Pilot Study of Effect of Kaletra on CD4 Response in HIV Positive (+) Patients With Viral Suppression KIMBO Study
Pilot Study of Effect of Kaletra on CD4 Response in HIV Positive (+) Patients With Viral Suppression KIMBO Study
To explore the hypothesis that the use of Lopinavir/ritonavir will be associated with
 improved CD4 immune reconstitution in volunteers who fail to demonstrate a significant CD4
 cell increase (while on their first antiretroviral treatment regimen) despite sustained viral
 suppression by a non-Lopinavir/ritonavir-containing regimen
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.