Merck's HIV integrase inhibitor Isentress (raltegravir) tablets, 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 in combination with anti-HIV medicines, according to two phase III studies.
Patients in the studies of 699 treatment-experienced patients failing antiretroviral therapies (ARTs) had HIV resistant to at least one drug in each of three classes [nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs)] of oral antiretroviral medicines.
In October, the US Food and Drug Administration (FDA) granted Isentress accelerated approval for use in combination with other antiretroviral agents for the treatment of HIV-1 infection in treatment-experienced adult patients with evidence of viral replication with HIV-1 strains resistant to multiple antiretroviral agents. The approval was based on analyses of viral load reductions and CD4 cell count increases from baseline through 24 weeks in two phase III studies of Isentress. This week, 48-week data from those same studies were presented at the 15th Conference on Retroviruses and Opportunistic Infections (CROI).
The use of other active agents with Isentress is associated with a greater likelihood of treatment response. The safety and efficacy of Isentress have not been established in treatment-naïve adult patients or paediatric patients. There are no study results demonstrating the effect of Isentress on clinical progression of HIV-1 infection.
"The 48-week efficacy results are consistent with what we observed at Week 24," said Roy Steigbigel M.D., professor of medicine, pathology, microbiology and pharmacology, State University of New York at Stony Brook and lead study investigator for one of the studies.
The data presented are from Week 48 results from two identical ongoing multi-centre, double-blind, randomised, placebo-controlled phase III studies (BENCHMRK-1 and BENCHMRK-2) that compare Isentress in combination with optimised background therapy (OBT) to placebo plus OBT. The primary endpoint of this ongoing study is per centage of patients in each study arm that achieve HIV RNA viral levels less than 400 copies/mL at Week 16.
Patients in BENCHMRK-1 were enrolled in Europe, Asia/Pacific and Peru. The mean baseline viral load was 4.6 log10 copies/mL for the regimen with Isentress and 4.5 log10 copies/mL for the placebo regimen, respectively. The median baseline CD4 cell counts were 140 cells/mm3 for the regimen with Isentress and 105 cells/mm3 for the placebo regimen, respectively. Patients in BENCHMRK-2 were enrolled in North and South America. The mean baseline viral load was 4.7 log10 copies/mL for both the regimen with Isentress and the placebo regimen, respectively. The median baseline CD4 cell counts were 102 cells/mm3 for the regimen with Isentress and 132 cells/mm3 for the placebo regimen, respectively.
Patients who entered the study experienced treatment failure on prior antiretroviral therapies and were infected with HIV resistant to one or more drugs in each of three oral classes of ARTs (NRTIs, NNRTIs and PIs).
In BENCHMRK-2, 7 of 230 patients (3.0 per cent) receiving Isentress plus
"The results show that after 48 weeks Isentress in combination with other anti-HIV medicines continued to provide significantly greater antiretroviral activity and increases in CD4 cells compared to placebo with other antiretroviral medicines," said David Cooper M.D., D.Sc., professor of medicine and director of the National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia.
Isentress is a single 400 mg tablet taken twice daily without regard to food. It does not require boosting with ritonavir. Isentress is the first medicine to be approved in a new class of antiretroviral drugs called integrase inhibitors. It 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 Isentress is the only drug approved that inhibits the integrase enzyme.