A Retrospective Study to Evaluate the Safety and Efficacy of a Nucleoside-Sparing Regimen of Darunavir, Ritonavir, and Dolutegravir

• Sponsor: Southern Illinois Healthcare Foundation (Other)
• Overall Status: Completed
• CT.gov ID: NCT03198884
• Collaborator: Janssen Scientific Affairs, LLC (Industry)
• Enrollment: 20
• Actual Duration (Months): 15.9

Study Details

Study Description

Brief Summary

A Retrospective Study to Evaluate the Safety and Efficacy of a Nucleoside-Sparing Regimen of Darunavir, Ritonavir, and Dolutegravir

Condition or Disease	Intervention/Treatment	Phase
HIV-1-infection	Drug: Darunavir 800 MG, Norvir 100 MG, Dolutegravir 50 MG

Study Design

• Study Type: Observational
• Actual Enrollment: 20 participants
• Observational Model: Case-Control
• Time Perspective: Retrospective
• Official Title: A Retrospective Study to Evaluate the Safety and Efficacy of a Nucleoside-Sparing Regimen of Darunavir, Ritonavir, and Dolutegravir
• Actual Study Start Date: Jan 1, 2017
• Actual Primary Completion Date: Apr 18, 2018
• Actual Study Completion Date: May 1, 2018

Outcome Measures

Primary Outcome Measures

1. Number of Participants With RNA <50 Copies/mL at 48 Weeks [48 weeks]

   Our first primary endpoint evaluated the percent of study subjects with an RNA <50 copies/mL at 48 weeks after initiation of the once daily two-drug regimen.

2. The Change in Serum Creatinine From Baseline to 48 Weeks. [48 weeks]

   A second primary endpoint was evaluating the change in serum creatinine from baseline to 48 weeks for all subjects.

Secondary Outcome Measures

1. Change in Mean CD4+ Cell Count From Baseline. [48 weeks]

   A secondary endpoint included changes from baseline in CD4+ cell counts.

2. Incidence of Adverse Events. [48 weeks]

   10 study subjects reported an adverse event.

3. Number of Grade 1 Adverse Events Reported [48 weeks]

   10 study subjects reported adverse events. All adverse events reported (insomnia, diarrhea, headache) were of Grade 1 severity. There were no adverse events that led to discontinuation of the study regimen.

4. Number of Participants With RNA <50 Copies/mL at 24, 36, and 48 Weeks [48 weeks]

   This secondary outcome measure analyzed the percentage of subjects with < 50 copies/mL RNA at time points 24, 36 and 48 weeks. The percent of subjects with an RNA < 50 copies/mL at each time point was analyzed using McNemar's test following the guidelines of the Snapshot algorithm. Missing RNA data was considered a treatment failure.

5. Analysis of Creatinine Clearance at Time Points 24, 36 and 48 Weeks. [48 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• ≥18 years old

• Received a regimen of darunavir 800 mg/ritonavir 100 mg in combination with dolutegravir 50 mg QD for ≥24 weeks as documented in EMR

• Laboratory reports (CD4, viral load, SrCr) available at time points +/- 4 6 weeks from 12, 24, 36, 48 weeks from start of regimen

• Resistance data (if applicable)

Exclusion Criteria:

• Received a regimen of darunavir/ritonavir in combination with dolutegravir for <24 weeks duration

• Patients receiving darunavir/ritonavir + DTG+NRTI's

• Missing laboratory data in ≥2 study time points

• Patients missing more than five doses over two weeks prior study visit

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Southern Illinois Healthcare Foundation
• Janssen Scientific Affairs, LLC

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 2, 2019

More Information

Publications

None provided.

