A Guide to Primary Care of People with HIV/AIDS - Canadian Public ...

A Guide to Primary Care of People with HIV/AIDS
Chapter 5: Antiretroviral Therapy
Chapter 5:
Antiretroviral Therapy
THE PRINCIPLES OF
ANTIRETROVIRAL THERAPY
(ART)
What are the goals of therapy?
The overall objective of treatment
for HIV disease, as with treatment
for many other infectious diseases,
is to control the putative agent with
antimicrobial agents while providing
other appropriate therapies for HIV-related
complications. The single most important
goal of HIV antiretroviral therapy is to reduce
the HIV viral load to as low as possible for as
long as possible. The 5 other goals of antiretroviral
therapy (ART) are to
• Prevent HIV-associated complications
• Avoid the long-term and short-term adverse drug
reactions associated with antiretroviral agents
• Prevent HIV transmission
• Avoid HIV resistance
• Preserve HIV treatment options
THE PRINCIPLES OF ANTIRETROVIRAL THERAPY (ART)
WHEN TO START THERAPY
WHAT TO START
WHEN TO CHANGE THERAPY
WHAT TO CHANGE TO
RESISTANCE TESTING
KEY POINTS
SUGGESTED RESOURCES
CASES
Does antiretroviral therapy work?
Treatment recommendations have evolved greatly
since zidovudine (AZT), a nucleoside, was first tested
in 1986. The strategy was revolutionized in 1996-97
with the introduction of protease inhibitors (PIs) and
then subsequently non-nucleoside reverse transcriptase
inhibitors (NNRTIs). Combined with AZT and other
nucleosides (see Table 5-1), the result was potent
combination ART (also referred to as highly active
antiretroviral therapy, or HAART) that had an immediate
and dramatic impact on the prognosis for HIV infection,
in fact one of the most impressive changes in any
disease since the introduction of penicillin in the
1940s. Within 2 years there was a 60%-80% decrease
See Glossary of
Antiretroviral
Drugs on
page viii and the
Pocket Guide
John G. Bartlett, MD
in mortality, AIDS rates, and hospitalizations for HIVassociated
complications. Nevertheless, this treatment
was also associated with some disappointments:
there is still no cure for HIV infection, many of the
patients given ART develop serious side effects, and
drug resistance causes many patients to
eventually have virologic failure so that longterm
benefit may be difficult to sustain.
Also, adherence has been shown to be
critical to treatment success, and the level of
adherence required is among the stiffest for
the treatment of any disease in medicine.
WHEN TO START THERAPY
What are the criteria for starting therapy?
The decision to start therapy, like most medical
decisions, depends on the risk-to-benefit ratio of
treatment. ART is given to control HIV replication and
the consequent immune dysfunction, but therapy is also
associated with the development of some substantial
side effects and the risk of developing resistance that
would limit future options. The reduction in CD4 cells is
the pivotal event of HIV disease that renders the patient
susceptible to the unique opportunistic infections (OIs)
and tumors that have come to be known as AIDSdefining
diagnoses (see Table 5-2). The patient becomes
vulnerable to these diseases when the CD4 cell count
decreases from normal levels (500-1500 cells/mm 3 ) to