NCT lookup
Pull any trial record directly from ClinicalTrials.gov.
Sponsor: University of Washington
Conditions: HIV-1-infection, HIV Disease Progression, Inflammation, HIV
Interventions: Venipuncture, Targeted physical medical exam, Urine pregnancy test, Anoscopy, Esophagogastroduodenoscopy (EGD)
Countries: United States
The goal of the project is to determine the difference in immune activation and HIV reservoir size between People living with HIV (PWH) on tenofovir-containing antiretroviral therapy (ART) versus PWH on nucleoside reverse transcriptase inhibitor (NRTI)-sparing ART. Tenofovir (TFV), a phosphonated nucleoside reverse transcriptase inhibitor (NRTI), is being used for oral pre-exposure prophylaxis (PrEP). The investigators will test this hypothesis: tenofovir, and perhaps NRTIs in general, stimulate a type I/III interferon also in PWH who take these drugs. Because chronic interferon stimulation may promote the survival and proliferation of cells with integrated provirus, the investigators also hypothesize that these drugs antagonize decay of the HIV latent reservoir in PWH on ART. Consequently, the researchers hypothesize that PWH who have switched from NRTI-containing ART to NRTI-sparing ART exhibit lower type I/III interferon pathway activation and lower latent HIV reservoir size. The investigators also hypothesize that independently of treatment, the extent of type I/III interferon activation correlates with latent HIV reservoir size. Thus, the proposed study seeks to answer these two questions. Can the gastrointestinal epithelium be impacted by ART, and contribute to chronic immune activation and expansion of the HIV-1 reservoir? If so, what therapeutic approaches can the investigators implement to reduce the HIV-1 proviral load? The data will reveal pathways that can be targeted therapeutically to treat chronic immune activation in PWH. The findings of this study will immediately translate to optimize the standard of care in PWH.
Sex: ALL
Age: 18 Years to 65 Years
Healthy volunteers: No
Study type: OBSERVATIONAL
Inclusion Criteria:
1. Confirmed HIV infection, by two different positive antibody tests and/or detectable plasma HIV RNA on two different dates
2. ≥18 and ≤65 years of age
3. Stable use of ART medication for ≥ 1 year
4. No switch of ART regimen within the past 180 days
5. CD4 \> 350/mm3 within the past 180 days
6. HIV RNA \<40 copies / mL on ≥ 2 occasions during continuous ART of ≥ 1 years, with no blip of \>1000 HIV RNA copies / mL
7. Karnofsky score ≥80
8. Willingness and ability to provide informed consent for study participation
9. Willingness to undergo all required study procedures
Exclusion Criteria:
1. Active malignancy including myelodysplastic syndrome, or myeloproliferative disease within 24 weeks prior to study entry
2. Prior organ or bone marrow transplantation
3. Diagnosed autoimmune disease
4. Medical need for ongoing treatment with an immunosuppressive drug
5. Diagnosis of AIDS (defined as any AIDS-defining opportunistic infection or cancer, or a history of blood CD4+ T cell count \< 200/μL)
6. Active opportunistic infection
7. Vomiting or diarrhea which prohibits consistent use of ART
8. Pregnant or breastfeeding
9. Excessive ingestion of ethanol determined by an AUDIT score of \>8
10. Substance abuse
11. History of medical non-compliance
12. The following laboratory values (\< 30 days before enrollment):
* Hemoglobin \< 8.5 mg/dL
* Platelet count \< 100,000/μL
* Coagulation (PT/PTT) tests above the normal reference
* Creatinine clearance \< 60 mL/min
13. Using disallowed medications:
* Systemic corticosteroids
* Other immunosuppressive medications (e.g., cyclosporine, sirolimus, tacrolimus, pimecrolimus, tofacitinib)
14. BMI \> 40
15. Pulmonary dysfunction.
16. Use of narcotics.- Seattle, Washington, United States