Viremia is significantly lower in HIV-2 than in HIV-1 infection, irrespective of disease stage. Nevertheless, the comparable proviral DNA burdens observed for these two infections indicate similar numbers of infected cells. Here we investigated this apparent paradox by assessing cell-associated viral replication. We found that untreated HIV-1-positive (HIV-1 ؉ ) and HIV-2 ؉ individuals, matched for CD4 T cell depletion, exhibited similar gag mRNA levels, indicating that significant viral transcription is occurring in untreated HIV-2 ؉ patients, despite the reduced viremia (undetectable to 2.6 ؋ 10 4 RNA copies/ml). However, tat mRNA transcripts were observed at significantly lower levels in HIV-2 ؉ patients, suggesting that the rate of de novo infection is decreased in these patients. Our data also reveal a direct relationship of gag and tat transcripts with CD4 and CD8 T cell activation, respectively. Antiretroviral therapy (ART)-treated HIV-2 ؉ patients showed persistent viral replication, irrespective of plasma viremia, possibly contributing to the emergence of drug resistance mutations, persistent hyperimmune activation, and poor CD4 T cell recovery that we observed with these individuals. In conclusion, we provide here evidence of significant ongoing viral replication in HIV-2 ؉ patients, further emphasizing the dichotomy between amount of plasma virus and cell-associated viral burden and stressing the need for antiretroviral trials and the definition of therapeutic guidelines for HIV-2 infection.

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RESUMOA Síndrome nefrite túbulo intersticial e uveíte é uma síndrome rara e provavelmente sub-diagnosticado na prática clinica. É caracterizada pela ocorrência de nefrite intersticial e de uveíte, sendo um diagnóstico de exclusão. Granulomas não caseosos nos vários tecidos são raros, estando descritos apenas seis casos de granulomas não caseosos na medula óssea. Apresentamos um caso de uma mulher de 55 anos, com quadro de três meses de evolução de astenia e emagrecimento. Laboratorialmente apresentava anemia e insuficiência renal. A biopsia renal revelou nefrite intersticial e a biópsia da medula óssea mostrou granulomas não caseosos. Um mês depois surgiu uveíte anterior do olho esquerdo. A exclusão de todas as possíveis etiologias permitiu o diagnóstico final de Síndrome nefrite túbulo intersticial e uveíte com granulomas não caseosos na medula óssea. Considerando que as manifestações oculares e renais podem não ocorrer simultaneamente, a Síndrome nefrite túbulo intersticial e uveíte deve ser sistematicamente equacionada em doentes com nefrite intersticial e/ou uveíte, podendo os granulomas fazer parte desta rara patologia. Palavras-chave: Granuloma; Medula Óssea; Nefrite Intersticial; Uveíte. ABSTRACTThe Tubulointerstitial Nephritis and Uveitis syndrome is a very rare condition, probably under-diagnosed in clinical practice. It is characterized by the combination of an interstitial nephritis and uveitis, and is an exclusion diagnosis. Tissue non caseating granuloma can be rarely present, with only 6 cases reported on bone marrow. We present a case of a 55 year old female with a 3-month history of asthenia and weight loss. Blood tests showed anemia and renal insufficiency. Renal biopsy revealed interstitial nephritis and the bone marrow biopsy showed caseating granuloma. One month later anterior uveitis of the left eye appeared. An extensive exclusion of all possible causes allowed a diagnosis of Tubulointerstitial Nephritis and Uveitis syndrome with caseating granuloma in bone marrow. As ocular and renal manifestations may not occur simultaneously, Tubulointerstitial Nephritis and Uveitis Syndrome should be systematically considered in cases of interstitial nephritis and/or uveitis, and tissue granulomas can be part of this rare syndrome.