Safety Study of Lopinavir/Ritonavir With Raltegravir in HIV-infected Patients

This is an open-labeled, non-randomized exploratory trial in selected volunteers who meet the
stated enrollment criteria. This study will assess the impact of lopinavir/ritonavir in
combination with raltegravir on HIV-1

Patients will be evaluated frequently over the 52 weeks of the protocol. Patients will be
seen at screening, baseline, week 4, 12, 24, 36, 48, and 52, to include physical examination,
assessment for the development of AIDS-defining conditions, hematology, chemistry, lipid
profile, CD4, CD8 cell counts, plasma HIV-1 RNA ultrasensitive, and assessment of adverse
events. If HIV-1 RNA becomes detectable, this will be repeated for confirmation with 2 weeks.
HIV genotyping and phenotyping will be performed on patients who demonstrate repetitive
plasma viral load levels of > 1,000 copies/mL.

An interim analysis will be performed when all patients have reached the week 24 visit.

Inclusion Criteria:

1. HIV-1 infection, as documented by any licensed ELISA test kit, and confirmed by
Western blot, positive HIV-1 blood culture, positive HIV serum antigen, or plasma
viremia at any time prior to study entry. If no record exists, testing must occur at
screening.

2. Males and non-pregnant females > 18 years of age. (Children are being excluded as they
are immunologically different than adults)

3. HIV-1 RNA > 1000 copies/ml for both patient naive and experienced to antiretroviral
therapy in order for phenotypic susceptibility to be performed. There in no inclusion
criteria for CD4 count.

4. Treatment experienced patients , defined as having taken medications from two of the
following three classes of antiretrovirals: NRTI, NNRTI, or PI must have phenotypic
susceptability to lopinavir/ritonavir as resulted by Phenosense GT

5. Laboratory tests ( Cbc w/diff, comprehensive metabolic panel) within pre-specified
limits

6. Able to sign the informed consent, and is willing to comply with the requirements of
this clinical trial.

7. Available for at least 52 weeks of follow up

8. If female and of child bearing potential must consent to remain abstinent throughout
the study period and for 30 days after the last dose of study medications.( this is
standard language)

Exclusion Criteria:

1. Pregnant or breast-feeding woman (pregnant women are being excluded as drug kinetics
are different in pregnancy and the dynamics of immune reconstitution are unknown in
this group)

2. Current treatment for malignancy other than basal or squamous cell carcinoma of the
skin or carcinoma in situ of the cervix or isolated cutaneous Kaposi's Sarcoma that is
not being treated; those with prior cancer diagnosis, such as lymphomas must have been
disease-free for at least 5 years

3. Absolute neutrophil count < 500, platelet count < 50,000, hemoglobin < 8 gm/dL

4. Evidence of end-organ disease, defined as follows: renal (calculated creatinine
clearance of less than 50 mL/min); liver (liver-associated enzymes > 3 times the upper
limits of normal)

5. Grade 3 (ACTG Grading Scale) or higher cholesterol or triglyceride elevations

6. Acute, serious infection requiring prescription drug therapy within 30 days prior to
study entry

7. In the opinion of the investigator, there is evidence of an active ongoing
opportunistic infection

8. Must not currently be undergoing treatment for an opportunistic infection.

9. Use of immune stimulation agents known to impact CD4 cell count in the peripheral
circulation, to include IL2, interferon, G-CSF, GM-CSF, etc.

10. Use of immune suppressant drugs, with the exception of < 10 mg/day of prednisone .

11. Unwillingness to remain abstinent for duration of study

12. Experimental vaccines, to include HIV vaccines.

13. Patient who is currently enrolled in an experimental protocol, or is receiving an
experimental medication.

14. Patients on 2 NRTIs with an NNRTI and a PI combination will not be allowed in the
study.