Kaletra and Viread in Antiretroviral Naïve Patients

• Sponsor: Oklahoma State University Center for Health Sciences (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00679926
• Collaborator: Abbott (Industry)
• Enrollment: 6
• Location: 1
• Arm: 1
• Duration (Months): 36
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Drug: Once daily	Phase 4

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase IV Open Label Investigation of the Efficacy and Durability of Once Daily Antiretroviral Therapy With Kaletra and Viread in Antiretroviral Naïve Patients.
• Study Start Date: May 1, 2008
• Actual Primary Completion Date: May 1, 2011
• Actual Study Completion Date: May 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Once daily Patients taking 4 (four) lopinavir/ritonavir (200mg/50mg tablets) and 1 (one) tenofovir (300mg tablet) every 24 (twenty four) hours.	Drug: Once daily; Four tablets of lopinavir/ritonavir and one tablet of tenofovir given once daily; Other Names: Kaletra Viread

Outcome Measures

Primary Outcome Measures

1. 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. [4, 8, 12, 16, 24, 32, 40, and 48 weeks]

   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.

Secondary Outcome Measures

1. Proportion of Patients With <400copies/ml [4,8, and 12 weeks]

   Proportion of patients with <400copies/ml will be done by determining plasma HIV-1 RNA levels

2. Review Virologic Response to Assess Rate of Viral Decline. [weeks 4, 8, 12, 16, and 24]

   Review virologic response to assess rate of viral decline through CD4 count at baseline and throughout the study.

3. Proportion of Patients With <50 Copies/ml HIV-1 RNA [at weeks 4, 8, 12, 16, 24, 32, 40, and 48]

   Proportion of patients with <50 copies/ml HIV-1 RNA through evaluation of patients Plasma HIV-1 RNA levels

4. Change From Baseline CD4 Counts [at weeks 4, 8, 12, 16, 24, 32, 40, and 48]

   CD4 count done at baseline and throughout the study.

5. Time to Virologic Failure. [Week 48]

   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

6. Tolerability and Adverse Events. [48 weeks]

   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.

7. Change From Baseline Fasting Total Cholesterol and Fasting Triglyceride Levels. [48 weeks]

   Change from baseline fasting total cholesterol and fasting triglyceride levels will be measured by fasting lipid panels taken at baseline and at various timepoints.

8. Characterize Adherence Rates for This Therapeutic Regimen by the Use of Medication Electronic Monitoring Systems (MEMS) Caps. [48 weeks]

   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.

9. Characterize Adherence Rates for This Therapeutic Regimen by Use of Pharmacy Refill Records. [48 weeks]

   Characterize adherence rates for this therapeutic regimen by use of pharmacy refill records is assessed by an examination of pharmacy refill data for patients.

10. Assess Genotypic Changes in Patients With Virologic Failure. [48 weeks]

    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.

11. Assess Lopinavir Trough Levels in Patients Failing to Obtain Virologic Suppression. [48 weeks]

    Assess lopinavir trough levels in patients failing to obtain virologic suppression by measuring lopinavir trough level

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Male or female patients >18 years of age with documented HIV-1 infection

2. Naïve to antiretroviral therapy

3. Able and willing to provide written informed consent

4. No CD4 restriction

5. HIV-1 RNA levels >5000 c/mL

6. Female patients must meet these additional criteria

7. Non-childbearing potential

8. Negative serum pregnancy test at screen

9. Willingness to abstain from sexual intercourse or use double barrier contraception

Exclusion Criteria:

1. Presence of any of the following:

2. Aminotransferases >3xULN

3. Hemoglobin concentration <8.0g/dl

4. Absolute neutrophil count <800 cells/cubic mm

5. Platelet count <50,000 cells/cubic mm

6. Acute illness, or an acute illness ≤7 days

7. Presence of Opportunistic Infection, or an OI within 30 days of screening

8. Acute or chronic active Hepatitis B

9. Hepatitis C

10. Creatinine Clearance <50 mL/min

11. Pregnant or breast-feeding women

12. Presence of any illness, physical or behavioral conditions (i.e., substance abuse, excluding cannabis) that will impair the patient's ability participate

13. Patient who, in the opinion of the investigator, will be unlikely to complete the study protocol and adhere to the study drug regimens

14. 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.

