Pilot Study on the Effect of Adding Raltegravir +/- a Second Drug on HIV Levels in the Gut (PLUS)
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ClinicalTrials.gov Identifier: NCT00884793 |
Recruitment Status
:
Completed
First Posted
: April 21, 2009
Results First Posted
: July 23, 2012
Last Update Posted
: July 23, 2012
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
HIV Infections | Drug: raltegravir Drug: Study NNRTI Drug: Study PI | Not Applicable |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 8 participants |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Official Title: | A Prospective Longitudinal Pilot Study to Measure the Effect of Intensification With Raltegravir +/- a Protease Inhibitor (PI) or Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) on HIV-1 Levels in the Gut |
Study Start Date : | September 2008 |
Actual Primary Completion Date : | December 2009 |
Actual Study Completion Date : | December 2010 |

Arm | Intervention/treatment |
---|---|
Experimental: intensification with raltegravir +/- NNRTI or PI
Intensification with raltegravir 400mg PO BID +/- a study PI or NNRTI
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Drug: raltegravir
The baseline ART regimen will be intensified with raltegravir 400mg orally (PO) twice daily (BID) (all participants) +/- a study NNRTI or protease inhibitor (PI) (at the option of the participant and the study clinical team).
Other Name: Isentress
Drug: Study NNRTI
Subjects who are not already on an NNRTI and who are suitable candidates will have the option of adding a study NNRTI (either efavirenz or etravirine).
Other Names:
Drug: Study PI
Subjects who are not on a PI and who are suitable candidates will have the option of adding a study PI. PIs used as study drugs will include atazanavir (+/- ritonavir), fosamprenavir (+/-ritonavir), lopinavir/ritonavir, and darunavir/ritonavir.
Other Names:
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- Number of Subjects Who Had a Decrease in HIV RNA Per Million CD4+ T Cells in the Ileum [ Time Frame: 12 weeks ]Number of subjects who had a decrease from week 0 to week 12 in unspliced cell-associated HIV RNA per million CD4+ T cells in the ileum
- Number of Subjects Who Experienced an Increase in CD4+ T Cells (as a % of All Cells) in the Ileum. [ Time Frame: 12 weeks ]Number of subjects who experienced an increase in CD4+ T cells (as a % of all cells) in the ileum (by flow cytometry) from week 0 to week 12.
- Number of Subjects Who Experienced an Increase in CD4% in the Ileum. [ Time Frame: 12 weeks ]Number of subjects who experienced an increase from week 0 to week 12 in CD4+ T cells (as a % of T cells, by flow cytometry) in the ileum
- Average Change in "Activated" (CD38+HLADR+) CD8+ T Cells in the Ileum [ Time Frame: 12 weeks ]Average of changes(week 0-week 12) in the % of CD8+ T cells that are CD38+HLA-DR+, by flow cytometry

