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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Researchers continue to find evidence that the combination of lopinavir/ritonavir (Kaletra) provides prolonged potency while avoiding drug resistance. The Kaletra findings come on the heels of another study that found a high rate of drug resistance among HIV patients with measurable levels of virus in their blood.
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PMID:Drug resistance test shows encouraging results. 1186 40

Despite major advances in HIV research, eradication of HIV from the body is not yet possible. However, current antiretroviral (ARV) therapy can achieve disease control via viral suppression below the limits of detection of currently available assays. This has led to a marked decline in morbidity and mortality associated with the development of opportunistic infections and malignancies. Since viral suppression appears to be the most achievable goal of current therapy, there arises a need for new and more potent ARV agents in order to maintain viral suppression. Many of the currently available protease inhibitors (PIs) have a high protein-binding ability, short plasma half-life [1] and pharmacokinetic interactions with food or other drugs [2]. This can result in sub-optimal plasma drug concentrations, which may allow the virus to break through and replicate, leading to the development of resistant mutants [1]. Lopinavir/ritonavir (LPV/r; Kaletra, Abbott Laboratories) is a new PI consisting of a co-formulation of lopinavir and low-dose ritonavir. The sub-therapeutic dose of ritonavir (a potent cytochrome P450 [CYP] 3A4 inhibitor) inhibits the metabolism of lopinavir, resulting in higher lopinavir concentrations than when lopinavir is administered alone [3]. This pharmacokinetic interaction is associated with a high lopinavir trough level:wild type median effective concentration (EC(50)) ratio and good general tolerability when compared with other currently licensed PIs [4]. The concept of pharmacokinetic enhancement - boosting - is not new as ritonavir has previously been utilised in this context with other PIs. The relationship between plasma and intracellular drug levels has yet to be clarified. What has been ascertained from pharmacokinetic studies thus far is the correlation between ARV trough plasma concentrations (C(min)) and virological outcome [5,6]. LPV/r exemplifies how the pharmacokinetic profile of a drug can be modified to attain sufficient C(min) to suppress pheno- and genotypically resistant viral strains, as well as provide a pharmacological barrier to the emergence of resistance [7]. LPV/r reduces pill-burden and aids compliance, as shown by encouraging results in the treatment of both ARV-naive and -experienced patients.
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PMID:Lopinavir/ritonavir (ABT-378/r). 1186 71

The HIV protease inhibitor ritonavir (Norvir; ABT-578), currently used in combination with nucleoside analogs and other protease inhibitors in anti-HIV therapy, has previously been quantified by an HPLC procedure. Here, we report the first convenient one-step competitive ELISA for measuring plasma and intracellular ritonavir in HIV patients. Anti-ritonavir antibody was raised in rabbits using ritonavir-KLH conjugate as immunogen, and the enzymatic tracer was prepared by coupling the drug to acetylcholine esterase. Samples for analysis were first extracted with methanol. Bound/free separation was achieved in a microtiter plate previously coated with anti rabbit IgG monoclonal antibody. Fifty percent inhibition was observed at 1 ng/ml ritonavir and the method accurately and specifically detected as little as 3-4 ng/ml of plasma ritonavir as well as intracellular drug in the peripheral blood mononuclear cells of patients undergoing ritonavir therapy. Within-run and day to day coefficients of variation were below 10% and the drugs currently used in HIV therapy did not interfere with the test. The ELISA was applied to the measurement of plasma ritonavir and to the determination of the extracellular/intracellular drug level ratios in HIV patients receiving long-term multidrug therapy.
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PMID:Quantification of plasma and intracellular levels of the HIV protease inhibitor ritonavir by competitive ELISA. 1200 99

