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Switch Study in Children to Efavirenz from Protease Inhibitor
Reported by Jules Levin
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Grace Mccomsey, from Rainbow Babies and Children's Hospital and Case western University, said this is this first study investigating the effects of substituting a protease inhibitor with efavirenz. When switching there is a concern about viral suppression because children have a more difficult time with adherence. She is evaluating efficacy, safety, and metabolics in this study. Children were 1-17 yrs of age; stable on a PI regimen for greater than 6 months; viral load <400 copies/ml for more than 4 months; naive to NNRTIs. There was an exclusion for unstable opportunistic infections within 4 weeks prior to study entry. This was a 48-week prospective, open-label, multicenter study. Every 12 weeks evaluations included insulin, C peptide, glucose, lipid panel, bioelectric impedance and antropometrics for body changes.
A brief summary: viral suppression was maintained in all 17 children after the switch to efavirenz at week 48, although children had extensive prior NRTI experience. CD4 count increased significantly. Total cholesterol, LDL (bad cholesterol), total cholesterol/HDL ratio and triglycerides significantly declined by week 24. HDL (good cholesterol) trended up but change was not significant. Although there were no premature study discontinuations, 1-2 of out of 16 children experienced efavirenz side effects: vivid dreams, transient dizziness and insomnia. However, there were no changes in anthropometric measurements or fat content (by BIA). This is a small study and open-label with limited body composition change measurements. Mccomsey suggested that these results should lead to a larger randomized study of simplification of therapy in children, which should include better evaluation of body composition.
There were 17 children included (10 female, 7 male); 15 black & 2 white; average age: 120 months (range: 24-156 months). All children vertically infected from mom. They had 88 months of prior nuke therapy and had average duration of PI use of 21 months. They weighed on average 37 kg (2.2 lbs per kg). BMI was 19.1. 16 of 17 children had <400 copies viral load for an average of 13 months (range: 4-55). Pre-HAART HIV viral load was 15,395 copies/ml. 8 patients were on nelfinavir, 5 on ritonavir, 3 amprenavir, and 1 on ritonavir/saquinavir. 6 children were taking d4T/3TC, 5 d4T/ddI, 3 AZT/3TC, 1 abacavir/3TC, 1 abacavir/ddI, and 1 abacavir/d4T/ddI
Week 48 RESULTS
--16/17 children had <50 copies/ml viral load; viral load was 62 in 1 patient.
--Adverse events: transient dizziness: 1/16. Transient insomnia: 1/16. Vivid dreams: 2/16. One episode of seizure at week 6: no treatment required and no recurrence on EFV. No premature discontinuations. No rash or hepatotoxicity.
--CD4% remained stable: 35 at baseline, 37 at week 24 mean, and 38 at week 48.
--Fasting cholesterol declined significantly by 15% at week 48. Cholesterol was was 203 mg/dl at baseline and declined significantly at week 12 on EFV to on average 177, 174 at week 24, and 174 at week 48.
--Fasting LDL cholesterol declined significantly, 15% from baseline to week 48; from 124 mg/dl to 105 mg/dl. There was a significant decline at week 24 to 100 mg/dl.
--Fasting triglycerides declined significantly by 25% at week 48 from 126 mg/dl to 94 mg/dl. Their was a significant decline of 35% at week 24. 71% of children entered the study with elevated triglycerides and 35% had elevated triglycerides at week 48.
--HDL (good cholesterol trended to go up from 54 at baseline, 58 at week 12, 56 at week 24, and to 61 at week 48 for an overall non-significant increase of 13%.
--The artherogenic index of cholesterol/HDL ratio significantly declined by week 12 from 3.8 at baseline to 3.2 at week 12, 3.2 at week 24, and 3.0 at week 48. Declines at all time points were significant. The baseline to week 48 decline was a significant 21%.
--CD4% increase significantly but modestly from 35 to 38 from baseline to week 48. Blood pressure did not change when off protease inhibitors. Weight increased by 4 kg. By BIA increase was mostly due to increase in lean body mass, fat did not change significantly. Insulin (13 vs 13 IU/ml) and C peptide (2.3 vs 2.8 ng/ml) did not change for the 48 weeks of the study. Anthropometric measures (evaluating body changes) did not improve over the 48 weeks from baseline measures: waist to hip ratio (0.9 vs 0.9); MAC (cm) 24 vs 24; triceps skinfold (mm) 15 vs 16; mid-thigh circumfrance (cm) 41 vs 43; thigh skinfold (mm) 19 vs 19. Dietary history revealed no changes during the study.
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