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(2013) The safety and effect of multiple foses of vorinostat on HIV transcription in HIV+ patients receiving cART. [Abstract 50LB]. In: 20th Conference on Retroviruses and Opportunistic Infections 3\u20136 March 2013. Atlanta, Georgia, United States of America."},{"key":"ref40","unstructured":"Rasmussen T, CLEAR study group (2014). Panobinostat induces HIV transcription and plasma viremia in HIV patients on suppressive cART. [Abstract 438LB]. In : Conference on Retroviruses and Opportunistic Infections 3\u20136 March 2014. Boston, Massachusetts, United States of America."},{"key":"ref41","doi-asserted-by":"crossref","first-page":"5958","DOI":"10.1128\/JVI.00161-10","article-title":"Combinatorial latency reactivation for HIV-1 subtypes and variants","volume":"84","author":"JC Burnett","year":"2010","journal-title":"J Virol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"9078","DOI":"10.1128\/JVI.00836-11","article-title":"Epigenetic silencing of HIV-1 by the histone H3 lysine 27 methyltransferase enhancer of Zeste 2","volume":"85","author":"J Friedman","year":"2011","journal-title":"Journal of Virology"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1097\/QAD.0b013e32835535f5","article-title":"Histone methyltransferase inhibitors induce HIV-1 recovery in resting CD4(+) T cells from HIV-1-infected HAART-treated patients","volume":"26","author":"S 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