Long-term study evaluates boosted Prezista vs. lopinavir/ritonavir as part of HIV combination therapy in treatment-naive adults

- Ninety-six week efficacy and safety data presented at ICAAC - 

TORONTO, Nov. 12 /CNW/ - Ninety-six week results presented from a Phase 3, randomized, open-label, ongoing clinical trial showed that 79 per cent of treatment-naive HIV-1 infected adults taking PREZISTA* 800 mg (two 400 mg tablets) with 100 mg ritonavir (r) once daily reached an undetectable viral load (below 50 copies/mL) at week 96, compared with 71 per cent of patients taking lopinavir/r 800 mg/200 mg once daily (or 400 mg/100 mg twice daily), both with a fixed dose of emtricitabine and tenofovir disoproxil fumarate. In Canada PREZISTA is marketed by Tibotec, a division of Janssen-Ortho Inc.

Results from the study, known as ARTEMIS, were presented at the 48th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Washington, DC. ARTEMIS is a 192-week study comparing the efficacy and safety of the protease inhibitors (PIs) PREZISTA/r and lopinavir/r in treatment-naive adults with HIV (those who have never taken anti-HIV medication before).

At 48 weeks, the primary objective of ARTEMIS was reached when PREZISTA demonstrated non-inferiority to lopinavir/r based on the proportion of patients that achieved an undetectable viral load (HIV RNA below 50 copies/mL). The difference between the treatment arms was not significant at week 48. The pre-planned safety and efficacy analysis at 96 weeks was a secondary objective which showed PREZISTA/r was superior to lopinavir/r for virologic response - mean difference in response 8.3 per cent, 95 per cent confidence interval 1.8 - 14.7, p=0.012.

"The results of the ARTEMIS 96-week findings are consistent with earlier results, showing that a once-daily darunavir-based regimen allows significantly more treatment-naive patients to reach an undetectable viral load, and maintain it over the long term," said Dr. Anita Rachlis, Professor, Department of Medicine and Division of Infectious Diseases, Sunnybrook Health Sciences Center, University of Toronto. "Tolerability is important for my patients, so having a treatment that offers this along with the convenience of a once-daily dose is good news for Canadians with HIV/AIDS."

PREZISTA (darunavir), co-administered with 100 mg ritonavir, and with other antiretroviral agents, is only indicated in Canada for the treatment of HIV infection in treatment-experienced adult patients who have failed prior antiretroviral therapy.

In treatment-experienced patients, treatment history and, when available, genotypic or phenotypic testing, should guide the use of PREZISTA/r. The use of other active agents with PREZISTA/r is associated with a greater likelihood of treatment response.

The risks and benefits of PREZISTA/r have not been established in pediatric patients. No clinical studies have demonstrated the effect of PREZISTA/r on clinical progression of HIV-1. 

ARTEMIS 96-WEEK STUDY RESULTS 

In the 96-week per-protocol analysis of 689 patients, PREZISTA/r 800/100 mg once daily was shown to be non-inferior to lopinavir/r 800/200 mg once daily or 400/100 mg twice daily in treatment-naive adults with HIV-1. In addition, in the intent-to-treat analysis, the study showed that:

 

-   79 per cent of patients in the PREZISTA/r arm reached an undetectable

    viral load (below 50 copies/mL) vs. 71 per cent of patients in

    the lopinavir/r arm, (p less than 0.001)

-   Of patients with baseline viral load greater than and equal to

    100,000 copies/mL, 76 per cent of patients in the PREZISTA/r arm

    reached an undetectable viral load (below 50 copies/mL) vs. 63 per

    cent of patients in the lopinavir/r arm, (p=0.023)

-   Of patients with baseline viral load less than 100,000 copies/mL,

    81 per cent of patients in the PREZISTA/r arm reached an undetectable

    viral load (below 50 copies/mL) vs. 75 per cent of patients in

    the lopinavir/r arm, (p=not significant)

-   Of patients with baseline CD4+ cell count less than 200 cells per

    cubic millimeter, 79 per cent of patients in the PREZISTA/r arm

    reached an undetectable viral load (below 50 copies/mL) vs.

    65 per cent of patients in the lopinavir/r arm, (p=0.009)

-   Of patients with baseline CD4+ cell count greater than or equal to

    200 cells per cubic millimeter, 79 per cent of patients in the

    PREZISTA/r arm reached an undetectable viral load (below 50

    copies/mL) vs. 75 per cent of patients in the lopinavir/r arm,

    (p=not significant) 

ARTEMIS SAFETY FINDINGS 

-   Incidence of grade two-to-four treatment-related diarrhea reported in

    the PREZISTA/r arm was significantly lower than that in the

    lopinavir/r arm (four per cent vs. 11 per cent, respectively

    p less than 0.001). Nausea was reported in two per cent vs.

    three per cent, respectively

-   In both treatment arms, grade two-to-four treatment-related rash

    occurred infrequently; three per cent in the PREZISTA/r arm vs.

    one per cent in the lopinavir/r arm

-   Discontinuations due to adverse events were four per cent in the

    PREZISTA/r arm vs. nine per cent in the lopinavir/r arm

 

The latest recommendations from the International AIDS Society-USA Panel, which were published in the August 6, 2008 issue of the Journal of the American Medical Association, recommend darunavir/r as one of the initial treatment options as part of combination therapy for adults living with HIV.(1) 

ABOUT THE ARTEMIS STUDY 

ARTEMIS (AntiRetroviral Therapy with TMC114 ExaMined In naive Subjects) is an international ongoing, randomized, controlled, open-label non-inferiority Phase 3 trial that compares the efficacy and safety of PREZISTA/r with lopinavir/r in treatment-naive HIV-1-infected adult patients with viral load of at least 5,000 copies/mL. Patients were randomized to receive PREZISTA/r 800 mg/100 mg once daily (n=343) or lopinavir/r 800 mg/200 mg total daily dose (800/200 mg once daily or 400/100 mg BID) (n=346), plus a fixed-dose background regimen of tenofovir and emtricitabine once daily. Patient randomization was stratified based on viral load and CD4+ cell count.(2)

The main objective of the study was to demonstrate non-inferiority of once-daily PREZISTA/r versus lopinavir/r in proportion of patients achieving virologic response, defined as confirmed HIV-1 RNA (below 50 copies/mL. Non-inferiority of PREZISTA/r vs. lopinavir/r was defined as a maximum allowable difference of 12 per cent for virologic response, with a one-sided significance level of alpha equals to 0.025 and 90 per cent power. 

