Kaletra and Viread in Antiretroviral Naïve Patients

Study Overview
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Brief Summary
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Once daily antiretroviral therapy with Viread (tenofovir DF, 300mg) plus Kaletra (LPV/r, 800mg/200mg) will be effective in suppressing and maintaining suppression of HIV RNA to <50 copies/ml in antiretroviral naïve patients through 48 weeks of therapy.

Detailed Description
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This study is a phase IV prospective, open-label, controlled treatment protocol consisting of once daily Kaletra dosed at 800mg lopinavir with 200mg ritonavir in four combination tablets plus Viread dosed as 300 mg tenofovir DF. This will be a single site, multi-investigator, study for 48 weeks. Consecutive eligible patients will be enrolled into the study to reach the enrollment goal of 30 patients. Eligible patients will be identified and screened during routine initial or follow-up visits at the Internal Medicine Specialty Services Clinic. This clinic serves as the HIV/AIDS specialty care clinic and is a subdivision of the Department of Internal Medicine, Oklahoma State University Center for Health Sciences College of Osteopathic Medicine. The study site currently serves >700 persons living with HIV in northeast Oklahoma with four to five antiretroviral naïve patients seen each week. Patients meeting all inclusion criteria will receive routine standard of care for our program as prescribed by the DHHS guidelines. Patients will have a Complete Blood Count (CBC), Complete Metabolic Profile (CMP), fasting lipid profile, CD4 count, HIV-1 RNA level, and other prescribed or indicated laboratory preformed at baseline and throughout the study as described in the Visits and Evaluations section of this protocol. All of the aforementioned laboratory tests will be performed at the Diagnostic Laboratories of Oklahoma, a division of Quest Diagnostics. Any antiretroviral resistance testing will be performed at Virologic Labs, Inc. Adherence will be assessed at discontinuation of the study and when indicated for evaluation of virologic failure by Memory Electronic Monitoring Systems caps and pharmacy refill data. Patients will be monitored at each study visit for tolerability and adverse events. Patients who develop a study related Grade 1 or 2 Adverse Events (Aes) may continue the study. Those who develop Grade 3 or 4 AEs will have study medications discontinued. Patients with asymptomatic elevations of triglyceride or Low Density Lipoprotein (LDL) cholesterol levels may be treated with appropriate lipid lowering therapy at the investigators discretion.

Official Title
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A Phase IV Open Label Investigation of the Efficacy and Durability of Once Daily Antiretroviral Therapy With Kaletra and Viread in Antiretroviral Naïve Patients.

