Page 55 - AIDSBK23C

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RNA levels in plasma. The HIV-1 RNA in plasma gives a good indication of the level of a
therapeutic response.[368] The toxic effects of the medications and intolerance may require that
an alternative regimen be considered. In addition, failure of patient compliance may force a
change. If the patient were on a suboptimal regimen, such as a single antiretroviral agent, then a
change would be indicated. A minimum of two CD4 cell counts and two HIV-1 RNA assays are
recommended prior to initiating or changing antiretroviral therapy.[256]
The use of combinations of antiretroviral drugs mitigates onset of HIV resistance. Every
HIV-infected person has multiple genetically related viral variants because of the high
replication rate of HIV coupled with its error-prone replication process that has frequent
recombination events leading to new HIV variants. Combinations of antiretroviral drugs are
advantageous for treatment because it is unlikely that pre-existing viral variants will be resistant
to more than three drugs in treatment naïve subjects. Suppression of viremia will slow the rate of
viral evolution. New antiretroviral drugs may be more efficacious against mutants. In addition,
increased drug levels can be obtained by use of pharmacokinetic enhancement with ritonavir or
other compounds. Virologic failure not adequately addressed can lead to greater evolution of
viral resistance that can include cross-resistance that requires more complex at toxic
antiretroviral regimens that are less tolerable, making patient adherence more difficult, with a
downward spiral to shorter duration of HIV suppression and re-emergence of virologic failure.
Drug potency coupled with viral suppression is inversely proportional to evolution of viral
resistance.[303]
Prevention and management of antiretroviral drug resistance can be summarized as
follows:[303]

 Systematically screen for the presence of primary antiretroviral resistance in all patients
entering clinical care, preferably as soon as possible after infection.
 Adjust the design of first-time treatment regimens to the genotypic resistance information
obtained if needed. Obtaining a genotype from a patient as soon as he/she enters into
clinical care may allow an increased detection of transmitted resistant viruses, which
becomes harder to detect with time.
 Once primary resistance is ruled out, good adherence, forgiving pharmacology, drug
potency, and high genetic barrier are the principal factors associated with reduced
emergence of antiretroviral resistance.
 Ritonavir-boosted protease inhibitor (PI)-containing regimens are associated with low
rates of PI resistance at treatment failure and lower rates of NRTI resistance than
NNRTI-based regimens.
 On the other hand, first-line efavirenz-based regimens are more resilient to virological
failure than ritonavir-boosted PIs tested to date, possibly due to lower compliance on
PI regimens because of side effects.
 It is crucial to detect virological failure early and change failing therapy as soon as failure
is confirmed, with the aim to re-suppress viral replication to <50 copies/mL.
 Use 2 or 3 new agents to achieve durable viral suppression and prevent the future
emergence of viruses with resistance to 6-drug classes.

Despite antiretroviral therapy, proliferating CD4 lymphocytes and follicular dendritic
cells within lymphoid tissues, and macrophages throughout the body, particularly in the central