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3–30 | Clinical Manual for Management of the HIV-Infected Adult/2006
Fusion Inhibitor
Antiretroviral Drug Pharmacokinetics in Pregnancy Concerns in Pregnancy Rationale for Recommended Use in Pregnancy
Insufficient Data to Recommend Use
Enfuvirtide (Fuzeon) No studies in human pregnancy. No experience in human
pregnancy.
Safety and pharmacokinetics data in pregnancy are insufficient to
recommend use during pregnancy.
Source: Centers for Disease Control and Prevention. Table 3. Antiretroviral Drug Use in Pregnant HIV-Infected Women: Pharmacokinetic and Toxicity Data in Human Pregnancy and Recommendations for Use in Pregnancy.
In: Public Health Service Task Force Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV-1 Transmission in the United States.
October 12, 2006. Available online at http://aidsinfo.nih.gov/Guidelines/GuidelineDetail.aspx?GuidelineID=9.
Key to abbreviations: HGC = hard-gel capsule; NNRTI = nonnucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; NtRTI = nucleotide reverse transcriptase inhibitor; PI = protease
inhibitor; PK = pharmacokinetic; SGC = soft-gel capsule.
Adverse Antiretroviral Drug
Events during Pregnancy
Concerns have been raised about complications and
toxicities related to ART during pregnancy. For
example, a European study found a 2-fold increase in
preterm birth among mothers who started combination
therapy before pregnancy. A metaanalysis of 7 U.S.
clinical trials, however, found that ARV use was not
associated with preterm labor, low birth-weight,
low Apgar scores, or stillbirth. Until more is known,
pregnant women who are taking combination regimens
should be monitored closely for complications and
toxicities and should be educated about the signs of
premature labor.
Nucleoside reverse transcriptase inhibitors can cause
mitochondrial dysfunction with long-term use. Clinical
disorders linked to mitochondrial dysfunction include
symptomatic lactic acidosis and hepatic steatosis, which
are seen more commonly in women than in men. Three
maternal deaths were reported in the United States in
women taking ARV regimens that included ddI and
d4T in combination with other ARVs. Patients with
lactic acidosis with hepatic steatosis often present with
1-6 weeks of symptoms including nausea, vomiting,
abdominal pain, dyspnea, and weakness. Because some
of the symptoms of lactic acidosis/hepatic steatosis
syndrome can mimic those of pregnancy, clinicians must
be alert for early signs and symptoms of lactic acidosis
and evaluate them promptly. The combination of ddI
and d4T should be avoided during pregnancy, and used
only when other effective options are not available
(Table 2).
Women, including pregnant women, who begin
nevirapine therapy when their CD4 count is >250 cells/
µL have a 9.8 times higher incidence of hepatotoxicity
than women initiated on nevirapine at lower CD4
counts. Symptoms of hepatotoxicity include fatigue,
malaise, anorexia, nausea, jaundice, liver tenderness,
and hepatomegaly. Nevirapine should be initiated as
part of an ARV regimen in pregnant women with CD4
cell counts >250 cells/µL only if the benefits clearly
outweigh the risks (Table 2).
Hyperglycemia, new-onset diabetes, worsening diabetes,
and diabetic ketoacidosis have been reported in patients
taking protease inhibitors. In addition, pregnancy
itself is a risk factor for hyperglycemia. Clinicians
should monitor closely the glucose level of pregnant
women taking PIs and should educate them about the
symptoms of hyperglycemia. (See chapter Care of HIV-
Infected Pregnant Women.)
Recommendations for Antiretroviral Chemoprophylaxis
to Reduce Perinatal HIV Transmission
The Perinatal HIV Working Group has offered
recommendations on ARV prophylaxis to reduce
perinatal HIV transmission based on 4 clinical
scenarios:
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♦
♦
♦
HIV-infected women who have not received
previous ARV therapy
HIV-infected women receiving ARV therapy during
the current pregnancy
HIV-infected women in labor who have had no
previous therapy
Infants born to HIV-infected women who received
no ARV therapy during pregnancy or intrapartum
Recommendations for ART in these 4 clinical scenarios
are listed in Table 3.