RESUMO
Human immunodeficiency virus (HIV) genetic compartmentalization is defined as genetic differences in HIV in different tissue compartments or subcompartments that characterize viral quasispecies. This descriptive, longitudinal study assessed the dynamics of inflammation, humoral immune response, blood-brain barrier, blood-cerebrospinal fluid (CSF) barrier, as well as neuronal injury biomarkers in serially obtained CSF and serum samples from an antiretroviral (ARV) therapy-naïve patient with HIV-1 subtype C with CSF HIV genetic compartmentalization that resolved spontaneously without ARV treatment. The first CSF sample showed an increase in white blood cell (WBC) count (382 cells/mm3) and a marked increase in the levels of inflammatory cytokines and chemokines, including tumor necrosis factor (TNF)α, interleukin (IL)-10, IP-10, and regulated on activation, normal T cell expressed and secreted (RANTES), which raise the suspicion of dual infection. Serum sample analysis showed all cytokine levels to be normal, with only IP-10 slightly increased. These results corroborate the hypothesis that the CNS immunologic response in a patient with HIV infection was independent of the systemic immunologic response. The patient also had persistently elevated levels of sCD14, neopterin, and ß2M, which were strongly suggestive of persistent CNS immunologic stimulation. This report describes a patient with HIV subtype C who developed a transient episode of asymptomatic HIV meningitis with compartmentalization of HIV in the CSF that resolved independently of ARV therapy. Extensive CSF studies were performed as part of an ongoing longitudinal study, which revealed CNS immune abnormalities. This case presents evidence of HIV-1 subtype C neurotropism and compartmentalization.
Assuntos
Complexo AIDS Demência/líquido cefalorraquidiano , Complexo AIDS Demência/virologia , HIV-1/fisiologia , Meningite/líquido cefalorraquidiano , Meningite/virologia , Biomarcadores/líquido cefalorraquidiano , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-IdadeRESUMO
Despite the effective suppression of viremia with antiretroviral therapy, HIV can still replicate in the central nervous system (CNS). This was a longitudinal study of the cerebrospinal fluid (CSF) and serum dynamics of several biomarkers related to inflammation, the blood-brain barrier, neuronal injury, and IgG intrathecal synthesis in serial samples of CSF and serum from a patient infected with HIV-1 subtype C with CNS compartmentalization.The phylogenetic analyses of plasma and CSF samples in an acute phase using next-generation sequencing and F-statistics analysis of C2-V3 haplotypes revealed distinct compartmentalized CSF viruses in paired CSF and peripheral blood mononuclear cell samples. The CSF biomarker analysis in this patient showed that symptomatic CSF escape is accompanied by CNS inflammation, high levels of cell and humoral immune biomarkers, CNS barrier dysfunction, and an increase in neuronal injury biomarkers with demyelization. Independent and isolated HIV replication can occur in the CNS, even in HIV-1 subtype C, leading to compartmentalization and development of quasispecies distinct from the peripheral plasma. These immunological aspects of the HIV CNS escape have not been described previously. To our knowledge, this is the first report of CNS HIV escape and compartmentalization in HIV-1 subtype C.
Assuntos
Sistema Nervoso Central/virologia , Encefalite Viral/virologia , Infecções por HIV/virologia , HIV-1/patogenicidade , Evasão da Resposta Imune , RNA Viral/líquido cefalorraquidiano , Adulto , Fármacos Anti-HIV/uso terapêutico , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Barreira Hematoencefálica/imunologia , Barreira Hematoencefálica/virologia , Sistema Nervoso Central/imunologia , Sistema Nervoso Central/patologia , Quimiocina CCL5/sangue , Quimiocina CCL5/líquido cefalorraquidiano , Encefalite Viral/tratamento farmacológico , Encefalite Viral/imunologia , Encefalite Viral/patologia , Anticorpos Anti-HIV/sangue , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Infecções por HIV/patologia , HIV-1/imunologia , Humanos , Imunoglobulina G/sangue , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/virologia , Receptores de Lipopolissacarídeos/sangue , Estudos Longitudinais , Masculino , Proteína Básica da Mielina/sangue , Proteína Básica da Mielina/líquido cefalorraquidiano , Proteínas de Neurofilamentos/sangue , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Filogenia , Replicação ViralRESUMO
HIV proviral DNA integration into the host chromosome is carried out by integrase becoming an important target antiretroviral therapy. Raltegravir was the first integrase inhibitor approved for use in HIV therapy and elvitegravir is in the late phase of clinical development; both show good results in monotherapy studies and may be used worldwide for rescue therapy. In this work we analyzed 57 integrase sequences obtained from samples from drug-naive and first line regime-failing patients from Maputo, Mozambique, to evaluate the presence of natural polymorphisms and resistance mutations associated with raltegravir and elvitegravir. No major mutations conferring resistance to integrase inhibitors were found and polymorphic accessory mutations were solely observed in low frequency among subtype C sequences-L74M (3.4%), T97A (1.8%), and E157Q (1.8%)-suggesting that this new antiretroviral drug class will be effective in Mozambique providing a good perspective to the introduction of this class of drugs in that country.