15. Patient suffers from a serious medical condition that may in the opinion of the investigator compromise his or her safety.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	OSU Internal Medicine Specialty Clinic	Tulsa	Oklahoma	United States	74127

Sponsors and Collaborators

• Oklahoma State University Center for Health Sciences
• Abbott

Investigators

• Principal Investigator: Damon Baker, D.O., Oklahoma State University Center for Health Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Johnny Stephens, Associate Professor, Oklahoma State University Center for Health Sciences
• ClinicalTrials.gov Identifier: NCT00679926
• Other Study ID Numbers: Baker - 001
• First Posted: May 19, 2008
• Last Update Posted: Dec 4, 2020
• Last Verified: Dec 1, 2020

• Keywords provided by Johnny Stephens, Associate Professor, Oklahoma State University Center for Health Sciences: HIV; AIDS; HIV/AIDS; Treatment Naive
• Additional relevant MeSH terms: HIV Infections

Study Results

Participant Flow

Recruitment Details	Recruitment was July 2009 to January 2011 and was completed at the Internal Medicine Specialty Clinic at OSU-CHS.
Pre-assignment Detail	There are no significant events prior to enrollment. Patients had to be naive to HIV therapy prior to treatment drug.

Arm/Group Title	Single Treatment Arm
Arm/Group Description	Patients taking lopinavir/ritonavir and tenofovir once daily. Lopinavir/ritonavir and tenofovir : Four tablets of lopinavir/ritonavir and one tablet of tenofovir given once daily
Period Title: Overall Study
STARTED	15
COMPLETED	2
NOT COMPLETED	13

Baseline Characteristics

Arm/Group Title	Single Treatment Arm
Arm/Group Description	Patients taking lopinavir/ritonavir and tenofovir once daily. Lopinavir/ritonavir and tenofovir : Four tablets of lopinavir/ritonavir and one tablet of tenofovir given once daily
Overall Participants	15
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	15 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	36 (12)
Sex: Female, Male (Count of Participants)
Female	2 13.3%
Male	13 86.7%
Region of Enrollment (participants) [Number]
United States	15 100%

Outcome Measures

1. Primary Outcome

Title	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.
Description	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.
Time Frame	4, 8, 12, 16, 24, 32, 40, and 48 weeks

Outcome Measure Data

Analysis Population Description

The study was terminated due to lack of enrollment and data were not collected from 13 out of 15 participants.

Arm/Group Title	Single Treatment Arm
Arm/Group Description	Patients taking lopinavir/ritonavir and tenofovir once daily. Lopinavir/ritonavir and tenofovir : Four tablets of lopinavir/ritonavir and one tablet of tenofovir given once daily
Measure Participants	0

2. Secondary Outcome

Title	Proportion of Patients With <400copies/ml
Description	Proportion of patients with <400copies/ml will be done by determining plasma HIV-1 RNA levels
Time Frame	4,8, and 12 weeks

Outcome Measure Data

Analysis Population Description

The study was terminated due to lack of enrollment and data were not collected from 13 out of 15 participants.

Arm/Group Title	Once Daily
Arm/Group Description	Patients taking 4 (four) lopinavir/ritonavir (200mg/50mg tablets) and 1 (one) tenofovir (300mg tablet) every 24 (twenty four) hours. Once daily: Four tablets of lopinavir/ritonavir and one tablet of tenofovir given once daily
Measure Participants	0

3. Secondary Outcome

Title	Review Virologic Response to Assess Rate of Viral Decline.
Description	Review virologic response to assess rate of viral decline through CD4 count at baseline and throughout the study.
Time Frame	weeks 4, 8, 12, 16, and 24

Outcome Measure Data

Analysis Population Description

The study was terminated due to lack of enrollment and data were not collected from 13 out of 15 participants.

Arm/Group Title	Single Treatment Arm
Arm/Group Description	Patients taking lopinavir/ritonavir and tenofovir once daily. Lopinavir/ritonavir and tenofovir : Four tablets of lopinavir/ritonavir and one tablet of tenofovir given once daily
Measure Participants	0

4. Secondary Outcome

Title	Proportion of Patients With <50 Copies/ml HIV-1 RNA
Description	Proportion of patients with <50 copies/ml HIV-1 RNA through evaluation of patients Plasma HIV-1 RNA levels
Time Frame	at weeks 4, 8, 12, 16, 24, 32, 40, and 48

Outcome Measure Data

Analysis Population Description

The study was terminated due to lack of enrollment and data were not collected from 13 out of 15 participants.

Arm/Group Title	Single Treatment Arm
Arm/Group Description	Patients taking lopinavir/ritonavir and tenofovir once daily. Lopinavir/ritonavir and tenofovir : Four tablets of lopinavir/ritonavir and one tablet of tenofovir given once daily
Measure Participants	0

5. Secondary Outcome

Title	Change From Baseline CD4 Counts
Description	CD4 count done at baseline and throughout the study.
Time Frame	at weeks 4, 8, 12, 16, 24, 32, 40, and 48

Outcome Measure Data

Analysis Population Description

The study was terminated due to lack of enrollment and data were not collected from 13 out of 15 participants.

