New Era Study: Treatment With Multi Drug Class (MDC) HAART in HIV Infected Patients

NCT00908544 | Completed Results DMC

• 6 other identifiers: MUC_NewEra_3.32008-002070-35403493208101ID 8879IISP #35576
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 8

Brief Summary

This is a multi-center, open-label, non-randomized proof-of-concept trial. Two cooperating HIV-specialized centres represented by Dr. med. Hans Jaeger and Prof. Dr. Johannes Bogner are planning to perform an IIT (investigator initiated trial) with the goal to eradicate HIV in N=40 HIV-infected patients with either primary infection or chronic infection and successful HAART (Highly Active Antiretroviral Treatment) of several years. All patients will be started on a multi-drug HAART including two Nucleoside-Reverse-Transcriptase-Inhibitors (NRTI´s), one Protease-Inhibitor (PI), a CCR5-inhibitor and an Integrase-Inhibitor (INI). Decay of viral reservoirs like latently HIV-infected CD4+ T-cells will be monitored over time.

Conditions

HIV Infections

Keywords

HIV-infection; Primary HIV-infection; Proviral DNA; Eradication; Multi drug class HAART

Outcome Measures

Primary Outcomes (1)

• Combined Endpoint Including HIV RNA and HIV DNA

  The primary outcome measure (i.e. achievement of 'eradication') is a combined endpoint including cell-associated proviral DNA and plasma HIV RNA and is defined as undetectable cell-associated HIV DNA (copies per 10exp6 PBMC (peripheral blood mononuclear cells) and per 10exp6 CD4 cells) for at least 2 years (measurement by the French ANRS Group) combined with plasma viral load \< 50 copies/ml for at least 5 years and undetectable plasma viral load (HIV RNA \< 1 copy/ml, 1-copy assay) for at least 2 years.

  Screening, month -3 (= pre-baseline only for CHI-patients), baseline, months 1, 3, 6 and then every 6 months until month 84

Secondary Outcomes (17)

• Mean Change in HIV DNA in PBMC (Month 36 and Month 84)

  Change from baseline at months 36 and 84

• Mean Change in HIV DNA in CD4+T Cells (Month 36 and Month 84)

  Change from baseline at months 36 and 84

• HIV RNA <50 Copies/ml (Proportion)

  Baseline and at months 1, 3, 6 and then every 6 months until month 84

• Median Change in HIV DNA in PBMC Over Time

  Change from baseline at months 1, 3, 6 and then every 6 months until month 84

• Median Change in HIV DNA in CD4+T Cells Over Time

  Change from baseline at months 1, 3, 6 and then every 6 months until month 84

Study Arms (2)

PHI-patients

EXPERIMENTAL

Patients with primary HIV infection (PHI) (see also "Eligibility") are immediately treated with 2 NRTI + 1 PI/r + Maraviroc + Raltegravir

Other: PHI-patients

CHI-patients

EXPERIMENTAL

Patients with chronic HIV infection (CHI) and with suppressed plasma viral load for at least three years under continuous HAART (2 NRTI + 1 PI/r see also "Eligibility") intensified by Maraviroc + Raltegravir

Other: CHI-patients

Interventions

PHI-patients OTHER

Treatment initiation with multi drug class (MDC) HAART. 2 NRTI + 1 PI/r + Maraviroc + Raltegravir

PHI-patients

CHI-patients OTHER

Treatment intensification of PI-based HAART with Maraviroc and Raltegravir. 2 NRTI + 1 PI/r + Maraviroc + Raltegravir

CHI-patients

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For all patients:
• HIV-infected patient
• Age greater 18 years
• No acute AIDS-defining disease or history of AIDS- defining disease
• CD4-cell nadir above or equal 200 cells/µL
• Hemoglobin greater 8 g/dl
• Neutrophil count greater 750 cells/µL
• Platelet count greater 50.000 cells/µL
• AST/ALT below 5x upper limit of normal range
• No evidence for drug intolerability
• No prior use of an HIV integrase inhibitor or CCR5 antagonist
• No presence of malignancy (requiring active treatment and malignancy within 5 years prior to enrolment (even if in complete remission)
• No significant underlying disease (non-HIV) that might impinge upon disease progression or death
• No history of alcohol or other substance abuse or other condition which in the opinion of the investigator would interfere with the patient compliance or safety.
• Written informed consent

