Lipid-Lowering Efficacy and Safety After Switching to Atazanavir-Ritonavir–Based Highly Active Antiretroviral Therapy in Patients with Human Immunodeficiency Virus

Texas Tech University Health Sciences Center School of Pharmacy, Dallas-Fort Worth Regional Campus, Dallas, Texas 75216, USA.
Pharmacotherapy (Impact Factor: 2.66). 03/2008; 28(3):323-30. DOI: 10.1592/phco.28.3.323
Source: PubMed


To evaluate the efficacy, safety, and lipid-lowering effects after switching from a non-atazanavir-containing, protease inhibitor-based highly active antiretroviral therapy (HAART) to atazanavir-ritonavir-based HAART in patients infected with human immunodeficiency virus (HIV).
Multicenter, noncontrolled, retrospective study.
Three tertiary teaching hospitals.
Thirty-six patients with HIV infection, aged 18 years or older, who were receiving non-atazanavir-containing, protease inhibitor-based HAART that was switched to atazanavir 300 mg-ritonavir 100 mg-based HAART without changes in nucleoside reverse transcriptase inhibitors and confounders known to alter serum lipid levels.
Lipid profiles measured 4 weeks-6 months before the switch, as well as follow-up lipid profiles measured 4 weeks-6 months after receiving the new HAART regimen, were evaluated. The switch resulted in the following changes in lipid levels: total cholesterol -9% (p=0.002), low-density lipoprotein cholesterol -13% (p<0.001), high-density lipoprotein cholesterol (HDL) -2% (p=0.431), triglycerides -23% (p=0.007), non-HDL -11% (p=0.002), total cholesterol:HDL ratio -10% (p=0.004), and triglyceride:HDL ratio -24% (p=0.019). A subgroup analysis was conducted on the lipid profiles of nine patients who still met the strict inclusion and exclusion criteria up to 9 months after the switch; it showed that the reductions in their lipid profiles were sustained. In addition, 33% more patients achieved their National Cholesterol Education Panel (NCEP) Adult Treatment Panel (ATP) III cholesterol goals. No significant changes were noted in median (interquartile range) CD4+ counts (372 [236-551] and 361 [217-464] cells/mm(3), p=0.118) or in number of patients with undetectable HIV viral loads ([defined as < 50 copies/ml] 32/36 and 31/36 patients, p>0.05) between baseline and after the switch, respectively.
Switching to an atazanavir-ritonavir-based HAART regimen was associated with significant improvement in lipid profiles, similar to those seen in clinical trials, without compromising safety or viral and immunologic control. In addition, more patients were able to achieve their NCEP ATP III goals.

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    • "In recent years, the most studied simplification approach remains within the family of protease inhibitors and concerns atazanavir, a lipid-friendly compound. All the trials demonstrated a decline in total cholesterol and tryglicerides, in particular the large SWAN [37], SLOAT [46], and ATAZIP trials [44], but when a deeper look was brought, also HDL cholesterol tended to decrease [45] or remained stable [83], 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 [84]. "
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    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.
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