HIV - Monotherapy in Switzerland (MOST-ch) (MOST)

HIV- Monotherapy in Switzerland (MOST- ch)

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.

Study Overview

• Status: Terminated
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Lopinavir-Monotherapy; Drug: HAART

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• Switzerland
  • Geneva, Switzerland, 1211
    • Hirschel
  • Bellariastrasse 38
    • Zürich, Bellariastrasse 38, Switzerland, 8038
      • Flepp
  • INF KP PKT 2B Freiburgstr.
    • Bern, INF KP PKT 2B Freiburgstr., Switzerland, 3010
      • Furrer
  • Petersgraben 4
    • Basel, Petersgraben 4, Switzerland, 4031
      • Nuesch
  • Rue Du Bugnon 21
    • Lausanne, Rue Du Bugnon 21, Switzerland, 1005
      • Cavassini
  • Rämistrasse 100
    • Zürich, Rämistrasse 100, Switzerland, 8091
      • Opravil

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: Kaletra
Active Comparator: Continued ART; Continuation Therapy, conventional triple HAART	Drug: HAART; Patients will continued their current HAART; Other Names: Any ART

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Failure in CNS	Week 48

Secondary Outcome Measures

Outcome Measure	Time Frame
Predictors of failure	week 48

Collaborators and Investigators

• Sponsor: Cantonal Hospital of St. Gallen
• Collaborators: Swiss National Science Foundation; Swiss HIV Cohort Study
• Investigators: Principal Investigator: Pietro Vernazza, Professor, Swiss HIV Cohort Study

Publications and helpful links

General Publications

• Gutmann C, Cusini A, Gunthard HF, Fux C, Hirschel B, Decosterd LA, Cavassini M, Yerly S, Vernazza PL; Swiss HIV Cohort Study (SHCS). Randomized controlled study demonstrating failure of LPV/r monotherapy in HIV: the role of compartment and CD4-nadir. AIDS. 2010 Sep 24;24(15):2347-54. doi: 10.1097/QAD.0b013e32833db9a1.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): September 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: September 18, 2007
• First Submitted That Met QC Criteria: September 18, 2007
• First Posted (Estimate): September 19, 2007

Study Record Updates

• Last Update Posted (Actual): July 18, 2018
• Last Update Submitted That Met QC Criteria: July 16, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Treatment Experienced; 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)
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Lopinavir
• Other Study ID Numbers: SHCS-Projekt Nr.: 490; SHCS 490