ANTIRETROVIRAL DRUGS IN THE PERINATAL PERIOD

1. ANTIRETROVIRAL DRUGS INTHE PERINATAL PERIOD

2. Use of ARV Drugs by HIV-Infected Pregnant Women and Their Infants • Considerations for choice of ARV drugs for pregnant women include: • Possible changes in dosing requirements resulting from physiologic changes associated with pregnancy • Potential exacerbation of ARV drug toxicities • Pharmacokinetics and toxicity of transplacentally transferred drugs • Potential short- and long-term effects of ARV drugs on fetuses and newborns www.aidsetc.org

3. Combination ART and Pregnancy Outcome • Possible small increased risk of preterm birth in pregnant women receiving protease inhibitor (PI)-based ART; however, given the clear benefits, PIs should not be withheld for fear of altering pregnancy outcome. (AII) www.aidsetc.org

4. Pharmacokinetic Changes • Altered dosing during pregnancy may be required for some PIs, such as lopinavir/ritonavir. (AII) • Concentrations of the following drugs are reduced during the 2nd and/or 3rd trimesters • Lopinavir/ritonavir (LPV/r) • Atazanavir (ATV) • Darunavir (DRV) • Nelfinavir (NFV) • The need for dosage adjustment depends on the patient’s treatment experience and use of concomitant medications. www.aidsetc.org

5. Teratogenicity • Women of childbearing potential should undergo pregnancy testing before initiating efavirenz(EFV) and receive counseling about the potential risk to the fetus and desirability of avoiding pregnancy while on EFV. (AIII) • Consider non-EFV regimens in patients who are: (BIII) • Planning to become pregnant • Sexually active and not using effective contraception www.aidsetc.org

6. Report all cases of ARV use in pregnant women to the Antiretroviral Pregnancy Registry: http://www.APRegistry.com(AIII) The registry collects observational, nonexperimental data regarding ARV exposure during pregnancy to assess potential teratogenicity. www.aidsetc.org August 2012

7. Nevirapine and Hepatic/Rash Toxicity • Avoid initiating NVP in women with CD4 counts >250 cells/µL unless the benefits outweigh the risks. (AII) • Risk of hepatotoxicity/hypersensitivity reaction • Women who are tolerating NVP-containing regimens and become pregnant can continue regardless of CD4 count. (AII) www.aidsetc.org

8. NRTI Drugs and Mitochondrial Toxicity • The combination of stavudine (d4T) and didanosine (ddl) should not be prescribed during pregnancy because of reports of lactic acidosis and maternal/neonatal mortality with prolonged use during pregnancy. (AII) • Mitochondrial dysfunction should be considered in uninfected children with perinatal exposure to ARV drugs who present with severe clinical findings, particularly neurologic. (AII) • Long-term clinical follow-up is recommended for any child with in utero exposure to ARV drugs. (AIII) www.aidsetc.org

9. Protease Inhibitors and Hyperglycemia • HIV-infected women taking ARV regimens during pregnancy should undergo standard glucose screening at 24-28 weeks’ gestation. (AIII) • Owing to linkage with hyperglycemia: • Consider earlier glucose screening in women receiving PI-based regimens initiated before pregnancy. (BIII) www.aidsetc.org

10. Nucleoside and Nucleotide Reverse Transcriptase Inhibitors (1) www.aidsetc.org

11. Nucleoside and Nucleotide Reverse Transcriptase Inhibitors (2) www.aidsetc.org

12. Nucleoside and Nucleotide Reverse Transcriptase Inhibitors (3) www.aidsetc.org

13. Nucleoside and Nucleotide Reverse Transcriptase Inhibitors (4) www.aidsetc.org

14. Nonnucleoside Reverse Transcriptase Inhibitors (NRTIs) (1) www.aidsetc.org

15. NonnucleosideReverse Transcriptase Inhibitors (NRTIs) (2) www.aidsetc.org

16. NonnucleosideReverse Transcriptase Inhibitors (NRTIs) (3) www.aidsetc.org

17. Protease Inhibitors (1) Class concerns for PIs: hyperglycemia, diabetes, question of increased risk of preterm delivery www.aidsetc.org

18. Protease Inhibitors (2) www.aidsetc.org

19. Protease Inhibitors (3) www.aidsetc.org

20. Additional Recommendations by Class Integrase Inhibitors Entry Inhibitors www.aidsetc.org