First In Class Integrase Inhibitor, 'Isentress'(R) (Raltegravir), Introduced In The UK
There are now an estimated 73,000 people living with HIV in the UK.1 While the condition is still serious, great advances in medicine mean that people living with HIV, when diagnosed early and treated appropriately, can hope for a relatively normal life-span. However, the HIV virus constantly mutates. In the UK, one of the biggest challenges now is the threat of resistance to treatment. There is therefore a need for new ways to fight the HIV virus.
Raltegravir has a unique mode of action: it is the first antiretroviral treatment to target the integrase enzyme. Integrase is one of three HIV enzymes required by the HIV virus in order to replicate (reproduce); the other two enzymes being reverse transcriptase and protease. Integrase is responsible for inserting (integrating) the viral DNA into the DNA of the host cell. By preventing this essential function, an integrase inhibitor affects the ability of the virus to replicate and thus can help to prevent infection of other cells, and to reduce the viral load - the amount of virus present in the blood.
Dr Mark Nelson, Director of HIV Services, Chelsea and Westminster Hospital, London, says, "HIV is a clever virus which adapts and mutates quickly, producing drug resistant strains of the virus. The more ways we have to attack the virus, the more chance we have of successfully managing the disease. But we've got to be smart about how we use these new drugs; we don't want to repeat past mistakes where resistance arose from using single therapies. When used as part of individually tailored combination therapy, raltegravir will be an important step forward in our fight against HIV".
Two recent studies, BENCHMRK-1 and BENCHMRK-2, examined the tolerability and efficacy of raltegravir, its ability to reduce viral load and raise CD4 cell count in treatment-experienced, triple class resistant patients living with HIV, a difficult to treat patient population.2
24 week outcomes of the pooled studies have shown that 75 percent of patients receiving raltegravir plus Optimised Background Therapy (OBT - a regime of active antiretroviral drugs tailored to individual patients, chosen by their physicians as most likely to be of benefit) achieved HIV viral load reduction to less than 400 copies/ml at 24 weeks compared to 40 percent taking placebo plus OBT.
In the same studies, it was shown that 63 percent of patients receiving raltegravir plus OBT achieved HIV viral load reduction to less than 50 copies/ml at 24 weeks compared to 34 percent taking placebo plus OBT.
The studies also found the increases in CD4 cell counts from baseline were 84 cells/mm3 for patients receiving raltegravir compared with 37 cells/mm3 for those receiving placebo.
An analysis of the same trials at 16 weeks showed that after 16 weeks of treatment, 'Isentress' plus OBT was generally well-tolerated.3,4 The most commonly reported therapy-related side effects, as reported in at least three per cent of patients, were diarrhoea, nausea, abdominal distension, abdominal pain, flatulence, headache and fatigue.5
Roger Pebody, treatment advisor, Terrence Higgins Trust, commented, "This is excellent news for people who are resistant to other HIV drugs. A combination of drugs is used to stop HIV at different stages of the process of entering and destroying the body's immune cells. If someone becomes resistant to any of their drugs, their treatment needs to be changed, and drugs which work in innovative ways can make a real difference."
Merck Sharp & Dohme Ltd (the UK subsidiary of Merck & Co., Inc. of Whitehouse Station, New Jersey, USA. ) has over 20 years of heritage in HIV research, which includes the protease inhibitor 'Crixivan'® (indinavir) and the non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz. Research is currently underway on additional treatment options.
Notes :
Price
The NHS price of 'Isentress' 400mg is £21.58 per day.
Viral Load
Viral load is the term used to describe the amount of HIV in the blood. A viral load above 100,000 copies/ml is considered high, and one below 10,000 copies/ml is considered low. A viral load below 50 copies/ml is said to be 'undetectable' and is a key goal of anti-HIV treatment, though it does not mean that the virus has been eradicated.6
CD4 Count
CD4 count refers to the measurement of the number of CD4 cells in a cubic millimetre of blood7. The British HIV Association (BHIVA) recommends treatment should start before an individual's CD4 count falls below 200 cells/mm3 8. The CD4 count of a person who is not infected with HIV is usually between 500-12006.
'Isentress'® is a Registered Trademark of Merck & Co., Inc., Whitehouse Station, New Jersey, USA.
Merck Sharp & Dohme Limited (MSD) is the UK subsidiary of Merck & Co., Inc., of Whitehouse Station, New Jersey, USA, a leading research-based pharmaceutical company that discovers, develops, manufactures and markets a wide range of innovative pharmaceutical products to improve human health.
References:
1. Health Protection Agency. 2007. Testing Times: HIV and other Sexually Transmitted Infections in the United Kingdom: 2007 [online]. Available here.[accessed 28 November 2007].
2. Summary of Product Characteristics
3. Cooper DA, Gatell J, Rockstroh, J, et al. Results of BENCHMRK-1, a Phase III Study Evaluating the Efficacy and Safety of MK-0518, a Novel HIV-1 Integrase Inhibitor, in Patients with Triple-class Resistant Virus. Presented at the 14th Conference on Retroviruses and Opportunistic Infections (CROI), February 27, 2007.
4. Steigbigel R, Kumar P, Eron J. Results of BENCHMRK-2, a Phase III Study Evaluating the Efficacy and Safety of MK- 0518, a Novel HIV-1 Integrase Inhibitor, in Patients with Triple-class Resistant Virus. Presented at the 14th Conference on Retroviruses and Opportunistic Infections (CROI), February 27, 2007.
5. Data on file.
6. Aidsmap. 2007. Viral Load [online]. Available here. [accessed 28 November 2007].
7. Dawson, R. 2007. viral load & CD4. 7th ed. London: NAM.
8. British HIV Association. 2006. British HIV Association (BHIVA) guidelines for the treatment of HIV-infected adults with antiretroviral therapy (2006) [online]. Available at: http://www.bhiva.org/files/file1001303.pdf [accessed 28 November 2007].
http://www.merck.com
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