Predicting AIDS progression
Mallal, S. (1996) Predicting AIDS progression. In: Australasian Society for HIV Medicine 8th Annual Conference: Preventing Transmission, Promoting Health, 14 - 17 November 1996, Australian Jockey Club, Sydney
Most of the potential opportunistic pathogens which threaten a patient with progressive HIV-induced immunodeficiency are either ubiquitous or already present in the host. An opportunistic infection gradually develops as the critical protective immune responses to that organism fail. The risk of a particular opportunistic infection such as PCP can be predicted by clinical and laboratory markers of immunodeficiency, taking into account prophylactic and antiretroviral treatment. Primary prophylactic treatments have altered the pattern of AIDS illnesses. However these prophylactic regimens are only partially effective and infection, albeit less severe, still occurs with profound immunodeficiency. Antiretroviral therapy (ART) restores immune responses to potential opportunistic pathogens to a variable extent. However, unlike prophylactic therapies whose efficacy remains relatively constant over time, ART may have a transient or time limited benefit. Relevant statistical modelling approaches will be discussed. It is interesting to consider the statistical models of progressive HIV-induced immunodeficiency in the context of the evolution of host immunity. HIV infection results in the loss of the relatively recently evolved adaptive CD4 T-cell mediated immunity to intracellular parasites and the host may compensate using older, more innate protective responses. Like most immune responses, these compensatory responses are polymorphic and therefore genetic and ethnic differences between individuals may be revealed as HIV disease progresses. Data will be presented from the WA HIV Cohort study to support a two-stage model of immunopathology. The first stage of loss of mucosal immunity occurs at a variable CD4 count (of between 400/cu mm and zero) and is marked by a loss of cutaneous delayed type hypersensitivity responses and oral candidiasis, seborrhoeic dermatitis and Pneumocystic pneumonia. The second stage of loss of systemic immunity requires profound CD4 T-cell lymphopaenia (CD4 count less than 50/cu mm) and is marked by infections such as Cytomegalovirus and disseminated Mycobacterium avium infection. The influence of HLA type on the risk of such opportunistic infections becomes apparent during this late phase.
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