With the advent of highly active antiretroviral therapy (HAART), HIV positivity is no longer a contraindication for liver transplantation. Some of the antiretroviral agents, particularly protease inhibitors (e.g., ritonavir, indinavir, and nelfinavir) have been described as potent inhibitors of the metabolism of certain immunosuppressive drugs. In this article we describe a profound interaction between tacrolimus and Kaletra (Abbott Laboratories, Chicago, IL) (a combination of lopinavir and ritonavir) in 3 liver transplantation patients. Patient 1, who was maintained on a 5 mg twice daily dose of tacrolimus with a trough blood concentration around 10.6 ng/mL, required only 0.5 mg of tacrolimus per week after addition of Kaletra to achieve similar tacrolimus blood concentrations, with a half-life of 10.6 days. In patient 2, the area under the blood concentration versus time curve for tacrolimus increased from 31 ng/mL/h to 301 ng/mL/h after addition of Kaletra, with a corresponding half-life of 20 days. When the patient was subsequently switched to nelfinavir, the half-life decreased to 10.3 days. Patient 3, who was maintained with 4 to 8 mg/d of tacrolimus and a corresponding blood concentration of 10 ng/mL before Kaletra, required a tacrolimus dose of 1 mg/wk and tacrolimus concentrations of 5 ng/mL with Kaletra. In conclusion, a combination of lopinavir and ritonavir led to a much more profound increase in tacrolimus blood concentrations than use of single protease inhibitor, nelfinavir. A tacrolimus dose of less than 1 mg/wk may be sufficient to maintain adequate blood tacrolimus concentrations in patients on Kaletra. Patients may not need a further dose of tacrolimus for 3 to 5 weeks depending on liver function when therapy with Kaletra is initiated. Great caution is required in the management of tacrolimus dosage when Kaletra is introduced or withdrawn in HIV-positive patients after liver transplantation, particularly in the presence of hepatic dysfunction.
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PMID:Effect of coadministered lopinavir and ritonavir (Kaletra) on tacrolimus blood concentration in liver transplantation patients. 1294 57

Severe acute respiratory syndrome (SARS), caused by a highly infectious novel coronavirus (CoV), predominantly presents with severe pneumonitis leading to respiratory failure and death in approximately 10% of victims. Most cases present, after an incubation of 2 to 11 days, with fever and chills, which are followed by dry cough and dyspnea before the onset of respiratory failure. The management of SARS is controversial, largely due to the lack of data from controlled trials, which were logistically impossible to design or execute at the time of the overwhelming outbreak between March and June 2003. The use of an antiviral is logical although there is no effective agent against SARS-CoV, with the widespread use of ribavirin in 2003 attracting considerable scepticism. The use of ribavirin as a monotherapy in SARS is not recommended. Retrospective data suggest that administration of the anti-HIV drug Kaletra in combination with ribavirin could reduce mortality and incidence of respiratory failure. The use of corticosteroid was based on the similarity between SARS and bronchiolitis obliterans organizing pneumonia. Corticosteroid use is considered important in subsets of patients with SARS. As SARS may still resurge, it is imperative that past experience is analyzed. This review will attempt to address the rationale for pharmacotherapy in SARS using anecdotal and the limited published data.
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PMID:Severe acute respiratory syndrome: scientific and anecdotal evidence for drug treatment. 1504 92

The 5th Antiviral Drug Discovery and Development Summit provided an up-to-date snapshot of the ongoing developments in the area. The topics covered ranged from updates on recently launched drugs (Kaletra), Fuzeon) and new investigational inhibitors (T-1249, Reverset, UK-427857, L-870810, PA-457, remofovir, VX-950), to the discovery of new antiviral targets and advances in technologies that may provide the substrate for the next generation of therapeutics. It is apparent from the range of presentations that much of today's efforts are focused on developing new classes of HIV inhibitors (gp41, integrase), while there is also considerable progress in hepatitis C, where a number of inhibitors have or should reach proof-of-concept studies in the coming months. Here we provide the highlights of this meeting, with particular emphasis on the new developments in HIV and hepatitis C virus.
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PMID:5th Antiviral Drug Discovery and Development Summit. 1526 42

On December 3, 2003, Abbott Laboratories, the pharmaceutical company that makes lopinavir (Kaletra), announced that it was going to raise the price of its other anti-HIV drug, ritonavir (Norvir), from $2.14 to $10.72 per capsule in the U.S.--an increase of 400%. (These prices reflect the Average Wholesale Price, or AWP, a national average of list prices charged by wholesalers to pharmacies.)
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PMID:Backlash over ritonavir price hike. 1538 39

