HIV-1-infection
Conditions
Brief summary
A Retrospective Study to Evaluate the Safety and Efficacy of a Nucleoside-Sparing Regimen of Darunavir, Ritonavir, and Dolutegravir
Interventions
DRUGDarunavir 800 MG, Norvir 100 MG, Dolutegravir 50 MG
Sponsors
Janssen Scientific Affairs, LLC
Southern Illinois Healthcare Foundation
Study design
Observational model
CASE_CONTROL
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Change in Mean CD4+ Cell Count From Baseline. | 48 weeks | A secondary endpoint included changes from baseline in CD4+ cell counts. |
| Analysis of Creatinine Clearance at Time Points 24, 36 and 48 Weeks. | 48 weeks | — |
| 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. |
| Incidence of Adverse Events. | 48 weeks | 10 study subjects reported an adverse event. |
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Retrospective Chart Review |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| HIV RNA (copies/mL) | 22.63 copies/mL |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 20 |
| other Total, other adverse events | 10 / 20 |
| serious Total, serious adverse events | 0 / 20 |
Outcome results
Primary
Number of Participants With RNA <50 Copies/mL at 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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Retrospective Chart Review | Number of Participants With RNA <50 Copies/mL at 48 Weeks | 19 Participants |
p-value: <0.05McNemar
Primary
The Change in Serum Creatinine From Baseline to 48 Weeks.
A second primary endpoint was evaluating the change in serum creatinine from baseline to 48 weeks for all subjects.
Time frame: 48 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Retrospective Chart Review | The Change in Serum Creatinine From Baseline to 48 Weeks. | 73.4 mg/dL |
p-value: <0.05Wilcoxon (Mann-Whitney)
Secondary
Analysis of Creatinine Clearance at Time Points 24, 36 and 48 Weeks.
Time frame: 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).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Retrospective Chart Review | Analysis of Creatinine Clearance at Time Points 24, 36 and 48 Weeks. | 75.8 mg/dL |
| Week 36 | Analysis of Creatinine Clearance at Time Points 24, 36 and 48 Weeks. | 69.1 mg/dL |
| Week 48 | Analysis of Creatinine Clearance at Time Points 24, 36 and 48 Weeks. | 77.7 mg/dL |
Secondary
Change in Mean CD4+ Cell Count From Baseline.
A secondary endpoint included changes from baseline in CD4+ cell counts.
Time frame: 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).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Retrospective Chart Review | Change in Mean CD4+ Cell Count From Baseline. | 454 cells/μL | Standard Deviation 301 |
| Week 36 | Change in Mean CD4+ Cell Count From Baseline. | 428 cells/μL | Standard Deviation 254 |
| Week 48 | Change in Mean CD4+ Cell Count From Baseline. | 456 cells/μL | Standard Deviation 291 |
Secondary
Incidence of Adverse Events.
10 study subjects reported an adverse event.
Time frame: 48 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Retrospective Chart Review | Incidence of Adverse Events. | Insomnia | 6 Participants |
| Retrospective Chart Review | Incidence of Adverse Events. | Diarrhea | 4 Participants |
| Retrospective Chart Review | Incidence of Adverse Events. | Headache | 3 Participants |
Secondary
Number of Grade 1 Adverse Events Reported
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
Population: 20 patients were evaluted for adverse events.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Retrospective Chart Review | Number of Grade 1 Adverse Events Reported | Insomnia | 6 Adverse Events |
| Retrospective Chart Review | Number of Grade 1 Adverse Events Reported | Diarrhea | 4 Adverse Events |
| Retrospective Chart Review | Number of Grade 1 Adverse Events Reported | Headache | 3 Adverse Events |
Secondary
Number of Participants With RNA <50 Copies/mL at 24, 36, and 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.
Time frame: 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).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Retrospective Chart Review | Number of Participants With RNA <50 Copies/mL at 24, 36, and 48 Weeks | 19 Participants |
| Week 36 | Number of Participants With RNA <50 Copies/mL at 24, 36, and 48 Weeks | 14 Participants |
| Week 48 | Number of Participants With RNA <50 Copies/mL at 24, 36, and 48 Weeks | 19 Participants |