June 03, 2016
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Acquisition, impact of HIV drug resistance differs in children, adults

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HIV drug resistance is a concern for both pediatric and adult patients, although the ways in which resistance is acquired – and its impact on patients – differs between the two populations, according to Lisa M. Frenkel, MD, co-director of the Center for Global Infectious Disease Research at Seattle Children’s Hospital.

The acquisition of HIV drug resistance in children occurs in two ways, Frenkel told Healio Infectious Disease. Mother-to-child transmission of resistance is one possibility; children may also develop resistance to ART that was prescribed in order to prevent transmission of the virus. In the case of mother-to-children transmission, it may or may not be combined with wild-type virus, according to Frenkel.

Lisa Frenkel

Lisa M. Frenkel

“If [drug resistance] is combined with wild-type virus, the drug resistance sometimes goes away or decays over 1 to 2 years, and it doesn’t become part of the long-term reservoir,” she said. This is different from adult patients with HIV drug resistance, where “most of the time people continue their medications long enough that the drug resistance becomes archived in the long-term reservoir.”

Because the drug-resistant variants are not as fit as the wild-type variants, the wild-type virus comes to prevail in the plasma when patients — either adults or children — stop ART, according to Frenkel.

“So, if you test someone, it looks like wild-type virus,” Frenkel said. “But, when you start therapy again, the wild-type virus will be outgrown by the mutant virus.”

Another way in which HIV drug resistance differs between children and adults is that children have a “a much higher viral load,” according to Frenkel.

“This is thought to occur because [children] have about 4,000 lymphocytes per microliter at birth compared with the average normal adult, who has 1,000,” she said. “So they have a lot more viral replication. This could lead to the generation of random mutations quite rapidly.”

Additionally, drug resistance may result in ART ineffectiveness, leading to virologic failure. The presence of virologic failure often forces patients, both children and adults, to switch to a different ART regimen, which is more of a challenge in children.

“One of the complications [for children] is there aren’t a lot of medicines that come in liquids and so young babies have a limited number of drugs they can change to,” Frenkel said. – by Ryan McDonald

Disclosure: Frenkel reports no relevant financial disclosures.