Seven-Year Efficacy of a Lopinavir/Ritonavir-Based Regimen in Antiretroviral—Naïve HIV-1-Infected Patients

Murphy, Robert L.; Silva, Barbara A. da; Hicks, Charles B.; Eron, Joseph J.; Gulick, Roy M.; Thompson, Melanie; McMillan, F; King, Martin; Hanna, George J.; Brun, Scott

doi:10.1310/hct0901-1

Cited by 68 publications

(44 citation statements)

References 31 publications

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“…Diarrhea, nausea, and abdominal pain are common with lopinavir/ritonavir [90]. Lopinavir/ ritonavir is more likely than other combinations to cause hypertriglyceridemia [82].…”

Section: Lopinavir (Abt)mentioning

confidence: 99%

A Review of the Toxicity of HIV Medications

et al. 2013

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Antiretroviral therapy has changed human immunodeficiency virus (HIV) infection from a near-certainly fatal illness to one that can be managed chronically. More patients are taking antiretroviral drugs (ARVs) for longer periods of time, which naturally results in more observed toxicity. Overdose with ARVs is not commonly reported. The most serious overdose outcomes have been reported in neonates who were inadvertently administered supratherapeutic doses of HIV prophylaxis medications. Typical ARV regimens include a "backbone" of two nucleoside reverse transcriptase inhibitors (NRTI) and a "base" of either a protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor. New classes of drugs called entry inhibitors and integrase inhibitors have also emerged. Older NRTIs were associated with mitochondrial toxicity, but this is less common in the newer drugs, emtricitabine, lamivudine, and tenofovir. Mitochondrial toxicity results from NRTI inhibition of a mitochondrial DNA polymerase. Mitochondrial toxicity manifests as myopathy, neuropathy, hepatic failure, and lactic acidosis. Routine lactate assessment in asymptomatic patients is not indicated. Lactate concentration should be obtained in patients taking NRTIs who have fatigue, nausea, vomiting, or vague abdominal pain. Mitochondrial toxicity can be fatal and is treated by supportive care and discontinuing NRTIs. Metabolic cofactors like thiamine, carnitine, and riboflavin may be helpful in managing mitochondrial toxicity. Lipodystrophy describes changes in fat distribution and lipid metabolism that have been attributed to both PIs and NRTIs. Lipodystrophy consists of loss of fat around the face (lipoatrophy), increase in truncal fat, and hypertriglyceridemia. There is no specific treatment of lipodystrophy. Clinicians should be able to recognize effects of chronic toxicity of ARVs, especially mitochondrial toxicity.

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“…Diarrhea, nausea, and abdominal pain are common with lopinavir/ritonavir [90]. Lopinavir/ ritonavir is more likely than other combinations to cause hypertriglyceridemia [82].…”

Section: Lopinavir (Abt)mentioning

confidence: 99%

A Review of the Toxicity of HIV Medications

et al. 2013

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“…Data from prospective observational studies did not show substantial differences between NNRTI-based and PI/r-based regimens with reference to virologic efficacy and/or clinical outcome [34,35]. However, in prospective non-randomized studies and in non-comparative randomized trials, LPV/r-containing regimens had a persistent immunologic efficacy, a better immunologic recovery, and no primary resistance-associated mutation development in patients with suppressed viral load [36,37].…”

Section: Choice Of Antiretroviral Treatmentmentioning

confidence: 99%

Italian Consensus Statement on Management of HIV-Infected Individuals with Advanced Disease Naïve to Antiretroviral Therapy

et al. 2009

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“…The LPV/r regimen is generally well tolerated (Murphy et al, 2008;Gathe et al, 2009). For example, the incidence of severe liver events was relatively low in HIV patients receiving LPV/r (Bonfanti et al, 2005;Palacios et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

CPY3A4-Mediated Lopinavir Bioactivation and Its Inhibition by Ritonavir

Lu²,

2011

Drug Metab Dispos

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ABSTRACT:The combination of lopinavir (LPV) and ritonavir (RTV) is one of the preferred regimens for the treatment of HIV infection with confirmed efficacy and relatively low toxicity. LPV alone suffers the poor bioavailability due to its rapid and extensive metabolism. RTV boosts the plasma concentration of LPV by suppressing its metabolism and thus increasing LPV efficacy. In the current study, we found that RTV also inhibits LPV bioactivation. LPV bioactivation was investigated in human liver microsomes and cDNA-expressed human cytochromes P450. Twelve GSH-trapped reactive metabolites of LPV were identified by using a metabolomic approach. Semicarbazide-trapped reactive metabolites of LPV were also detected. RTV effectively suppressed all pathways of LPV bioactivation via CYP3A4 inhibition. Our data together with previous reports suggest that LPV plus RTV is an ideal combination because RTV not only boosts LPV plasma concentration, but it decreases LPV bioactivation.

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Seven-Year Efficacy of a Lopinavir/Ritonavir-Based Regimen in Antiretroviral—Naïve HIV-1-Infected Patients

Abstract: LPV/r-based therapy demonstrated sustained efficacy with no protease inhibitor or stavudine resistance through 7 years in antiretroviral-naïve patients. Switching from stavudine to tenofovir resulted in significant improvements in multiple metabolic parameters.

Cited by 68 publications

References 31 publications

A Review of the Toxicity of HIV Medications

A Review of the Toxicity of HIV Medications

Italian Consensus Statement on Management of HIV-Infected Individuals with Advanced Disease Naïve to Antiretroviral Therapy

CPY3A4-Mediated Lopinavir Bioactivation and Its Inhibition by Ritonavir

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