A new class of anti-HIV drug which inhibits an as-yet untargeted enzyme in the virus has proven effective in a drug trial, according to an Article in this week’s edition of The Lancet.
There is an urgent need for new antiretroviral drugs due to existing rates of failure in existing combination antiretroviral therapies. The current study looked at the new "integrase-inhibitor" raltegravir when used in conjunction with optimised background combination therapies, in patients with advanced HIV infection whose existing treatments were failing.
There are three types of enzyme essential to the successful replication of HIV – reverse-transcriptase, protease and integrase. Integrase is responsible for insertion of HIV DNA into the host cell’s DNA. Until now all antiretroviral drugs for HIV which target enzymes have been reverse-transcriptase or protease inhibitors.
Dr Bach-Yen Nguyen, Merck Research Laboratories, Westpoint, Pennsylvania, USA, and colleagues divided their patients into four groups. One group received the background treatment plus placebo only, and the other three received the background treatment plus 200, 400 or 600mg of raltegravir twice daily. All 178 patients across the four groups had been receiving antiretroviral therapy for an average of just under 10 years.
The researchers measured the amount of HIV genetic material (HIV RNA) in the blood of patients after 24 weeks, and found that patients taking raltegravir experienced an average of 98% drop in their HIV RNA count, compared to just 45% drop in the placebo group.
The number of CD4 cells – which give an indication of the immune response – were also significantly boosted in patients taking raltegravir. Patients receiving the 400mg and 600mg doses increased their CD4 count by 113 and 94 cells per ml of blood respectively.
Raltegravir also proved safe, well tolerated and potent in most of the patients.
In related studies of raltegravir*, 60% of the patients taking the drug reduced their HIV RNA loads to below 50 copies per ml – the lowest recordable value. Only 30% of patients in the placebo group achieved this
The authors conclude: "Taken together with the results of raltegravir in another study, these data confirm that HIV-1 Integrase is a valid target for antiretroviral therapy.
They add: "The promising efficacy and tolerability profile of raltegravir suggest that this drug has the potential to become an important component of combination treatment regimens used to treat heavily pretreated patients failing current therapies with multidrug-resistant virus and limited treatment options."
In an accompanying Comment, Dr Pedro Cahn and Dr Omar Sued, of the Fundación Huesped, Buenos Aires, Argentina, said that a new era of antiretroviral therapy had arrived and AIDS-related illness and deaths would be expected to continue to drop.
But they added: "Unfortunately, for more than 85% of patients living with HIV/AIDS [worldwide], access to basic care, including first-line antiretrovirals, is still unachievable. Will the new generation antiretrovirals help to bridge this gap, or will these extraordinary scientific achievements make the current differences even more painful?"
Notes to editors: The related raltegravir studies referred to are BENCHMRK-1 and BENCHMRK-2 recently presented at the 14th Conference on Retrovirus and Opportunistic Infections in Los Angeles in February 2007 (Abstracts 104aLB, 104bLB)
Journal
The Lancet