Appendix B: Supplement: Safety and Toxicity of Individual Antiretroviral Agents in Pregnancy
Nucleoside and Nucleotide Analogue Reverse Transcriptase Inhibitors
Nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs) interfere with HIV reverse transcriptase by competitive inhibition. Nucleoside analogue drugs require three intracellular phosphorylation steps to form the triphosphate nucleoside, which is the active drug moiety. The nucleotide analogue tenofovir contains a monophosphate component attached to the adenine base and requires only two phosphorylation steps to form the active moiety.
For information regarding the nucleoside analogue drug class and potential mitochondrial toxicity in pregnant women and infants, see Recommendations for Use of Antiretroviral Drugs During Pregnancy and Long-Term Follow-Up of Infants Exposed to Antiretroviral Drugs.
Non-Nucleoside Reverse Transcriptase Inhibitors
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) interfere with HIV reverse transcriptase by binding directly to the enzyme.
Protease inhibitors (PIs) block the activity of the protease enzyme, which is required to assemble new HIV viral particles that are capable of infecting new cells.
Using PIs during pregnancy may increase the risk of adverse maternal and neonatal outcomes; see Combination Antiretroviral Drug Regimens and Maternal and Neonatal Outcomes for more information.
Fosamprenavir, indinavir, nelfinavir, saquinavir, and tipranavir are no longer recommended for use in pregnant women. Amprenavir is no longer available in the United States. Information on these drugs can be found in the Archived Drugs section.
Entry and Attachment Inhibitors
Entry and attachment inhibitors block viral binding or fusion of HIV to host cells.
Integrase inhibitors block integrase, the viral enzyme that catalyzes the two-step process that inserts HIV DNA into the genome of the host cell.
For information regarding the possible increased risk of neural tube defects in infants born to women who were receiving dolutegravir at the time of conception, see Teratogenicity and Recommendations for Use of Antiretroviral Drugs During Pregnancy.
Pharmacoenhancers reduce the metabolism of antiretroviral drugs and prolong their presence in plasma, allowing for more convenient dosing regimens.