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Ages Eligible for Study: | 18 Years to 65 Years (Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Age 18 to 65 years
- Infection with HIV-1, as documented by a licensed ELISA and confirmed by a Western blot or HIV-1 RNA at any time prior to study entry
- On ART for at least 12 months prior to study entry with a regimen that includes at least two NRTIs and either an NNRTI or PI
- No change in ART for at least 3 months prior to study entry.
- CD4+ T cell count of 200 or greater within 30 days prior to study entry.
- HIV-1 RNA level consistently below the limit of detection of commercial ultrasensitive assays (<50 copies/mL) for at least 6 months before study entry.
- Women of reproductive potential (those who have not undergone surgical sterilization via hysterectomy, bilateral oophorectomy, or tubal ligation and who have had menses in the preceding 24 months) must have a negative urine or serum pregnancy test within 48 hours prior to study entry.
- All subjects must agree not to participate in the process of conception (such as active attempts to impregnate or become pregnant, sperm or egg donation, in vitro fertilization) while receiving study drugs and for 6 weeks after stopping study drugs. If participating in sexual activity that could lead to pregnancy, the subject and/or partner should use at least two reliable methods of contraception, including oral contraceptive pills, an intrauterine device (IUD), condoms, and a diaphragm or cervical cap with spermicide.
- Ability and willingness to provide informed consent.
Exclusion Criteria:
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Any condition that, in the opinion of the GI specialist, would either be a contraindication to endoscopy or would increase the risk from sedation, endoscopy, or mucosal biopsies. These conditions may include, but are not limited to:
- Significant complication (such as perforation) from prior endoscopy
- Known bleeding diathesis
- Platelet count < 100,000 per microliter
- INR > 1.6
- Current use of antiplatelet agents (aspirin, other NSAIDS, clopidogrel (Plavix), other antiplatelet agents) or anticoagulants (heparin, low molecular weight heparin, warfarin, lepirudin, or other anticoagulants) and inability to temporarily hold such medications for endoscopy.
- Active angina, unstable angina, or MI within 2 months prior to study entry
- Decompensated CHF
- Respiratory insufficiency with FEV1 < 1L, resting hemoglobin saturation of <92%, or need for oxygen supplementation
- OSA requiring CPAP
- Ongoing substance abuse
- Peripheral glucose > 350 mg/dL
- Prior use of raltegravir
- Any condition that, in the opinion of the infectious disease (ID) specialist, would be a contraindication to raltegravir. These conditions may include, but are not limited to: unstable clinical condition (such as recent hospitalization, cancer with need for chemotherapy or radiation); severe hepatic insufficiency; need for contraindicated medicines; breastfeeding; or high risk for myopathy or rhabdomyolysis.
- Calculated creatinine clearance (CrCl) < 50 mL/min, as estimated by the Cockcroft-Gault equation
- AST (SGOT), ALT (SGPT), alkaline phosphatase, or bilirubin > 3x the upper limit of normal (ULN).
- LDL > 200 mg/dL or TG > 400 mg/dL in fasting lipids, as measured within three months prior to screening or at the time of screening
- Plan to change the background ART within 16 weeks after study entry
- Receipt of any HIV vaccine
- Receipt of a non-HIV vaccine within 30 days prior to study entry
- An opportunistic infection within 60 days prior to study entry
- Use of significant immunosuppressive medications (such as systemic corticosteroids, tacrolimus, sirolimus, mycophenolate, azathioprine, interferon, and cancer chemotherapy) within 60 days prior to study entry.
- Active drug or alcohol abuse that, in the opinion of the investigator, would interfere with adherence to the requirements of the study

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00884793
United States, California | |
San Francisco General Hospital | |
San Francisco, California, United States, 94110 | |
San Francisco VA Medical Center (SFVAMC) | |
San Francisco, California, United States, 94121 |
Principal Investigator: | Diane Havlir, MD | San Francisco General Hospital (SFGH) and University of California San Francisco (UCSF) | |
Principal Investigator: | Joseph K Wong, MD | San Francisco VA Medical Center (SFVAMC) and University of California, San Francisco (UCSF) | |
Principal Investigator: | Steven Yukl, MD | SFVMAC and UCSF |
Publications of Results:
Responsible Party: | University of California, San Francisco |
ClinicalTrials.gov Identifier: | NCT00884793 History of Changes |
Other Study ID Numbers: |
PLUS1 |
First Posted: | April 21, 2009 Key Record Dates |
Results First Posted: | July 23, 2012 |
Last Update Posted: | July 23, 2012 |
Last Verified: | June 2012 |
Keywords provided by University of California, San Francisco:
HIV persistence reservoirs residual replication |
gut gut-associated lymphoid tissue treatment experienced |
Additional relevant MeSH terms:
HIV Infections Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Ritonavir Lopinavir Atazanavir Sulfate HIV Protease Inhibitors Fosamprenavir Raltegravir Potassium |
Efavirenz Etravirine Protease Inhibitors Reverse Transcriptase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors HIV Integrase Inhibitors Integrase Inhibitors Nucleic Acid Synthesis Inhibitors |