Choice of Initial Antiretroviral Therapy

Antiretroviral monotherapy with zidovudine, didanosine, lamivudine, and stavudine slows disease progression, improves survival, reduces viral RNA, and delays development of neurocognitive dysfunction. Recent pedi-atric clinical trials of symptomatic children who have not previously received antiretroviral therapy demonstrate that combination therapy with either zidovudine and lamivudine or zidovudine and didanosine is superior to monotherapy with respect to clinical, immunologic, and virologic parameters. Combination antiretroviral therapy that includes a protease inhibitor is superior to dual nucleoside therapy. In this regard, monotherapy with the currently available antiretroviral drugs is no longer recommended to treat HIV. Many infants born to seropositive mothers are receiving zidovudine monotherapy; therefore, those infants who are infected will require reassessment for more aggressive antiretroviral therapy when discovered to be infected. The goal of antiretroviral therapy is to suppress viral replication, i.e., to bring viral RNA levels below 50 copies; however, this is somewhat more difficult in children than adults owing to the initial higher RNA levels in children.

There are two protease inhibitors available for infants and children who cannot swallow pills: nelfinavir (Viracept™), which is available in a powder formulation which can be mixed with water or food, and, ritonavir (Norvir®) , which is available in a liquid formulation. Indinavir (Crixovan™) and Saquinavir (Invirase ™, hard gel capsule, and Fortivase ™, soft gel capsule) are not available in liquid formulations. Saquinavir is the protease inhibitor with the fewest pediatric data available. Indinavir is recommended for children who can swallow pills.

Recommended antiretroviral regimens for initial therapy include one highly active protease inhibitor plus two NRTIs. An alternative regimen would be the combination of neviripine, zidovudine, and didanosine, which has produced substantial and sustained suppression of viral replication in two of six infants who were first treated at 4 months of age.27 A secondary, alternative regimen might be the use of dual NRTIs, but initial viral suppression with such a regimen may not be sustained. Participation in a controlled clinical trial is recommended when available.

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