AIDS, HIV Infections
Conditions
Keywords
HIV Positive, AIDS, Antiretroviral Therapy, Gastrointestinal-Associated Lymphoid Tissue, Immune Reconstitution, treatment experienced
Brief summary
This research is being done to study how the immune system in the small intestine improves after taking antiretroviral (anti-HIV) medications. The main purpose is to measure the increase in the numbers of immune cells in the intestine to see if one type of HIV medication gives different results than other types of HIV medications.
Detailed description
While the world-wide AIDS epidemic continues to impact millions of individuals, effective anti-HIV medications have substantially reduced morbidity and mortality for those patients able to adhere to combination regimens. Despite improved survival, durable virologic suppression, and increases in peripheral CD4+T-cell counts in patients receiving potent antiretroviral therapy (ART), immune reconstitution remains incomplete as measured by a number of additional surrogate markers. Perhaps critically important among areas of apparent incomplete immune recovery is the gastrointestinal-associated lymphoid tissue (GALT), where CD4+T-cells repopulate very slowly, if at all. Raltegravir is a new ART agent from a novel class of HIV inhibitors, integrase inhibitors, that results in rapid suppression of HIV and recovery of peripheral CD4+T-cells. This project proposes to examine whether volunteers receiving raltegravir recover GALT immune cells more completely than those taking comparator ART.
Interventions
DRUGraltegravir
400mg tablet twice daily by mouth for nine months
DRUGefavirenz
600mg capsule once daily by mouth without regard to food
Sponsors
University of California, Davis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* willing to sign consent form * no known GI pathology * no anticipated antiretroviral therapy adjustments or changes * males & females between the ages of 18 & 50 years * no active opportunistic infections (OI) or therapy for OI within 30 days of entry * can be on secondary prophylaxis with a history of AIDS defining illness * per standard of care requirements, all females of child-bearing potential must agree to use barrier methods to prevent pregnancy or be abstinent from activity while on study
Exclusion criteria
* abnormal coagulation parameters (PT \> or equal to 1.2 ULN) * thrombocytopenia (platelet count \< 50,000 within 6 weeks) * contra-indications to upper endoscopy or conscious sedation * anemia (\> or equal to grade 1) * aspirin, ibuprofen, warfarin or other agents that interfere with the coagulation cascade are prohibited within 1 week of endoscopy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| the Percentage of CD3+/CD4+ Cells Per Cubic Millimeter at the Effector Sites in the Duodenal Tissues Obtained From Volunteers to the Antiretroviral Therapy Regimen Over Time. | nine months | Duodenal tissue immune cell subsets were measured by flow cytometry. |
Countries
United States
Participant flow
Recruitment details
Subjects are recruited from the specialty clinic and their friends or family.
Pre-assignment details
no special pre-assignment details
Participants by arm
| Arm | Count |
|---|---|
| Negative Volunteers HIV Negative volunteers | 5 |
| HIV-postive Randomized to Raltegravir HIV-Positive volunteers taking raltegravir in combination with two other nucleoside reverse transcriptase inhibitors (NRTI) medications | 10 |
| HIV-postive Randomized to NNRTI HIV-Positive volunteers taking efavirenz or any other non-nucleoside reverse transcriptase inhibitors (NNRTI) in combination with two other nucleoside reverse transcriptase inhibitor (NRTI) medications | 10 |
| Total | 25 |
Baseline characteristics
| Characteristic | HIV-postive Randomized to Raltegravir | HIV-postive Randomized to NNRTI | Negative Volunteers | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 10 Participants | 5 Participants | 25 Participants |
| Age, Continuous | 37 years STANDARD_DEVIATION 5 | 45 years STANDARD_DEVIATION 5 | 35 years STANDARD_DEVIATION 5 | 38 years STANDARD_DEVIATION 5 |
| Region of Enrollment United States | 10 participants | 10 participants | 5 participants | 25 participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 1 Participants | 8 Participants |
| Sex: Female, Male Male | 6 Participants | 7 Participants | 4 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 5 | 0 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 5 | 0 / 10 | 0 / 10 |
Outcome results
Primary
the Percentage of CD3+/CD4+ Cells Per Cubic Millimeter at the Effector Sites in the Duodenal Tissues Obtained From Volunteers to the Antiretroviral Therapy Regimen Over Time.
Duodenal tissue immune cell subsets were measured by flow cytometry.
Time frame: nine months
Population: all subjects who completed all study visits
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Negative Volunteers | the Percentage of CD3+/CD4+ Cells Per Cubic Millimeter at the Effector Sites in the Duodenal Tissues Obtained From Volunteers to the Antiretroviral Therapy Regimen Over Time. | 55.3 % CD3/CD4 T-cells in GALT tissue |
| HIV-postive Randomized to Raltegravir | the Percentage of CD3+/CD4+ Cells Per Cubic Millimeter at the Effector Sites in the Duodenal Tissues Obtained From Volunteers to the Antiretroviral Therapy Regimen Over Time. | 11.7 % CD3/CD4 T-cells in GALT tissue |
| HIV-postive Randomized to NNRTI | the Percentage of CD3+/CD4+ Cells Per Cubic Millimeter at the Effector Sites in the Duodenal Tissues Obtained From Volunteers to the Antiretroviral Therapy Regimen Over Time. | 9.9 % CD3/CD4 T-cells in GALT tissue |