Efficacy and Safety of Atazanavir, With or Without Ritonavir, as Part of Once-Daily Highly Active Antiretroviral Therapy Regimens in Antiretroviral-Naive Patients
ABSTRACT Atazanavir (ATV), the first once-daily protease inhibitor approved for the treatment of HIV-1 infection, is recommended for use in antiretroviral (ARV) treatment-naive and -experienced patients. Study AI424-089 was a prospective, randomized, open-label, 96-week study comparing 2 ATV-based treatment regimens in ARV-naive HIV-infected patients.
Adults with HIV RNA levels > or =2000 copies/mL were randomized (1:1) to once-daily ATV at a dose of 300 mg with ritonavir at a dose of 100 mg (ATV300/RTV) or ATV at a dose of 400 mg (ATV400); both regimens included lamivudine and an investigational extended-release formulation of stavudine. The primary endpoint for this noninferiority study was the proportion of patients (response rate) with an HIV RNA load <400 copies/mL at week 48.
Response rates at week 48 were 86% and 85% on the ATV300/RTV and ATV400 regimens, respectively (difference estimate [95% confidence interval] = 1.5 [-8.2 to 11.1]). There were 3 and 10 patients with virologic failure in the ATV300/RTV and ATV400 groups, respectively. One patient (ATV400) developed phenotypic resistance to ATV associated with an I50L substitution. Adverse event-related discontinuations were 8% among ATV300/RTV-treated patients and <1% among ATV400-treated patients. Plasma lipid elevations were low with both regimens. Both regimens were well tolerated.
These findings demonstrate the safety and efficacy of the ATV300/RTV regimen and confirm the safety and efficacy of ATV400 in an ARV-naive patient population.
- SourceAvailable from: José Vicente Fernández-Montero
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- "The AI424-089 study,19 a randomized, multicenter, 96-week study, compared the efficacy and safety of boosted vs unboosted ATV in drug-naïve patients. Although overall efficacy results were comparable, rates of response were higher and emergence of PI resistance mutations lower in subjects on ATV plus RTV than with ATV alone. "
ABSTRACT: The introduction of highly-active antiretroviral therapy (HAART) remains a major milestone in the management of HIV-infected patients. Protease inhibitors (PI) are commonly used as part of triple combinations, given that to antiviral potency, better tolerance and convenience has been achieved in recent years. To summarize and update evidence-based information about atazanavir (ATV) on initial, simplification, and rescue interventions in HIV patients. Review of observational and randomized trials reported in medical conferences, peer-reviewed journals, and treatment guidelines. ATV is a second-generation PI, which has shown across studies potent antiviral activity and high genetic barrier, both in HAART-naïve patients or after virological failure. Indulgent metabolic profile, in terms of insulin glucose and lipid levels, adds value to this drug for the long-term management of HIV infection.HIV/AIDS - Research and Palliative Care 09/2010; 2:157-66. DOI:10.2147/HIV.S5069
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- "The results of a phase 3 study comparing EFV and TAZ based regimens demonstrate similar virologic efficacy with the use of either agent, though EFV use resulted in dyslipidemia while TAZ use did not.  However, the current treatment paradigm favors the use of TAZ in combination with low dose ritonavir (boosted TAZ) and not unboosted TAZ. Since, the addition of ritonavir to TAZ results in dyslipidemia , there is a need to compare and contrast the magnitude of the effects of boosted TAZ and EFV based regimens on serum lipids. To this end, we utilized data from a racially diverse group of HIV-infected individuals with the specific aims of comparing the effects of boosted TAZ and EFV on serum lipids. "
ABSTRACT: Antiretrovirals used to treat HIV-infected patients have the potential to adversely affect serum lipid profiles and increase the risk of cardiovascular disease which is an emerging concern among HIV-infected patients. Since boosted atazanavir and efavirenz are both considered preferred antiretrovirals a head to head comparison of their effects on serum lipids is needed. The primary objective of the study was to compare the effects of atazanavir (boosted and unboosted) and efavirenz based regimens on serum lipid profiles. Prospective cohort study nested within three ongoing cohorts of HIV-infected individuals. Participants initiating either atazanavir or efavirenz based regimens with documented pre- and post-initiation lipid values. Multivariate linear regression was conducted to estimate adjusted mean differences between treatment groups for high density lipoprotein cholesterol (HDL-c), non-HDL-c, and log total cholesterol (TC) to HDL-c ratio outcomes; log-linear regression models were used to estimate differences in prevalence of low HDL-c and desirable TC. The final study population was comprised of 380 efavirenz and 281 atazanavir initiators. Both atazanavir and efavirenz users had increases in serum HDL-c and decreases in TC/HDL ratio. In comparison to individuals initiating efavirenz, boosted atazanavir users on average had lower HDL-c (-4.12 mg/dl, p < 0.001) and non HDL-c (-5.75 mg/dl, p < 0.01), but similar declines in TC/HDL ratio. Both efavirenz and atazanavir-based regimens (boosted and unboosted) resulted in similar beneficial declines in the TC/HDL ratio.AIDS Research and Therapy 06/2009; 6(1):13. DOI:10.1186/1742-6405-6-13 · 1.46 Impact Factor