4.1. AIDS General Treatment Information: Beginning Therapy -- What and When
Description
This article is from the AIDS FAQ, by Dan Greening with numerous contributions by others.
4.1. AIDS General Treatment Information: Beginning Therapy -- What and When
Probably the easiest question at the moment in the field of HIV
therapy is which drug to use to begin treatment. Data from ACTG 116A
make it clear that zidovudine is superior to ddI as a monotherapy in
previously untreated patients, and data from other studies show the
superiority of zidovudine over ddC. An independent "State of the Art
Panel" recently convened by the National Institute of Allergy and
Infectious Diseases (NIAID) and chaired by Merle Sande, MD, UCSF chief
of the medical service at San Francisco General Hospital, found an
easy consensus that zidovudine monotherapy is the initial therapy of
choice. Even here, however, other opinions may be heard, especially
concerning the potential for initial use of combinations of nucleoside
analogs. For example, the recent ACTG 155 trial in much more advanced
disease tended to show a superiority of the combination of zidovudine
and ddC, which was limited to patients with the highest CD4 cells
(between 150 and 300). A large study, ACTG 175, is comparing initial
combination with monotherapy, but the results from this trial are not
anticipated before the end of 1995. In the meantime, combinations
including zidovudine with ddI or zidovudine with ddC as initial
therapy remain of interest. When best to initiate antiretroviral
therapy is probably the most controversial question in the field of
HIV management. Extended data from ACTG 019 demonstrate durable
clinical progression benefit with the use of 500 mg of zidovudine
daily in patients with asymptomatic HIV infection and with CD4 cell
counts between 300 and 500, but these data are in apparent conflict
with those from the recently completed Concorde Study. Concorde,
enrolling more than 1700 patients with any level of CD4 count,
compared the initial use of one gram of zidovudine daily with the same
therapy deferred until after the person developed AIDS or ARC. After a
median treatment duration of three years, and despite a clear and
sustained CD4 improvement with the immediate use of zidovudine, there
was no apparent benefit in the immediate treatment group either in
clinical progression or survival. When the investigators analyzed a
subset of the overall group with CD4 counts below 500 cells and after
one year of therapy, a benefit similar to that seen in ACTG 019 was
observed. Although Concorde was a powerful study, given the size and
duration of follow-up, concerns have been raised that the dosage at
one gram was excessively high and that the large number of patients
allowed to begin therapy before they became symptomatic complicates
the analysis. Also adding to the confusion are the recently published
results of the European-Australian cooperative Group trial, which
tended to find a clinical benefit with the use of zidovudine in
patients with CD4 counts up to 750 cells. The State of the Art Panel
recommended two broad options after considering the available
data--initiating therapy in asymptomatic individuals with CD4 counts
under 500 cells, or delaying this therapy until symptomatic HIV
disease intervened. Another option favored by many clinicians is to
follow patients, delaying therapy until evidence of more rapid disease
progression becomes apparent as manifested by rapid declines in CD4
count or by a rise in p24 antigen or, especially, a rise in beta-2
microglobulin. At any rate, the clinician must discuss the various
options with each patient, individualizing this decision according to
the clinical and laboratory status of the patient and according to the
patient's own desires.
Continue to:
My Books