• Responsible Party: John Verna, Physician Assistant, Southern Illinois Healthcare Foundation
• ClinicalTrials.gov Identifier: NCT03198884
• Other Study ID Numbers: 16-1108-100C
• First Posted: Jun 26, 2017
• Last Update Posted: Sep 1, 2020
• Last Verified: Aug 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Darunavir; Dolutegravir

Study Results

Participant Flow

Recruitment Details	A retrospective chart review of appoximately 400 HIV+ patients receiving treatment at an urban diverse FQHC was conducted to identify those who were receiving an NRTI-sparing regimen of DRV and DTG.
Pre-assignment Detail	Subjects included were at least 18 years of age, receiving DRV/r + DTG QD for at least 24 weeks and had laboratory data through 48 weeks of follow up. Those excluded were not taking the study regimen, missed more than five doses of medication over two weeks prior to study visit or if there was missing lab data for 2 or more study time points.

Arm/Group Title	Retrospective Chart Review
Arm/Group Description	We conducted a retrospective chart review of approximately 400 HIV+ patients receiving treatment at an urban diverse FQHC to identify those who were receiving a NRTI-sparing regimen of DRV and DTG. Subjects were included if they were ≥ 18 years of age, receiving DRV/r + DTG QD for ≥ 24 weeks, and had laboratory data through 48 weeks of follow up. Subjects were excluded if they received a regimen of DRV/r in combination with DTG for <24 weeks duration, if they received DRV/r + DTG + NRTI's, missed more than five doses over two weeks prior to study visit or if there was missing laboratory data for ≥2 or more study time points. The primary endpoints evaluated were the percent of patients with an RNA <50 copies/mL at 48 weeks after initiation of the regimen, as well as, the change in serum creatinine from baseline to 48 weeks.
Period Title: Overall Study
STARTED	20
COMPLETED	20
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Retrospective Chart Review
Arm/Group Description	We conducted a retrospective chart review of approximately 400 HIV+ patients receiving treatment at an urban diverse FQHC to identify those who were receiving a NRTI-sparing regimen of DRV and DTG. Subjects were included if they were ≥ 18 years of age, receiving DRV/r + DTG QD for ≥ 24 weeks, and had laboratory data through 48 weeks of follow up. Subjects were excluded if they received a regimen of DRV/r in combination with DTG for <24 weeks duration, if they received DRV/r + DTG + NRTI's, missed more than five doses over two weeks prior to study visit or if there was missing laboratory data for ≥2 or more study time points. The primary endpoints evaluated were the percent of patients with an RNA <50 copies/mL at 48 weeks after initiation of the regimen, as well as, the change in serum creatinine from baseline to 48 weeks.
Overall Participants	20
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	20 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	8 40%
Male	12 60%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	20 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	15 75%
White	5 25%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	20 100%
HIV RNA (copies/mL) (copies/mL) [Median (Full Range) ]
Median (Full Range) [copies/mL]	22.63

Outcome Measures

1. Primary Outcome

Title	Number of Participants With RNA <50 Copies/mL at 48 Weeks
Description	Our first primary endpoint evaluated the percent of study subjects with an RNA <50 copies/mL at 48 weeks after initiation of the once daily two-drug regimen.
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

19 patients meeting the inclusion criteria were analyzed for this study. We evaluated the percentage of study subjects with an HIV RNA < 50 copies at 48 weeks after initiation of the once daily two-drug regimen.

Arm/Group Title	Retrospective Chart Review
Arm/Group Description	We conducted a retrospective chart review of approximately 400 HIV+ patients receiving treatment at an urban diverse FQHC to identify those who were receiving a NRTI-sparing regimen of DRV and DTG. Subjects were included if they were ≥ 18 years of age, receiving DRV/r + DTG QD for ≥ 24 weeks, and had laboratory data through 48 weeks of follow up. Subjects were excluded if they received a regimen of DRV/r in combination with DTG for <24 weeks duration, if they received DRV/r + DTG + NRTI's, missed more than five doses over two weeks prior to study visit or if there was missing laboratory data for ≥2 or more study time points. The primary endpoints evaluated were the percent of patients with an RNA <50 copies/mL at 48 weeks after initiation of the regimen, as well as, the change in serum creatinine from baseline to 48 weeks.
Measure Participants	19
Count of Participants [Participants]	19 95%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Retrospective Chart Review
	Comments
	Type of Statistical Test	Other
	Comments	The percent of patients with an RNA <50 copies/mL at each time point was analyzed using McNemar's test following the guidelines of the Snapshot algorithm. Missing RNA data was considered a treatment failure. Change in mean serum creatinine from baseline was analyzed using Wilcoxon signed rank test.
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	McNemar
	Comments
Other Statistical Analysis		Change in mean CD4+ cell counts from baseline was analyzed using a paired t-test. All analyses used a p-value of less than or equal to 0.05 as significant. Statistical analyses were performed using R software, version 3.4.3.

