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Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States

Appendix A: Supplement: Safety and Toxicity of Individual Antiretroviral Agents in Pregnancy

Integrase Inhibitors

(Last updated:9/14/2011)

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Glossary of Terms for Supplement:

Clastogenic = causing disruption of or breakages in chromosomes

Mutagenic = inducing or capable of inducing genetic mutation

Genotoxic = damaging to genetic material such as DNA and chromosomes

Carcinogenic = producing or tending to produce cancer

Notes:
• Some agents, such as certain chemicals or forms of radiation, are both mutagenic and clastogenic.
• Genetic mutations and/or chromosomal damage can contribute to cancer formation.

One drug has been approved in this new class of antiretrovirals (ARVs) aimed at inhibiting integrase, the viral enzyme that catalyzes the two-step process of insertion of HIV DNA into the genome of the host cell. Integrase catalyzes a preparatory step that excises two nucleotides from one strand at both ends of the HIV DNA and a final “strand transfer” step that inserts the viral DNA into the exposed regions of cellular DNA. This second step in the integration process is targeted by the integrase inhibitor drug class. Integration is required for the stable maintenance of the viral genome as well as for efficient viral gene expression and replication. Integrase also affects retrotranscription and viral assembly. Host cells lack the integrase enzyme. Because HIV integrase represents a distinct therapeutic target, integrase inhibitors would be expected to maintain activity against HIV that is resistant to other classes of ARV drugs.

Raltegravir (Isentress)