One report has described the use of abacavir during human lactation. In a study involving nine mother-infant pairs, the median breast milk and serum levels for abacavir at 1 month postpartum were 0.057 mcg/mL and 0.067 mcg/mL, respectively. The median milk to plasma ratio was 0.85. The authors suggest that this may help lower milk HIV RNA levels but may increase the risk for potential resistance (11). The most common adverse effects in nonpregnant adults were nausea, headache, malaise and fatigue, nausea, vomiting, and dreams/sleep disorders (1). If a woman is receiving this drug while breastfeeding, her nursing infant should be monitored for these effects.

Reports on the use of abacavir during human lactation are unlikely because the drug is used in the treatment of HIV-1 infections. HIV-1 is transmitted in milk, and in developed countries, breastfeeding is not recommended (5,6,8,12, 13, 14). In developing countries, as above, breastfeeding is undertaken despite the risk because there are no affordable milk substitutes available. Until 1999, no studies had been published that examined the effect of any antiretroviral therapy on HIV-1 transmission in milk. In that year, a study involving zidovudine was published that measured a 38% reduction in vertical transmission of HIV-1 infection despite breastfeeding when compared with controls (see Zidovudine).

Abacavir is a synthetic carbocyclic nucleoside analog that is converted by cellular enzymes to the active metabolite, carbovir triphosphate. It is an NRTI used for the treatment of HIV type 1 (HIV-1) (1). Other drugs in this class are didanosine, emtricitabine, lamivudine, stavudine, and zidovudine.

Animal Data: In reproduction studies, doses of abacavir up to 8 times the human therapeutic dose (HTD) based on BSA had no effect on the fertility or mating performance of male and female rats. However, embryo toxicity (increased resorptions, decreased body weight) was observed. During organogenesis, doses up to 35 times the human exposure based on AUC (about 16 times the HTD) resulted in fetal growth restriction (reduced body weight and crown-rump length), as well as increased incidences of fetal anasarca and skeletal malformations. Offspring exposed from implantation through weaning had an increased incidence of stillbirth and survivors had decreased body weights throughout life. In contrast, no developmental toxicity or malformations were observed in rabbits at doses up to 8.5 times the human exposure based on AUC (1).

Placental Transfer: Abacavir crosses the human placenta. In four women being treated with multiple agents for HIV infection, the mean abacavir cord:maternal blood ratio was 1.03 at a mean of 3.5 hours (range 0.4-9.0 hours) after a dose (dose not specified), and the amniotic fluid concentration in one woman was 1.6 mg/L (2). These results are consistent with the relatively low molecular weight (about 671) and high lipophilic properties of abacavir. In an ex vivo human placental model, the antiviral agent readily crossed to the fetal side with a high clearance index of about 50% that of antipyrine (3). No accumulation of the drug was found on the fetal side.

Human Data: The Antiretroviral Pregnancy Registry reported, for the period January 1989 through July 2009, prospective data (reported before the outcomes were known) involving 4702 live births that had been exposed during the 1st trimester to one or more antiretroviral agents (4). Congenital defects were noted in 134, a prevalence of 2.8% (95% confidence interval [CI] 2.4-3.4). In the 6100 live births with earliest exposure in the 2nd/3rd trimesters, there were 153 infants with defects (2.5%, 95% CI 2.1-2.9). The prevalence rates for the two periods did not differ significantly. There were 288 infants with birth defects among 10,803 live births with exposure anytime during pregnancy (2.7%, 95% CI 2.4-3.0). The prevalence rate did not differ significantly from the rate expected in a nonexposed population. There were 1547 outcomes exposed to abacavir (628 in the 1st trimester and 919 in the 2nd/3rd trimesters) in combination with other antiretroviral agents. There were 45 birth defects (19 in the 1st trimester and 26 in the 2nd/3rd trimesters). In reviewing the birth defects of prospective and retrospective (pregnancies reported after the outcomes were known) registered cases, the Registry concluded that except for isolated cases of neural tube defects with efavirenz exposure in retrospective reports, there was no other pattern of anomalies (isolated or syndromic) (4) (see Lamivudine for required statement).

Two reviews, one in 1996 and the other in 1997, concluded that all women receiving antiretroviral therapy should continue to receive therapy during pregnancy and that treatment of the mother with monotherapy should be considered inadequate therapy (5,6). The same conclusion was reached in a 2003 review with the added admonishment that therapy must be continuous to prevent emergence of resistant viral strains (7). In 2009, the updated U.S. Department of Health and Human Services guidelines for the use of antiretroviral agents in HIV-1-infected patients continued the recommendation that therapy, with the exception of efavirenz, should be continued during pregnancy (8). If indicated, abacavir should not be withheld in pregnancy because the expected benefit to the HIV-positive mother outweighs the unknown risk to the fetus. Updated guidelines for the use of antiretroviral drugs to reduce perinatal HIV-1 transmission were also released in 2010 (9). Women receiving antiretroviral therapy during pregnancy should continue the therapy but, regardless of the regimen, zidovudine administration is recommended during the intrapartum period to prevent vertical transmission of HIV to the newborn (9).

A French study of nine antiretroviral agents and birth defects was published in 2014 (10). The study included 5388 live births between 1994 and 2010 that were exposed to an antiretroviral agent in the 1st trimester. No association was found between birth defects and abacavir (10).