What should be considered when selecting an HIV antiretroviral treatment regimen for a pregnant patient?
||Response from Elise Gilbert, PharmD
Clinical Pharmacist, Northwestern Memorial Hospital, Chicago, Illinois
For pregnant women with HIV infection, treatment with combination antiretroviral therapy (ART) is essential to prevent the transmission of HIV from mother to child. In all patients, irrespective of pregnancy, ART is selected based on patient-specific HIV factors to optimize therapeutic effectiveness, including pre-existing resistance to ART, drug-drug interactions, and adverse drug effects.
Recommendations for ART are similar between pregnant and nonpregnant individuals, in that patients should receive at least three drugs from two different therapeutic classes. Preferred regimens for pregnant patients who have never previously been on HIV therapy include two nucleoside reverse transcriptase inhibitors with either a ritonavir-boosted protease inhibitor or a non-nucleoside reverse transcriptase inhibitor. Examples include, but are not limited to, tenofovir/emtricitabine or lamivudine/zidovudine plus ritonavir-boosted atazanavir, ritonavir-boosted lopinavir, or efavirenz.
In pregnancy, special consideration must also be given to the safety of ART with regard to the fetus. The Antiretroviral Pregnancy Registry, which has collected data on live birth outcomes following in utero exposure to antiretroviral agents during all trimesters of pregnancy since 1989, offers insight into rates of birth defects seen with antiretrovirals. To date, increased risk for overall birth defects has not been seen with in utero antiretroviral exposure compared with the national rate of birth defects. Lamivudine, zidovudine, and lopinavir are categorized as US Food and Drug Administration (FDA) pregnancy category C; while emtricitabine, tenofovir and atazanavir are regarded as FDA pregnancy category B. All of these agents have substantial literature reporting safe and effective use during pregnancy.
The use of efavirenz in pregnancy has been a point of much discussion. Efavirenz is categorized as FDA pregnancy category D, based on early animal data that indicated a possible association between in utero efavirenz exposure and neural tube defects. However, data in humans to date do not support this association. Specifically, a meta-analysis of over 2000 infants with in utero efavirenz exposure found only one instance of neural tube defect, representing a lower incidence than in the general population (0.05% vs 0.1%). Because the neural tube closes in week 5-6 of pregnancy, current perinatal HIV treatment guidelines in the United States recommend initiating efavirenz in women after 8 weeks gestation for women starting or changing treatment regimens containing efavirenz. However, for women who become pregnant while taking efavirenz and present during the first trimester, guidelines now support continuation of efavirenz treatment if the patient has effective HIV viral suppression.
Overall, combination ART is safe and effective for use in pregnancy, with preferred treatment regimens having a strong safety profile. Focusing on adherence to a treatment regimen is important to ensure maternal virologic suppression, which is closely associated with minimization of risk for mother-to-child HIV transmission. Clinicians may offer suggestions for patients to help with adherence, including offering pill boxes and use of reminder alarms or keychain pill holders, among other options. Working with patients to understand if they are experiencing adverse effects and offering treatments or solutions to mitigate these issues may help promote optimal HIV treatment for the pregnant patient.
Clinicians should consider enrolling their patients who receive antiretrovirals during pregnancy in the Antiretroviral Pregnancy Registry. Resulting registry data, like that referenced above, can help clinicians and patients weigh antiretroviral risks and benefits.