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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

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ClinicalTrials.gov Identifier: NCT01116817
Recruitment Status : Completed
First Posted : May 5, 2010
Last Update Posted : July 14, 2011
Sponsor:
Information provided by:

Study Description
Brief Summary:
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.

Condition or disease Intervention/treatment Phase
HIV Procedure: Lumbar puncture Phase 4

Detailed Description:

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.


Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 35 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : August 2010
Primary Completion Date : June 2011
Study Completion Date : June 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: LPV/r monotherapy 400/100 mg twice daily, orally administered
LPV/r monotherapy 400/100 mg twice daily, orally administered
Procedure: Lumbar puncture
Lumbar puncture at week 0
Other Name: NP
Active Comparator: Lumbar puncture
LPV/r 400/100 mg twice daily + 2 NRTI, orally administered.
Procedure: Lumbar puncture
Lumbar puncture at week 0
Other Name: NP


Outcome Measures

Primary Outcome Measures :
  1. Ultrasensitive HIV-1 RNA in CSF [ Time Frame: week 0 ]

Secondary Outcome Measures :
  1. CD4 cell count [ Time Frame: week 0 ]
  2. Plasmatic HIV-1 Viral load [ Time Frame: week 0 ]
  3. Plasmatic and CSF trough-LPV concentration [ Time Frame: weeks 0 ]
  4. Neurocognitive alteration, present when there is a diagnosis of any neurocognitive disorders associated with HIV (HAND). [ Time Frame: week 0 ]
  5. Overall deficit ratio (GDS) [ Time Frame: week 0 ]
    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.

  6. Adverse events [ Time Frame: week 0 ]

Eligibility Criteria

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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01116817


Locations
Spain
Germans Trias i Pujol Hospital
Badalona, Barcelona, Spain, 08916
Sponsors and Collaborators
Germans Trias i Pujol Hospital
More Information

Responsible Party: Lluita Sida Foundation
ClinicalTrials.gov Identifier: NCT01116817     History of Changes
Other Study ID Numbers: LCR-MONOKAL
First Posted: May 5, 2010    Key Record Dates
Last Update Posted: July 14, 2011
Last Verified: July 2011

Keywords provided by Germans Trias i Pujol Hospital:
Long-term Lopinavir/ritonavir monotherapy
neurocognitive performance
ultrasensitive CSF-viraemia

Additional relevant MeSH terms:
Ritonavir
Lopinavir
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors