Biology Reference
In-Depth Information
sent the major cause of virological failure. Furthermore, in spite of the apparent
large number of drugs and the high number of theoretical combinations, cross
reactivity among drugs of the same class means that therapeutic options remain
limited. More potent drugs that are safer and easier to administer, with better
pharmacological properties and with activity against drug-resistant viruses are
therefore needed. In the meantime, all e¨orts should be directed toward pro-
longing the e¨ect of the initial antiretroviral treatment. Indeed, many con-
trolled studies have proven that the nadir of initial response correlates well with
the durability of response and that achieving an early sustained response (by
week 4 and/or 8 of therapy) is predictive of subsequent virologic suppression
( Raboud et al., 1998). Plasma HIV-1 RNA levels should decrease rapidly after
therapy is initiated (a minimum of a 1.5±2.0 log decline should occur over the
®rst 4 weeks of therapy) and failure to achieve the target level of <50 copies/ml
by 16±24 weeks (although in persons with higher plasma HIV RNA levels at
baseline, e.g., >100,000 copies/ml, maximal viral suppression may take longer)
should raise concern and prompt review of drug adherence, drug absorption, or
the presence of drug-resistant virus. Intensi®cation strategy is actually inves-
tigated in two di¨erent situations: failure to establish initial control of virus
replication and ``early'' treatment failure after initial complete virological re-
sponse. In persons with low but detectable HIV RNA following 12±16 weeks of
potent therapy (but without identi®ed resistance to drugs in current regimen),
or with early HIV-RNA rebound after full suppression, the addition of a new
drug could be an alternative to a complete change, after other causes of the
treatment failure ( particularly incomplete adherence) are ruled out.
Advantages of intensi®cation strategies may include the fact that the lack of
su½cient potency of a regimen does not necessarily imply drug resistance and
that this strategy may allow preservation of drugs that remain potentially use-
ful. Moreover, it could avoid initial use of additional drugs in persons who may
not need them.
However, disadvantages of intensi®cation strategies include the fact that
inadequate virologic response could be due to the presence of drug-resistant
variants. In this case, because there is a thin line between intensi®cation and
incremental therapy, further drug resistance may be promoted. Moreover, in-
tensi®cation could aggravate problems with adherence in the poorly adherent
patient and could complicate problems with drug interactions.
Structured Treatment Interruptions
Two di¨erent approaches are guiding the ongoing e¨orts to de®ne the role of
structured (or strategic) treatment interruptions (STI ) in current antiretroviral
strategies.
The original targets for STI strategy were persons having experienced mul-
tiple failures and with no residual therapeutic options. The principle behind STI
was a possible reversion of the mutant virus to the wild type, with a potential
Search WWH ::




Custom Search