DHA) supplementation can reduce hypertriglyceridemia and modify fat distribution in HIV-infected patients. METHODS: We conducted a randomized, double-blind, placebo-controlled trial with 84 antiretroviral-treated patients who had fasting TG levels from 2.26 to 5.65 mmol/l and were randomized to receive DHA or placebo for 48 weeks. TG levels were assessed at baseline, week 4 and every 12 weeks. Body composition was assessed at baseline and at week 48. Registered under ClinicalTrials.gov Identifier no. NCT02005900. RESULTS: Patients receiving DHA had a 43.9% median decline in fasting TG levels at week 4 (IQR: -31% to -56%), compared with -2.9% (-18.6% to 16.5%) in the placebo group (P < 0.0001). DHA levels and decrease in TG at week 4 in the DHA arm correlated significantly (r = 0.7110, P < 0.0001). The median reduction in TG levels in the DHA arm was -43.7% (-32.4% to -57.5%), and in the placebo arm +2.9% (-21.3% to +30.1%) at week 12. The difference remained statistically significant at week 48 (P = 0.0253). LDL cholesterol levels significantly increased at week 4 by 7.1% (IQR: -4.8% to +35.3%) in the DHA arm but not in the placebo group. No significant changes were observed in HDL cholesterol, insulin, and HOMA-IR during the study. Limb fat significantly increased in both arms, without statistically significant differences between groups (P = 0.3889). DHA was well tolerated; only 3 patients experienced treatment-limiting toxicity. CONCLUSIONS: Supplementation with DHA reduced fasting TG levels in antiretroviral-treated HIV-infected patients with mild hypertriglyceridemia. DHA was well tolerated with minor GI symptoms. Peripheral fat significantly increased in the DHA group but did not increase significantly compared with placebo.

Evaluation of the pharmacogenetics of immune recovery in treated HIV-infected patients.

INTRODUCTION: Combination antiretroviral therapy has markedly improved the survival rate and quality of life in patients infected with HIV due to the powerful suppressor effect that current antiretroviral drugs have on the viral load. Consequently, the immune system undergoes a substantial qualitative and quantitative improvement; and this leads to an increase in the absolute CD4(+) T-lymphocyte count and the restoration of lost T-cell responses against certain opportunistic pathogens. Unfortunately, not all patients who successfully suppress plasma viremia experience sufficient CD4(+) T-cell gain and these patients, in turn, are associated with worse outcomes. Pharmacogenetic studies have been used to investigate how a patient's genetic predisposition may affect their response to antiretroviral drugs. AREAS COVERED: This article reviews the investigations that have been published on the association between host genetic determinants of CD4(+) T-cell gain in treated HIV-infected patients. Studies were identified through a PubMed database search. Longitudinal studies into pharmacogenetic association were specifically selected. EXPERT OPINION: While the possibility of genetic predisposition to HIV therapeutics has potential, most studies provide inconsistent data. Inconsistency is often due to partial genetic evaluation, different categorization of poor immune recovery or due to small numbers of patients evaluated. Currently, studies still belong to the research laboratory stage and more studies are required to improve our understanding.

Previous ciprofloxacin exposure is associated with resistance to beta-lactam antibiotics in subsequent Pseudomonas aeruginosa bacteremic isolates.

BACKGROUND: Pseudomonas aeruginosa cross-resistance to ceftazidime, imipenem, meropenem, piperacillin, and fluoroquinoles has been shown in experimental studies, but information regarding its impact in the clinical setting is scarce and inconsistent. The aim of this study was to assess whether previous exposure to ciprofloxacin influences on the sensitivity of those antibiotics in subsequent P aeruginosa bacteremic isolates. METHODS: Patients with P aeruginosa bacteremia were recorded from a blood culture surveillance program (1997-2007). Demographic characteristics, underlying diseases, setting of the infection, source of infection, previous antibiotic exposure, and antibiotic sensitivity were analyzed. RESULTS: We studied 572 cases of P aeruginosa bacteremia. There were 327 men (57.2%), and the mean age was 61.2 +/- 18 years. The bacteremia was nosocomial in 62.4% of episodes. Resistance rates of P aeruginosa isolates were 15.5% for ceftazidime, 16.7% for imipenem, 11.2% for meropenem, 12.3% for piperacillin-tazobactam, and 23.1% for ciprofloxacin. Exposure to ciprofloxacin during the previous 30 days was an independent predictor of resistance to ceftazidime (odds ratio [OR], 3; 95% confidence interval [CI]: 1.7-5.3; P < .001), imipenem (OR, 2; 95% CI: 1.1-3.7; P = .02), meropenem (OR, 2.7; 95% CI: 1.4-5.3; P = .004), piperacillin-tazobactam (OR, 2.4; 95% CI: 1.3-4.7; P = .007), ciprofloxacin (OR, 2.9; 95% CI: 1.7-4.9; P < .001), and multidrug resistance (OR, 2.5; 95% CI: 1.2-5.2; P = .02). CONCLUSION: P aeruginosa bacteremic isolates from patients who have been exposed to ciprofloxacin during the 30 days prior to the development of bacteremia have an increased risk of being resistant to ceftazidime, imipenem, meropenem, piperacillin-tazobactam, or ciprofloxacin and to have multidrug resistance.