IMPORTANT SAFETY INFORMATION 

PREZISTA does not cure HIV infection or AIDS, and does not prevent passing HIV to others.

PREZISTA was granted approval under Health Canada's Notice of Compliance with Conditions (NOC/c) policy in July of 2006, based on studies that established its efficacy in significantly reducing viral load and increasing CD4 counts in treatment-experienced patients, compared with patients taking an investigator-selected PI. The most common side effects reported during treatment with PREZISTA in these studies were nausea, diarrhea and headache.(3)

The recommended dose of PREZISTA is 600 mg (two 300 mg tablets) twice daily (BID) taken with ritonavir 100 mg BID and with food.

Co-administration of PREZISTA/r is contraindicated with drugs that are highly dependent on CYP3A4 for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events.

Co-administration of PREZISTA/r with various drugs is contraindicated or requires dose adjustment or increased clinical or laboratory monitoring, due to the potential for pharmacokinetic interactions; the PREZISTA Product Monograph should be consulted for guidance in this regard.

PREZISTA is contraindicated in patients with severe (Child-Pugh Class C) hepatic insufficiency. Patients with mild or moderate hepatic impairment (Child-Pugh Class A or B, respectively) should be closely monitored.

Cases of severe skin rash, including Stevens-Johnson syndrome and erythema multiforme have been reported in subjects receiving PREZISTA. In clinical trials (n=924), rash, which was generally mild-to-moderate, occurred in seven per cent of subjects treated with PREZISTA. The rate of discontinuation due to rash was 0.3 per cent. PREZISTA should be discontinued if severe rash develops.

PREZISTA should be used with caution in patients with known sulfonamide allergy.

Redistribution and/or accumulation of body fat have been observed in patients receiving antiretroviral therapy. A causal relationship, mechanism, and long-term consequences of these events have not been established.

Immune reconstitution syndrome has been reported in patients treated with antiretroviral therapy.

The potential for HIV cross-resistance among protease inhibitors has not been fully explored in PREZISTA/r treated patients.

PREZISTA should be used during pregnancy only if the potential benefit justifies the potential risk. No adequate and well-controlled studies have been conducted in pregnant women. HIV-infected mothers should not breast-feed their infants to avoid risking postnatal transmission of HIV.

This is not a complete summary of the safety information for PREZISTA/r. Please see the approved Product Monograph for more details. A copy of the Product Monograph can be obtained by visiting www.janssen-ortho.com

ABOUT HIV/AIDS 

Acquired Immune Deficiency Syndrome (AIDS) is an illness caused by a chronic infection with a retrovirus (HIV, Human Immunodeficiency Virus). The breakdown of the immune system resulting from HIV leads to increased susceptibility to other infections and immune disorders.

It is estimated that between 2,300 and 4,500 new HIV cases occurred in Canada in 2005, and incidence does not appear to be decreasing.(4) In Canada, over 63,000 positive HIV tests had been reported by the end of June 2007.(5) During a five-year period, the number of positive HIV test reports increased from 2,104 in 2000 to 2,557 in 2006.(5) 

TIBOTEC - DIVISION OF JANSSEN-ORTHO INC. 

Tibotec, a division of Janssen-Ortho Inc., is dedicated to delivering innovative virology therapeutics that improve Canadian patients' survival and quality of life and that address serious unmet healthcare needs. 

TIBOTEC PHARMACEUTICALS LTD. 

Tibotec Pharmaceuticals Ltd., based in Cork, Ireland, is a pharmaceutical research and development company. The Company's main research and development facilities are in Mechelen, Belgium with offices in Yardley, PA, USA. Tibotec is dedicated to the discovery and development of innovative HIV/AIDS drugs and anti-infectives for diseases of high unmet medical need. 

* All trademarks used under license. 

 

References:

--------------------------

(1) Hammer SM et al. Antiretroviral Treatment of Adult HIV Infection.

    JAMA 2008;300(5):555-570.

(2) Ortiz R, DeJesus E, Khanlou H et al. Efficacy and safety of once-

    daily darunavir/ritonavir versus lopinavir/ritonavir in treatment-

    naive HIV-1-infected patients at week 48. AIDS 2008; 22(12): 1389-

    1397.

(3) PREZISTA* Product Monograph, Janssen-Ortho Inc., 2008.

(4) Public Health Agency of Canada. HIV/AIDS Epi Updates, November 2007.

http://www.phac-aspc.gc.ca/aids-sida/publication/epi/pdf/epi2007_e.pdf,

    accessed 28 October, 2008.

(5) Public Health Agency of Canada. HIV and AIDS in Canada: Selected

    Surveillance Tables to June 30, 2007. http://www.phac-

    aspc.gc.ca/aids-sida/publication/survreport/pdf/tables0607.pdf,

    accessed 27 October, 2008.

     -30-  /For further information: MS&L, Collin Matanowitsch, (416) 847-1330; Tibotec, a division of Janssen-Ortho Inc., Maggie Wang, (416) 449-9444/   
 

Posted: November 2008

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