Is it a good idea to use Trizivir twice per day in the case of a patient who, after suspending Zerit/Epivir/Videx therapy for hepatitis for three months in Aug., 2000, developed medium to severe resistance to these antiretrovirals in Dec., 2001(severe resistance developed to Videx)? The virus count grew from 400 copies/mL to 14,000 copies/mL, the CD4 count is 750 cells/mm3, and there is no protease inhibitor resistance. What is the outlook in this situation?
Dr. Brian Conway responds: As I understand it, the situation involves an HIV-infected patient with viral hepatitis who was placed on ddI/d4T/3TC and developed resistance while on therapy. Although you state that he has developed resistance to ddI, I would be quite concerned that the virus has lost susceptibility to 3TC, as high-grade phenotypic resistance develops as a result of the development of a single mutation, while it evolves much more slowly in the case of ddI and d4T. If resistance to ddI has occurred, it is likely that zidovudine and abacavir would not be active either. As long as there are not more than three nucleoside-associated mutations (NAMs), tenofovir should remain active.
The tenofovir could be combined with agents from the other two classes of antiretroviral agents, to which the patient is apparently naïve. As a PI, I would select nelfinavir, as the least toxic to the liver. As an NNRTI, it would be tempting to select delavirdine (with minimal hepatotoxicity, according to a recent ACTG review of agents in this class), but it is relatively contraindicated due to a negative pharmacokinetic interaction with nelfinavir, leading to significantly decreased circulating delavirdine levels. Thus, efavirenz or nevirapine could be used, while carefully watching for abnormalities of liver function tests (especially ALT) over the first 4-8 weeks of therapy.
