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Abstract: The viral enzymes reverse transcriptase
and protease are the current targets for antiretroviral
therapy (ART). The use of a combination of inhibitors
targeting these enzymes can reduce viral load for a
prolonged period and delay disease progression. However,
complications of ART, including the emergence of viruses
resistant to current drugs, are driving the development
of new antiretroviral agents targeting not only the
reverse transcriptase and protease enzymes but novel
targets as well. CCR5 and Integrase inhibitors have
recently been approved for use in HIV treatment. The
durg targets, which are under investigation, include
CCR5 and CXCR4, maturation inhibitors, gene therapy,
viral envelope protein (env). Novel virus that targets
HIV-1-infected cells and Human deoxyhypusine synthase
(DHS) are discussed as novel targets for HIV therapy.A
multifaceted approach to ART, using combinations of
inhibitors that target different steps of the viral life
cycle, has the best potential for long-term control of
HIV infection. This review outlines the key drug targets
and steps where pharmacologic intervention can have a
favorable therapeutic benefit.
Introduction: Current targets for antiretroviral
therapy (ART) include the viral enzymes reverse
transcriptase and protease. The use of a combination of
inhibitors reduce viral load for a prolonged period and
delay disease progression. The existence of viruses
resistant to current antiretroviral, and transmission of
drug-resistant strains, complication and toxicity of
current regimen are driving the development of new
antiretroviral agents targeting not only the reverse
transcriptase and protease enzymes but novel targets as
well.
HIV entry into susceptible cells, the integration of HIV
DNA into the host cell genome, virion maturation etc.
are currently promising emerging targets for ART as
shown in figure 1. Inhibitors of novel targets are most
likely to be fully active against resistant viruses and
present new treatment options for individuals with multi
drug resistant viruses. Therefore, inhibitors against
new targets will complement and diversify current
treatment options, and may act additively or
synergistically with other inhibitors.
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