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While protection against reinfection is only effective in a restricted set of circumstances, we find that resolution of the primary infection requires persistence of CTL precursors (CTLp), as well as a fast rate of activation of the CTLp. Since these are commonly the defining characteristics of CTL memory, we propose that CTL memory may have evolved in order to clear the virus during primary challenge. W e show experimental data from lymphocytic choriomeningitis virus infection in mice, supporting our theory on CTL memory. We adapt our models to HIV and find that immune impairment during the primary phase of the infection may result in the failure to establish CTL memory which in turn leads to viral persistence. Based on our models we suggest conceptual treatment regimes which ensure establishment of CTL memory. This would allow the immune response to control HIV in the long term in the absence of continued therapy.<\/jats:p>","DOI":"10.1098\/rstb.2000.0570","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T19:55:21Z","timestamp":1027713321000},"page":"329-343","source":"Crossref","is-referenced-by-count":68,"title":["A new theory of cytotoxic T\u2013lymphocyte memory: implications for HIV treatment"],"prefix":"10.1098","volume":"355","author":[{"given":"Dominik","family":"Wodarz","sequence":"first","affiliation":[{"name":"Institute for Advanced Study, Olden Lane, Princeton, NJ 08540, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen M.","family":"Page","sequence":"additional","affiliation":[{"name":"Centre for Mathematical Biology, Mathematical Institute, University of Oxford, 24-29 St Giles', Oxford 0X1 3LB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramy A.","family":"Arnaout","sequence":"additional","affiliation":[{"name":"The Wellcome Trust Centre for the Epidemiology of Infectious Disease, Department of Zoology, University of Oxford, South Parks Road, Oxford 0X1 3PS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan R.","family":"Thomsen","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology and Immunology, The Panum Institute, 3C Blegdamsvej, DK\u20132200 N Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey D.","family":"Lifson","sequence":"additional","affiliation":[{"name":"Laboratory of Retroviral Pathogenesis, AIDS Vaccine Program, SAIC Frederick, National Cancer Institute\u2013Frederick Cancer Research and Development Center, Building 535, Fifth Floor, Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin A.","family":"Nowak","sequence":"additional","affiliation":[{"name":"Institute for Advanced Study, Olden Lane, Princeton, NJ 08540, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2000,3,29]]},"reference":[{"key":"p_1","doi-asserted-by":"crossref","unstructured":"Altman J. 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