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.
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ABSTRACT: Despite great advances in antiretroviral therapy in the last decade, several limitations still remain such as adverse effects, lack of adherence and drug-drug interactions. Switching antiretroviral therapy in stable, virologically suppressed patients with the aim of improving tolerability and convenience is an expanding strategy in clinical practice. Several factors need to be taken into consideration when switching a suppressive regimen, such as previous virologic failure, genetic barrier of the new regimen, prior duration of virologic suppression and expected level of adherence. The most frequently used strategies include reductions in the number of pills, drugs or doses. Although switching strategies may be useful, not all the regimens used in clinical practice are based on data from randomized clinical trials and some may not be the best option for certain patients; therefore, therapy should be individualized taking into consideration available information as well as patient and drug characteristics.Expert Review of Anti-infective Therapy 07/2014; DOI:10.1586/14787210.2014.944506 · 3.06 Impact Factor
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ABSTRACT: Simplification of antiretroviral therapy in patients with suppressed viremia may minimize long-term adverse effects. The study's primary objective was to determine whether abacavir/lamivudine + atazanavir (ABC/3TC+ATV) was virologically non-inferior to tenofovir/emtricitabine + atazanavir/ritonavir (TDF/FTC+ATV/r) over 24 weeks in a population of virologically suppressed, HIV-1 infected patients. This open-label, multicenter, non-inferiority study enrolled antiretroviral experienced, HIV-infected adults currently receiving a regimen of TDF/FTC+ATV/r for ≥6 months with no history of virologic failure and whose HIV-1 RNA had been ≤75 copies/mL on 2 consecutive measurements including screening. Patients were randomized 1∶2 to continue current treatment or simplify to ABC/3TC+ATV. The primary endpoint was the proportion of patients with HIV-RNA<50 copies/mL at Week 24 by the Time to Loss of Virologic Response (TLOVR) algorithm. Secondary endpoints included alternative measures of efficacy, adverse events (AEs), and fasting lipids. Exploratory endpoints included inflammatory, coagulation, bone, and renal biomarkers. After 24 weeks, ABC/3TC+ATV (n = 199) was non-inferior to TDF/FTC+ATV/r (n = 97) by both the primary analysis (87% in both groups) and all secondary efficacy analyses. Rates of grade 2-4 AEs were similar between the two groups (40% vs 37%, respectively), but an excess of hyperbilirubinemia made the rate of grade 3-4 laboratory abnormalities higher in the TDF/FTC+ATV/r group (30%) compared with the ABC/3TC+ATV group (13%). Lipid levels were stable except for HDL cholesterol, which increased significantly in the ABC/3TC+ATV group. Bone and renal biomarkers improved significantly between baseline and Week 24 in patients taking ABC/3TC+ATV, and the difference between groups was significant at Week 24. No significant changes occurred in any inflammatory or coagulation biomarker within or between treatment groups. After 24 weeks, simplification to ABC/3TC+ATV from TDF/FTC+ATV/r maintained viral suppression was well-tolerated, and led to improvements in bone and renal biomarkers and HDL cholesterol. ClinicalTrials.gov NCT01102972 GlaxoSmithKline Clinical Study Register #113734.PLoS ONE 05/2014; 9(5):e96187. DOI:10.1371/journal.pone.0096187 · 3.53 Impact Factor
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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