You may not qualify if:

• Evidence for drug intolerability or contraindication concerning any drug foreseen for MDC HAART
• Documented HIV-1 resistance to PI and/or NRTI.
• CD4 nadir \<200/µL
• Acute AIDS-defining disease or history of AIDS-defining disease
• CHI: preceding virological failure
• History of alcohol or other substance abuse or other condition which in the opinion of the investigator would interfere with the patient compliance or safety.
• Any of the following abnormal laboratory test results in screening:
• Hemoglobin \< 8 g/dL
• Neutrophil count \< 750 cells/µL
• Platelet count \< 50,000 cells/µL
• AST or ALT \> 5x the upper limit of normal
• Presence of malignancy (requiring active treatment and malignancy within 5 years prior to enrolment (even if in complete remission)
• Significant underlying disease (non-HIV) that might impinge upon disease progression or death
• Prior use of any experimental HIV- Integrase-Inhibitor or CCR5-antagonist.
• Patient is pregnant or breastfeeding, or expecting to conceive (within the duration of the study). Patient is expecting to donate eggs (within the duration of the study). Patient is expecting to donate sperm (within the duration of the study).

Sponsors & Collaborators

• MUC Research GmbH: lead
• Merck Sharp & Dohme LLC: collaborator
• AbbVie: collaborator
• Pfizer: collaborator
• German Center for Infection Research: collaborator

Study Sites (8)

Onkology Karlsruhe

Karlsruhe, Baden-Wurttemberg, 76135, Germany

Location

Private Practice for Internal Medicine, Hematology and Oncology

Mannheim, Baden-Wurttemberg, 68161, Germany

Location

Private Practice Drs Ulmer/Frietsch/Mueller

Stuttgart, Baden-Wurttemberg, 70197, Germany

Location

Practice Dr. med. Lothar Schneider

Fürth, Bavaria, 90762, Germany

Location

Private Practice Drs Pauli/Becker

Munich, Bavaria, 80331, Germany

Location

MVZ Karlsplatz

Munich, Bavaria, 80335, Germany

Location

University Munich University Hospital, Dept. of Infectious Diseases

Munich, Bavaria, 80336, Germany

Location

ICH Study Center

Hamburg, 20354, Germany

Location

Related Publications (12)

• Di Mascio M, Dornadula G, Zhang H, Sullivan J, Xu Y, Kulkosky J, Pomerantz RJ, Perelson AS. In a subset of subjects on highly active antiretroviral therapy, human immunodeficiency virus type 1 RNA in plasma decays from 50 to <5 copies per milliliter, with a half-life of 6 months. J Virol. 2003 Feb;77(3):2271-5. doi: 10.1128/jvi.77.3.2271-2275.2003.

  PMID: 12525664 BACKGROUND

• Lehrman G, Hogue IB, Palmer S, Jennings C, Spina CA, Wiegand A, Landay AL, Coombs RW, Richman DD, Mellors JW, Coffin JM, Bosch RJ, Margolis DM. Depletion of latent HIV-1 infection in vivo: a proof-of-concept study. Lancet. 2005 Aug 13-19;366(9485):549-55. doi: 10.1016/S0140-6736(05)67098-5.

  PMID: 16099290 BACKGROUND

• Ramratnam B, Mittler JE, Zhang L, Boden D, Hurley A, Fang F, Macken CA, Perelson AS, Markowitz M, Ho DD. The decay of the latent reservoir of replication-competent HIV-1 is inversely correlated with the extent of residual viral replication during prolonged anti-retroviral therapy. Nat Med. 2000 Jan;6(1):82-5. doi: 10.1038/71577.

  PMID: 10613829 BACKGROUND

• Sedaghat AR, Siliciano JD, Brennan TP, Wilke CO, Siliciano RF. Limits on replenishment of the resting CD4+ T cell reservoir for HIV in patients on HAART. PLoS Pathog. 2007 Aug 31;3(8):e122. doi: 10.1371/journal.ppat.0030122.

