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 : December 5, 2019
|Condition or disease||Intervention/treatment||Phase|
|HIV||Drug: Lumbar puncture (Lopinavir/ritonavir monotherapy) Drug: Lumbar puncture (HAART: Lopinavir/ritonavir + 2 NRTI)||Phase 4|
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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||35 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Primary Completion Date :||June 2011|
|Actual Study Completion Date :||June 2011|
Experimental: LPV/r monotherapy 400/100 mg twice daily, orally administered
LPV/r monotherapy 400/100 mg twice daily, orally administered
Drug: Lumbar puncture (Lopinavir/ritonavir monotherapy)
Lumbar puncture at week 0
Other Name: NP
Active Comparator: Lumbar puncture
LPV/r 400/100 mg twice daily + 2 NRTI, orally administered.
Drug: Lumbar puncture (HAART: Lopinavir/ritonavir + 2 NRTI)
Lumbar puncture at week 0
Other Name: NP
- Ultrasensitive HIV-1 RNA in CSF [ Time Frame: week 0 ]
- CD4 cell count [ Time Frame: week 0 ]
- Plasmatic HIV-1 Viral load [ Time Frame: week 0 ]
- Plasmatic and CSF trough-LPV concentration [ Time Frame: weeks 0 ]
- Neurocognitive alteration, present when there is a diagnosis of any neurocognitive disorders associated with HIV (HAND). [ Time Frame: week 0 ]
- 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.
- Adverse events [ Time Frame: week 0 ]
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
|Germans Trias i Pujol Hospital|
|Badalona, Barcelona, Spain, 08916|