ritonavir and Encephalitis--Viral

We report the case of a 59-year-old man who moved from Cape Verde to Massachusetts at the age of 29. He had multiple sexual contacts with female partners in Cape Verde and with West African women in Massachusetts, as well as multiple past indeterminate HIV-1 antibody tests. He presented to our facility with 2-3 months of inappropriate behaviors, memory impairment, weight loss, and night sweats, at which time he was found to have an abnormal enhancing lesion of the corpus collosum on brain magnetic resonance imaging (MRI). Laboratory testing revealed a CD4 count of 63 cells/mm(3), positive HIV-2 Western blot, serum HIV-2 RNA polymerase chain reaction (PCR) of 1160 copies per milliliter and cerebrospinal fluid (CSF) HIV-2 RNA PCR of 2730 copies per milliliter. Brain biopsy demonstrated syncytial giant cells centered around small blood vessels and accompanied by microglia, which correlated with prior pathologic descriptions of HIV-2 encephalitis and with well-described findings of HIV-1 encephalitis. Based on genotype resistance assay results, treatment guidelines, and prior studies validating success with lopinavir-ritonavir, he was treated with tenofovir-emtricitabine and lopinavir-ritonavir, which has led to virologic suppression along with steady neurologic and radiologic improvement, although he continues to have deficits.

Topics: Adenine; Anti-HIV Agents; Brain; CD4 Lymphocyte Count; Deoxycytidine; Drug Combinations; Emtricitabine; Encephalitis, Viral; HIV-2; Humans; Lopinavir; Magnetic Resonance Imaging; Male; Middle Aged; Organophosphonates; Ritonavir; RNA, Viral; Tenofovir; Viral Load

Although currently available data suffice to support the use of protease inhibitor monotherapy in selected patients, there is concern about the antiviral activity of this regimen in the long term and in viral sanctuaries, such as the central nervous system. We report a case of encephalitis related to viral escape while receiving darunavir/ritonavir monotherapy in a carefully selected patient for participation in a clinical trial.

Topics: Adult; Brain; Darunavir; Encephalitis, Viral; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Magnetic Resonance Imaging; Male; Ritonavir; Treatment Failure; Viral Load

Monotherapy with boosted protease inhibitors has emerged as an antiretroviral therapy simplification alternative for selected patients, endorsed by the results of some randomized clinical trials. However, there are some concerns about the efficacy of such a strategy in achieving successful viral suppression in those anatomic compartments or reservoirs in which antiretroviral drug penetration is lower, such as the central nervous system (CNS). Several studies have demonstrated better neurocognitive performance in patients receiving antiretroviral drugs with better cerebrospinal fluid (CSF) penetration. Nevertheless, cases of CSF viral escape accompanied by moderate or severe neurological symptoms have been reported with both standard triple therapy and boosted protease inhibitor (PI) monotherapy, and it is not well established whether ritonavir-boosted protease inhibitor (PI/r) monotherapy is associated with a higher risk of symptomatic CSF viral escape or not. Herein, we present a case of viral rebound and resistance emergence exclusively in CSF associated with an unusual clinical manifestation of focal encephalitis in a patient with plasma HIV-1 RNA suppression while receiving lopinavir/ritonavir monotherapy. Clinical resolution and CSF viral suppression were observed after switching to a genotype-guided combined antiretroviral regimen with good CSF penetration.

Topics: Adult; Encephalitis, Viral; Female; HIV Infections; HIV Protease Inhibitors; Humans; Lopinavir; Ritonavir