Abstract
Nucleoside analogues continue to play a central role in the treatment of HIV infection. The recently published Concorde I.rial has been misinterpreted as demonstrating a Jack of efficacy of zidovudine in the treatment of HIV disease. This is clearly not the case because zidovudine was prescribed to patients in both arms of the study. The Concorde study did confirm, however, the limitations of monotherapy in the treatment of this disease. Increased availability of other nucleoside analogues has allowed the development of newer therapeutic strategies. In this context, sequential use of zidovudine, followed by didanosine, has proved to be safe and effective in patients in varying stages of HIV disease. Preliminary results suggest that this strategy could be improved upon by using simultaneous combinations of zidovudine with didanosine or zalcitabine in full closes. The relative efficacy of these combinations remains to be established by phase III clinical trials, currently underway, Several new agents, including d4T, 3TC, nevirapine, other non-nucleoside reverse transcriptase inhibitors and the more recent protein inhibitors. are being tested either a lone or in combination therapy regimens. It is anticipated that one or more of these agents will be clinically available soon. At present. the British Columbia Centre for Excellence in HIV/AIDS continues to recommend initiation of antiretroviral therapy with zidovudine in doses of 500 mg/day for all HIV-infected individuals who are symptomatic (ie. who have AIDS or AIDS-related complex) and for those who are asymptomatic with a CD4 count consistently below 500/mm3. If the CD4 count is lower than 350/mm3, it is recommended that combination antiretroviral therapy be considered. namely zidovudine plus didanosine or zalcitabine in full doses. Obviously, the available evidence should be thoroughly discussed with eligible individuals to ensure that they have a full understanding of the potential benefits, adverse effects and limitations of currently available therapy.