Interim results of Abbott's PROGRESS study showed that Kaletra® combined with raltegravir suggested a more rapid initial viral load decline when compared to a traditional triple-drug combination therapy of Kaletra and Truvada®.1 PROGRESS is an open-label, 96-week evaluation of the safety and efficacy of Abbott's HIV protease inhibitor Kaletra (lopinavir/ritonavir) in combination with raltegravir, the integrase inhibitor manufactured by Merck, compared to Kaletra and the nucleoside reverse transcriptase inhibitor (NRTI) Truvada (tenofovir and emtricitabine) in antiretroviral-naive, HIV-1-infected patients. Abbott conducted an eight-week analysis to compare rates of viral decay between the two regimens. The study results were presented at the 15th Annual Conference of the British HIV Association (BHIVA).

"These interim results from the PROGRESS study are the first data to suggest that more rapid viral suppression may be possible with a dual regimen that includes Kaletra and raltegravir versus a standard triple-therapy regimen," said Scott C. Brun, M.D., divisional vice president, infectious diseases and immunology development, Global Pharmaceutical Research and Development, Abbott. "Lowering a patient's viral load to an undetectable level and maintaining viral load suppression are key success markers for patients beginning antiretroviral treatment."

Other key findings of the study include:

A greater proportion of patients had HIV-1 RNA levels <40 copies/mL at weeks two, four and eight when treated with Kaletra and raltegravir compared with Kaletra and Truvada. Intent-to-treat results were similar to the observed data.

Both treatment groups had statistically significant mean increases from baseline in CD4+ T-cell count at weeks four and eight (p<0.001).

Overall, the incidences of treatment-emergent adverse events were similar between treatment groups. The most commonly-reported events in both treatment groups, regardless of severity or relationship to study drug, were gastrointestinal in nature, including diarrhoea, nausea and flatulence. Headache was also commonly reported and did not differ between groups.

Cholesterol elevations ≥7.77 mmol/L were observed in 7 percent (seven out of 101 patients) of Kaletra and raltegravir patients and 3 percent (three out of 102 patients) of Kaletra and Truvada patients.

Triglyceride increases ≥8.475 mmol/L were detected in 6 percent (six out of 101) of Kaletra and raltegravir patients, but were not observed in Kaletra and Truvada patients (p=.014).

Kaletra is a protease inhibitor and is always used in combination with other anti-HIV-1 medicines for the treatment of HIV-1 infection. Kaletra is indicated for adults and for children age two years and older.2 Raltegravir is an integrase inhibitor indicated for use in combination therapy in treatment-experienced adult patients who have HIV-1 that is resistant to multiple antiretroviral medications. The safety and efficacy of raltegravir have not been established in treatment-naïve adult patients or paediatric patients.3

The rapid viral suppression observed for Kaletra and raltegravir is consistent with the Merck 004 Study,4 in which raltegravir in combination with two NRTIs was shown to be as effective in suppressing viral load in treatment-naïve HIV-infected patients as efavirenz administered with two NRTIs in a triple-therapy regimen. In the study, viral decay rates were significantly higher for the raltegravir arm compared to the efavirenz arm.

"The initial PROGRESS results suggest that a nucleoside-free dual regimen may perform as well as the standard triple-therapy regimen," said Jose Arribas, M.D., senior attending physician, HIV Unit, Hospital Universitario La Paz, Madrid, Spain.

About the PROGRESS Study

PROGRESS is an open-label 96-week evaluation of the safety and efficacy of Kaletra in combination with raltegravir, compared to Kaletra and Truvada in antiretroviral-naïve subjects.

The PROGRESS study combines Kaletra with raltegravir, an integrase inhibitor.

PROGRESS is a global, multicenter study of approximately 200 patients. The study is fully enrolled and 48-week data are planned for the first half of 2010.

Merck supplied raltegravir for the PROGRESS study.

The primary endpoints of the 96-week PROGRESS study evaluate the antiviral activity, safety and tolerability of the two regimens. Secondary endpoints include metabolic effects, fat distribution, time to loss of virologic response, incidence of resistance to each drug in the study and patient-reported outcomes.

More Information on Kaletra

Kaletra was studied for seven years in Abbott Study 720,5 one of the longest clinical trials for any antiretroviral agent, which was completed in April 2005. The Kaletra tablet is the first and only co-formulated protease inhibitor tablet that does not require refrigeration and can be taken with or without food, two important factors in delivering HIV medicine, especially in developing countries.

More Information on Raltegravir

Raltegravir is the first medicine to be approved in a new class of antiretroviral drugs called integrase inhibitors.

Raltegravir is approved for use in combination with other antiretroviral agents for the treatment of HIV-1 infection in treatment-experienced adult patients who have evidence of viral replication and HIV-1 strains resistant to multiple antiretroviral agents.

The safety and efficacy of raltegravir have not been established in treatment-naïve adult patients or pediatric patients.

Raltegravir works by inhibiting the insertion of HIV-1 DNA into human DNA by the integrase enzyme. Inhibiting integrase from performing this essential function limits the ability of the virus to replicate and infect new cells. There are drugs in use that inhibit two other enzymes critical to the HIV-1 replication process - protease and reverse transcriptase - but raltegravir is the only drug approved that inhibits the integrase enzyme.

Abbott and HIV/AIDS

Abbott has been a leader in HIV/AIDS research since the early years of the epidemic. In 1985, the company developed the first licensed test to detect HIV antibodies in the blood and remains a leader in HIV diagnostics. Abbott retroviral and hepatitis tests are used to screen more than half of the world's donated blood supply. Abbott has developed two protease inhibitors for the treatment of HIV.

Reference

1. Thomas Podsadecki, M.D., Min Tian, M.S., Linda Fredrick, M.S., Adebayo Lawal, M.D., Barry Bernstein, M.D. Lopinavir/Ritonavir (LPV/r) Combined With Raltegravir (RAL) Provides More Rapid Viral Decline Than LPV/r Combined With Tenofovir Disoproxil Fumarate/Emtricitabine (TDF/FTC) in Treatment-naïve HIV-1 Infected Subjects. 15th Annual Conference of the British HIV Association (BHIVA) • 1-3 April 2009 • Liverpool, UK

2. Kaletra Summary of Product Characteristics, 2007

3. Raltegravir Summary of Product Characteristics 2008

4. Martin Markowitz, MD,* Bach-Yen Nguyen, MD,† Eduardo Gotuzzo, MD,‡ Fernando Mendo, MD, et cal, Rapid and Durable Antiretroviral Effect of the HIV-1. Integrase Inhibitor Raltegravir as Part of Combination Therapy in Treatment-Naive Patients With HIV-1 Infection. Results of a 48-Week Controlled Study, J Acquir Immune Defic Syndr _ Volume 46, Number 2, October 1, 2007

5. R Murphy, B da Silva, F McMillan, C Hicks, J Eron, P Wolfe et al. Seven year follow-up of a lopinavir/ritonavir (LPV/r)-based regimen in antiretroviral-naïve subjects. Poster presentation at the 10th European AIDS Conference; Dublin, November 17-20, 2005 - Abstract #P7.9/3

Source
Abbott