Boosted Invirase (saquinavir) 500 Has Similar Efficacy And An Overall Beneficial Lipid Profile In HIV Positive Patients Compared With Lopinavir

Main Category: HIV / AIDS
Also Included In: Pharma Industry / Biotech Industry;  Cardiovascular / Cardiology
Article Date: 25 Jul 2007 - 1:00 PDT

email to a friend   printer friendly   view / write opinions   rate article

Encouraging 24 week, full cohort head to head results of an international trial demonstrate that HIV-infected patients initiating treatment with the boosted protease inhibitor Invirase 500/r (saquinavir boosted with ritonivir) achieved similar efficacy, in terms of viral suppression and increases in CD4 cells, and are less likely to develop elevated lipid levels above current accepted guidelines6 than those treated with lopinavir/r.1,2 These results, from the Gemini study, were presented at the 4th International AIDS Society (IAS) Conference (Sydney).

Current treatment guidelines for highly active antiretroviral therapy (HAART) include a boosted protease inhibitor (PI) as an option for first-line treatment of HIV-infected patients.3,4 However, PI-based regimens can be associated with varying degrees of lipid abnormalities, potentially increasing the long-term risk of cerebrovascular and cardiovascular disease.5 As people with HIV are living for longer due to advances in treatment, it is especially important to establish regimens that minimise the adverse effects on lipids to reduce the risk of cardiovascular disease.

"The full interim results from the Gemini study further consolidate boosted saquinavir as one of the preferred options for first-line treatment of HIV infection, " said Dr Francois Raffi, University Hospital, Nantes, France and a leading investigator in the Gemini trial. "Beyond potency, we need to be able to offer [well tolerated] options for patients on combination HIV therapy - and establishing a PI-based regimen that is associated with fewer lipid abnormalities could have a real impact on HIV management, particularly in patients at increased cardiovascular risk."

Summary of results from the GEMINI Trial [Poster WePeB027 and Poster TuPeB069 ]1,2

The results also showed that 69.9% and 69% of patients treated respectively with saquinavir/r and lopinavir/r achieved undetectable virus levels (<50 copies; ITT analysis).1 The same proportion of patients (81.3%) in both groups achieved reduction of HIV-1 RNA levels <400 copies.1 Furthermore, the rate and extent of increases in CD4 counts were comparable in both groups with a median increase from baseline of 127 for the saquinavir/r-treated patients and 134 for lopinavir/r patients.1

At 24 weeks, fewer saquinavir/r-treated patients experienced an increase in their overall lipid levels, above those recommended by the current accepted NCEP* guidelines,6 than those treated with lopinavir/r. The absolute levels of increase from baseline to above NCEP and ACTG guidelines6,7 of total cholesterol (TC) and triglycerides (TC) were lower in the group treated with saquinavir/r than in the group treated with lopinavir/r, whilst patients on saquinavir/r were more likely to experience an increase in low density lipoprotein (LDL) levels. In the saquinavir/r group, the absolute difference from baseline to above guideline levels for

-- TC levels was +8 compared to +17.3 for the lopinavir/r group8 (>200mg/dL)
-- LDL levels +9.2 compared to +3.6 for the lopinavir/r group8 (>100mg/dL)
-- TG levels -0.6 compared to +6.5 for the lopinavir/r group8 (>400mg/dL)

This, therefore, means that more than twice as many patients taking lopinavir/r experienced a rise in total cholesterol from below to above the guidelines than those receiving saquinavir/r (8% v 17.3%) . Furthermore the number of patients experiencing levels of triglycerides increasing from below to above accepted guidelines fell by 0.6% in patients receiving saquinavir/r ,in comparison to an increase of 6.5% in patients receiving lopanivir/r. The increase in LDL from a baseline below 100 mg/dL to above this level was an absolute difference of 9.2% in patients receiving saquinavir/r compared to 3.6% receiving lopanavir/r. However the percentage of patients whose LDL increased from below to above the more dangerous level of 130 mg/dl was 3.7% in those receiving saquinavir/r and 6% in those receiving lopinavir/r.

These findings, from a planned 24 week full interim analysis of all 337 patients from the Gemini study1,2 are important for patients and HIV physicians when considering PI treatment options, particularly for patients already at increased cardiovascular risk.

