Document 0833
 DOCN  M95A0833
 TI    Early versus delayed treatment of HIV infection. Zidovudine should be
       given before symptoms develop.
 DT    9510
 AU    Richman DD; Havlir D; Department of Pathology, University of California
       San Diego, La; Jolla, USA.
 SO    Drugs. 1995;49 Suppl 1:9-16; discussion 38-40. Unique Identifier :
       AIDSLINE MED/95339783
 AB    An understanding of the virology and pathogenesis of HIV infection
       provides a rationale for initiating early intervention with
       antiretroviral drugs. Even at the earliest stages of infection when
       HIV-infected patients are asymptomatic, viral replication is ongoing,
       particularly in lymphoid tissues. Initiation of antiretroviral therapy
       can reduce viral replication and delay disease progression. A possible
       objection to early intervention therapy with zidovudine is the risk of
       selecting out resistant isolates of HIV, which would be difficult to
       treat. In practice, zidovudine-resistant isolates occur significantly
       less frequently in patients with early-stage disease compared with those
       with late-stage HIV infection, thus supporting the early use of
       zidovudine; in addition, alternative therapies, active against
       zidovudine-resistant isolates, are available. Clinical trials with
       zidovudine in asymptomatic patients have differed in terms of length of
       follow-up, patient inclusion criteria, dosages and end-points. However,
       a number of conclusions are possible based on the results obtained:
       early intervention delays the progression of AIDS, delays the onset of
       symptomatic disease, has a favourable effect on surrogate markers of HIV
       infection and is well tolerated; it does not, however, seem to produce
       any benefit in terms of survival. It is this last point that has given
       rise to much of the controversy regarding early intervention with
       zidovudine in asymptomatic patients. Since the disease is progressive in
       nature with persistent and high levels of viral replication and as
       prolonging the period of relative health and quality of life when the
       patient is asymptomatic is desirable, the choice to treat before
       symptoms develop would appear to be the optimal therapeutic strategy.
 DE    Clinical Trials  Comparative Study  CD4 Lymphocyte Count  Human  HIV
       Infections/*DRUG THERAPY/IMMUNOLOGY/MORTALITY  Support, U.S. Gov't,
       Non-P.H.S.  Support, U.S. Gov't, P.H.S.  Survival Analysis  Time Factors
       Virus Replication/DRUG EFFECTS  Zidovudine/*ADMINISTRATION & DOSAGE
       JOURNAL ARTICLE  REVIEW  REVIEW, TUTORIAL

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