Antiretroviral Failure

Posted by Graham McMahon • June 18th, 2010

This week’s Case Record of the Massachusetts General Hospital is A 7-Year-Old Boy with Elevated HIV RNA Levels despite Antiretroviral Medications.

In light of recent reports indicating excess mortality in apparently healthy infants who had high CD4 counts and high CD4 percentages and who did not receive early antiretroviral therapy, HIV exposure and infection should be investigated in all babies presenting to health services, particularly in the first few months of life.

Clinical Pearls

When should antiretroviral treatment generally be initiated in children infected with HIV?

International guidelines for the management of pediatric HIV infection now recommend that all children under 1 year of age start antiretroviral therapy.

What are the common causes of virologic failure among children infected with HIV?

Lack of adherence to the therapeutic regimen, poor choice and dosing of antiretroviral drugs, and possible adverse interactions with other medications may all contribute to an inadequate therapeutic response. Poor adherence to antiretroviral therapy is the commonest reason for virologic failure.

Morning Report Questions

Q: What combination of drugs is optimal to treat HIV infection?

A: In most of the developing world, three classes of antiretroviral drugs are available for the management of HIV-1 infection: nucleoside analogue reverse-transcriptase inhibitors (NRTIs), nonnucleoside reverse-transcriptase inhibitors (NNRTIs), and protease inhibitors. A combination of at least three drugs from these classes, usually consisting of at least one reverse-transcriptase inhibitor and a protease inhibitor, provides optimal suppression of viral replication and lowers the risk of the acquisition of drug resistance.

Q: What strategies can be used when multiple protease-inhibitor mutations are found in the HIV genotype?

A: In cases in which multiple protease-inhibitor mutations are detected, full viral suppression is likely to be achieved only when another boosted protease inhibitor is used. Recently, protease inhibitors such as darunavir and tipranavir have shown good control in this situation. Darunavir is a nonpeptide protease inhibitor that binds rapidly to protease at a unique site and disassociates slowly, resulting in a binding strength that is two times as high as that of other protease inhibitors. Darunavir is potent even against strains that are resistant to protease inhibitors.

Table 2. Results and Interpretation of HIV Resistance Genotype Mutations.

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