Improvement in lipid profiles in antiretroviral-experienced HIV-positive patients with hyperlipidemia after a switch to unboosted atazanavir.
ABSTRACT 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.
- SourceAvailable from: Jean-Pierre Van Geertruyden[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
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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 · 3.43 Impact Factor