Lopinavir/ritonavir in the treatment of HIV-1 infection: a review

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Abstract

Lopinavir/ritonavir is the first and only coformulated HIV-1 protease inhibitor (PI). Large clinical trials have demonstrated lopinavir/ritonavir’s clinical efficacy in both antiretroviral-naïve and -experienced patients. The immunologic and virologic benefits of treatment with this agent have been proven in HIV-infected adults, adolescents, and children. Smaller studies support the use of lopinavir/ritonavir monotherapy as a therapeutic option in certain patients. The drug is characterized by a high genetic barrier to resistance, and appears to be more forgiving of non-adherence than earlier, unboosted PIs. The most frequent side effects observed are diarrhea, nausea, and vomiting. These gastrointestinal adverse effects are generally mild to moderate. Metabolic derangements, including hyperlipidemia and glucose intolerance, have also been observed in lopinavir/ritonavir recipients. As the menu of available antiretroviral agents continues to expand, lopinavir/ritonavir remains a proven and effective drug for the treatment of HIV infection.

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Adherence to protease inhibitor therapy and outcomes in patients with HIV infection.

David L. Paterson, Susan Swindells, Jeffrey T. Mohr … (2000)

Combination antiretroviral therapy with protease inhibitors has transformed HIV infection from a terminal condition into one that is manageable. However, the complexity of regimens makes adherence to therapy difficult. To assess the effects of different levels of adherence to therapy on virologic, immunologic, and clinical outcome; to determine modifiable conditions associated with suboptimal adherence; and to determine how well clinicians predict patient adherence. Prospective, observational study. HIV clinics in a Veterans Affairs medical center and a university medical center. 99 HIV-infected patients who were prescribed a protease inhibitor and who neither used a medication organizer nor received their medications in an observed setting (such as a jail or nursing home). Adherence was measured by using a microelectronic monitoring system. The adherence rate was calculated as the number of doses taken divided by the number prescribed. Patients were followed for a median of 6 months (range, 3 to 15 months). During the study period, 45,397 doses of protease inhibitor were monitored in 81 evaluable patients. Adherence was significantly associated with successful virologic outcome (P < 0.001) and increase in CD4 lymphocyte count (P = 0.006). Virologic failure was documented in 22% of patients with adherence of 95% or greater, 61% of those with 80% to 94.9% adherence, and 80% of those with less than 80% adherence. Patients with adherence of 95% or greater had fewer days in the hospital (2.6 days per 1000 days of follow-up) than those with less than 95% adherence (12.9 days per 1000 days of follow-up; P = 0.001). No opportunistic infections or deaths occurred in patients with 95% or greater adherence. Active psychiatric illness was an independent risk factor for adherence less than 95% (P = 0.04). Physicians predicted adherence incorrectly for 41% of patients, and clinic nurses predicted it incorrectly for 30% of patients. Adherence to protease inhibitor therapy of 95% or greater optimized virologic outcome for patients with HIV infection. Diagnosis and treatment of psychiatric illness should be further investigated as a means to improve adherence to therapy.

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Class-sparing regimens for initial treatment of HIV-1 infection.

Sharon A Riddler, Richard Haubrich, A. Gregory DiRienzo … (2008)

The use of either efavirenz or lopinavir-ritonavir plus two nucleoside reverse-transcriptase inhibitors (NRTIs) is recommended for initial therapy for patients with human immunodeficiency virus type 1 (HIV-1) infection, but which of the two regimens has greater efficacy is not known. The alternative regimen of lopinavir-ritonavir plus efavirenz may prevent toxic effects associated with NRTIs. In an open-label study, we compared three regimens for initial therapy: efavirenz plus two NRTIs (efavirenz group), lopinavir-ritonavir plus two NRTIs (lopinavir-ritonavir group), and lopinavir-ritonavir plus efavirenz (NRTI-sparing group). We randomly assigned 757 patients with a median CD4 count of 191 cells per cubic millimeter and a median HIV-1 RNA level of 4.8 log10 copies per milliliter to the three groups. At a median follow-up of 112 weeks, the time to virologic failure was longer in the efavirenz group than in the lopinavir-ritonavir group (P=0.006) but was not significantly different in the NRTI-sparing group from the time in either of the other two groups. At week 96, the proportion of patients with fewer than 50 copies of plasma HIV-1 RNA per milliliter was 89% in the efavirenz group, 77% in the lopinavir-ritonavir group, and 83% in the NRTI-sparing group (P=0.003 for the comparison between the efavirenz group and the lopinavir-ritonavir group). The groups did not differ significantly in the time to discontinuation because of toxic effects. At virologic failure, antiretroviral resistance mutations were more frequent in the NRTI-sparing group than in the other two groups. Virologic failure was less likely in the efavirenz group than in the lopinavir-ritonavir group. The virologic efficacy of the NRTI-sparing regimen was similar to that of the efavirenz regimen but was more likely to be associated with drug resistance. (ClinicalTrials.gov number, NCT00050895 [ClinicalTrials.gov].). Copyright 2008 Massachusetts Medical Society.

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HIV-protease inhibitors.

C Flexner (1998)

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Author and article information

Journal

Journal ID (nlm-ta): Ther Clin Risk Manag

Journal ID (publisher-id): Therapeutics and Clinical Risk Management

Title: Therapeutics and Clinical Risk Management

Publisher: Dove Medical Press

ISSN (Print): 1176-6336

ISSN (Electronic): 1178-203X

Publication date (Print): October 2008

Publication date (Electronic): October 2008

Volume: 4

Issue: 5

Pages: 1023-1033

Affiliations

[1 ]Division of Infectious Diseases, Montefiore Medical Center and the Albert Einstein College of Medicine, Bronx, NY, USA;

[2 ]AIDS Center and Division of Infectious Diseases, Montefiore Medical Center and the Albert Einstein College of Medicine, Bronx, NY, USA

Author notes

Correspondence: Jonathan Shuter, Montefiore Medical Center AIDS Center, 111 East 210th Street, Bronx, NY 10467, USA, Tel +1 718 920 7845, Fax +1 718 405 0610, Email jshuter@ 123456montefiore.org

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Publisher ID: tcrm-4-1023

DOI: 10.2147/tcrm.s3285

PMC ID: 2621403

PubMed ID: 19209283

SO-VID: 0e272d90-a8a3-4359-8c9b-993c1ec8f804

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Lopinavir/ritonavir in the treatment of HIV-1 infection: a review

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Abstract

Most cited references 72

Adherence to protease inhibitor therapy and outcomes in patients with HIV infection.

Class-sparing regimens for initial treatment of HIV-1 infection.

HIV-protease inhibitors.

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