Impact of a Short-Term Analytical Treatment Interruption and Re-Initiation of Antiretroviral Therapy on Immunologic and Virologic Parameters in HIV-Infected Individuals

NCT03225118 | Completed

• 2 other identifiers: 17010617-I-0106
• Study Type: observational
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

Background: The immune system helps the body fight off disease. Most people infected with HIV cannot control the infection and need daily medicine. Combination antiretroviral therapy (cART) are drugs taken to prevent HIV infection from damaging the immune system. Researchers want to study why some people develop resistance to the drugs or have permanent side effects. Objective: To study the impact of a short-term treatment stop on HIV that persists even while taking cART. Eligibility: Adults 18-65 years old with HIV who are being treated with cART Design:

• Participants will first be screened with a physical exam and medical history. They may have a chest x-ray. They will have heart, blood, and urine tests.
• At the baseline visit, participants will repeat the screening tests except the x-ray. They will get counseling about HIV and risk behavior.
• Participants will have leukapheresis. Blood will be removed through a needle in one arm. A machine will separate white blood cells from the rest of the blood. The remainder of the blood will be returned to the body by a different needle.
• Participants will stop their current treatment on day 0. They will visit the clinic each week until they meet the criteria to restart cART. These visits will have the same procedures as the baseline visit.
• Before restarting cART, most participants will have leukapheresis.
• After restart, participants will be seen weekly for 4 weeks and then monthly for about 11 months. Participants will have blood drawn, physical exam, and medical history. They will have leukapheresis 2 more times over 1 year.

Conditions

HIV

Keywords

Rebound; Reinitiation; ART; Reservoirs; Immune Exhaustion

Outcome Measures

Primary Outcomes (1)

• The time to plasma viral rebound in HIV-infected individuals undergoing analytical treatment interruption.

  The outcome will be satisfied when each subject meets restart criteria.

Secondary Outcomes (1)

• The difference in frequency of HIV infected CD4+ and CD8+ T cells and the respective expression of immune exhaustion markers prior to and following ATI and after re-initiation of ART.

  The time points to evaluate the outcome differences will be at baseline, during treatment interruption and after cART is restarted.

Study Arms (1)

HIV/ATI

HIV-infected Adults (age 18-65 years) on ART with suppressed viremia willing to interrupt treatment and then restart once criteria is met.

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

HIV patients which will be recruited from natural history and training protocols currently enrolling in clinic and the community

You may qualify if:

• Age, 18-65 years
• Documented HIV-1 infection and clinically stable
• In general good health, with an identified primary health care provider for medical management of HIV infection and willing to maintain a relationship with a primary health care provider for medical management of HIV infection while participating in the study
• CD4+ T cell count greater than 450 cells/mm\^3 at screening
• Documentation of continuous ART treatment with suppression of plasma viral level below the limit of detection for greater than or equal to 2 years. Subjects with blips (i.e., detectable viral levels on ART) prior to creening may be included provided they satisfy the following criteria:
• The blips are less than 400 copies/mL, and
• Succeeding viral levels return to levels below the limit of detection on subsequent testing
• Willingness to undergo ATI
• Willingness to restart ART once restart criteria are met
• Laboratory values within pre-defined limits at screening:
• Absolute neutrophil count greater than 1,000/mm\^3
• Hemoglobin (Hgb) levels greater than 10.0 g/dL for men and greater than 9.0 g/dL for women
• Platelet count greater than 150,000/mm\^3
• Estimated glomerular filtration rate (eGFR) greater than or equal to 60 mL/min as determined by the NIH Clinical Center (CC) laboratory
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels of less than 2.5 x upper limit normal (ULN)

You may not qualify if:

