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
Condition: HIV
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Lumbar puncture (Lopinavir/ritonavir monotherapy); Lumbar puncture (HAART: Lopinavir/ritonavir + 2 NRTI)
Intervention type(s): Drug; Drug
Intervention description(s): Lumbar puncture at week 0; Lumbar puncture at week 0
Other intervention name(s): NP; NP
Intervention MeSH terms: Ritonavir; Lopinavir
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Long-term Lopinavir/ritonavir monotherapy; neurocognitive performance; ultrasensitive CSF-viraemia