The primary objective was to compare the change in fasting low-density lipoprotein (LDL) cholesterol from baseline to week 12 between patients receiving an atazanavir-containing regimen and those receiving comparator protease inhibitor (PI) regimens.
AI424-067 was a 48-week, open-label, randomized, prospective study of 246 patients on PI-based regimens with hyperlipidemia [fasting LDL cholesterol >130 mg/dL (>3.4 mmol/L)] and with HIV RNA <50 copies per milliliter. Patients were randomized to switch to atazanavir (400 mg once daily) on day 1 (immediate switch) or maintain current PI regimen for the first 24 weeks, then switch to atazanavir (delayed switch).
Plasma lipid levels were compared with baseline values at weeks 12, 24, and 48. Safety, viral load, and CD4 profiles were also evaluated.
At week 12, the mean percent changes in LDL cholesterol from baseline for the immediate-switch and delayed-switch groups were -15% and +1%, respectively (P < 0.0001). Favorable LDL cholesterol levels in the immediate-switch group were sustained through week 48. Both groups maintained comparable virologic control. Switching to atazanavir did not produce a significant change in safety or tolerability.
A switch-either immediate or delayed-from a boosted or unboosted PI to unboosted atazanavir in patients with hyperlipidemia was associated with improvements in plasma lipid parameters without loss of virological suppression.
"Alterations in lipoproteins in treated HIV infected people varies with the ARV combinations used. Unlike the early PI drugs (Lopinavir, Indinavir), newer PI drugs (Atazanavir, Duranavir) have less dyslipidaemic effects (Sension et al., 2009, Murphy et al., 2010). NNRTI drugs have even lesser dyslipidaemic effects compared to the PI drugs and are therefore considered safer than the PI drugs. "
[Show abstract][Hide abstract] ABSTRACT: Studies on dyslipidaemia in human immunodeficiency virus (HIV) infected people have reported on lipoproteins and lipoprotein subclass profiles. Lipoprotein subclasses are regarded as more accurate measures of cardiovascular disease (CVD) risk than levels of lipoproteins. In this review, the primary objective was to compare and contrast the distribution patterns of lipoprotein and lipoprotein subclasses in highly active antiretroviral therapy (HAART) naïve people and those on HAART based on available literature. PubMed, Science Direct and Google were searched using a combination of various keywords, and relevant English language articles were selected. HIV infection is associated with a decrease of high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), total cholesterol (TC), with increased triglycerides (TG) accompanied by noticeable decreases in total HDL-particles (HDL-p), small dense HDL-p, total LDL-particles (LDL-p) and small dense LDL-p. Acquired immunodeficiency syndrome (AIDS) is associated with increase in small dense LDL-p and decreased HDL-p. HAART, especially protease inhibitor (PI)-based, is associated with increase in lipoprotein levels and levels of total LDL-p and small dense LDL-p, while the non-nucleoside reverse transcriptase inhibitors (NNRTI)-based HAART is associated with smaller increase in lipoprotein levels and significant increase in HDL-p. In addition to a predominance of small dense LDL-p, patients on HAART, especially PI-based have low HDL-p levels. This subclass pattern increases the risk of CVD in HIV-infected people. The use of NNRTI-based HAART or newer PI drugs such as atazanavir, associated with a less atherogenic subclass profile could defer premature CVD in HIV-infected people. As most studies were conducted in Western countries and in people whose ethnicity is different from the ethnicity of people from sub-Saharan Africa, there is a need to analyse lipoprotein subclasses in HIV- infected people, especially in sub-Saharan Africa where HIV infection is most prevalent
