Trial Outcomes & Findings for A Retrospective Study to Evaluate the Safety and Efficacy of a Nucleoside-Sparing Regimen of Darunavir, Ritonavir, and Dolutegravir (NCT NCT03198884)

NCT ID: NCT03198884

Last Updated: 2020-09-01

Results Overview

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.

• Recruitment status: COMPLETED
• Target enrollment: 20 participants
• Primary outcome timeframe: 48 weeks
• Results posted on: 2020-09-01

Participant Flow

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.

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.

Participant milestones

Measure	Retrospective Chart Review 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 Study STARTED	20
Overall Study COMPLETED	20
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Retrospective Chart Review n=20 Participants 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.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	20 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	20 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	15 Participants n=5 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	20 participants n=5 Participants
HIV RNA (copies/mL)	22.63 copies/mL n=5 Participants

PRIMARY outcome

Timeframe: 48 weeks

Population: 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.

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.

Outcome measures

Measure	Retrospective Chart Review n=19 Participants 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.	Week 36 Data shows mean change in CD4+ cell count (cells/μL) from baseline to week 36.	Week 48 Data shows mean change in CD4+ cell count (cells/μL) from baseline to week 48.
Number of Participants With RNA <50 Copies/mL at 48 Weeks	19 Participants	—	—

PRIMARY outcome

Timeframe: 48 weeks

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

Outcome measures

Measure	Retrospective Chart Review n=20 Participants 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.	Week 36 Data shows mean change in CD4+ cell count (cells/μL) from baseline to week 36.	Week 48 Data shows mean change in CD4+ cell count (cells/μL) from baseline to week 48.
The Change in Serum Creatinine From Baseline to 48 Weeks.	73.4 mg/dL Interval 69.1 to 77.7	—	—

SECONDARY outcome

Timeframe: 48 weeks

Population: 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).

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

Outcome measures

Measure	Retrospective Chart Review n=20 Participants 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.	Week 36 n=14 Participants Data shows mean change in CD4+ cell count (cells/μL) from baseline to week 36.	Week 48 n=20 Participants Data shows mean change in CD4+ cell count (cells/μL) from baseline to week 48.
Change in Mean CD4+ Cell Count From Baseline.	454 cells/μL Standard Deviation 301	428 cells/μL Standard Deviation 254	456 cells/μL Standard Deviation 291

SECONDARY outcome

Timeframe: 48 weeks

10 study subjects reported an adverse event.

Outcome measures

Measure	Retrospective Chart Review n=20 Participants 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.	Week 36 Data shows mean change in CD4+ cell count (cells/μL) from baseline to week 36.	Week 48 Data shows mean change in CD4+ cell count (cells/μL) from baseline to week 48.
Incidence of Adverse Events. Insomnia	6 Participants	—	—
Incidence of Adverse Events. Diarrhea	4 Participants	—	—
Incidence of Adverse Events. Headache	3 Participants	—	—

SECONDARY outcome

Timeframe: 48 weeks

Population: 20 patients were evaluted for adverse events.

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.

Outcome measures

Measure	Retrospective Chart Review n=20 Participants 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.	Week 36 Data shows mean change in CD4+ cell count (cells/μL) from baseline to week 36.	Week 48 Data shows mean change in CD4+ cell count (cells/μL) from baseline to week 48.
Number of Grade 1 Adverse Events Reported Insomnia	6 Adverse Events	—	—
Number of Grade 1 Adverse Events Reported Diarrhea	4 Adverse Events	—	—
Number of Grade 1 Adverse Events Reported Headache	3 Adverse Events	—	—

SECONDARY outcome

Timeframe: 48 weeks

Population: 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).

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.

Outcome measures

Measure	Retrospective Chart Review n=19 Participants 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.	Week 36 n=14 Participants Data shows mean change in CD4+ cell count (cells/μL) from baseline to week 36.	Week 48 n=19 Participants Data shows mean change in CD4+ cell count (cells/μL) from baseline to week 48.
Number of Participants With RNA <50 Copies/mL at 24, 36, and 48 Weeks	19 Participants	14 Participants	19 Participants

SECONDARY outcome

Timeframe: 48 weeks

Population: 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).

Outcome measures

Measure	Retrospective Chart Review n=19 Participants 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.	Week 36 n=14 Participants Data shows mean change in CD4+ cell count (cells/μL) from baseline to week 36.	Week 48 n=19 Participants Data shows mean change in CD4+ cell count (cells/μL) from baseline to week 48.
Analysis of Creatinine Clearance at Time Points 24, 36 and 48 Weeks.	75.8 mg/dL Interval 56.4 to 95.4	69.1 mg/dL Interval 47.4 to 90.7	77.7 mg/dL Interval 57.0 to 98.5

Adverse Events

Retrospective Chart Review

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Retrospective Chart Review n=20 participants at risk 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.
Nervous system disorders insomnia	30.0% 6/20 • Number of events 6 • Adverse event data was collected for a total of 3 months.
Gastrointestinal disorders Diarrhea	20.0% 4/20 • Number of events 4 • Adverse event data was collected for a total of 3 months.
Nervous system disorders Headache	15.0% 3/20 • Number of events 3 • Adverse event data was collected for a total of 3 months.

Additional Information

John Verna

SIHF Healthcare

Phone: 618-337-8153

Email: jverna@sihf.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place