7 February 2008, London – New data presented at CROI, the 15th Conference on Retroviruses and Opportunistic Infections (Boston, USA), has demonstrated that ‘Isentress’® (raltegravir), the first in a new class of antiretroviral treatments called integrase inhibitors, in combination with other anti-HIV medicines, maintained significant HIV-1 viral load suppression and increased CD4 cell counts through 48 weeks of therapy compared to placebo.1,2 Raltegravir was introduced last month in the UK for use in combination with other antiretroviral medical products for the treatment of HIV-1 infection in treatment-experienced adult patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy.
The data presented this week are the Week 48 results of two identical, ongoing multicentre, double-blind randomised placebo-controlled Phase III studies (BENCHMRK-1 and BENCHMRK- 2)1,2. The studies involve approximately 700 patients and compare raltegravir in combination with 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) to placebo plus OBT.
In BENCHMRK-1, at 48 weeks, raltegravir plus OBT achieved HIV viral load reduction to less than 400 copies/mL in 74 percent of patients compared to 36 percent of patients receiving placebo plus OBT (p<0.001).1 In the companion study BENCHMRK-2 raltegravir plus OBT suppressed viral loads below 400 copies/mL in 71 percent of patients compared to 38 percent of patients receiving placebo plus OBT (p<0.001).2
In addition, in BENCHMRK-1, after 48 weeks of therapy, raltegravir plus OBT suppressed viral load to below 50 copies/mL in 65 percent of patients compared to 31 percent of patients receiving placebo plus OBT (p<0.001). Raltegravir plus OBT increased CD4 cell counts from baseline by 120 cells/mm3 compared to 49 cells/mm3 for patients receiving placebo plus OBT (p<0.001).1 In BENCHMRK-2, after 48 weeks, 60 percent of patients receiving raltegravir plus OBT achieved viral loads below 50 copies/mL compared to 35 percent of patients receiving placebo plus OBT 2 (p<0.001). Raltegravir plus OBT increased CD4 cell counts from baseline by 98 cells/mm3 compared to 40 cells/mm3 for those patients receiving placebo plus OBT (p<0.001).2
Dr Mark Nelson, Director of HIV Services, Chelsea and Westminster Hospital, London, commented, "The 48 week efficacy data are consistent with, if not better than, what we observed at week 24. The reduction in viral load and increases in CD4 cells that we’ve seen with raltegravir in combination with other anti-HIV medicines compared to placebo, clearly shows that there is a very important place for this integrase inhibitor. The more ways we have to attack the HIV virus, the more chance we have of successfully managing this disease.”
After 48 weeks of therapy, in BENCHMRK-1, four of 232 patients (1.7 percent) receiving raltegravir plus OBT and four of 118 patients (3.4 percent) receiving placebo plus OBT discontinued therapy due to adverse experiences. In addition, seven of 232 patients (3.0 percent) receiving raltegravir plus OBT and one of 118 patients (0.8 percent) receiving placebo plus OBT experienced a serious drug-related adverse event. The most commonly reported (reported in at least two percent of patients) study therapy-related side effects in patients receiving raltegravir plus OBT were diarrhoea, nausea, vomiting, fatigue, injection site pain or reaction (due to enfuvirtide), joint pain, headache and itching1.
In BENCHMRK-2, seven of 230 patients (3.0 percent) receiving raltegravir plus OBT and three of 119 patients (2.5 percent) receiving placebo plus OBT discontinued therapy. In addition, four of 230 patients (1.7 percent) receiving raltegravir plus OBT and six of 119 patients (5.0 percent) receiving placebo plus OBT experienced a serious drug-related adverse event. The most commonly reported (reported in at least two percent of patients) study therapy-related side effects in patients receiving raltegravir plus OBT were bloating, abdominal pain, constipation, diarrhoea, gas, nausea, vomiting, fatigue, injection site reaction (due to enfuvirtide), dizziness and headache2. These data are not inconsistent with the safety and tolerability data presented in the UK SmPC3.
There are now an estimated 73,000 people living with HIV in the UK.4 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. In the UK, one of the biggest challenges now is the threat of resistance to treatment but the chance of resistance developing is lower if treatment reduces the viral load to undetectable, and patients adhere to their treatment regimens5. There is therefore a need for new and effective ways to fight the virus while retaining quality of life for patients. 3
Raltegravir is a single 400mg tablet taken twice daily with or without food. 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.
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Last updated on: 27/08/2010