2. Primary Outcome

Title	The Change in Serum Creatinine From Baseline to 48 Weeks.
Description	A second primary endpoint was evaluating the change in serum creatinine from baseline to 48 weeks for all subjects.
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Retrospective Chart Review
Arm/Group Description	We conducted a retrospective chart review of approximately 400 HIV+ patients receiving treatment at an urban diverse FQHC to identify those who were receiving a NRTI-sparing regimen of DRV and DTG. Subjects were included if they were ≥ 18 years of age, receiving DRV/r + DTG QD for ≥ 24 weeks, and had laboratory data through 48 weeks of follow up. Subjects were excluded if they received a regimen of DRV/r in combination with DTG for <24 weeks duration, if they received DRV/r + DTG + NRTI's, missed more than five doses over two weeks prior to study visit or if there was missing laboratory data for ≥2 or more study time points. The primary endpoints evaluated were the percent of patients with an RNA <50 copies/mL at 48 weeks after initiation of the regimen, as well as, the change in serum creatinine from baseline to 48 weeks.
Measure Participants	20
Mean (Full Range) [mg/dL]	73.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Retrospective Chart Review
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Secondary Outcome

Title	Change in Mean CD4+ Cell Count From Baseline.
Description	A secondary endpoint included changes from baseline in CD4+ cell counts.
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

For week 36 data, 6 study subjects did not have reportable data. These missing data included patient no-shows for labs and lab error (ex, lost sample, insufficient blood/serum drawn to run test).

Arm/Group Title	Week 24	Week 36	Week 48
Arm/Group Description	Data shows mean change in CD4+ cell count (cells/μL) from baseline to week 24.	Data shows mean change in CD4+ cell count (cells/μL) from baseline to week 36.	Data shows mean change in CD4+ cell count (cells/μL) from baseline to week 48.
Measure Participants	20	14	20
Mean (Standard Deviation) [cells/μL]	454 (301)	428 (254)	456 (291)

4. Secondary Outcome

Title	Incidence of Adverse Events.
Description	10 study subjects reported an adverse event.
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Retrospective Chart Review
Arm/Group Description	We conducted a retrospective chart review of approximately 400 HIV+ patients receiving treatment at an urban diverse FQHC to identify those who were receiving a NRTI-sparing regimen of DRV and DTG. Subjects were included if they were ≥ 18 years of age, receiving DRV/r + DTG QD for ≥ 24 weeks, and had laboratory data through 48 weeks of follow up. Subjects were excluded if they received a regimen of DRV/r in combination with DTG for <24 weeks duration, if they received DRV/r + DTG + NRTI's, missed more than five doses over two weeks prior to study visit or if there was missing laboratory data for ≥2 or more study time points. The primary endpoints evaluated were the percent of patients with an RNA <50 copies/mL at 48 weeks after initiation of the regimen, as well as, the change in serum creatinine from baseline to 48 weeks.
Measure Participants	20
Insomnia	6 30%
Diarrhea	4 20%
Headache	3 15%

5. Secondary Outcome

Title	Number of Grade 1 Adverse Events Reported
Description	10 study subjects reported adverse events. All adverse events reported (insomnia, diarrhea, headache) were of Grade 1 severity. There were no adverse events that led to discontinuation of the study regimen.
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

20 patients were evaluted for adverse events.

