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.

High FGF21 levels are associated with altered bone homeostasis in HIV-1-infected patients.

BACKGROUND: Fibroblast growth factor-21 (FGF21) has emerged as an important regulator of glucose, lipid, and body weight homeostasis. However, recent experimental studies have reported that increased FGF21 levels may lead to bone loss. OBJECTIVE: To assess the relationship of serum FGF21 levels and altered bone homeostasis in HIV-1-infected patients. DESIGN: Cross-sectional study of 137 HIV-1-infected patients and 35 healthy controls conducted at the Hospital de la Santa Creu i Sant Pau, Barcelona. Among HIV-1-infected patients, 35 were untreated (naïve), 43 were treated with antiretrovirals (HIV-1/ART) with no lipodystrophy, and 59 patients were HIV-1/ART and experienced lipodystrophy. Bone mineral density (BMD) and content (BMC) were assessed using dual-energy X-ray absorptiometry. Serum levels of FGF21, receptor activator of nuclear factor (NF)-KB ligand (RANKL), and C-telopeptide of type-I collagen (CTX-1) were measured by enzyme-linked immunosorbent assays. Serum levels of osteocalcin, osteoprotegerin, leptin, tumor necrosis factor-α, interleukin-6, interleukin-8, and monocyte chemoattractant protein-1 were determined using an antibody-linked, fluorescently labeled microsphere bead-based multiplex analysis system. RESULTS: Alterations in bone parameters and bone homeostasis marker levels were consistent with higher turnover and bone loss in HIV-1 infected patients. FGF21 correlated negatively with BMD and BMC. FGF21 correlated positively with serum levels of osteoprotegerin and CTX-1, as well as with the CTX-1/osteocalcin ratio. CONCLUSIONS: Elevated FGF21 levels are associated with poor bone homeostasis in HIV-1-infected patients. Increases in FGF21 serum level may be an indicator not only of metabolic derangement but it may also serve as a biomarker of altered bone homeostasis in HIV-1 infected patients.

Stavudine extended release (once-daily, Bristol-Myers Squibb) for the treatment of HIV/AIDS.

INTRODUCTION: Stavudine extended release (d4T XR) was a formulation which tried to solve the two main problems associated with the use of stavudine immediate release (d4T IR). These were twice daily dosing schema at a time when most formulations were long-life allowing once daily dosing; and that the use of d4T IR was associated with long-term toxicity through mitochondrial toxicity clinically expressed as peripheral neuropathy, pancreatitis and above all, lipodystrophy. The link between stavudine exposure and lipodystrophy had a great negative impact on its use in clinical practice. AREAS COVERED: The authors cover the most relevant papers related to the efficacy and safety of d4T XR-based antiretroviral therapy. EXPERT OPINION: The development of d4T XR has only been partially successful with regard to its objectives. Improved pharmacokinetic properties allow its once daily dosing, and although it exhibits less mitochondrial toxicity it is still hampered by its development in a significant proportion of patients. This has caused its use to be almost residual in industrialised countries. As of now, d4T XR has not been made available in developing countries, despite the extended use of the immediate-release formulation. Currently, if there is no other chance of starting combination antiretroviral therapy, d4T XR could play a role in the treatment of HIV infection.