RESUMO
BACKGROUND: The pathogenesis and natural history of HIV-associated immune complex kidney disease (HIVICK) is not well understood. Key questions remain unanswered, including the role of HIV infection and replication in disease development and the efficacy of antiretroviral therapy (ART) in the prevention and treatment of disease. METHODS: In this multicentre study, we describe the renal pathology of HIVICK and compare the clinical characteristics of patients with HIVICK with those with IgA nephropathy and HIV-associated nephropathy (HIVAN). Poisson regression models were used to identify risk factors for each of these pathologies. RESULTS: Between 1998 and 2012, 65 patients were diagnosed with HIVICK, 27 with IgA nephropathy and 70 with HIVAN. Black ethnicity and HIV RNA were associated with HIVICK, receipt of ART with IgA nephropathy and black ethnicity and CD4 cell count with HIVAN. HIVICK was associated with lower rates of progression to end-stage kidney disease compared with HIVAN and IgA nephropathy (P < 0.0001). Patients with HIVICK who initiated ART and achieved suppression of HIV RNA experienced improvements in estimated glomerular filtration rate and proteinuria. CONCLUSIONS: These findings suggest a pathogenic role for HIV replication in the development of HIVICK and that ART may improve kidney function in patients who have detectable HIV RNA at the time of HIVICK diagnosis. Our data also suggest that IgA nephropathy should be viewed as a separate entity and not included in the HIVICK spectrum.
Assuntos
Nefropatia Associada a AIDS/patologia , Glomerulonefrite por IGA/virologia , Falência Renal Crônica/virologia , Nefropatia Associada a AIDS/sangue , Nefropatia Associada a AIDS/imunologia , Nefropatia Associada a AIDS/terapia , Adulto , Contagem de Linfócito CD4 , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Glomerulonefrite por IGA/sangue , Glomerulonefrite por IGA/imunologia , Glomerulonefrite por IGA/terapia , Humanos , Rim/patologia , Rim/fisiopatologia , Falência Renal Crônica/sangue , Falência Renal Crônica/imunologia , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Proteinúria/sangue , Proteinúria/imunologia , Proteinúria/virologia , RNA Viral/sangue , Fatores de Risco , Resultado do TratamentoRESUMO
We report a case of EBV+ and HHV-8+ multicentric Castleman disease with plasmablastic aggregates in an HIV-positive individual. A 41-year-old man presented in early 2015 with fevers, sweats, weight loss, intractable itching, and on subsequent testing was found to be HIV positive. Investigations showed cervical lymphadenopathy and splenomegaly. He was treated for HIV and his symptoms resolved. His symptoms recurred in January 2016, and a provisional diagnosis of multicentric Castleman disease was entertained. The HHV-8 (human herpesvirus-8) and EBV (Epstein-Barr virus) viral load was elevated. A left supraclavicular lymph node core biopsy was performed, which showed features of multicentric Castleman disease with plasmablastic aggregates that are EBV (EBER) and HHV-8 positive. He responded well to rituximab treatment and remains well with no symptoms at recent follow-up.
Assuntos
Hiperplasia do Linfonodo Gigante/complicações , Hiperplasia do Linfonodo Gigante/patologia , Hiperplasia do Linfonodo Gigante/virologia , Infecções por HIV/complicações , Adulto , Infecções por Vírus Epstein-Barr/complicações , Infecções por Herpesviridae/complicações , Herpesvirus Humano 4 , Herpesvirus Humano 8 , Humanos , MasculinoRESUMO
Despite an increase in the variety of anti-retroviral agents in the market, there remains a need for novel agents to treat HIV 1 infected individuals, in order to overcome existing problems with adherence, toxicities, drug interactions and viral resistance. In this article, we will describe Pro 140, one of the recently developed class of anti-retroviral agent, the CCR5 co-receptor inhibitor. We will also describe several preclinical and clinical studies that have evaluated the efficacy, tolerability and toxicity profiles of Pro-140. We will also look at how its mechanism of action and mode of delivery may change the way patients take highly active anti-retroviral therapy. There are some promising patents discussed in this short review for the use of PRO 140 as CCR5 co-receptor Inhibitor.