• Chronic hepatitis B, as evidenced by a positive test for hepatitis B surface antigen (HBsAg), an isolated positive Hepatitis B core antibody (negative HBsAg and anti-HBV Ab) and/or positive Hepatitis B virus (HBV) DNA.
• Chronic hepatitis C virus (HCV) infection as evidenced by a positive test for HCV RNA. Subjects with a positive test for HCV antibody and a negative test for HCV RNA are eligible.
• Has a history of institution of ART within 12 weeks of being diagnosed with acute or early HIV-1, where acute/early infection is defined by any one of the following:
• Positive HIV-1 enzyme immunoassay (EIA) with negative/indeterminate HIV-1 western blot that subsequently becomes positive
• Negative HIV-1 EIA within the past 4 months and HIV-1 RNA levels of greater than 400,000 copies/mL, in the setting of a potential exposure to HIV-1.
• Negative rapid HIV-1 within one month prior to a positive HIV-1 EIA and HIV-1 western blot
• Low level HIV antibodies (positive EIA or western blot) with a non-reactive detuned EIA
• Documented nadir CD4+ T cell count less than 200 cells /mm\^3
• Patients with a nadir CD4+ T cell count between 100-200 are not excluded, provided their current CD4+ T cell count has been \>450 the past 3 years
• Subjects with dips (i.e., transient decreases in their CD4 count) prior to screening may be included provided they satisfy the following criteria:
• a. The dips are \> 350 cells/mL, and
• b. Succeeding CD4 counts return to levels above 450 cells/mL on subsequent testing
• Any history of AIDS defining opportunistic infections
• Subjects with history of receiving ART consisting of mono or dual drug therapy
• Documented multiclass antiretroviral drug resistance that, in the judgement of the investigator, would pose a risk of virologic failure should additional mutations develop during the study

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Davey RT Jr, Bhat N, Yoder C, Chun TW, Metcalf JA, Dewar R, Natarajan V, Lempicki RA, Adelsberger JW, Miller KD, Kovacs JA, Polis MA, Walker RE, Falloon J, Masur H, Gee D, Baseler M, Dimitrov DS, Fauci AS, Lane HC. HIV-1 and T cell dynamics after interruption of highly active antiretroviral therapy (HAART) in patients with a history of sustained viral suppression. Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):15109-14. doi: 10.1073/pnas.96.26.15109.

  PMID: 10611346 BACKGROUND

• Bar KJ, Sneller MC, Harrison LJ, Justement JS, Overton ET, Petrone ME, Salantes DB, Seamon CA, Scheinfeld B, Kwan RW, Learn GH, Proschan MA, Kreider EF, Blazkova J, Bardsley M, Refsland EW, Messer M, Clarridge KE, Tustin NB, Madden PJ, Oden K, O'Dell SJ, Jarocki B, Shiakolas AR, Tressler RL, Doria-Rose NA, Bailer RT, Ledgerwood JE, Capparelli EV, Lynch RM, Graham BS, Moir S, Koup RA, Mascola JR, Hoxie JA, Fauci AS, Tebas P, Chun TW. Effect of HIV Antibody VRC01 on Viral Rebound after Treatment Interruption. N Engl J Med. 2016 Nov 24;375(21):2037-2050. doi: 10.1056/NEJMoa1608243. Epub 2016 Nov 9.

  PMID: 27959728 BACKGROUND

• Strategies for Management of Antiretroviral Therapy (SMART) Study Group; El-Sadr WM, Lundgren J, Neaton JD, Gordin F, Abrams D, Arduino RC, Babiker A, Burman W, Clumeck N, Cohen CJ, Cohn D, Cooper D, Darbyshire J, Emery S, Fatkenheuer G, Gazzard B, Grund B, Hoy J, Klingman K, Losso M, Markowitz N, Neuhaus J, Phillips A, Rappoport C. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med. 2006 Nov 30;355(22):2283-96. doi: 10.1056/NEJMoa062360.

  PMID: 17135583 BACKGROUND

• Sneller MC, Huiting ED, Clarridge KE, Seamon C, Blazkova J, Justement JS, Shi V, Whitehead EJ, Schneck RF, Proschan M, Moir S, Fauci AS, Chun TW. Kinetics of Plasma HIV Rebound in the Era of Modern Antiretroviral Therapy. J Infect Dis. 2020 Oct 13;222(10):1655-1659. doi: 10.1093/infdis/jiaa270.

  PMID: 32443148 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

Study Officials

• Michael C Sneller, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2017
• First Posted: July 21, 2017
• Study Start: July 17, 2017
• Primary Completion: January 16, 2020
• Study Completion: January 16, 2020
• Last Updated: January 18, 2020

Record last verified: 2020-01

Locations

US (1)