Viremia lower in HIV-positive children who switch back to nevirapine after PI therapy

**Coovadia A. JAMA. 2010;304(10):1082-1090. doi:10.1001/jama.2010.1278**

Children who have HIV who were exposed to nevirapine at birth, then received protease inhibitor (PI) therapy before switching back to nevirapine achieved lower viremia rates compared with children who continued on PI therapy, study researchers concluded.

Current guidelines recommend that infants receive the PI therapy ritonavir-boosted with lopinavir (Kaletra), but Louise Kuhn, PhD, of Columbia University in New York City, and colleagues noted that this treatment can be impractical due to its high cost, highly unpleasant taste and potential for metabolic toxicity.

"Our results suggest that a majority of nevirapine-exposed children who are successfully treated with initial regimens based on ritonavir-boosted lopinavir and achieve viral suppression could benefit from the switch strategy, which would allow reductions in costs of pediatric treatment programs," Kuhn and colleagues wrote.

The study, conducted at a single hospital in Johannesburg, followed 195 nevirapine-exposed children who initiated PI therapy before 24 months of age and achieved viral suppression of less than 400 copies/mL for 3 or more months.

The children were randomized into a switch group, which received nevirapine in place of ritonavir-boosted lopinavir, or a control group, which continued to receive PI therapy.

After 52 weeks, the researchers found that viremia greater than 50 copies/mL occurred less frequently in the switch group (Kaplan-Meier probability, 0.438; 95% CI, 0.334-0.537) than in the control group (0.576; 95% CI, 0.470-0.668) (P = .02).

Additionally, CD4 cell response was superior in the switch group at 34.7%, versus 31.3% in the control group (P = .004).

"Our data indicate that children who switch to nevirapine-based therapy once they have achieved viral suppression after an average of 9 months of therapy based on ritonavir-boosted lopinavir are more likely to achieve viremia less than 50 copies/mL than children who kept their original regimen," the researchers wrote.

Conversely, the odds of reaching study's safety endpoint of viremia more than 1000 copies/mL were significantly higher in the switch group (probability 0.201; 95% CI, 0.125-0.289) than in the control group (0.022; 95% CI, 0.004-0.069) (P<.001).

The group that switched also had higher nevirapine resistance rates and poorer treatment adherence.

The findings "highlight the promise and pitfalls of switching nevirapine-exposed infants. …For about 20% of exposed children, the regimen is suboptimal. Therefore, switching can only be considered in situations in which adequate virologic monitoring can be conducted, both to identify who is eligible to switch and to identify as early as possible children who should be returned to the ritonavir-boosted lopinavir-based regimen," the researchers wrote. "As children become old enough and strong enough to resist their caregivers, the taste of this drug may play a larger role in adherence. More palatable formulations in pediatric doses are urgently needed," the researchers wrote.

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