Clinical trial NCT01116817: 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
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV
Keywords: Long-term Lopinavir/ritonavir monotherapy
neurocognitive performance
ultrasensitive CSF-viraemia
Lead sponsor: Germans Trias i Pujol Hospital
Sponsor class: OTHER
Collaborators: name: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
First posted: 2010-05-05
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Ultrasensitive HIV-1 RNA in CSF
timeFrame: week 0
Secondary outcomes:
measure: CD4 cell count
timeFrame: week 0
measure: Plasmatic HIV-1 Viral load
timeFrame: week 0
measure: Plasmatic and CSF trough-LPV concentration
timeFrame: weeks 0
measure: Neurocognitive alteration, present when there is a diagnosis of any neurocognitive disorders associated with HIV (HAND).
timeFrame: week 0
measure: Overall deficit ratio (GDS)
timeFrame: week 0
measure: Adverse events
timeFrame: week 0
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Germans Trias i Pujol Hospital
state: Barcelona
Study officials:
References: