Ritonavir-boosted darunavir (Prezista) was effective and generally well-tolerated at week 48 among treatment-experienced children and adolescents with HIV in the DELPHI study, according to a presentation at the 5th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention (IAS 2009) last month in Cape Town, South Africa. No change was seen in glucose levels after starting the drug, and triglyceride levels decreased significantly.

By Liz Highleyman

The Phase 2, open-label DELPHI (Darunavir EvaLuation in Pediatric HIV-1-Infected) trial included 80 pediatric HIV patients aged 6-17 years; 71% were male and 78% had been infected via mother-to-child transmission. At baseline, the average CD4 cell count was 330 cells/mm3 and the average CD4 percentage was 17%. Patients were highly treatment experienced, with all having used at least 2 NRTIs, 79% having used NNRTIs, and 96% having used protease inhibitors.

Participants received twice-daily darunavir/ritonavir dosed according to weight (11-19 mg/kg) plus an optimized background regimen containing at least 2 other antiretroviral drugs.

As previously reported, at 48 weeks, 48% of participants had HIV RNA < 50 copies/mL, 59% had viral load < 400 copies/mL, and 65% experienced at least a 1 log decrease in HIV RNA. Darunavir/ritonavir was generally well-tolerated and had a good safety profile.

In the present analysis, the investigators looked specifically at metabolic changes after starting darunavir/ritonavir. Participants were not permitted to use lipid-lowering agents to manage elevated cholesterol or triglycerides. Blood samples were collected at baseline and week 48 after patients had fasted for at least 10 hours.

Results

	At 48 weeks, the following grade 2-4 (moderate to severe) treatment-emergent lipid and glucose abnormalities were observed: 1 patient (1.3) with triglyceride elevation; 11 patients (13.8) with total cholesterol elevation; 11 patients (13.8) with LDL ("bad") cholesterol elevation; 9 patients (11.3) with hyperglycemia (elevated blood glucose).
	1 patient (1.3%) had HDL ("good") cholesterol above the upper limit of normal and 5 (6.3%) had HDL below the lower limit of normal (ungraded).
	The average blood glucose level did not change from baseline to week 48, being slightly above normal on both occasions.
	Mean total cholesterol (P < 0.05), LDL (P < 0.001), and HDL (P < 0.05) levels all rose significantly from baseline to week 48.
	The mean triglyceride level, however, decreased significantly, by about 50 mg/dL (P < 0.01).
	The proportion of patients with elevated triglycerides fell from 44% at baseline to 22% at week 48.

"The most frequent laboratory abnormalities were increased total cholesterol and LDL," they continued. "The most pronounced change was a significant reduction in mean triglycerides from baseline to Week 48."

"Small but statistically significant mean increases in total cholesterol, LDL, and HDL were observed," they noted. However, "no statistically significant changes in total cholesterol/HDL ratio and mean glucose were seen."

Chris Hani Baragwanath Hospital, University of the Witwatersrand, Johannesburg, South Africa; Hospital Dos Servidores Do Estado, Rio De Janeiro, Brazil; Hospital Geral De Nova Iguacu - HGNI DST/AIDS, Nova Iguacu, Brazil; Universidade Federal De Minas Gerais, Belo Horizonte, Brazil; Tibotec BVBA, Mechelen, Belgium; Hôpital Necker Enfants Malades, Paris, France.

8/18/09

Reference
T Meyers, E Joao, JH Pilotto, and others. 48-week lipid- and glucose-related safety profile of darunavir/ritonavir in treatment-experienced, paediatric patients in DELPHI. 5th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention (IAS 2009). July 19-22, 2009. Cape Town, South Africa. (Abstract TUAB202).

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