Remission of HIV-1-myelopathy and sharp drop of CSF viral load with lopinavir/ritonavir.

Walter A. Eyer-Silva^ab , Jose Carlos Couto-Fernandez^b , Marcelo R. Caetano^c,  Saada L. Chequer-Fernandez^b,  Jorge Francisco C. Pinto^a , Carlos Alberto Morais-de-Sa^a, Mariza G. Morgado^b. ^aUniversidade do Rio de Janeiro; ^bFundacao Oswaldo Cruz; ^cLaboratório Cardiolab (Brazil).

Background: HIV-1 is highly central nervous system (CNS)-tropic and can be found in cerebrospinal fluid (CSF) early in the course of infection. Impaired CNS antiretroviral penetration may lead to inappropriate viral suppression and emergence of resistance. Molecular HIV-1 analysis of CSF offers a unique opportunity to study this important CNS compartment. In spite of lopinavir and ritonavir being consistently undetectable in the CSF (probably due to protein binding), we report evidence of the efficacy of the co-formulation of lopinavir and ritonavir (lopinavir/r) in lowering CSF viral load and improving signs and symptoms of HIV-1-associated myelopathy (HM). Material and Methods: We report a patient with clinically severe HM and extensive previous use of highly active antiretroviral therapy (HAART) who obtained marked functional recovery on lopinavir/r. Results: A 32-year-old HIV-1-infected male patient who had completed 6 years of HAART developed a slowly progressive neurologic disorder of 5-month duration (AIDS 2002;16:2387). 3 sequential PI combinations had been prescribed with poor plasma HIV-1 viral load control. He was then on stavudine, lamivudine, nelfinavir and nevirapine. The disorder started with progressive urinary frequency and incontinence, soon followed by worsening gait difficulty to the point that he could not walk unassisted. Neurological examination disclosed signs and symptoms of HM. Laboratory evaluation excluded disorders with overlapping presentations. CSF studies found 10 mononuclears/mm³ with normal protein/glucose and were negative for neoplastic cells and pathogens. The albumin index was normal suggesting unimpaired blood-brain barrier. The CD4 cell count was 185/mm³ and the plasma viral load was 61,000 copies/mL. The CSF HIV-1 viral load was 4,800 copies/mL. Plasma and CSF-recovered HIV-1 RNA sequences displayed the following protease mutations: L10I, K20R, I54V, L63P, V82A, M36I and I54V. Lopinavir/r was prescribed in place of nelfinavir. The other drugs were maintained. Substantial and lasting neurologic improvement followed. The CD4 count rose to 227/mm³. Plasma and CSF viral load dropped, respectively, to 3,100 and 110 per mL, respectively. Standard CSF studies were then entirely normal and improvement of somatosensory evoked potentials was documented. Conclusion: Clinical and laboratory recovery (including a 3.6 log drop in CSF viral load) could only be attributed to replacement of nelfinavir by lopinavir/r and probably resulted from lopinavir/r’s activity in a compartment other than the CSF, such as blood or brain.