Trial Outcomes & Findings for Comparison of Virologic and Immunologic Responses to Raltegravir and Dolutegravir in the Gastrointestinal Tract of HIV-Positive Adults (NCT NCT02218320)

NCT ID: NCT02218320

Last Updated: 2018-12-26

Results Overview

• Recruitment status: COMPLETED
• Target enrollment: 20 participants
• Primary outcome timeframe: 2 to 6 hours post dose
• Results posted on: 2018-12-26

Participant Flow

Recruitment began upon IRB approval. Patients were enrolled from December 2014 to October 2015, at which time data analysis ensued. Enrollment continued until 20 subjects completed all study procedures. Patients were recruited from the Infectious Disease clinics associated with the University of North Carolina at Chapel Hill.

After informed consent, all patients underwent a screening visit to determine eligibility. This visit had to occur within the 6 weeks prior to study enrollment. Patients were enrolled into the group that matched their treatment regimen.

Participant milestones

Measure	Group A Ten HIV-infected adults will be in Group A and take the HIV medication raltegravir in combination with tenofovir and emtricitabine as their provider-prescribed antiretroviral regimen. Raltegravir Colonoscopy with biopsy: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples.	Group B Ten HIV-infected adults will be in Group B and take the HIV medication dolutegravir in combination with tenofovir and emtricitabine as their provider-prescribed antiretroviral regimen. Dolutegravir Colonoscopy with biopsy: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples.
Overall Study STARTED	10	10
Overall Study COMPLETED	10	10
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Comparison of Virologic and Immunologic Responses to Raltegravir and Dolutegravir in the Gastrointestinal Tract of HIV-Positive Adults

Baseline characteristics by cohort

Measure	Group A n=10 Participants Ten HIV-infected adults will be in Group A and take the HIV medication raltegravir in combination with tenofovir and emtricitabine as their provider-prescribed antiretroviral regimen. Raltegravir Colonoscopy with biopsy: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples. All 10 subjects underwent a bowel prep with subsequent colonoscopy to obtain tissue samples.	Group B n=10 Participants Ten HIV-infected adults will be in Group B and take the HIV medication dolutegravir in combination with tenofovir and emtricitabine as their provider-prescribed antiretroviral regimen. Dolutegravir Colonoscopy with biopsy: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples. All 10 subjects underwent a bowel prep with subsequent colonoscopy to obtain tissue samples.	Total n=20 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	10 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	54.5 years n=5 Participants	49.5 years n=7 Participants	52.5 years n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	9 Participants n=7 Participants	15 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	10 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants

PRIMARY outcome

Timeframe: 2 to 6 hours post dose

Outcome measures

Measure	Group A n=10 Participants Ten HIV-infected adults will be in Group A and take the HIV medication raltegravir in combination with tenofovir and emtricitabine as their provider-prescribed antiretroviral regimen. Raltegravir Colonoscopy with biopsy: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples.	Group B n=10 Participants Ten HIV-infected adults will be in Group B and take the HIV medication dolutegravir in combination with tenofovir and emtricitabine as their provider-prescribed antiretroviral regimen. Dolutegravir Colonoscopy with biopsy: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples.
Rectal Tissue Concentrations of Ralegravir and Dolutegravir	5308 ng/g Interval 3938.0 to 19600.0	810 ng/g Interval 510.0 to 1408.0

PRIMARY outcome

Timeframe: 2 to 6 hours post dose

We measured RNA concentrations in copies/1000cells for both drug groups

Outcome measures

Measure	Group A n=10 Participants Ten HIV-infected adults will be in Group A and take the HIV medication raltegravir in combination with tenofovir and emtricitabine as their provider-prescribed antiretroviral regimen. Raltegravir Colonoscopy with biopsy: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples.	Group B n=10 Participants Ten HIV-infected adults will be in Group B and take the HIV medication dolutegravir in combination with tenofovir and emtricitabine as their provider-prescribed antiretroviral regimen. Dolutegravir Colonoscopy with biopsy: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples.
RNA Concentrations From Gastrointestinal Tissues	0.05 copies/1000cells Interval 0.03 to 0.34	0.16 copies/1000cells Interval 0.01 to 36.19

