title: Simian-human immunodeficiency infection--is the course set in the acute phase?
abstract: Identifying early predictors of infection outcome is important for the clinical management of HIV infection, and both viral load and CD4+ T cell level have been found to be useful predictors of subsequent disease progression. Very high viral load or extensively depleted CD4+ T cells in the acute phase often result in failure of immune control, and a fast progression to AIDS. It is usually assumed that extensive loss of CD4+ T cells in the acute phase of HIV infection prevents the establishment of robust T cell help required for virus control in the chronic phase. We tested this hypothesis using viral load and CD4+ T cell number of SHIV-infected rhesus macaques. In acute infection, the lowest level of CD4+ T cells was a good predictor of later survival; animals having less than 3.3% of baseline CD4+ T cells progressed to severe disease, while animals with more than 3.3% of baseline CD4+ T cells experienced CD4+ T cell recovery. However, it is unclear if the disease progression was caused by early depletion, or was simply a result of a higher susceptibility of an animal to infection. We derived a simple relationship between the expected number of CD4+ T cells in the acute and chronic phases for a constant level of host susceptibility or resistance. We found that in most cases, the depletion of CD4+ T cells in chronic infection was consistent with the prediction from the acute CD4+ T cell loss. However, the animals with less than 3.3% of baseline CD4 T cells in the acute phase were approximately 20% more depleted late in the infection than expected based on constant level of virus control. This suggests that severe acute CD4 depletion indeed impairs the immune response.
authors.affiliation: Complex Systems in Biology Group, Centre for Vascular Research, University of New South Wales, Sydney, Australia.
authors.forename: Janka
authors.initials: J
authors.lastname: Petravic
authors.forename: Miles P
authors.initials: MP
authors.lastname: Davenport
mesh_terms: D000210:Acute-Phase Reaction / Q000209:etiology*; D000818:Animals; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000821:virology; D018450:Disease Progression; D015658:HIV Infections / Q000175:diagnosis* / Q000209:etiology* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000254:growth & development / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation; D008253:Macaca mulatta / Q000276:immunology / Q000821:virology; D008992:Monkey Diseases / Q000175:diagnosis / Q000209:etiology / Q000276:immunology / Q000821:virology; D011379:Prognosis; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000473:pathology / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology / Q000502:physiology; D019562:Viral Load