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.

Strategies in the treatment of HIV-1-associated adipose redistribution syndromes.

HIV-1/highly active antiretroviral therapy-associated lipodystrophy syndrome (HALS) is presently the most common long-term adverse effect limiting the doubtless efficacy of antiretroviral therapy. It has a great impact on the quality of life of patients, it is stigmatising and its psychologically devastating consequences may ultimately impact on the adherence to treatment of patients, eventually leading to treatment failure. Despite considerable advances in recent times, the pathogenesis of HALS remains elusive. Factors involved belong to three categories: those intrinsic to the host, some of them modifiable and some not, those associated with antiretroviral therapy, that are sometimes modifiable as well, and finally those related to HIV-1 infection and its consequences, most often not modifiable. The most commonly used strategies for HALS reversion have included host-dependent factors such as lifestyle and dietary modifications and antiretroviral-dependent factors such as switching or avoiding the use of drugs more prone to promote HALS. Lifestyle modifications and switching thymidine analogues have been associated with moderate success. Pharmacological interventions have included the use of insulin-sensitising agents and hormone therapy with disappointing results, whereas treatment with pravastatin or pioglitazone, and uridine supplementation seem to be associated with fat gain in preliminary studies. The only interventions with almost immediate results that may render a patient's appearance similar to his past one have included filling techniques for facial lipoatrophy and ultrasound-assisted liposuction for cervical fat pad hypertrophy. Among the filling options, semipermanent reabsorbable materials and autologous fat transfer have been associated with acceptable outcomes. As of now, the best hope should rely on the use of drugs friendly for fat, on defining the appropriate timing for starting antiretroviral and on continuing the research effort to understand the basic mechanisms underlying HALS pathogenesis. Only through this effort can the best chances for preventing or reverting established HALS be recognised.