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chapter 35 Antiretroviral Drugs 227
the most feared manifestations of nevirapine
hypersensitivity reactions. Interestingly, this
syndrome appears to be more frequent in patients
who are less immunocompromised (have higher
CD4 counts) when starting nevirapine. The risk
of nevirapine hypersensitivity syndrome may be
reduced by using a “reverse taper” upon drug initiation:
start with a lower dose and escalate to
full dose over two weeks, when the risk is highest.
Metabolic: Lipohypertrophy, manifesting as a
gradual accumulation of fat in the abdomen,
chest, and neck (as a “buffalo hump”), may
occur with the NNRTIs. Efavirenz and nevirapine
have also been linked to hyperlipidemia.
Compared to efavirenz, rilpivirine showed less
of an effect on lipid profiles.
Pregnancy/Lactation: Efavirenz is a pregnancy
category D agent and should not be offered to
pregnant women or those trying to conceive or
not using effective birth control. Other NNRTIs
are pregnancy category C, except rilpivirine,
which is category B.
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Important Facts
• A key limitation of NNRTIs has been the low
“genetic barrier” to resistance. A single point
mutation can lead to high-level resistance to
the entire class of drugs. Thus, even stricter
adherence may be necessary to NNRTI-based
regimens to prevent the emergence of resistance.
The advanced-generation agents etravirine
and rilpivirine possess activity against
viruses with some NNRTI mutations, and may
have roles for patients who have failed either
efavirenz or nevirapine.