KLEAN

The KLEAN study: 48-week results

An open-label, randomized non-inferiority trial comparing the safety and efficacy of LEXIVA/ritonavir and lopinavir/ritonavir, each in combination with abacavir/lamivudine

Background: First direct comparison of LEXIVA/ritonavir and lopinavir/ritonavir

Methods: 878 antiretroviral-naïve patients were randomized to either LEXIVA/ritonavir 700 mg/100 mg BID (n=434) or lopinavir/ritonavir 400 mg/100 mg BID (n=444), plus abacavir/lamivudine QD. The primary endpoint was the percentage of patients with HIV-1 RNA <400 copies/mL at 48 weeks. Safety and tolerability were measured by discontinuations due to adverse events

Results: Similar efficacy outcomes were observed in both groups at week 48. In the TLOVR analysis, 73% (315/434) in the LEXIVA/ritonavir group and 71% (317/444) in the lopinavir/ritonavir group achieved HIV-1 RNA <400 copies/mL at 48 weeks. The results were similar with HIV-1 RNA <50 copies/mL (66% and 65%, respectively). Increases from baseline in CD4 cell counts were also similar between groups

Both groups also showed similar outcomes in tolerability. Frequency of discontinuations due to adverse events was low (LEXIVA/ritonavir: 12% [53/424]; lopinavir/ritonavir: 10% [43/444]). The most frequent PI-related, grade 2-4 adverse events for LEXIVA/ritonavir and lopinavir/ritonavir were diarrhea (13% vs 11%) and nausea (6% vs 5%), respectively.

Conclusions: LEXIVA plus abacavir/lamivudine and lopinavir/ritonavir plus abacavir/lamivudine appear to provide similar efficacy and tolerability in antiretroviral treatment-naïve patients

The KLEAN Study Extension: 96-week results

Voluntary extension of an open-label, randomized non-inferiority study comparing the safety and efficacy of LEXIVA/ritonavir and lopinavir/ritonavir, each in combination with abacavir/lamivudine

Background: Voluntary 144-week extension of the KLEAN study with a planned 96-week interim analysis

Methods: Subjects at European or Canadian sites with viral loads <400 copies/mL at week 48 were permitted to continue for up to 144 weeks on either LEXIVA/ritonavir 700 mg/100 mg BID (n=105) or lopinavir/ritonavir 400 mg/100 mg BID (n=91), plus abacavir/lamivudine QD. Subjects in the United States made up 55% (n=483) of the original study population but did not participate in the extension

Results: Similar efficacy outcomes were observed in both groups at week 96. In the TLOVR analysis, 93% in the LEXIVA/ritonavir group and 87% in the lopinavir/ritonavir group achieved HIV-1 RNA <400 copies/mL. The results were similar with HIV-1 RNA <50 copies/mL (85% and 75%, respectively). Increases from baseline in CD4 cell count were also similar between groups (+292 and +286 cells/mm3, respectively)

Both groups also showed similar outcomes in safety and tolerability. For patients who continued in the extension phase of the study, the most frequent PI-related, grade 2-4 adverse events from baseline through 96 weeks were diarrhea (16% vs 11%) and nausea (6% vs 2%) for LEXIVA/ritonavir and lopinavir/ritonavir respectively

During the extension phase, 1 patient in each arm experienced virologic failure (defined as a confirmed viral load >400 copies/mL). Samples from the patient taking LEXIVA/ritonavir could not be genotypes, and samples from the patient taking lopinavir/ritonavir had one minor treatment-emergent protease mutation

Conclusions: Follow-up of a subset of patients in the KLEAN study confirms the sustained efficacy and tolerability of LEXIVA plus abacavir/lamivudine and lopinavir/ritonavir plus abacavir/lamivudine for up to 96 weeks

See the full Prescribing Information for LEXIVA

LEXIVA® (fosamprenavir calcium)

Indication and Usage:

LEXIVA is indicated in combination with other antiretroviral agents for the treatment of HIV infection in adults.

For PI-experienced patients, the following points should be considered:

The protease inhibitor-experienced patient study was not large enough to reach a definitive conclusion that LEXIVA/ritonavir and lopinavir/ritonavir are clinically equivalent
Once-daily administration of LEXIVA plus ritonavir is not recommended for protease inhibitor-experienced patients

Important Safety Information

LEXIVA is contraindicated in patients with previously demonstrated clinically significant hypersensitivity to any of the components of this product or to amprenavir
Hyperglycemia, new onset or exacerbations of diabetes mellitus, and spontaneous bleeding in hemophiliacs have been reported with protease inhibitors
Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including LEXIVA. During the initial phase of combination antiretroviral treatment, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment
Redistribution/accumulation of body fat have been observed in patients receiving antiretroviral therapy. The causal relationship, mechanism, and long-term consequences of these events are currently unknown
LEXIVA should be used with caution in patients with a known sulfonamide allergy
Severe or life-threatening skin reactions were reported in <1% of 700 patients treated with LEXIVA in clinical studies, including one case of Stevens-Johnson syndrome
Skin rash (all grades, without regard to causality) occurred in approximately 19% of patients treated with LEXIVA in the pivotal efficacy studies. This led to the discontinuation of LEXIVA in <1% of patients
Treatment with LEXIVA/r has resulted in increases in the concentration of triglycerides. Triglyceride and cholesterol testing should be performed prior to initiating therapy with LEXIVA and at periodic intervals during therapy
Caution should be exercised when administering LEXIVA to patients with hepatic impairment, including those with hepatitis B or C or marked elevation in transaminases prior to treatment. Increased AST/ALT monitoring should be considered in these patients
The most common grade 2-4 drug-related adverse events were diarrhea, nausea, vomiting, headache, and rash

DRUG INTERACTIONS

LEXIVA is contraindicated with ergot derivatives, cisapride, pimozide, midazolam, and triazolam. If LEXIVA is coadministered with ritonavir, flecainide and propafenone are also contraindicated
Caution should be used when coadministering medications that are substrates, inhibitors, or inducers of CYP3A4, or potentially toxic medications that are metabolized by CYP3A4
Serious and/or life-threatening drug interactions could occur between LEXIVA and amiodarone, lidocaine (systemic), tricyclic antidepressants, and quinidine. Concentration monitoring of these agents is recommended if these agents are used concomitantly with LEXIVA
LEXIVA should not be coadministered with rifampin, St. John's wort, lovastatin, simvastatin, or delavirdine
Particular caution should be used when prescribing phosphodiesterase (PDE-5) inhibitors for erectile dysfunction (eg, sildenafil or vardenafil) in patients receiving LEXIVA
This list of potential drug interactions is not complete
Concomitant use of LEXIVA and oral contraceptives is not recommended. LEXIVA taken with oral contraceptives may alter hormonal levels. LEXIVA plus ritonavir taken with oral contraceptives may result in clinically-significant hepatic transaminase elevations. Therefore, alternative methods of non-hormonal contraception are recommended