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

NCT ID: NCT01116817

Last Updated: 2019-12-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-08-31
• Study Completion Date: 2011-06-30

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.

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.

Conditions

HIV

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

LPV/r monotherapy 400/100 mg twice daily, orally administered

LPV/r monotherapy 400/100 mg twice daily, orally administered

Group Type: EXPERIMENTAL

Lumbar puncture (Lopinavir/ritonavir monotherapy)

Intervention Type: DRUG

Lumbar puncture at week 0

Lumbar puncture

LPV/r 400/100 mg twice daily + 2 NRTI, orally administered.

Group Type: ACTIVE_COMPARATOR

Lumbar puncture (HAART: Lopinavir/ritonavir + 2 NRTI)

Intervention Type: DRUG

Lumbar puncture at week 0

Interventions

Lumbar puncture (Lopinavir/ritonavir monotherapy)

Lumbar puncture at week 0

Intervention Type: DRUG

Lumbar puncture (HAART: Lopinavir/ritonavir + 2 NRTI)

Lumbar puncture at week 0

Intervention Type: DRUG

Other Intervention Names

NP; NP

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia

OTHER

Sponsor Role: collaborator

Germans Trias i Pujol Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Germans Trias i Pujol Hospital

Badalona, Barcelona, Spain

Countries

Spain

Other Identifiers

LCR-MONOKAL

Identifier Type: -

Identifier Source: org_study_id