Arm/Group Title	Adverse Events
Arm/Group Description	As per the studay protocol, an adverse event (AE) is an untoward medical occurence in a patient administered a medicinal product.
Measure Participants	20
Insomnia	6
Diarrhea	4
Headache	3

6. Secondary Outcome

Title	Number of Participants With RNA <50 Copies/mL at 24, 36, and 48 Weeks
Description	This secondary outcome measure analyzed the percentage of subjects with < 50 copies/mL RNA at time points 24, 36 and 48 weeks. The percent of subjects with an RNA < 50 copies/mL at each time point was analyzed using McNemar's test following the guidelines of the Snapshot algorithm. Missing RNA data was considered a treatment failure.
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

We analyzed data for all participants as indicated in the data table. There was missing data for one study subject at week 24 of the study and missing data for six study subjects at week 36 (blood draws were not completed by patients). Also, data was missing for one study subject at week 48 (blood draw not completed secondary incarceration).

Arm/Group Title	Analysis of HIV RNA at Week 24	Analysis of HIV RNA at Week 36	Analysis of HIV RNA at Week 48
Arm/Group Description	At week 24, 75% of subjects had an RNA of < 50 copies/mL. The percent of subjects with an RNA < 50 copies/mL at each time point was analyzed using McNemar's test following the guidelines of the Snapshot algorithm. Missing RNA data was considered a treatment failure.	At week 36, 65% of subjects had an RNA of < 50 copies/mL. The percent of subjects with an RNA < 50 copies/mL at each time point was analyzed using McNemar's test following the guidelines of the Snapshot algorithm. Missing RNA data was considered a treatment failure.	At week 48, 95% of subjects had an RNA of < 50 copies/mL. The percent of subjects with an RNA < 50 copies/mL at each time point was analyzed using McNemar's test following the guidelines of the Snapshot algorithm. Missing RNA data was considered a treatment failure.
Measure Participants	19	14	19
Count of Participants [Participants]	19 95%	14 NaN	19 NaN

7. Secondary Outcome

Title	Analysis of Creatinine Clearance at Time Points 24, 36 and 48 Weeks.
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

There was missing data for one study subject at week 24 of the study and missing data for six study subjects at week 36 (blood draws were not completed by patients). In addition, data was missing for one study subject at week 48 (blood draw not completed secondary incarceration).

Arm/Group Title	Analysis of Serum Creatinine at Week 24	Analysis of Serum Creatinine at Week 36	Analyis of Serum Creatinine at Week 48
Arm/Group Description	There were no significant differences in creatinine clearance from baseline to 24 weeks.	There were no significant differences in creatinine clearance from baseline to 36 weeks.	There were no significant differences in creatinine clearance from baseline to 48 weeks.
Measure Participants	19	14	19
Mean (Full Range) [mg/dL]	75.8	69.1	77.7

Adverse Events

Time Frame	Adverse event data was collected for a total of 3 months.
Arm/Group Title	Retrospective Chart Review
Arm/Group Description	We conducted a retrospective chart review of approximately 400 HIV+ patients receiving treatment at an urban diverse FQHC to identify those who were receiving a NRTI-sparing regimen of DRV and DTG. Subjects were included if they were ≥ 18 years of age, receiving DRV/r + DTG QD for ≥ 24 weeks, and had laboratory data through 48 weeks of follow up. Subjects were excluded if they received a regimen of DRV/r in combination with DTG for <24 weeks duration, if they received DRV/r + DTG + NRTI's, missed more than five doses over two weeks prior to study visit or if there was missing laboratory data for ≥2 or more study time points. The primary endpoints evaluated were the percent of patients with an RNA <50 copies/mL at 48 weeks after initiation of the regimen, as well as, the change in serum creatinine from baseline to 48 weeks.
All Cause Mortality
	Retrospective Chart Review
	Affected / at Risk (%)	# Events
Total	0/20 (0%)
Serious Adverse Events
	Retrospective Chart Review
	Affected / at Risk (%)	# Events
Total	0/20 (0%)
Other (Not Including Serious) Adverse Events
	Retrospective Chart Review
	Affected / at Risk (%)	# Events
Total	10/20 (50%)
Gastrointestinal disorders
Diarrhea	4/20 (20%)	4
Nervous system disorders
insomnia	6/20 (30%)	6
Headache	3/20 (15%)	3

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.