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Study to Compare the Virologic Efficacy in Cerebrospinal Fluid (CSF) and Neurocognitive State in Patients Infected by HIV-1 Long-term Treatment (> 3 Years) With Lopinavir / Ritonavir Monotherapy

This study has been completed.
Sponsor:
Information provided by:
Germans Trias i Pujol Hospital
ClinicalTrials.gov Identifier:
NCT01116817
First received: April 30, 2010
Last updated: July 13, 2011
Last verified: July 2011

April 30, 2010
July 13, 2011
August 2010
June 2011   (final data collection date for primary outcome measure)
Ultrasensitive HIV-1 RNA in CSF [ Time Frame: week 0 ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01116817 on ClinicalTrials.gov Archive Site
  • CD4 cell count [ Time Frame: week 0 ] [ Designated as safety issue: No ]
  • Plasmatic HIV-1 Viral load [ Time Frame: week 0 ] [ Designated as safety issue: No ]
  • Plasmatic and CSF trough-LPV concentration [ Time Frame: weeks 0 ] [ Designated as safety issue: No ]
  • Neurocognitive alteration, present when there is a diagnosis of any neurocognitive disorders associated with HIV (HAND). [ Time Frame: week 0 ] [ Designated as safety issue: Yes ]
  • Overall deficit ratio (GDS) [ Time Frame: week 0 ] [ Designated as safety issue: Yes ]
    Calculating a value of overall neurocognitive functioning, based on an evaluation of 7 representative areas in HIV infection (attention / working memory, speed of information processing, verbal memory, learning, verbal fluency.
  • Adverse events [ Time Frame: week 0 ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Study to Compare the Virologic Efficacy in Cerebrospinal Fluid (CSF) and Neurocognitive State in Patients Infected by HIV-1 Long-term Treatment (> 3 Years) With Lopinavir / Ritonavir Monotherapy
Exploratory, Cross-sectional Study to Compare the Virologic Efficacy in Cerebrospinal Fluid (CSF) and Neurocognitive State in Patients Infected by HIV-1 Long-term Treatment (> 3 Years) With Lopinavir / Ritonavir Monotherapy

The aim of this study is to describe and compare the percentage of patients infected by HIV-1 to maintain a complete virology suppression at the CSF (CSF CV 1 copy / mL) in patients with CV <50 copies / mL and treated with stable antiretroviral therapy for at least 3 years with LPV / r 400/100 mg twice daily + 2 NRTI.

Combinations of antiretroviral for the management of HIV infection recommended by the main treatment guidelines include a combination of two nucleoside analogue reverse transcriptase (NRTI) with a non-nucleoside reverse transcriptase (NNRTI) or an inhibitor protease (IP) .1 However, NRTIs can inhibit mitochondrial DNA gamma polymerase, causing mitochondrial dysfunction, which in turn can result in related adverse effects such as peripheral neuropathy, pancreatitis, hepatitis, abnormal lipid profile or lipodystrophy. Therefore, it is advisable to design and search for therapeutic strategies to avoid prolonged exposure to NRTIs and their adverse events.

IP monotherapy as a strategy of simplification, after an induction period with standard triple therapy may be useful to minimize the risk of mitochondrial toxicity by NRTIs. Additionally, this strategy may be useful to improve treatment adherence, reduce costs and preserve future treatment options. In this sense, monotherapy with lopinavir / ritonavir (LPV / r) can be an effective option for the treatment of HIV-1 as a simplification strategy in routine clinical practice.3 OK04 study showed that in patients with sustained viral suppression simplified to monotherapy with LPV / r, rates of viral load <50 copies / mL were similar to that patients continuing on standard triple therapy.4, 5 However, the virological efficacy of this strategy in the CSF compartments has been questioned by some authors. Like most protease inhibitors, lopinavir has a poor penetration in CSF. Thus, despite the concentration of lopinavir in CSF usually exceed the inhibitory concentration (IC50) of wild strains of HIV, it is possible that some patients may present lopinavir concentrations insufficient to achieve sustained suppression of viral replication in that compartment. In this sense, according to results from a recent study, up to 10% of patients treated with lopinavir / ritonavir monotherapy may present detectable levels of viral load in CSF while maintaining a CV <50 copies / mL in plasma.9

