Study of Lopinavir, Ritonavir, Tenofovir and Emtricitabine in HIV-Infected Antiretroviral Naïve Subjects

A Randomized, Open-Label Study of 800 Mg Lopinavir/200 Mg Ritonavir QD in Combination With Tenofovir and Emtricitabine Vs. 400 Mg Lopinavir /100 Mg Ritonavir BID in Combination With Tenofovir and Emtricitabine in HIV-Infected Antiretroviral Naïve Subjects

The purpose of this study is to compare the safety, tolerability and antiviral activity between once-daily (QD) and twice-daily (BID) dosing of lopinavir/ritonavir and to further characterize the pharmacokinetics of once-daily dosing of lopinavir/ritonavir.

Inclusion Criteria:

• Subject is at least 18 years of age.
• If female, subject is 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) *contraceptives (oral or parenteral) for three months prior to study drug administration) *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) and a urine pregnancy test performed on Study Day -1 are both negative and the subject agrees to use a barrier method of contraception throughout the study.
• 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 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, herbal medications, alcohol or recreational drugs without the knowledge and permission of the principal investigator.
• Subject has a Karnofsky Score greater than or equal to 70
• Subject has not been treated for an active AIDS-defining opportunistic infection within 30 days of screening. Subjects who are on stable maintenance therapy for an opportunistic infection may be enrolled after consultation with Abbott.
• Subject is naive to antiretroviral treatment (< 7 days ARV treatment).
• Subject has a plasma HIV RNA level of greater than 1,000 copies/mL at screening.
• Subject agrees to take all doses of the lopinavir/ritonavir from the bottles provided by the sponsor (rather than take doses from a personal "dosette" 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 lopinavir/ritonavir, tenofovir or emtricitabine or to drugs similar to study drug.
• Subject has a recent (within the past 6 months) history of drug and/or alcohol abuse.
• Subject has a positive result on the screening tests for drugs of abuse.
• 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 ≤ 8.0 g/dL *Absolute neutrophil count ≤ 750 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.