Which medications in the drug class Protease Inhibitors are used in the treatment of Pediatric HIV Infection?

Updated: Mar 05, 2020
  • Author: Delia M Rivera, MD; Chief Editor: Russell W Steele, MD  more...
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Answer

Protease Inhibitors

Protease inhibitors inhibit HIV protease, which is required for HIV replication and the formation of mature, infectious viral particles.

Nelfinavir (Viracept, NPV)

Nelfinavir inhibits HIV-1 protease, resulting in the production of an immature and noninfectious virus. It is approved by the FDA in combination with 2 NRTIs in children aged ≥ 2 years and adolescents.

Lopinavir and ritonavir (Kaletra, LVP/r)

Lopinavir inhibits HIV protease and renders enzyme incapable of processing polyprotein precursors, leading to production of noninfectious, immature HIV particles. Ritonavir inhibits CYP3A metabolism of lopinavir, increasing plasma levels. It is approved for children (including infants aged > 14 days), children, and adolescents. This product is available in tablets (200 mg/50 mg LPV/r), pediatric tablets (100 mg/25 mg LPV/r), and PO solution (80 mg/20 mg LPV/r; 42.4% alcohol by volume).

Ritonavir (Norvir, RTV)

Ritonavir is an HIV protease inhibitor used as part of double or triple therapy with nucleosides and other protease inhibitors. It is used as a boosting agent to other ARDs.

Atazanavir (ATV, Reyataz)

Atazanavir is an azapeptide HIV-1 protease inhibitor. It prevents virion maturation by selectively inhibiting Gag and Gag-Pol polyproteins in HIV-1 infected cells. It is approved by the FDA for infants (aged ≥ 3 months who weigh at least 5 kg), children, and adolescents.

Darunavir (DRV, Prezista)

An HIV-1 protease inhibitor, darunavir selectively inhibits HIV-encoded Gag-Pol polyprotein cleavage in infected cells, preventing formation of mature virus particles. It is indicated to treat HIV disease not responding to other ARDs. Coadminister with low-dose ritonavir (ritonavir-boosted therapy decreases elimination and increases darunavir serum concentration).

Darunavir is typically coadministered with other anti-HIV agents (eg, NRTIs). Food increases maximum concentration (Cmax) and area under the concentration-time curve (AUC). Coadministered with ritonavir, it is approved by the FDA as a part of an ART regimen in treatment-naïve and treatment- experienced children aged ≥ 3 years.

Fosamprenavir (f-APV, Lexiva)

A prodrug of amprenavir (inhibitor of HIV protease), fosamprenavir is rapidly converted to amprenavir by cellular phosphatases in vivo. Amprenavir inhibits HIV-1 protease and binds its active site, preventing the processing of viral Gag and Gag-Pol polyprotein precursors and resulting in immature, noninfectious viral particles. Although approved by the FDA in children as young as 4 weeks, the AIDSinfo Panel members recommend use in children aged 6 months or older. The panel also recommends fosamprenavir only be used as boosted therapy, since unboosted fosamprenavir may select for mutations associated with resistance to darunavir.

Tipranavir (TPV, Aptivus)

A nonpeptidic protease inhibitor, tipranavir inhibits HIV replication. It is indicated for combination antiretroviral treatment of HIV-1 infected patients aged 2 years or older who are treatment-experienced and infected with HIV-1 strains resistant to >1 protease inhibitor. This agent must be coadministered with ritonavir 200 mg to attain therapeutic levels. It is ineffective if used alone without ritonavir-boosted levels. Results of genotypic or phenotypic testing and/or treatment history should guide use. It is available as 250 mg caps or as PO solution of 100 mg/mL.

Saquinavir (Invirase)

Saquinavir is an HIV protease inhibitor used as part of double or triple therapy with nucleosides and other protease inhibitors. It must be used in combination with ritonavir as a boosting agent. It is available as a 200-mg hard gel cap or 500-mg film-coated tablet. It is not approved by the FDA for use in children or adolescents aged <16 years. Limited data are available from investigational trials in children aged ≥ 2 years.

Indinavir (Crixivan, IDV)

This agent prevents formation of protein precursors necessary for HIV infection of uninfected cells and viral replication. Indinavir has not been approved by the FDA for use in the pediatric population. Although indinavir was one of the first protease inhibitors to be studied in children, its use in pediatrics has never been common and is currently very rare. Indinavir is not recommended by the AIDSinfo Panel members for use in children because of its unfavorable toxicity profile, limited efficacy data, and uncertain pharmacokinetics.


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