BLADE: Comparison of Once Daily Lopinavir/Ritonavir to Lopinavir/Ritonavir BID Dosing in HIV-Infected Subjects

Inclusion Criteria:

- Documentation HIV infection

- Male or Female

- 18 years of age

- Previously failed an NNRTI and/or 1 previous PI containing regimen

- Currently virologically controlled (VL<50 copies/mL) on a LPV/r containing regimen ≥
3 months

- Any CD4+ cell count

- Cognitive ability to understand and provide written informed consent and willingness
to participate in and comply with the study protocol

- Patient does not currently have or has not been treated for an active opportunistic
infection (OI) consistent with CDC definition (Appendix B) within 30 days of
screening

- Vital signs, physical examination and laboratory results do not exhibit evidence of
acute illness

- A female is eligible to enter and participate in this study if she is of:

- Non-childbearing potential (i.e., physiologically incapable of becoming
pregnant, including any female who is post-menopausal) or

- Child-bearing potential, has a negative serum pregnancy test at screen, and
agrees to one of the following:

- Complete abstinence from intercourse from 2 weeks prior to administration
of the study drug, throughout the study, and for at least 2 weeks after
completion or premature discontinuation of the study to account for
elimination of the investigational drug. Should a patient decide to become
sexually active during the course of the study, she must be counseled and
be willing to use one of the birth control methods below:

- Double barrier method (male condom/spermicide, male condom/diaphragm,
diaphragm/spermicide)

- Any intrauterine device(IUD) with published data showing that the expected
failure rate is <1% per year (not all IUD's meet this criterion)

- Sterilization (female patient or male partner of female patient)

- Any other methods with published data showing that the lowest expected
failure rate for that method is <1% per year NOTE: Data are insufficient to
exclude a clinically important interaction of LPV/r with drugs, such as
hormonal contraceptives, that are highly metabolized by the cytochrome P450
enzyme system. As a result, hormonal contraception is not considered
adequate.

Exclusion Criteria:

- Pregnancy or breastfeeding

- Hemodialysis or peritoneal dialysis

- Patients unable to provide written informed consent

- Use of concurrent medications known to affect lopinavir and/or ritonavir
concentrations (as listed in the attached Kaletra package insert)

- Patient with active AIDS-defining opportunistic infection or disease according to the
1993 CDC AIDS surveillance definition (Clinical Category C) that, in the opinion of
the investigator, would prelude the patient from participating in the study (See
Appendix B)

- History of active substance abuse, excluding cannabis, or psychiatric illness that,
in the opinion of the investigator, would preclude compliance with the protocol,
dosing schedule and assessments.

- Patient is either pregnant at the time of screening evaluation or breast-feeding

- Patient, in the opinion of the investigator, is unlikely to be able to complete the
48-week dosing period and protocol evaluations and assessments or adhere to the study
drug regimen

- Patient suffers from a serious medical condition, such as diabetes, congestive heart
failure, cardiomyopathy or other cardiac dysfunction, which in the opinion of the
investigator would compromise the safety of the patient

- Patient has malabsorption syndrome or other gastrointestinal dysfunction, which may
interfere with drug absorption or render the patient unable to take oral medication

- HBV coinfection

- Patient has any of the following laboratory results within 30 days prior to the first
dose of study medication:

- Hemoglobin concentration <8.0g/dl

- Absolute neutrophil count <750cells/mm3

- Platelet count <50,000cells/mm3

- Aminotransferase (AST, ALT) >3 times ULN

- Serum creatinine >1.5 times the Upper Limits of Normal (ULN)

- Patient has required treatment with radiation therapy or cytotoxic chemotherapeutic
agents within 4 weeks prior to entry, or has an anticipated need for these agents
within the study period

- Patient requires treatment with immunomodulating agents, such as systemic
corticosteroids, interleukins, or interferon's within 4 weeks prior to study entry,
or patients who have received an HIV immunotherapeutic vaccine within 3 months prior
to entry. Asthmatic patients using inhaled corticosteroids are eligible for
enrollment.

- Patient receiving methadone therapy

- Patients requiring foscarnet therapy or therapy with other agents with documented
activity against HIV-1 invitro

- Patient prescribed/taking astemizole, terfenadine, cisapride, midazolam, triazolam,
flecainide, pimozide, propafenone, St. John's Wort, lovastatin, simvastatin, and
rifampin or ergot derivatives (see section 5.5 Concomitant Medications and Non-Drug
Therapies and Appendix C

- Patient has a history of allergy to any of the study drugs or any excipients therein.

- In addition, patients non-compliant with study medication during 2-4 week study
periods despite adherence counseling will not be retained in the study due to
increased risk for selective pressure and potential development of protease
resistance.

- Patient requires inhaled or intranasal fluticasone