On the other hand, about half of patients on antiretroviral therapy (HAART), despite achieving virologic control and the treatment is performed properly, have been neurocognitive dysfunction.10 This has been associated with multiple risk factors, including the presence of HIV in CSF.11 In fact, even though achieving undetectable viral load in plasma, up to 40% of patients on HAART show presence of virus in CSF.12 This also has been associated with a worse neurocognitive functioning. Therefore, the maximum control of viral replication is shown as a priority for the improvement of CNS dysfunction.

Based on the above, the objective of this study is to explore and evaluate the virological efficacy and safety at long-term neurocognitive level (> 3 years) of monotherapy with lopinavir / ritonavir as a strategy to simplify antiretroviral therapy in patients infected by HIV.

Interventional
Phase 4
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
HIV
Procedure: Lumbar puncture
Lumbar puncture at week 0
Other Name: NP
  • Experimental: LPV/r monotherapy 400/100 mg twice daily, orally administered
    LPV/r monotherapy 400/100 mg twice daily, orally administered
    Intervention: Procedure: Lumbar puncture
  • Active Comparator: Lumbar puncture
    LPV/r 400/100 mg twice daily + 2 NRTI, orally administered.
    Intervention: Procedure: Lumbar puncture
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
35
June 2011
June 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

Experimental group:

  1. Patients having a diagnosis of HIV infection, on stable treatment at least 3 years with LPV/r monotherapy, the inclusion of patients with at least 2 years will be permitted if it is not possible to include the expected number of patients.
  2. Initiating monotherapy with lopinavir / ritonavir maintaining values of plasma HIV-1 RNA undetectable (cv <50 copies / mL).
  3. Maintain complete virologic suppression (CV <50 copies / ml) in plasma for at least 3 years in treatment with LPV / r monotherapy. (Or 2 years, if not complied with the expected number of patients with at least 3 years with LPV / r monotherapy).
  4. Good adherence to treatment (> 90%).
  5. Signing of informed consent.

Control group:

  1. Patients having a diagnosis of HIV infection, on stable treatment at least 3 years with LPV/r 400/100 mg twice a day + 2 ITIAN, the inclusion of patients with at least 2 years will be permitted if it is not possible to include the expected number of patients.
  2. Maintain complete virologic suppression (CV <50 copies / ml) in plasma for at least 3 years in treatment with LPV / r monotherapy. (Or 2 years, if not complied with the expected number of patients with at least 3 years with LPV / r 400/100 mg 2 twice a day + 2 ITIAN).
  3. Patients that can be put into pairs with the experimental ones following these characteristics: age, sex, presence of previous virologic failures, nadir CD4 + T lymphocytes and viral load <50 copies / mL time prior to inclusion in the study. Patients having a diagnosis of HIV.
  4. Good adherence to treatment (> 90%).
  5. Signing of informed consent.

Exclusion Criteria:

  1. Vaccine administration, acute or chronic uncontrolled infection in the 2 months prior to the inclusion or medical assessment which in the opinion of the investigator, might compromise the results of the study.
  2. Pregnancy or breastfeeding.
  3. Therapies that include interferon, interleukin-2, cytotoxic chemotherapy or immunosuppressant at baseline.
  4. Do not sign the informed consent.
  5. Existence of any contraindication to the performance of lumbar puncture.
  6. Presence of psychiatric disorders or being in psychopharmacological treatment.
  7. Active alcohol consumption (> 50 g / day) or illicit drugs.
  8. Existence current or past opportunistic infection involving CNS functioning alteration.
Both
18 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
Spain
 
NCT01116817
LCR-MONOKAL
No
Lluita Sida Foundation
Germans Trias i Pujol Hospital
Not Provided
Not Provided
Germans Trias i Pujol Hospital
July 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP