Biology Reference
In-Depth Information
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Treatment of asymptomatic patients with CD4
cell counts >500 mm
3
should be deferred as long as the probability of signi®cant immune system
damage and of clinical progression of HIV infection remains low.
It should be remembered that CD4
and HIV-1 RNA are good but in-
complete surrogate markers for both natural history and treatment e¨ect, that
thresholds are arbitrary, that the disease process is a biologic continuum, and
that treatment decisions should be individualized according to both baseline
and the trajectory of the available immunological and virological markers
(Chaisson et al., 2000).
Initiation of therapy must be fully discussed with the HIV-infected person,
who should begin a regimen only if he or she is committed to complete adher-
ence and fully understands the advantages and the potential drawbacks and
burden of antiretroviral therapy.
Finally, it has to be considered that current debate surrounding initiation
of therapy underscores inadequacies of current agents. When simple, potent,
durable, nontoxic regimens become available, the pendulum may swing again
toward a more aggressive approach.
GOAL OF ANTIRETROVIRAL THERAPY AND AVAILABLE OPTIONS
FOR THERAPY INITIATION
Data from several studies indicate that the nadir of the virologic response and
the rapidity with which virus replication is suppressed are strongly predictive of
the likelihood of achieving a durable virologic response, suggesting that little or
no virus evolution occurs in the residual virus population when plasma HIV-1
RNA is persistently suppressed to below the limits of quanti®cation of ultra-
sensitive assays for viral load. In particular, no evidence was found for the
emergence of drug resistance mutations when viral sequences recovered from
lymph nodes or peripheral blood lymphocytes of these subjects were analyzed.
As previously pointed out, physicians and persons living with HIV/acquired
immunode®ciency syndrome (AIDS) need, therefore, to weigh the risks and
bene®ts of starting antiretroviral therapy and make individualized decisions
about when to initiate therapy. However, once the decision to start has been
made, the ultimate goal of treatment should be the maximal suppression of HIV
replication, because the major short-term risk of any continuing viral replication
in the presence of antiretroviral therapy is the emergence of drug resistance.
To achieve this goal, particularly in persons being treated for the ®rst time,
several strategies are now available.
Regimens are usually composed of three or four drugs and may include (on
a two nucleoside reverse transcriptase inhibitors [NRTI] backbone), one (or
two) protease inhibitors ( PI ), or a non-nucleoside reverse transcriptase inhibi-
tor ( NNRTI). Regimens including three NRTIs are also increasingly being
used.
