Table 3. Guide for Healthcare Providers on Counseling Women About Dolutegravir Use[ref: DHHS Perinatal]

Use of Dolutegravir in Pregnant Women or Women Who Are Trying to Conceive

 

  • Background risk of neural tube defects in the general population is 0.07%.

 

  • The US DHHS Panel on Treatment of Pregnant Women with HIV Infection and Prevention of Perinatal Transmission recommends [drug: dolutegravir] as a preferred antiretroviral drug in women who are trying to conceive and throughout pregnancy, in combination with the appropriate counseling and informed decision-making.[ref: DHHS Perinatal]

 

  • An analysis of a National Institutes of Health – funded birth surveillance study in Botswana including 3591 women revealed that the neural tube defect prevalence among infants born to women receiving [drug: dolutegravir] are much more comparable to the prevalence for infants exposed to non-[drug: dolutegravir] ART during conception (0.19% vs 0.11%, respectively),[ref: Zash 2020] and thus, the risk is higher than the risk for neural tube defects in infants born to women who were receiving [drug: efavirenz] (0.05%) and women without HIV (0.08%). But, the risk of neural tube defects in infants exposed to [drug: dolutegravir] around the time of conception was no longer significantly increased when compared with infants exposed to any non-[drug: dolutegravir] ARV drug around the time of conception.
  • Data have not shown an increased risk of neural tube defects in infants born to women who started [drug: dolutegravir] during pregnancy With the exception of [drug: efavirenz], there are not enough data to determine the risk of neural tube defects with periconception use of any of the other currently recommended preferred or alternative drugs. The Botswana data rule out a ≥ 3-fold increase in the risk of neural tube defects associated with periconception use of [drug: efavirenz].
  • Data available studies have not shown an increase in the risk of neural tube defects in infants born to women who started [drug: dolutegravir] during pregnancy.
  • Not enough [drug: dolutegravir] periconceptional exposures have been reported to the Antiretroviral Pregnancy Registry to evaluate whether an increased risk of neural tube defects exists in the United States at this time.
  • H ealthcare pr ofessionals and patients should discuss future childbearing plans, the potential risks and benefits of conceiving while receiving specific ARV medications, including [drug: dolutegravir], and contraceptive options to prevent unintended pregnancy.
  • Folic acid has been shown to lower the risk of neural tube defects in the general population and 400 μ g/day is recommended during conception and throughout pregnancy by the US Public Health Service. Food in the United States, unlike in Botswana, is routinely fortified with folate. However, a causal association has not been established between [drug: dolutegravir] and impaired folate metabolism, and it is not known if folic acid supplementation will help prevent neural tube defects in infants of women receiving [drug: dolutegravir].

 

  • Healthcare professionals should help women adequately consider the risks of neural tube defects with [drug: dolutegravir] against the available information about risks of neural tube defects with other ARV drugs recommended for use in pregnancy. Despite a warning in the FDA label against use in the first trimester of pregnancy, a 3-fold (or greater) increase in the risk of neural tube defect s in infants who were exposed to [drug: efavirenz] has been ruled out with data from Botswana, and thus, the Panel recommends [drug: efavirenz] as an “alternative” ARV drug for pregnant women and women who are attempting to conceive.

 

  • Healthcare professionals should help women consider any other risks associated with ARV drugs, such as other birth defects or adverse pregnancy outcomes, such as preterm delivery.

 

 

 

  • ART changes during pregnancy can lead to viral load increases and, therefore, an increased risk of perinatal HIV transmission. In addition, this viral rebound may adversely affect future ARV choices due to the potential development of drug resistance.

 

  • Women receiving ARVs that are not “preferred” or “alternative” options for pregnant women and women who are attempting to conceive should be counseled about the risks and benefits of remaining on their current ART or changing to another ARV drug

 

  • When assessing the benefits and risks of switching a patient from an effective current regimen to another for the purpose of reproduction health, healthcare professionals and patients should consider 1) the feasibility of the switch being successful; 2) each drug’s tolerability; 3) the ability to maintain viral suppression; 4) drug anticipated efficacy, including in prevention of perinatal HIV transmission; and 5) the risk of adverse pregnancy and neonatal outcomes, including, but not limited to, neural tube defects, preterm birth, small for gestational age; 6) the likelihood of adherence to the new regimen (eg, when changing from a simple daily to a twice-daily regimen).

 

  • Women who are trying to conceive should make informed decisions before becoming pregnant, which can be enabled by receipt of information on the use of specific ARV regimens during pregnancy.
  • All cases of ARV drug exposure during pregnancy should be reported to the Antiretroviral Pregnancy Registry.

 

Other ARV Drugs That Are Recommended for Use in Pregnancy

Other preferred ARV drug options for women who are initiating ART while pregnant or trying to conceive include [drug: raltegravir], [drug: atazanavir]/[drug: ritonavir], and [drug: darunavir]/[drug: ritonavir]. Although data are reassuring on pregnancy outcomes and birth defects with these agents, rigorous, systematic birth surveillance programs like the Botswana study do not exist for these drugs. In addition, the risk of neural tube defects in the United States is low in the general population due to mandatory food folate fortification, and there are currently insufficient data in the United States to be able to determine whether there is an increase in the risk of neural tube defects associated with [drug: dolutegravir] in the United States.

  • [drug: Efavirenz], and [drug: rilpivirine] are recommended as alternative ARV drug options in pregnancy. These drugs may have more limited data on use in pregnancy vs preferred drugs or may be associated with more pharmacokinetic, dosing, tolerability, drug interaction, or resistance concerns.
  • Not all drugs recommended for use in adults and nonpregnant women are preferred or alternative options for women who are pregnant or who are trying to conceive because:
  • Not enough is known about the safety of using some ARV drugs before or during pregnancy because studies about their use in pregnancy are limited. Of note, a lack of data does not indicate the absence or presence of risk — only that data are lacking.
  • For some ARV drugs, pharmacokinetic changes during pregnancy decrease blood levels of those agents, potentially leading to loss of virologic control and an increased risk of perinatal transmission or adverse events on maternal HIV infection. Pharmacokinetic and safety data may not be available with newer ARV drugs.

 

  • Regimens containing [drug: atazanavir/cobicistat], [drug: darunavir/cobicistat], or [drug: elvitegravir]/[drug: cobicistat] are not recommended for pregnant women because of pharmacokinetic changes that may lead to increased viral loads later in pregnancy. Healthcare providers should discuss with patients whether to continue the regimen or switch to one that is recommended for use in pregnant women. If a regimen with pharmacokinetic concerns is continued, the patient should be counseled to closely follow instructions for use to optimize absorption (eg, taking certain drugs with or without food, avoiding antacids or divalent cation-containing vitamins). Viral load should be monitored more frequently, approximately every 1-2 months, in these patients.

 

  • An ARV switch during pregnancy should contain ARV drugs that are recommended for use in pregnancy and viral load should be checked 2-4 weeks after the switch.

 

  • Recommendations regarding specific ARVs or ARV regimens are subject to change as more data on these drugs in pregnancy become available.