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chapter 35 Antiretroviral Drugs 231
with other PIs. Management is with all the
mainstays of cardiovascular risk prevention
(diet, exercise, drugs).
Gastrointestinal: All PIs are pretty hard on the
GI tract (nausea, vomiting, diarrhea). Taking
the drugs with food may reduce the symptoms
somewhat. Many patients find the effects
more tolerable with time. Severe cases may
require administration with antiemetics or
antidiarrheals.
Hepatotoxicity: The potential for hepatotoxicity
exists with all PIs, ranging from asymptomatic
transaminase elevations to clinical hepatitis.
Risk may be highest with boosted tipranavir.
Metabolic: One means by which PIs increase cardiovascular
risk is through adverse effects on
the lipid profile. The PIs are also associated
with lipohypertrophy (fat accumulation in
abdomen, breasts, and neck).
Nephrotoxicity: Renal toxicity caused by certain
PIs precipitating in the kidneys or ureters has
been reported. This toxicity is most common
with the now infrequently used agent indinavir,
and it is reported rarely with atazanavir
and fosamprenavir. Adequate fluid intake is
recommended for prevention.
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Important Facts
• Compared with the NNRTIs, PIs are more robust
to antiviral resistance. Typically, several mutations
in the target enzyme are required to confer
high-level resistance. Thus, PI-based regimens
may be slightly more “forgiving” of less than perfect
adherence—although, of course, that’s probably
not the message to convey to your patients.