Lopinavir/Ritonavir in Combination With Saquinavir Mesylate or Lamivudine/Zidovudine to Explore Metabolic Toxicities in Antiretroviral HIV-Infected Subjects

A Phase II Study of Lopinavir/Ritonavir in Combination With Saquinavir Mesylate or Lamivudine/Zidovudine to Explore Metabolic Toxicities in Antiretroviral HIV-Infected Subjects

The objectives of this study are to explore the metabolic toxicities associated with lopinavir/ritonavir (LPV/r) plus saquinavir mesylate (INV) versus LPV/r plus Combivir in antiretroviral naïve subjects and to assess the overall safety, tolerability and efficacy of LPV/r plus INV versus LPV/r plus Combivir in antiretroviral naïve subjects and to assess the pharmacokinetics of 400 mg INV taken twice a day (BID), 600 mg INV BID and 800 mg INV BID in combination with 400 mg lopinavir/100 mg ritonavir plus 150 mg lamivudine/300 mg zidovudine BID.

Inclusion Criteria:

• Subject is naïve to antiretroviral treatment (subjects may not have more than 7 days of any antiretroviral treatment).
• Subject is at least 18 years of age, inclusive.
• If female, subject is either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy), or is of childbearing potential and practicing one of the following methods of birth control:condoms, sponge, foams, jellies, diaphragm or intrauterine device(IUD), a vasectomized partner, total abstinence from sexual intercourse
• If female, the results of a urine pregnancy test performed at screening (urine specimen obtained no earlier than 28 days prior to study drug administration) is negative.
• Subject is not breast-feeding.
• Vital signs, physical examination and laboratory results do not exhibit evidence of acute illness.
• Subject has no significant history of cardiac, renal, neurologic, psychiatric, oncologic, endocrinologic, metabolic or hepatic disease that would in the opinion of the investigator adversely affect his/her participating in this study.
• Subject does not require and agrees not to take any of the following medications for the duration of the study: midazolam, triazolam, terfenadine, astemizole, cisapride, pimozide, propafenone, flecainide, certain ergot derivatives (ergotamine, dihydroergotamine, ergonovine, and methylergonovine), rifampin, lovastatin, simvastatin, and St. John's wort.
• Subject agrees not to take any medication during the study, including over-the-counter medicine, alcohol or recreational drugs without the knowledge and permission of the principal investigator.
• Subject has not been treated for an active AIDS-defining opportunistic infection within 30 days of screening.
• Subject has a plasma HIV RNA level of greater than 400 copies/mL at screening.
• Subject agrees to take all doses of the study drug from the bottles provided by the sponsor (rather than other containers, i.e., "pill box").
• Subject has voluntarily signed and dated an informed consent form, approved by an Institutional Review Board (IRB)/Independent Ethics Committee (IEC), after the nature of the study has been explained and the subject has had the opportunity to ask questions. The informed consent must be signed before any study-specific procedures are performed.

Exclusion Criteria:

• Subject has a history of an allergic reaction or significant sensitivity to LPV/r, INV or Combivir.

• Subject has a history of substance abuse or psychiatric illness that could preclude adherence with the protocol.

• Screening laboratory analyses show any of the following abnormal laboratory results:

  • Hemoglobin ≤ 10.0 g/dL
  • Absolute neutrophil count ≤ 1000 cells/µL
  • Platelet count ≤ 50,000 per mL
  • ALT or AST ≥ 3.0 x Upper Limit of Normal (ULN)
  • Creatinine ≥ 1.5 x Upper Limit of Normal (ULN)

• Subject has received any investigational drug within 30 days prior to study drug administration.

• For any reason, subject is considered by the investigator to be an unsuitable candidate for the study.