PRIMARY outcome

Timeframe: 2 to 6 hours post dose

Local immunologic markers in gastrointestinal tract tissues

Outcome measures

Measure	Group A n=10 Participants Ten HIV-infected adults will be in Group A and take the HIV medication raltegravir in combination with tenofovir and emtricitabine as their provider-prescribed antiretroviral regimen. Raltegravir Colonoscopy with biopsy: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples.	Group B n=10 Participants Ten HIV-infected adults will be in Group B and take the HIV medication dolutegravir in combination with tenofovir and emtricitabine as their provider-prescribed antiretroviral regimen. Dolutegravir Colonoscopy with biopsy: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples.
Percentage of Total CD8+ T-cells With CCR5 Expression	0.15 percentage of total cells Interval 0.07 to 0.52	0.64 percentage of total cells Interval 0.24 to 1.6

Adverse Events

Group A

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Group B

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Group A n=10 participants at risk Ten HIV-infected adults will be in Group A and take the HIV medication raltegravir in combination with tenofovir and emtricitabine as their provider-prescribed antiretroviral regimen. Raltegravir Colonoscopy with biopsy: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples. All participants underwent a bowel prep with subsequent colonoscopy to obtain tissue samples.	Group B n=10 participants at risk Ten HIV-infected adults will be in Group B and take the HIV medication dolutegravir in combination with tenofovir and emtricitabine as their provider-prescribed antiretroviral regimen. Dolutegravir Colonoscopy with biopsy: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples.All participants underwent a bowel prep with subsequent colonoscopy to obtain tissue samples.
Blood and lymphatic system disorders Thombophlebitis	0.00% 0/10 • Adverse events were collected from the time of informed consent at the screening visit (up to 42 days prior to enrollment) through study completion (Up to 14 days after last sampling). Adverse events were assessed at all visits with a standardized IRB-approved questionnaire.	10.0% 1/10 • Number of events 1 • Adverse events were collected from the time of informed consent at the screening visit (up to 42 days prior to enrollment) through study completion (Up to 14 days after last sampling). Adverse events were assessed at all visits with a standardized IRB-approved questionnaire.
Respiratory, thoracic and mediastinal disorders Hypertension	0.00% 0/10 • Adverse events were collected from the time of informed consent at the screening visit (up to 42 days prior to enrollment) through study completion (Up to 14 days after last sampling). Adverse events were assessed at all visits with a standardized IRB-approved questionnaire.	10.0% 1/10 • Number of events 1 • Adverse events were collected from the time of informed consent at the screening visit (up to 42 days prior to enrollment) through study completion (Up to 14 days after last sampling). Adverse events were assessed at all visits with a standardized IRB-approved questionnaire.
Gastrointestinal disorders Anal Irritation	10.0% 1/10 • Number of events 1 • Adverse events were collected from the time of informed consent at the screening visit (up to 42 days prior to enrollment) through study completion (Up to 14 days after last sampling). Adverse events were assessed at all visits with a standardized IRB-approved questionnaire.	0.00% 0/10 • Adverse events were collected from the time of informed consent at the screening visit (up to 42 days prior to enrollment) through study completion (Up to 14 days after last sampling). Adverse events were assessed at all visits with a standardized IRB-approved questionnaire.
Gastrointestinal disorders Abdominal gas cramps	10.0% 1/10 • Number of events 1 • Adverse events were collected from the time of informed consent at the screening visit (up to 42 days prior to enrollment) through study completion (Up to 14 days after last sampling). Adverse events were assessed at all visits with a standardized IRB-approved questionnaire.	10.0% 1/10 • Number of events 1 • Adverse events were collected from the time of informed consent at the screening visit (up to 42 days prior to enrollment) through study completion (Up to 14 days after last sampling). Adverse events were assessed at all visits with a standardized IRB-approved questionnaire.
Gastrointestinal disorders Diarrhea	10.0% 1/10 • Number of events 1 • Adverse events were collected from the time of informed consent at the screening visit (up to 42 days prior to enrollment) through study completion (Up to 14 days after last sampling). Adverse events were assessed at all visits with a standardized IRB-approved questionnaire.	0.00% 0/10 • Adverse events were collected from the time of informed consent at the screening visit (up to 42 days prior to enrollment) through study completion (Up to 14 days after last sampling). Adverse events were assessed at all visits with a standardized IRB-approved questionnaire.

Additional Information

Dr. Angela Kashuba

University of North Carolina at Chapel Hill

Phone: 919 966-9998

Email: akashuba@unc.edu

Results disclosure agreements

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