About the Gemini study

The Gemini study is a Phase IIIb multi-centre, randomised open-label, 48 week study, designed to evaluate the efficacy and safety of Invirase 500/r versus lopinavir/r. These treatments are given at their approved twice-daily dosages in combination with two nucleoside reverse transcriptase inhibitors (NRTIs; emtricitabine/tenofovir (Truvada), once daily) in treatment naïve adults. Gemini enrolled 337 patients from Canada, France, Puerto Rico, Thailand and the USA. The primary endpoint of the trial is the number of patients with an HIV-1 RNA viral load of <50 copies m/L at week 48. There were two planned interim analyses.

About boosted Invirase (saquinavir)

Saquinavir, originally approved by the FDA in 1995, was the first protease inhibitor on the market. Its introduction represented a major milestone in the treatment of HIV/AIDS. In December 2003, the FDA approved saquinavir for use in boosted dosing regimens with ritonavir (1000 mg Invirase/100 mg ritonavir bid). Co-administering saquinavir with ritonavir enhances therapeutic blood levels of the drug ("boosting") and enables simplified dosing.

The saquinavir 500 mg formulation received approval from the US Food and Drug Administration (FDA) in December 2004 and from the European Commission in May 2005. The new formulation significantly simplifies the saquinavir dosing regimen by reducing the daily tablet count by more than half, from five tablets twice-daily to two tablets twice-daily.

Boosted saquinavir provides consistent and well proven control of HIV. Data from the Staccato clinical study show reductions in patients'HIV RNA recorded in the first 24 weeks on therapy that are the best ever seen in a large cohort of patients given HAART. Some 96% of patients achieved viral load reductions to <400 HIV RNA copies m/L and 89% were shown to have undetectable levels (<50 copies m/L). Over the 24 week induction phase of the study, these reductions in patient viral load were accompanied by a median increase of CD4 cells of 109 cells/mm.

The Summary of Product Characteristics and Patient Information for saquinavir can be found at http://www.rocheuk.com.

About Roche in the UK

Roche aims to improve people's health and quality of life with innovative products and services for the early detection, prevention, diagnosis and treatment of disease. Part of one of the world's leading healthcare groups, Roche in the UK employs nearly 2,000 people in pharmaceuticals and diagnostics. Globally Roche is the leader in diagnostics, and a major supplier of medicines for the treatment of cancer, transplantation, virology, bone and rheumatology, obesity and renal anaemia. Find out more at http://www.rocheuk.com

References

1. Raffi F, Ward D, Ruxrungtham K, Brunetta J, Schutz M. Saquinavir/r (SQV/r) BID vs lopinavir/r (LPV/r) BID plus emtricitabine/tenofovir (FTC/TDF) QD as initial therapy in HIV-1 infected patients: the GEMINI Study 24-week interim analysis. Presented at 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention, 22-25 July 2007, Sydney, Australia. Abstract WEPEB027.

2. Walmsley S, Bredeek U, Avihingsanon A, Slim J, Guittari C. Evaluation of the impact of highly active antiretroviral therapy (HAART) on lipid profiles - data from the 24-week interim analysis of the Gemini Study: saquinavir/r (SQV/r) BID vs lopinavir/r (LPV/r) BID plus emtricitabine/tenofovir (FTC/TDF) QD in ARV-naïve HIV-1-infected patients. Presented at Conference on HIV Pathogenesis, Treatment and Prevention, 22-25 July 2007, Sydney, Australia.

3 Hammer SM, Saag MS, Schechteret M, et al. JAMA 2006; 296:827-843

4. The EACS Executive Committee 2005. Available here. (accessed 27 June 2007).

5. Koppel K, Bratt G, Eriksson M, Sandström E. Int J STD AIDS. 2000;11:451-455.

6. National Cholesterol Education Program (NCEP) Expert Panel. Available here. (accessed 27 June 2007)

7. Dube MP, Sprecher D, Henry WK, et al. Adult AIDS Clinical Trial Group Cardiovascular Disease Focus Group. Clin Infect Dis 2000; 31: 1216-1224.

8. Roche data on file.