Prospective Open-Label Study of the Emergence of Drug Resistance in Patients Infected With HIV-1 Who Are Taking Oral U-87201E

Pharmacia & Upjohn

Status: Completed

Conditions: HIV Infections

Treatments: Drug: Atevirdine mesylate

Study type: Interventional

Funder types: Industry

Identifiers

NCT00002094

117A

M/3330/0007

Details and patient eligibility

About

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.

Sex: Male

Ages: 18 to 45 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

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.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Clinically significant hypersensitivity to piperazine type drugs (Antepar, Stelazine).
• Severe uncontrollable diarrhea or vomiting or known malabsorption.
• Symptomatic hyperlipidemia.

Concurrent Medication:

Excluded:

• 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.

Prior Medication:

Excluded:

• Experimental drugs within 4 weeks prior to study entry.