Biology Reference
In-Depth Information
tration that dramatically impact adherence to the regimens. All available drugs
also have important short- and long-term toxicities, and broad cross-resistance
can emerge among existing drugs of the same class.
CONSIDERATIONS ON WHEN TO START
ANTIRETROVIRAL THERAPY
Controversies continue over the best time to initiate antiretroviral therapy
(Carpenter et al., 2000; US-DHHS, 2000). Ideally, to prevent progressive or
irreversible immune damage, treatment should be initiated early in the course
of the disease. Early initiation of antiretroviral treatment seems justi®ed for
several reasons: HIV infection almost invariably causes progressive immune
damage; disruption of the immune system and the building of viral reservoirs
are early events; and the natural history of untreated HIV infection includes
selection for more diverse and more virulent strains of HIV.
Early start, however, must be balanced against the drawbacks of long-term
therapy. Evidence is now present that the risk of disease progression is low until
substantial CD4 cell loss has occurred, and that immune recovery is impressive
even in delayed therapy (Autran et al., 1999; Kaufman et al., 2000). Early
initiation of treatment may expose patients to unnecessary medication-related
risks, which range from adherence problems and impact on quality of life to the
potential for early development of resistance to antiretroviral agents and the
possibility of serious metabolic complications.
Moreover, the ®nal target of therapy is not viral load per se, but preservation
of the overall health of the patient, taking care of the quality in addition to the
quantity of life. It is well known that long-term adverse e¨ects of therapy are
su½ciently serious, and many patients achieve only incomplete or transient
control of viral replication, resulting in selection for resistant strains of HIV.
Given all these reasons, it is now considered inappropriate to initiate therapy,
in the asymptomatic individual, at a time when the CD4 count indicates no
appreciable risk for serious opportunistic infections. This has translated, in the
past 2 years, into an increasing tendency to defer initiation of therapy until
immune de®ciency becomes relevant and the risk of disease progression be-
comes signi®cant.
The following criteria may guide selection of patients for initiation of
therapy:
.
All patients with symptomatic HIV infection, regardless of CD4
count
and viral load levels and all patients with CD4
counts <350/mm
3
should
start antiretroviral therapy.
.
Treatment could also be considered for patients with a high viral load (i.e.,
>50,000±100,000 copies/ml) regardless of the absolute number of CD4
lymphocytes, and for persons with CD4
cell counts between 350 and
500/mm
3
.
