48-Week Efficacy and Safety of Ritonavir-boosted Tipranavir in Children and Teenagers

Currently there are few approved treatment options for HIV positive children and adolescents with resistant virus.

In adults, tipranavir (Aptivus), a recently approved protease inhibitor (PI), is active against multiple strains of HIV that are resistant to other currently available drugs in its class.

An international team of researchers conducted a study to evaluate the safety and efficacy of an experimental oral solution of tipranavir co-administered with ritonavir in children.

The study included 115 children and teenagers; 25 were between 2 and 6 years old, 38 were 6-12 years old, and 52 were 12-18 years old. Most (97.4%) had prior antiretroviral treatment experience. The mean baseline HIV viral load was 4.7 log copies/mL, the mean CD4 cell count was 492 cells/mm3, and the mean CD4 percentage was 20%. Patients had taken a median of 6 previous antiretroviral drugs. Nearly half (49.6%) had genotypic evidence of resistance to all PIs.

The participants were randomly assigned to receive low-dose (290/115 mg/m2; n = 58) or high-dose (375/150 mg/m2; n = 57) tipranavir/ritonavir plus an optimized background regimen (OBR); 13% took enfuvirtide (Fuzeon, T-20). All patients started on tipranavir solution; after 4 weeks, patients older than 12 years could start taking 500/200 mg tipranavir/ritonavir capsules.

Results

Mean viral load reductions at week 48 are shown in the table below:

At week 48, 39.7% (23 out of 58) low-dose patients and 45.6% (26 out of 57) high-dose patients achieved viral loads below 400 copies/mL.

34.5% (20 out of 58) low-dose patients and 35.1% (20 out of 57) high-dose patients achieved viral loads below 50 copies/mL.

The mean CD4 count increased by 157 and 96 cells/mm3 in the low-dose and high-dose arms; the mean CD4 percentage increased by 5% and 3%, respectively.

Tipranavir/ritonavir was well tolerated, with just 4 out of 115 patients (3.5%) experiencing drug-related serious adverse events.

The most common adverse events were gastrointestinal.

The most frequent DAIDS grade 3 or 4 laboratory abnormalities were elevated GGT (a liver enzyme) and creatine phosphokinase (CPK; a marker of muscle damage) (10.7%).

The rate of grade 3 or higher alanine aminotransferase (ALT) elevation in children who received high-dose tipranavir/ritonavir was similar to that observed in adults taking 500/200 mg tipranavir/ritonavir.

10 patients (8.7%) -- 6 in the low-dose arm and 4 in the high-dose arm -- discontinued tipranavir/ritonavir due to adverse events.

Conclusion

In conclusion, the researchers noted that:

Despite a lack of available active background drugs, 40%-46% and 35% of participants achieved viral load below 400 and 50 copies/mL, respectively, by Week 48.

Tipranavir/ritonavir plus OBR was generally well tolerated, no unexpected adverse events were reported, and the safety profile was similar to that seen in adults.

In antiretroviral experienced pediatric patients with PI-resistant HIV isolates, high dose tipranavir/ritonavir appeared to offer a better risk/benefit profile.

Clinically relevant virological and immunological improvements were seen with [tipranavir/ritonavir] therapy in treatment-experienced children aged 2-18 years at Week 48," the authors wrote. "[Tipranavir/ritonavir] provides a potent and well-tolerated therapeutic option for children and teenagers."

08/29/06

Reference
J Salazar, P Cahn, M Della Negra, and others. Efficacy and safety results of 48 weeks of treatment with APTIVUS oral solution co-administered with low dose ritonavir (Aptivus/r) in children and teenagers (PACTG 1051: phase I/IIa study). XVI International AIDS Conference. Toronto, August 13-18, 2006. Abstract WEAB0301.