Safety and Anti-HIV Activity of Capravirine Alone and in Combination With Other Anti-HIV Drugs

CONTROL Documented HIV-1 seronegative, confirmed by ELISA and Western blot. Male or female, at least 18 years of age. Laboratory values within established National Institute of Allergy and Infectious Diseases (NIAID) guidelines for participation in clinical studies. Unremarkable physical exam Signed written informed consent. Must not use (or, depending on the agent, must not have used up to the last 28 days) of medications known to inhibit or induce cytochrome P450 during the initial period of the study period (Arm 1: Screening visit to Day 17; Arm 2: Screening visit to Day 15). After this initial period, use of these agents will be permitted on a case-by-case basis as per Investigator's clinical judgement; where necessary, additional PK studies may be performed. The prohibited medications include, but are not limited to: isoniazid, rifampin, rifabutin, astemizole, terfenadine, cisapride, cimetidine, triazolam, midazolam, quinidine, nifedipine, diltiazem, verapamil, amiodarone, or ergot alkaloids, carbamazepine, phenytoin and other hydantoins, phenobarbital and other barbiturates, propoxyphene, dexamethasone, oral contraceptives, antidepressants (fluoxetine, paroxetine, imipramine, amitriptyline, nefazodone), azole antifungals (ketoconazole, fluconazole, itraconazole) macrolide antibiotics (erythromycin, clarithromycin, dirithromycin), or grapefruit juice. Must not use highly plasma protein bound drugs, including but not limited to , warfarin and phenytoin. Must not be receiving treatment of chronic Hepatitis B infection with lamivudine (3TC). Must not be using any antiretroviral therapy other than as indicated by the study regimen. Must not have a history of significant allergy, hypersensitivity reaction, or adverse reactions to abacavir, efavirenz, or ritonavir. Must be able to obtain venous access for sample collection. Must not have any psychological/sociological condition or addictive disorder which would preclude compliance with the protocol. Females must not be pregnant or lactating. Must be willing to use adequate barrier contraception methods (other than oral contraceptives) if procreation potential exists. PATIENT Document HIV-1 seropositive, confirmed by ELISA and Western blot. CD4 greater than 300/mm(3) and HIV-1 RNA viral load greater than 5,000 copies per mL. Male or female, at least 18 years of age. Adequate hematology (absolute neutrophil count greater than or equal to 1500/mm(3), platelets greater than or equal to 75,000/mm(3), hemoglobin greater than or equal to 9 g/dL). Adequate renal function (serum creatinine less than or equal to 1.5 times upper-limit-of-normal [ULN]). Adequate liver function (aspartate aminotransferase [AST/SGOT], alanine aminotransferase [ALT/SGPT] and total bilirubin less than or equal to 1.5 times ULN). Signed written informed consent. Must not have had any prior treatment with any non-nucleoside reverse transcriptase inhibitors. Must not have a history of significant allergy, hypersensitivity reaction, or adverse reactions to abacavir or ritonavir. Must not have evidence of clinical or genotypic resistance to abacavir. Must not have an active uncontrolled infection. Must not have unstable or severe concurrent medical conditions. Must not have concomitant use of any antiretroviral therapy other than as indicated by the study regimen. Must not have current treatment of chronic Hepatitis B with lamivudine (3TC). Must not use (or, depending on the agent, must not have used up to the last 28 days) of medications known to inhibit or induce cytochrome P450 during the initial period of the study period (Screening visit to Day 14). After this initial period, use of these agents will be permitted on a case-by-case basis as per Investigator's clinical judgement; where necessary, additional PK studies may be performed. The prohibited medications include, but are not limited to: isoniazid, rifampin, rifabutin, astemizole, terfenadine, cisapride, cimetidine, triazolam, midazolam, quinidine, nifedipine, diltiazem, verapamil, amiodarone, or ergot alkaloids, carbamazepine, phenytoin and other hydantoins, phenobarbital and other barbiturates, propoxyphene, dexamethasone, oral contraceptives, antidepressants (fluoxetine, paroxetine, imipramine, amitriptyline, nefazodone), azole antifungals (ketoconazole, fluconazole, itraconazole) macrolide antibiotics (erythromycin, clarithromycin, dirithromycin), or grapefruit juice. Must not have current use of highly plasma bound drugs, including but not limited to, warfarin and phenytoin. Must not have current use, or use within the last 28 days, of any investigational agent. Must not have cytotoxic chemotherapy, interferon treatment or radiation therapy within the last 28 days. Must not have any psychological/sociological condition or addictive disorder which would preclude compliance with the protocol. Females must not be pregnant or lactating. Must be willing to use adequate barrier contraception methods (other than oral contraceptives) if procreation potential exists. (male or female)