HIV - Monotherapy in Switzerland (MOST-ch)

This study has been terminated.
(Unexpectedely high rates of treatment-failure)
Sponsor:
Collaborators:
Swiss National Science Foundation
Swiss HIV Cohort Study
Information provided by:
Cantonal Hospital of St. Gallen
ClinicalTrials.gov Identifier:
NCT00531986
First received: September 18, 2007
Last updated: May 29, 2009
Last verified: May 2009
  Purpose

The investigators plan to conduct a two arm study, to compare failure rates in the central nervous system (CNS) and genital compartment in virologically fully suppressed patients continuing a highly active antiretroviral therapy (HAART) versus patients switching to ritonavir boosted lopinavir (Kaletra®) HIV-monotherapy. The study is composed of two phases of 48 weeks duration.

In addition, neuropsychological tests (Color trial test A 1 and 2; Grooved pegboard; EWIA Digit Symbol form) and evaluation of side effects will be performed.


Condition Intervention Phase
HIV Infections
Drug: Lopinavir-Monotherapy
Drug: HAART
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: HIV- Monotherapy in Switzerland (MOST- ch)

Resource links provided by NLM:


Further study details as provided by Cantonal Hospital of St. Gallen:

Primary Outcome Measures:
  • Failure in CNS [ Time Frame: Week 48 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Predictors of failure [ Time Frame: week 48 ] [ Designated as safety issue: No ]

Enrollment: 60
Study Start Date: January 2007
Study Completion Date: December 2008
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Monotherapy
Ritonavir-boosted lopinavir (Kaletra®) will be used as monotherapy
Drug: Lopinavir-Monotherapy
Patients on triple HAART will be switched to LPV/r-monotherapy
Other Name: Kaletra
Active Comparator: Continued ART
Continuation Therapy, conventional triple HAART
Drug: HAART
Patients will continued their current HAART
Other Name: Any ART

Detailed Description:

In the first phase (phase A), ritonavir-boosted lopinavir (Kaletra®) will be compared with continued HAART. In the second year (phase B) patients on conventional HAART are also offered LPV/r monotherapy to extend the longterm experience of this new strategy.

Only patients willing to give a genital secretion and a spinal fluid sample will be included. All patients must be on a fully suppressive HAART with at least 2 consecutive values of HIV-RNA at the screening visit . After performance of lumbar puncture at baseline, patients will be randomized to continued HAART or LPV/r monotherapy. During the first year of randomized treatment patients will be followed at week 6/ 12 /18 /24 /32 /40 and 48. Lumbar puncture and genital secretion sampling will be repeated at week 48.

Follow up during the second phase (B: W48-96) of the study will be identical to phase A including genital and spinal sampling at week 96. After study termination at week 96, patients may opt to continue monotherapy if results of HIV-RNA in blood and CSF support this decision.

The primary endpoint of the study will be treatment failure in the compartment (CSF and / or genital tract). Since the variability of HIV-RNA determination in CSF and genital secretions is not very well known, a one log increase above the baseline value will be considered as treatment failure in the respective compartment. Only patients who had a complete viral suppression in blood will be considered for compartment evaluation. Patients treated in the monotherapy arm with a CSF HIV-RNA value at week 48 more than 1.0 log10 cp/ml above baseline (= compartment failure) will be switched to a conventional combination treatment. HIV-RNA testing in the genital samples will be performed batchwise at the end of the study.

In addition, patients with a blood treatment failure (two consecutive HIV-RNA detections > 400cp/ml) will be considered as full treatment failures and switched to a rescue regimen at the discretion of the treating physician. For the analysis, these patients will be considered as systemic treatment failure and will not be entered in the analysis of compartmentalized treatment failure. If the rescue strategy was only intensification of adherence and results in full blood viral load re-suppression, the patient will still be maintained in the study and compartment evaluations can be performed at w48 and/or 96, respectively.

The secondary aim of the study is the definition of prognostic markers for compartment failures. Potential risk factors associated with mono-maintenance failure are HIV-DNA load at time of treatment simplification, HIV-RNA at the time of first treatment initiation, duration of HIV-RNA suppression before simplification, history of HIV-RNA blips, presence of detectable HIV-RNA in spinal fluid at the time of treatment simplification, changes of level of c-reactive protein (high sensitive methodology, hsCRP) from baseline as a marker of immune-activation during the maintenance therapy.

If funding allows, we will test for the presence of resistant viruses and compare the presence of genetic polymorphism at baseline. We will also measure parameters of immunoactivation (hsCRP, CD8+, CD38+).

The study is financed by the Swiss National Science Foundation and the Swiss HIV Cohort Study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age > 18 years.
  • HIV seropositive.
  • HAART (> 6 months) with at least 3 months successfully suppressed HIV- RNA (two most recent RNA measurements < 50 cp/ml). HAART is defined as either:

    • 1 PI plus 2 NRTIs,
    • 1 NNRTI plus 2 NRTIs, or
    • 3 NRTIs.
  • HIV-RNA in plasma < 50 cp/ml at screening.
  • Stable antiretroviral therapy (unchanged drug combination) during the last four weeks.
  • If not currently on a LPV/ r based therapy, willing to switch to LPV/ r bid therapy in case patient is randomized to the monotherapy arm
  • Signed written informed consent.
  • Highly motivated patients able to understand the investigational nature of this open observational study and willing to participate in additional procedures.

Exclusion Criteria:

  • Other investigational substance or substances active against HIV.
  • Previous history of adverse events with the drugs under investigation.
  • Previous history of any virological treatment failure (does not include deliberate treatment interruption) or documented resistance against the drugs under investigation (LPV/r).
  • Patient who has no effective alternative treatment options in case the study treatment fails (according to the physician's judgment).
  • Pregnancy (negative pregnancy test for women of childbearing potential at screening).
  • Active AIDS-defining disease necessitating antibiotic or chemotherapy at the time of screening.
  • Chronic hepatitis B.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00531986

Locations
Switzerland
Hirschel
Geneva, 24 rue Micheli- du- Crest, Switzerland, 1211
Flepp
Zürich, Bellariastrasse 38, Switzerland, 8038
Furrer
Bern, INF KP PKT 2B Freiburgstr., Switzerland, 3010
Nuesch
Basel, Petersgraben 4, Switzerland, 4031
Cavassini
Lausanne, Rue du Bugnon 21, Switzerland, 1005
Opravil
Zürich, Rämistrasse 100, Switzerland, 8091
Sponsors and Collaborators
Cantonal Hospital of St. Gallen
Swiss National Science Foundation
Swiss HIV Cohort Study
Investigators
Principal Investigator: Pietro Vernazza, Professor Swiss HIV Cohort Study
  More Information

Additional Information:
No publications provided by Cantonal Hospital of St. Gallen

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pietro Vernazza, KSSG; 9007 St. Gallen, Switzerland, KSSG; 9007 St. Gallen, Switzerland
ClinicalTrials.gov Identifier: NCT00531986     History of Changes
Other Study ID Numbers: SHCS-Projekt Nr.: 490, SHCS 490
Study First Received: September 18, 2007
Last Updated: May 29, 2009
Health Authority: Switzerland: Ethikkommission
Switzerland: Swissmedic

Keywords provided by Cantonal Hospital of St. Gallen:
Monotherapy
Neuropsychological tests
HIV viral load in ZNS
HIV viral load in genital
Lumbar puncture and HIV viral load in ZNS
Monotherapy and compartment failure (ZNS and genital)
ZNS viral load under monotherapy
Genital viral load under monotherapy
Neuropsychological tests (HIV Dementia)
Treatment Experienced

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Lopinavir
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 09, 2014