Arm/Group Title	Single Treatment Arm
Arm/Group Description	Patients taking lopinavir/ritonavir and tenofovir once daily. Lopinavir/ritonavir and tenofovir : Four tablets of lopinavir/ritonavir and one tablet of tenofovir given once daily
Measure Participants	0

6. Secondary Outcome

Title	Time to Virologic Failure.
Description	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
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

The study was terminated due to lack of enrollment and data were not collected from 13 out of 15 participants.

Arm/Group Title	Single Treatment Arm
Arm/Group Description	Patients taking lopinavir/ritonavir and tenofovir once daily. Lopinavir/ritonavir and tenofovir : Four tablets of lopinavir/ritonavir and one tablet of tenofovir given once daily
Measure Participants	0

7. Secondary Outcome

Title	Tolerability and Adverse Events.
Description	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.
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

The study was terminated due to lack of enrollment and data were not collected from 13 out of 15 participants.

Arm/Group Title	Single Treatment Arm
Arm/Group Description	Patients taking lopinavir/ritonavir and tenofovir once daily. Lopinavir/ritonavir and tenofovir : Four tablets of lopinavir/ritonavir and one tablet of tenofovir given once daily
Measure Participants	0

8. Secondary Outcome

Title	Change From Baseline Fasting Total Cholesterol and Fasting Triglyceride Levels.
Description	Change from baseline fasting total cholesterol and fasting triglyceride levels will be measured by fasting lipid panels taken at baseline and at various timepoints.
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

The study was terminated due to lack of enrollment and data were not collected from 13 out of 15 participants.

Arm/Group Title	Once Daily
Arm/Group Description	Patients taking 4 (four) lopinavir/ritonavir (200mg/50mg tablets) and 1 (one) tenofovir (300mg tablet) every 24 (twenty four) hours. Once daily: Four tablets of lopinavir/ritonavir and one tablet of tenofovir given once daily
Measure Participants	0

9. Secondary Outcome

Title	Characterize Adherence Rates for This Therapeutic Regimen by the Use of Medication Electronic Monitoring Systems (MEMS) Caps.
Description	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.
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

The study was terminated due to lack of enrollment and data were not collected from 13 out of 15 participants.

Arm/Group Title	Single Treatment Arm
Arm/Group Description	Patients taking lopinavir/ritonavir and tenofovir once daily. Lopinavir/ritonavir and tenofovir : Four tablets of lopinavir/ritonavir and one tablet of tenofovir given once daily
Measure Participants	0

10. Secondary Outcome

Title	Characterize Adherence Rates for This Therapeutic Regimen by Use of Pharmacy Refill Records.
Description	Characterize adherence rates for this therapeutic regimen by use of pharmacy refill records is assessed by an examination of pharmacy refill data for patients.
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

The study was terminated due to lack of enrollment and data were not collected from 13 out of 15 participants.

Arm/Group Title	Once Daily
Arm/Group Description	Patients taking 4 (four) lopinavir/ritonavir (200mg/50mg tablets) and 1 (one) tenofovir (300mg tablet) every 24 (twenty four) hours. Once daily: Four tablets of lopinavir/ritonavir and one tablet of tenofovir given once daily
Measure Participants	0

11. Secondary Outcome

Title	Assess Genotypic Changes in Patients With Virologic Failure.
Description	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.
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

The study was terminated due to lack of enrollment and data were not collected from 13 out of 15 participants.

Arm/Group Title	Once Daily
Arm/Group Description	Patients taking 4 (four) lopinavir/ritonavir (200mg/50mg tablets) and 1 (one) tenofovir (300mg tablet) every 24 (twenty four) hours. Once daily: Four tablets of lopinavir/ritonavir and one tablet of tenofovir given once daily
Measure Participants	0

12. Secondary Outcome

Title	Assess Lopinavir Trough Levels in Patients Failing to Obtain Virologic Suppression.
Description	Assess lopinavir trough levels in patients failing to obtain virologic suppression by measuring lopinavir trough level
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

The study was terminated due to lack of enrollment and data were not collected from 13 out of 15 participants.

Arm/Group Title	Once Daily
Arm/Group Description	Patients taking 4 (four) lopinavir/ritonavir (200mg/50mg tablets) and 1 (one) tenofovir (300mg tablet) every 24 (twenty four) hours. Once daily: Four tablets of lopinavir/ritonavir and one tablet of tenofovir given once daily
Measure Participants	0

Adverse Events

Arm/Group Title	Single Treatment Arm
Arm/Group Description	Patients taking lopinavir/ritonavir and tenofovir once daily. Lopinavir/ritonavir and tenofovir : Four tablets of lopinavir/ritonavir and one tablet of tenofovir given once daily
All Cause Mortality
	Single Treatment Arm
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Single Treatment Arm
	Affected / at Risk (%)	# Events
Total	0/15 (0%)
Other (Not Including Serious) Adverse Events
	Single Treatment Arm
	Affected / at Risk (%)	# Events
Total	0/15 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.