To determine the time course of development of resistance to atevirdine mesylate ( U-87201E
) in patients with HIV isolates showing in vitro resistance to zidovudine ( AZT ). To
determine the genotype changes in HIV reverse transcriptase associated with in vitro AZT
resistance to U-87201E. To determine the genotype and phenotype effects of treatment with a
nondideoxynucleoside agent on the alterations of the HIV-1 population associated with in
vitro AZT resistance. To determine whether serial passage of patient pre-drug HIV isolates
in the presence of U-87201E will generate the resistant mutants that may subsequently emerge
in the patients.
Patients must have:
- Enrollment on protocol RV-43 (AZT resistance study).
- Development of a primary RV-43 study endpoint-opportunistic infection.
- HIV isolate with an AZT IC50 > 50 times that of the sensitive type strain.
- Able to swallow tablets without difficulty.
- Normal QTc interval on EKG.
Patients with the following symptoms or conditions are excluded:
- Clinically significant hypersensitivity to piperazine type drugs (Antepar,
- Severe uncontrollable diarrhea or vomiting or known malabsorption.
- Symptomatic hyperlipidemia.
- Other experimental drugs.
- AZT, ddI, ddC, foscarnet, immunomodulators or other agents with primary
antiretroviral activity (exemptions by principal investigator permitted).
Patients with the following prior conditions are excluded:
History of clinically significant cardiovascular disease or nervous system or muscle
disease, including seizures, peripheral neuropathy, dementia, or motor dysfunction.
- Experimental drugs within 4 weeks prior to study entry.