Resistance mutations may be decreasing among children with HIV

CHICAGO — Children with HIV born after 2000 were less likely to have triple-class drug-resistant strains than children born earlier, according to findings presented here.

German Andres Contreras Cuellar, MD, an MS epidemiology candidate in the Division of Epidemiology and Disease Control at The University of Texas School of Public Health, told Infectious Disease Newsthat the aim of the trial was determine the incidence rate of resistance mutations by antiretroviral class.

Data from 66 children were used in the final analysis. There were four birth cohorts evaluated: those born between 1980 and 1990; those born between 1991 and 1995; those born between 1996 and 1999; and those born between 2000 and 2007.

“Children born at different times were exposed to different risk factors,” Contreras said. “Eligible children in our study had only one genotype.”

The median follow-up duration was 10.1 years (intraquartile range: 6.6-14.4).

Nucleoside reverse transcriptase inhibitors (NRTIs) had the highest mutation incidence rate, at 6.3. Protease inhibitors (PI) yielded an incidence rate of 4.1, and non-nucleoside reverse transcriptase inhibitors (NNRTIs) had a rate of 3.2.

NRTIs had higher 5- and 10-year point estimates than PI and NNRTI.

Multivariate analysis results indicated that for all antiretroviral classes, resistance mutations were more likely to be detected in children who were tested at a younger age (NRTI: HR=0.56, 95% CI, 0.45-0.68; PI: HR=0.53, 95% CI, 0.43-0.65; NNRTI: HR=0.78, 95% CI, 0.66-0.93).

For NRTI, children in the earliest cohort had a higher incidence rate of resistance mutations than children in the later birth cohorts (1996-1999: HR=0.12, 95% CI, 0.02-0.73; 2000-2007: HR=0.02, 95% CI, 0.002-0.24).

“We saw a general decrease in the incidence of resistance mutations from the oldest to the youngest cohort,” Contreras said. “Triple class resistance was highest in the oldest cohort and non-existent in the youngest cohort.”

Hispanic children were more likely than black children to have an NRTI resistance mutation (HR=2.39; 95% CI, 1.06-5.4) and a PI mutation (HR=2.67; 95% CI, 1.20-5.89).

“We also wanted to see how quickly children were developing resistance,” Contreras said. “Most of the children born in the early cohorts often already had a mutation at the moment of the first genotyping. They are developing in their system quickly. However, we must keep in mind that there is a bias because genotyping was not introduced in the early cohorts.”

Children who had changed therapies before their first resistance test were at an increased risk for a PI mutation (HR=3.61; CI, 1.15-11.35).

“If you are in clinical practice and you have children who are coming in new, if they were born in the 1980s or early 1990s, the likelihood that they have a resistance mutation is high,” Contreras said. “However, if they were born in the 2000s, there may not be resistance mutations, so there is more time to develop a regimen.”

Contreras also noted that a history of monotherapy was linked to increased likelihood of a resistance mutation, but that being born after 2000 had a protective effect.

“Children born after 2000 are getting genotyped much earlier, and they are being followed much more closely,” he said.

For PIs, history of monotherapy, dual therapy and extended time to genotyping was linked to an increased risk for mutation, according to Contreras.

For more information:

Contreras GA. #H1-1403. Comparison of Risk Factors for the Development of NRTI, NNRTI and PI Resistance in a Cohort of Perinatally HIV-Infected Children. Presented at: 51st ICAAC. Sept. 17-20, 2011. Chicago.

Disclosure: Dr. Contreras reports no relevant disclosures.

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Resistance mutations may be decreasing among children with HIV