  PMID: 17784786 BACKGROUND

• Sedaghat AR, Siliciano RF, Wilke CO. Low-level HIV-1 replication and the dynamics of the resting CD4+ T cell reservoir for HIV-1 in the setting of HAART. BMC Infect Dis. 2008 Jan 2;8:2. doi: 10.1186/1471-2334-8-2.

  PMID: 18171475 BACKGROUND

• Siliciano JD, Kajdas J, Finzi D, Quinn TC, Chadwick K, Margolick JB, Kovacs C, Gange SJ, Siliciano RF. Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4+ T cells. Nat Med. 2003 Jun;9(6):727-8. doi: 10.1038/nm880. Epub 2003 May 18.

  PMID: 12754504 BACKGROUND

• Zhang L, Ramratnam B, Tenner-Racz K, He Y, Vesanen M, Lewin S, Talal A, Racz P, Perelson AS, Korber BT, Markowitz M, Ho DD. Quantifying residual HIV-1 replication in patients receiving combination antiretroviral therapy. N Engl J Med. 1999 May 27;340(21):1605-13. doi: 10.1056/NEJM199905273402101.

  PMID: 10341272 BACKGROUND

• Henrich TJ, Hanhauser E, Marty FM, Sirignano MN, Keating S, Lee TH, Robles YP, Davis BT, Li JZ, Heisey A, Hill AL, Busch MP, Armand P, Soiffer RJ, Altfeld M, Kuritzkes DR. Antiretroviral-free HIV-1 remission and viral rebound after allogeneic stem cell transplantation: report of 2 cases. Ann Intern Med. 2014 Sep 2;161(5):319-27. doi: 10.7326/M14-1027.

  PMID: 25047577 BACKGROUND

• Hutter G, Ganepola S. Eradication of HIV by transplantation of CCR5-deficient hematopoietic stem cells. ScientificWorldJournal. 2011 May 5;11:1068-76. doi: 10.1100/tsw.2011.102.

  PMID: 21552772 BACKGROUND

• Persaud D, Gay H, Ziemniak C, Chen YH, Piatak M Jr, Chun TW, Strain M, Richman D, Luzuriaga K. Absence of detectable HIV-1 viremia after treatment cessation in an infant. N Engl J Med. 2013 Nov 7;369(19):1828-35. doi: 10.1056/NEJMoa1302976. Epub 2013 Oct 23.

  PMID: 24152233 BACKGROUND

• Saez-Cirion A, Bacchus C, Hocqueloux L, Avettand-Fenoel V, Girault I, Lecuroux C, Potard V, Versmisse P, Melard A, Prazuck T, Descours B, Guergnon J, Viard JP, Boufassa F, Lambotte O, Goujard C, Meyer L, Costagliola D, Venet A, Pancino G, Autran B, Rouzioux C; ANRS VISCONTI Study Group. Post-treatment HIV-1 controllers with a long-term virological remission after the interruption of early initiated antiretroviral therapy ANRS VISCONTI Study. PLoS Pathog. 2013 Mar;9(3):e1003211. doi: 10.1371/journal.ppat.1003211. Epub 2013 Mar 14.

  PMID: 23516360 BACKGROUND

• Grutzner EM, Hoffmann T, Wolf E, Gersbacher E, Neizert A, Stirner R, Pauli R, Ulmer A, Brust J, Bogner JR, Jaeger H, Draenert R. Treatment Intensification in HIV-Infected Patients Is Associated With Reduced Frequencies of Regulatory T Cells. Front Immunol. 2018 Apr 30;9:811. doi: 10.3389/fimmu.2018.00811. eCollection 2018.

  PMID: 29760693 RESULT

MeSH Terms

Conditions

HIV Infections; Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases

Results Point of Contact

• Title: Dr. phil. Eva Wolf
• Organization: MUC Research GmbH

Eva.Wolf@MUCResearch.de

+49 (0)89-558703-0

Study Officials

• Hans Jaeger, MD

  MUC Research GmbH

  STUDY CHAIR

• Johannes Bogner, Prof., MD

  University Munich, University Hospital, Dept. of Infectious Diseases,

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2009
• First Posted: May 27, 2009
• Study Start: May 15, 2009
• Primary Completion: April 3, 2018
• Study Completion: May 1, 2018
• Last Updated: August 28, 2019
• Results First Posted: August 28, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

DE (8)