As the HIV pandemic enters its third decade, more sophisticated and efficacious therapies are continually being developed. This article provides an in-depth review of the first coformulated boosted protease inhibitor available on the world market, lopinavir/ritonavir (Kaletra). Included in this review is an overview of the current market place, the chemistry, pharmacokinetics, clinical efficacy and side-effect profile of lopinavir/ritonavir. In addition, an expert opinion and commentary on the clinical applications of this drug is provided.
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PMID:The role of lopinavir/ritonavir (Kaletra) in the management of HIV infected adults. 1548 36

Efavirenz (Sustiva), Bristol-Myers Squibb) is a non-nucleoside reverse transcriptase inhibitor that has been used successfully since the late 1990s to treat HIV-1 infection, and has since become a cornerstone of antiretroviral therapy. The efficacy and potency of efavirenz has been established in many clinical trials and cohort studies, where it has been compared with unboosted or ritonavir (Norvir, Abbott Laboratories Ltd)-boosted protease inhibitors, nevirapine (Viramune, Boehringer Ingelheim Ltd); and three nucleoside analog-based regimens. Pharmacokinetics allowing for a convenient once-daily administration make efavirenz one of the first agents to be included in once-daily regimens. Tolerability of efavirenz is satisfactory, although CNS-related toxicity can occur, and is still poorly understood. New insights into the pharmacokinetics of efavirenz could help to manage this unwanted toxicity. This drug profile will examine the principal data concerning the efficacy, pharmacokinetics and safety that have made efavirenz a standard of care in HIV-1 therapy, and will comment on new data that could change the way efavirenz is used in the near future.
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PMID:Efavirenz for HIV-1 infection in adults: an overview. 1548 31

Antiretroviral treatment of HIV-infected pregnant women is widely used to prevent mother-to-child HIV transmission and as primary therapy of maternal HIV infection. The physiological changes associated with pregnancy have a large impact on drug disposition, and changes in antiretroviral pharmacokinetics during pregnancy must be understood for these drugs to be used safely and effectively in pregnant women. Zidovudine and didanosine, two of the nucleoside reverse transcriptase inhibitors, demonstrate an increase in clearance and decrease in area under the concentration-time curve during pregnancy. The clinical significance of these changes is unknown due to the lack of a clear relationship between plasma concentrations of nucleoside reverse transcriptase inhibitors and clinical effects. Pharmacokinetic parameters of lamivudine, stavudine and abacavir are not significantly changed during pregnancy. There are no data describing the effect of pregnancy on the pharmacokinetics of the other nucleoside/nucleotide analogues (zalcitabine, emtricitabine and tenofovir). Pregnancy does not appear to have a significant effect on the pharmacokinetics of the non-nucleoside reverse transcriptase inhibitor nevirapine and there are no data describing the pharmacokinetics of the other non-nucleoside reverse transcriptase inhibitors (efavirenz and delavirdine) during pregnancy. Reduced plasma concentrations during pregnancy have been described for several of the protease inhibitors, including nelfinavir (with administration of 750 mg three times daily), indinavir, saquinavir and Kaletra (a co-formulation of lopinavir and ritonavir). Plasma concentrations equivalent to those in nonpregnant adults have been reported in pregnant women receiving nelfinavir at doses of 1250 mg twice daily, and the addition of ritonavir to saquinavir greatly increases saquinavir exposure to therapeutic concentrations in pregnant women. No pregnancy pharmacokinetic data are available for the newer protease inhibitors atazanavir and fosamprenavir, or with other dual protease inhibitor combinations that include low dose ritonavir to boost concentrations of the coadministered protease inhibitor. Further investigations of antiretroviral pharmacology during pregnancy, including protein binding studies, are urgently needed.
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PMID:Pharmacokinetics of antiretrovirals in pregnant women. 1556 88


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