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Once daily


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients >18 years of age with documented HIV-1 infection Naïve to antiretroviral therapy Able and willing to provide written informed consent No CD4 restriction HIV-1 RNA levels >5000 c/mL Female patients must meet these additional criteria Non-childbearing potential Negative serum pregnancy test at screen Willingness to abstain from sexual intercourse or use double barrier contraception Exclusion Criteria: Presence of any of the following: Aminotransferases >3xULN Hemoglobin concentration <8.0g/dl Absolute neutrophil count <800 cells/cubic mm Platelet count <50,000 cells/cubic mm Acute illness, or an acute illness ≤7 days Presence of Opportunistic Infection, or an OI within 30 days of screening Acute or chronic active Hepatitis B Hepatitis C Creatinine Clearance <50 mL/min Pregnant or breast-feeding women Presence of any illness, physical or behavioral conditions (i.e., substance abuse, excluding cannabis) that will impair the patient's ability participate Patient who, in the opinion of the investigator, will be unlikely to complete the study protocol and adhere to the study drug regimens Concurrent use of medications that may potentially interact with study medications including: astemizole, terfenadine, rifampin, dihydroergotamine, ergonovine, ergotamine, methylergonovine, cisapride, St. John's wort, lovastatin, simvastatin, pimozide, midazolam, triazolam, adefovir, cidofovir, acyclovir, ganciclovir, and valganciclovir. Patient suffers from a serious medical condition that may in the opinion of the investigator compromise his or her safety.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Once daily<br>Patients taking 4 (four) lopinavir/ritonavir (200mg/50mg tablets) and 1 (one) tenofovir (300mg tablet) every 24 (twenty four) hours. | Drug: Once daily<br>* Four tablets of lopinavir/ritonavir and one tablet of tenofovir given once daily<br>* Other names: Viread;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Assess the Efficacy of Once Daily Antiretroviral Therapy With Viread 300mg and Kaletra 800mg/200mg in Suppressing HIV RNA Levels to <50 Copies/ml in Antiretroviral naïve Patients. | To assess the efficacy of once daily antiretroviral therapy with Viread 300mg and Kaletra 800mg/200mg in suppressing HIV RNA levels to <50 copies/ml in antiretroviral naïve patients. This will be done by the proportion of patients with plasma HIV-1 RNA levels M 50 copies/ml at the end of 48 weeks of therapy. | 4, 8, 12, 16, 24, 32, 40, and 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients With <400copies/ml | Proportion of patients with <400copies/ml will be done by determining plasma HIV-1 RNA levels | 4,8, and 12 weeks | 
| Review Virologic Response to Assess Rate of Viral Decline. | Review virologic response to assess rate of viral decline through CD4 count at baseline and throughout the study. | weeks 4, 8, 12, 16, and 24 | 
| Proportion of Patients With <50 Copies/ml HIV-1 RNA | Proportion of patients with <50 copies/ml HIV-1 RNA through evaluation of patients Plasma HIV-1 RNA levels | at weeks 4, 8, 12, 16, 24, 32, 40, and 48 | 
| Change From Baseline CD4 Counts | CD4 count done at baseline and throughout the study. | at weeks 4, 8, 12, 16, 24, 32, 40, and 48 | 
| Time to Virologic Failure. | Virologic failure is defined by any of the following: 1) <1 log10 decline in HIV RNA by week 8 of therapy; 2) failure to achieve <50 c/mL by week 24; 3) HIV RNA> 500 c/ML on two consecutive occasions (less than 30 days apart), with no evidence of suppression after adherence counseling. When HIV RNA levels are obtained >500 copies/mL it will be repeated within 2 weeks. If after adherence counseling, HIV RNA demonstrates > 1 log 10 decline but remains >500, the patient will receive a final adherence counseling session and have his/her HIV RNA measure repeated at day 30: if a third consecutive HIV RNA remains 500 c/mL the patient will be removed from study, if <500c/mL the patient will remain on study | Week 48 | 
| Tolerability and Adverse Events. | Adverse events and safety parameters are monitored for ll subjects for the duration of the study. Toxicities and adverse events will be graded using the modified ACTG toxicity ratings scale. Study drugs may be interrupted for safety reasons and/or based on grade of toxicity/adverse event. | 48 weeks | 
| Change From Baseline Fasting Total Cholesterol and Fasting Triglyceride Levels. | Change from baseline fasting total cholesterol and fasting triglyceride levels will be measured by fasting lipid panels taken at baseline and at various timepoints. | 48 weeks | 
| Characterize Adherence Rates for This Therapeutic Regimen by the Use of Medication Electronic Monitoring Systems (MEMS) Caps. | The medication event monitoring system (MEMS) is a cap that fits on standard medicine bottles and records the time and date each time the bottle is opened and closed. | 48 weeks | 
| Characterize Adherence Rates for This Therapeutic Regimen by Use of Pharmacy Refill Records. | Characterize adherence rates for this therapeutic regimen by use of pharmacy refill records is assessed by an examination of pharmacy refill data for patients. | 48 weeks | 
| Assess Genotypic Changes in Patients With Virologic Failure. | At time of virologic failure genotypes will be performed on baseline and failure isolates; phenotypic testing will be performed on failure isolates to examine LPV susceptibility. | 48 weeks | 
| Assess Lopinavir Trough Levels in Patients Failing to Obtain Virologic Suppression. | Assess lopinavir trough levels in patients failing to obtain virologic suppression by measuring lopinavir trough level | 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, AIDS, HIV/AIDS, Treatment Naive