Pilot Study of Effect of Kaletra on CD4 Response in HIV Positive (+) Patients With Viral Suppression KIMBO Study

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 on CD4
immune reconstitution. All volunteers must have been on antiretroviral therapy with sustained
viral load suppression of < 400 copies/mL for at least 24 months (or, HIV-1 RNA < 400
copies/mL for 12 months, during which HIV-1 RNA was < 50 copies/mL for 6 months prior to
screen). Despite induction of viral suppression, all volunteers must have demonstrated
limited post-antiretroviral CD4 increase.

Lopinavir/ritonavir will be substituted for one of the 3 ARV drugs in the current (baseline)
antiretroviral treatment regimen. Lopinavir/ritonavir will be substituted for any of the
following: 3rd NRTI, an NNRTI, a PI or a boosted PI, while the nucleoside backbone will
remain the same. If the subject is currently on a three-drug nucleoside/nucleotide plus a 4th
anchor drug such as a NRTI, NNRTI, PI or boosted PI regimen, the triple nucleoside will
remain constant and only the anchor drug is to be substituted with Lopinavir/ritonavir.
Patients on 2 NRTIs with an NNRTI and a PI combination will not be allowed in the study.

Patients will be evaluated frequently, 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 assessment of memory and naïve T cell response to antiretroviral regimen change will be
performed in this study.

Dose and dose selection Lopinavir/ritonavir is also approved for once a day dosing. The dose
of lopinavir/ritonavir (Kaletra) for this study will be 400/100mg. BID or 800/200mg. qd. New
tablet formulation no longer requires that lopinavir/ritonavir be taken with food. We will
give the volunteer the option for once a day dosing or BID dosing of Kaletra. However, those
switching from an NNRTI to Kaletra will initially be placed on BID dosing of Kaletra, and
allowed to switch to once-a-day dosing of Kaletra after 4 weeks on study drug.

Inclusion criteria

1. Human Immunodeficiency Virus type-1 (HIV-1)infection, as documented by any licensed
enzyme-linked immunosorbent assay 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.

3. Currently on a stable antiretroviral regimen for at least 6 months prior to
enrollment. This stable regimen must be their first treatment regimen, however, prior
changes could have been made for toxicity or intolerability, or where providers were
using an "induction /maintenance"type of treatment strategy.

4. HIV-1 RNA < 400 copies/ml (or <500 copies/ml for the bDNA test or <40 copies/ml for
the nucleic acid sequence based amplification [NASBA test]) for at least 24 months;
and an HIV-1 RNA < 50 copies/ml at screening; interim, non-consecutive viral load
blips of < 1,000 copies/mL will be allowed

5. Or, HIV-1 RNA < 400 copies/ml (or <500 copies/ml for the bDNA test or <40 copies/ml
for the NASBA test)for minimum of 12 months, during which the HIV-1 RNA was < 50
copies/ml (or <500 copies/ml for the bDNA test or <40 copies/ml for the NASBA test)
for 6 months prior to screening, and < 50 copies/mL at screen

6. At a minimum of twelve months post-initiation of antiretroviral therapy, CD4 count
remains < 200 cells/mm3, or if baseline CD4 count was between 200-300, and there is an
increase of < 50 cells/mm3 over a 12 month period.

7. Laboratory tests within pre-specified limits

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

9. Available for at least 48 weeks of follow up.

10. If female and of child bearing potential must consent to using at least two forms of
contraception

11. Participant must have a Primary Care Provider in order to be enrolled in this study.

Exclusion criteria

1. Pregnant or breast-feeding woman

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 Interleukin 2 (IL2), interferon,Granulocyte Colony-Stimulating
Factor(G-CSF),Granulocyte Macrophage Colony-stimulating Factor (GM-CSF), etc.

10. Use of immune suppressive drugs.

11. Subject is currently taking any of the following drugs: midazolam, triazolam,
terfenadine, astemizole, cisapride, pimozide, propafenone, flecainide, certain ergot
derivatives (ergotamine, dihydroergotamine, ergonovine, and methylergonovine),
rifampin, lovastatin, simvastatin, St. John's Wort, doxorubicin, ribavirin, coumadin.

12. Subject has significant history of cardiac, renal, neurologic, psychiatric, oncologic,
endocrinologic (including diabetes mellitus), metabolic, or hepatic disease that
would, in the opinion of the investigator, adversely affect his/her participation in
this study.

13. Unable or unwillingness to discontinue use of specific medications implicated in drug
interactions while on Lopinavir/ritonavir

14. Known hypersensitivity, allergic reactions, or intolerance to Lopinavir/ritonavir or
to ritonavir in the past

15. Have previously received Lopinavir/ritonavir for more than 3 months in the past

16. Active substance or alcohol abuse, in the opinion of the principal investigator would
interfere with protocol adherence

17. Unwillingness to use effective barrier contraception.

18. Experimental vaccines, to include HIV vaccines.

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

20. Patients on 2 nucleoside reverse transcriptase inhibitors(NRTIs) with an
Non-nucleoside-reverse transcriptase inhibitor(NNRTI) and a protease inhibitor (PI)
combination will not be allowed in the study.