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chapter 35 Antiretroviral Drugs 223
early—which is a problem because symptoms
are typically delayed (for months) in onset
and may be nonspecific in initial presentation.
Agents with a higher propensity for this toxicity
include stavudine, didanosine, and zidovudine.
Didanosine and zidovudine may also contribute
to hyperlipidemia, insulin resistance, and
lipoatrophy (loss of fat causing changes in
appearance, primarily in the face and buttocks).
Renal: Nephrotoxicity, evidenced by increased
serum creatinine and renal electrolyte and
protein wasting, is a well-documented adverse
effect of tenofovir and requires regular monitoring
of renal function.
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Important Facts
• Most of the NRTIs require dosage adjustment
in renal dysfunction. This may require avoiding
the fixed-dose combination preparations to
give more dose flexibility.
• NRTIs have fewer metabolic drug interactions
compared with the other antiretroviral drug
classes. Tenofovir should not be co-administred
with didanosine and when given with atazanavir
may require dosage adjustment of
atazanavir.
• Didanosine, stavudine, and zidovudine tend to
have the most toxicity and are now mostly used
as second-line treatment for resistant cases.
• Various patterns of cross-resistance among the
NRTIs occur. Expert interpretation of antiviral
susceptibility is required, and in some cases
NRTIs may confer a therapeutic benefit even
for resistant viruses.