Anti-HIV agent - DPC-083
AIDS is a serious threat to public health, with life expectancies in some areas having plummeted as a result of HIV infection having reached epidemic proportions. Prevention programmes are essential, but for those already infected the best hope is the pharmaceutical industry. The long term answer is likely to be a vaccine, but in the interim, medicines can suppress the virus within the body.
The strategy of giving HIV positive patients a cocktail of medicines that act by different mechanisms has proved very successful at reducing the viral load within the body, often to undetectable levels. But the virus mutates, and in time becomes resistant to one or more components of the drug cocktail. So new antiviral agents are needed to replace those that become inactive.
Non-nucleoside reverse transcriptase inhibitors (NNRTIs), notably delavirdine mesilate, efavirenz and nevirapine, are an essential part of the cocktail, but resistance is developing. A new NNRTI now in development at Bristol-Myers Squibb is DPC-083.1 In an ongoing randomised double blind Phase II clinical trial, 51 HIV infected patients who had failed nevirapine or efavirenz therapy were given 100 or 200mg once a day alongside two nucleoside reverse transcriptase inhibitors (NRTIs); response was higher for those patients given at least one new NNRTI.2
DPC-083's efficacy and tolerability in doses of 50, 100 and 200mg once a day was compared with a 600mg once a day dose of efavirenz. In a Phase II multi-centre, randomised double blind trial on 134 HIV infected patients who had not previously received antiretroviral therapy, subjects were given DPC-083 alongside Combivir (zidovudine/lamivudine). Fewer patients in the DPC-083 group experienced dizziness than those given efavirenz, and the development of a rash was dependent on the dose, with an incidence of 15, 33 and 53% respectively, compared with 28% with efavirenz. No significant differences were observed between the different treatment groups, and discontinuation rates similar for all groups 14, 17 and 24% for DPC-083 and 22% for efavirenz. The study is continuing.3
The rate at which HIV mutates and the potential for treatment failure means a steady stream of new antiretroviral agents is required. DPC-083 is undergoing Phase II trials, and could well become a further weapon in the arsenal of antiviral drugs for treating HIV.