"All the trials demonstrated a decline in total cholesterol and tryglicerides, in particular the large SWAN , SLOAT , and ATAZIP trials , but when a deeper look was brought, also HDL cholesterol tended to decrease  or remained stable , showing in this respect a difference from nevirapine simplification. Most recently it has been suggested that even the low dose ritonavir present in the boosted atazanavir-based regimens may do or maintain some metabolic harm and that the switch to unboosted atazanavir in virologically suppressed patients without resistance-associated mutations is associated with a more favourable lipid profile without risks of loosing the grip on HIV, and a large trial seems to confirm these data . A small pilot study of 9 patients with dyslipidemia and insulin resistance, tested through hyperinsulinemic euglycemic clamp (insulin dose, 200 mU/m minute), showed in all a relevant increase in insulin sensitivity (+28%; P = .008) "
[Show abstract][Hide abstract] ABSTRACT: Many infections favor or are directly implicated with lipid metabolism perturbations and/or increased risk of coronary heart disease (CHD). HIV itself has been shown to increase lipogenesis in the liver and to alter the lipid profile, while the presence of unsafe habits, addiction, comorbidities, and AIDS-related diseases increases substantially the risk of cardiovascular disease (CVD) in the HIV-infected population. Antiretroviral therapy reduces such stimuli but many drugs have intrinsic toxicity profiles impacting on metabolism or potential direct cardiotoxicity. In a moment when the main guidelines of HIV therapy are predating the point when to start treating, we mean to highlight the contribution of HIV-1 to lipid alteration and inflammation, the impact of antiretroviral therapy, the decisions on what drugs to use to reduce the probability of having a cardiovascular event, the increasing
use of statins and fibrates in HIV-1 infected subjects, and finally the switch strategies, that balance effectiveness and toxicity to move the decision to change HIV drugs. Early treatment might reduce the negative effect of HIV on overall cardiovascular risk but may also evidence the impact of drugs, and the final balance (reduction or increase in CHD and lipid abnormalities) is not known up to date.
"Cmax ~ 10 µmol/L) (Solas et al., 2008). The lack of effects of ATV on adipogenesis in the range of concentrations observed in the plasma of treated HIV patients is in line with the clinical findings that treatment with ATV is associated with fewer lipid abnormalities and alterations in body fat composition generally associated with lipodystrophy (Haerter et al., 2004;Jemsek et al., 2006;Möbius et al., 2005;Sension et al., 2009), and in keeping with in vitro data showing that differentiation of preadipocytes was significantly inhibited by RTV, but not by ATV a concentration of 10 µmol/ L (Jones et al., 2008). However, although ATV may overall have less negative impact on fat differentiation than RTV, the effect on preadipocyte replication suggests the potential for a reduction in overall adipose tissue formation. "
[Show abstract][Hide abstract] ABSTRACT: Protease inhibitors (PIs) have been implicated in the development of HIV-associated lipodystrophy through a reduction in the differentiation of preadipocytes. While atazanavir (ATV) is associated with fewer clinical metabolic abnormalities in the short-term, the effects of long-term exposure are not known. ATV effects on preadipocyte replication or differentiation would indicate the potential for long-term problems. This study compared ritonavir (RTV) and ATV effects on preadipocyte replication and differentiation in human primary cultures. Preadipocytes from subcutaneous fat were studied in the presence of therapeutic concentrations of RTV and ATV for replication, differentiation, and adipokine secretion. The effects of the drugs on the expression of PPARgamma and related genes during differentiation were also assessed by real-time quantitative PCR. RTV induced a significant inhibition of preadipocyte proliferation, differentiation and adiponectin secretion. ATV at concentrations within the range of therapeutic levels did not affect differentiation or adiponectin secretion, but did have inhibitory effects on preadipocyte proliferation. Inhibition of differentiation by PIs was associated with decreased expression of PPARgamma, C/EBPalpha, and aP2 genes. In summary, although ATV at therapeutic levels has a smaller impact on adipogenesis, alterations in preadipocyte proliferation suggest the potential for adverse effects with long-term use.
Antiviral research 02/2010; 86(2):137-43. DOI:10.1016/j.antiviral.2010.02.004 · 3.94 Impact Factor
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