Report Ten from Lisbon
Switch from PI based regmen to Efavirenz regimen
Summary: Moyle reported no improvements in cholesterol and triglycerides due to switch to EFV from a PI but viral load suppression was well maintained (9/9 <50 copies/ml at week 48; 19/20 <50 copies/ml at week 24). Patients reported they had some improvement in their body appearance. There were improvements in glucose tolerance test.
This is a study of individuals who were on a PI therapy and requested to either stop therapy or be switched to another due to experiencing lipodystrophy. It's a non-comparative study group because participants did not want to be on their current regimen. So, its an open-label single arm prospective observational cohort of persons with clinical lipodystrophy and/or metabolic abnormalities virologically controlled on PI based regimen.
Patents were either self-reported or their doctor referred them to study as having lipodystrophy from a specialist lipodystrophy assessment clinic. For the study they were clinically examined to confirm clinical body shape changes. There were a few individuals who only had metabolic elevations (cholesterol >6.5 mmol/l; fasting triglycerides >2.2 mol/l; diabetes). Participants had viral load <500 copies/ml (bDNA).
EFV 600 mg was substituted for the evening dose of PI with no overlap and people stayed on nucleoside analogues. Abacavir was added in some patients on dual PI or with prior transient NNRTI exposure.
At baseline and every 3 months they performed—fasting lipids, CD4s, viral load, insulin, testosterone, 2 hour glucose tolerance test, assessment of body composition by DEXA, anthropometrocs, and single slice-CT scan.
Moyle reported on two groups of patients: 9 (1 female, 8 male) who completed 48 weeks and 20 individuals ( 2 female, 18 male) who were out to 24 weeks. 8/9 and 18/20 were taking d4T/3TC. 7/9 and 15/20 were taking IDV as their PI. Three in the 20 person group were taking dual PI. CD4 counts were 231 in 9 person group and 408 in 20 person group. All participants had received mean 20 months prior PI therapy.
At baseline in cohort 1 (n=9, 48 weeks), clinical manifestations were: facial (5), legs (6), arms (5), abdomen (5), all above (1), metabolic only (1). Cohort 2 (24 weeks, n=20) clinical manifestations: facial (12), legs (13), arms (15) abdomen fat accumulation (16), all above (8), metabolic only (2).
In cohort 1 (48 weeks) 9/9 had viral load <50 copies/ml at week 48 and their CD4s increased 114. Two of 9 changed therapy: one person switched from EFV to NVP after 4 weeks due to concentration problems due to EFV, and a second person who switched from d4T to abacavir after 1 month due to neuropathy. In cohort 2 (24 weeks, n=20) 5 people added abacavir as mentioned above. One person switched from d4T to abacavir at week 40 due to elevated triglycerides. 19/20 had <50 copies/ml at week 24 except one person who stopped therapy due to PCP.
In both cohorts cholesterol and triglycerides were modestly but not significantly increased at week 48 compared to baseline. Moyle reported significant improvements in glucose tolerance. By patient survey partial improvements in appearance were reported. Also Moyle reported significant increased weight that was initially mostly in fat free mass although in cohort 1 there was non-significant fat increase. Previous reports have observed improvements in good cholesterol and decreases in bad cholesterol. In cohort 1 Moyle reported significant improvement (12%) in VAT (visceral adipose tissue- stomach fat) by CT scan. Moyle reported a significant correlation between baseline insulin resistance and triglycerides, consistent with diabetes, and insulin resistance and VAT (CT-scan).
However, Moyle reported 6/7 individuals who had abnormal glucose tolerance at baseline (>7.8 mmol/l) had a normal glucose tolerance test at week 24. In the 1/7 Moyle sais person had family history of diabetes. Regarding triglycerides 2/14 individuals reduced triglycerides from above to below normal (2.2 mmol/l). As well 2 individuals had normal baseline values that became abnormal at week 24. The same response was seen with cholesterol.