Combined Antiretroviral Therapy (cART) During Pregnancy
There are two goals of cART during pregnancy. The first goal is to reduce maternal viral load below the limit of detection throughout pregnancy in order to sustain her immune system and controls opportunistic infection. The second goal is to reduce the risk of mother to child transfer (MTCT) by lowering maternal antepartum viral load and providing infant pre- and postexposure prophylaxis.
Pregnancy presents clinical issues that may require specialized OB/HIV care, including:
- Normal physiologic changes associated with pregnancy and their affects on cART
- altered drug metabolism
- placental drug metabolism
- altered drug absorption
- immune system changes
- fluid/electrolyte changes
- Potential serious maternal side effects of antiretroviral drugs in the pregnant woman
- Potential mother to child transmission
Patient counseling prior to cART should include:
- The importance of consistent and coordinated care between the HIV and Obstetric clinicians should be emphasized.
- Risks and benefits of all medication taken during pregnancy including cART should be discussed with the patient. The importance of reporting side effects and early management should be emphasized.
- The patient should understand the risk of antiretroviral drug-resistance and the critical importance of adherence to the cART regimen as well as the need for antiretroviral drug-resistance studies before starting or modifying a cART drug regimen.
- Individualized discussion of barrier contraception, social support services, mental health services, smoking cessation and drug abuse treatment plans should be included.
Combined Antiretroviral Therapy is recommended for all HIV+ pregnant women regardless of CD4 count and viral load. Current recommendations for beginning antiretroviral therapy are similar to those for a non-pregnant individual. In general, it is recommended that pregnant women who are starting therapy for their own health be treated as soon as possible, including in the first trimester. For women who are beginning therapy only to prevent mother-to-child transmission, delaying cART until after the first trimester can be considered. Regardless of the recommendations, a women's informed decision to use, refuse or delay cART must be respected.
Safety of antiretroviral drugs during pregnancy:
Almost all patients who undergo cART will experience some side effects. Recent studies indicate that there are differences in pharmacokenetics between men and women. Women appear to be at higher risk for ART associated lactic acidosis, nevirapine-associated rash and hepatotoxicity and fat redistribution. Patients need to be able to recognize side effect and report them as early as possible.
- Nucleoside reverse transcriptase inhibitors (NRTI's)
- Rare but serious side effects associated with Zidovudine (ZDV) include: lactic acidosis, hepatic steatosis, pancreatitis and disorders associated with mitochondrial dysfunction.
- Newborn mild anemia has been associated with gestational ZDV
- Non-nucleoside reverse transcriptase inhibitors (NNRTI's)
- Regimens including nevirapine (NVP) are associated with rash, liver toxicity and neurologic effects.
- Women are 3-7 times more likely then men to develop severe rash with NVP
- NVP associated symptomatic liver enzyme elevation may be 2 times greated in women
- NVP based cART increase the risk of serious side effects 10 fold when a pregnant women has a CD4 counts above 250.
- Protease inhibitors (PI)
- Long-term PI use is associated with lipodystrophy, hyperglycemia, onset or exacerbation
of diabetes mellitus and diabetic ketoacidosis.
- Pregnancy is associated with hyperglycemia, PI's may increase the risk.
- Fusion inhibitors
- Enfuvirtide (T-20) is the only FDA-approved fusion inhibitor.
- Little is known about the use of Enfuvirtide during pregnancy.
- Entry Inhibitors
- Maraviroc (Selzentry) is a Pregnancy Category B entry inhibitor, selective for CCR5 tropic HIV-1. It blocks binding between CCR5 and the HIV-1 gp120.
- Little is known about the use of maraviroc (Selzenrty) in humans during pregnancy.
- Pre-and post-natal development studies in the offspring of test animals indicate that the development of the offspring, including fertility and reproductive performance, was not affected by the maternal administration of maraviroc.
Fetal effects associated with ART use
- Chersich, MF; Urban, MF; et al. (2006) Efavirenz use during pregnancy and for women of child-bearing potential. Aids Research and Therapy. 2006 Apr 7;3:11
- no increase was detected in overall risk of birth defects following exposure to efavirenz in the first-trimester.
- DHHS Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission - Updated 8/6/15.
- Data from recently-reported cohort studies and updated Antiretroviral Pregnancy Registry data have reaffirmed the lack of clear association between first-trimester exposure to any ARV drug and increased risk of birth defects.
- The Panel reviewed an updated meta-analysis of studies of defects after efavirenz exposure; this analysis found no association between first-trimester exposure and increased risk of birth defects.
- Efavirenz is now listed in the preferred category, but only with initiation after 8 weeks gestation because of unresolved questions regarding teratogenicity.
- The Panel noted that a recent study found significantly lower bone mineral content in newborns exposed to tenofovir disoproxil fumarate (tenofovir) in utero compared with infants without tenofovir exposure. The clinical significance and long-term outcome of these findings is not clear
- Townsend, C.; Cortina-Borja, M.; et al. (2007) Antiretroviral therapy and premature delivery in diagnosed HIV-infected women in the United Kingdom and Ireland. AIDS 2007, 21:1019–1026
- increased risk of prematurity (<37 wks) associated with ART
- Lower birth weight and increased stillbirth may be associated
- Townsend, C; Willey, B; et al. (2009) Antiretroviral therapy and congenital abnormalities in infants born to HIV-infected women in the UK and Ireland, 1990-2007. AIDS 2009, 23:519-524
- No significant difference of anomaly in exposed infants by timing of exposure or class of drug
- No increased risk of abnormailities in infants exposed to efavirenz or didanosine (small n)
- ART in utero does not pose a major risk in first trimester.
- Watts, DH; Covington, DL; et al. (2004) Assessing the risk of birth defects associated with antiretroviral exposure during pregnancy. American Journal of Obstetrics and Gynecology 2004 Sep;191(3):985-92
- No increase in prevalence of birth defects overall or among women exposed to lamivudine, nelfinavir, nevirapine, stavudine, and zidovudine.
Reducing Mother to Child Transmission (MTCT):
Ideally, antepartum cART will suppress maternal HIV plasma levels to "undetectable" during pregnancy. Several studies indicate that Cesarean delivery prior to labor and rupture of membranes significantly reduces perinatal transmission of HIV. Finally, breast feeding is a known mode of transmission and should be avoided.