Effects of once-daily darunavir/ritonavir versus atazanavir/ritonavir on insulin sensitivity in HIV-infected persons over 48 weeks: results of an exploratory substudy of METABOLIK, a phase 4, randomized trial

Figures & data

Figure 1 Study design.

ARV, antiretroviral; ATV, atazanavir; DRV, darunavir; TDF, tenofovir disoproxil fumarate; FTC, emtricitabine; r, low-dose ritonavir; qd, once daily. ^a29 subjects due to over-enrollment. ^b14 subjects due to over-enrollment. ^c15 subjects due to over-enrollment. Two subjects withdrew before treatment initiation.

Table 1 Subject disposition

	DRV/r (n = 14)	ATV/r (n = 15)	Overall (n = 29)
Randomized and not treated, n	0	2	2
Intent-to-treat set, n	14	13	27
EHC-evaluable set, n (%)	12 (86)	12 (92)	24 (89)
Completed week 12 study visit, n (%)	13 (93)	12 (92)	25 (93)
Completed study, n (%)	12 (86)	10 (77)	22 (82)
Discontinued study, n (%)	2 (14)	3 (23)	5 (19)
Reason for discontinuing study
Adverse event, n (%)	0	1 (8)	1 (4)
Ineligible to continue the study, n (%)	0	1 (8)	1 (4)
Other,^a n (%)	2 (14)	1 (8)	3 (11)

Note: DRV, darunavir; r, low-dose ritonavir; ATV, atazanavir; EHC, euglycemic hyperinsulinemic clamp.

^a Two subjects on DRV were incarcerated, and there was a dispensing error for the subject on ATV.

Table 2 Demographics and baseline characteristics of subjects who initiated therapy

	DRV/r (n = 14)	ATV/r (n = 13)
Median age, years (range)	29 (20–47)	26 (20–48)
Male, n (%)	14 (100)	13 (100)
Race, n (%)
Black or African American	8 (57)	8 (62)
White	6 (43)	4 (31)
American Indian or Alaska Native	0	1 (8)
Median BMI, kg/m^2 (range)	24.1 (21.5–25.6)	23.4 (18.6–30.8)
Median total cholesterol, mg/dL (range)^a	138.5 (94–173)	140 (105–218)
Median LDL cholesterol, mg/dL (range)^a	81.5 (36–114)	82 (55–145)
Median HDL cholesterol, mg/dL (range)^a	44 (27–59)	42 (29–57)
Median triglycerides, mg/dL (range)^a	88.5 (50–235)	91 (53–330)
Median glucose, mg/dL (range)^a	85 (70–103)	91 (85–95)
Median insulin, mIU/L (range)^a	1.9 (1.9–9.6)	1.9 (1.9–19.1)
Median CD4 count (range)	234 (23–619)	271 (77–524)
Mean log10 HIV-1 RNA, copies/mL (SD)	5.11 (0.69)	4.77 (0.45)

Note: DRV, darunavir; r, low-dose ritonavir; ATV, atazanavir; BMI, body mass index; LDL, low-density lipoprotein; HDL, high-density lipoprotein; HIV, human immunodeficiency virus; SD, standard deviation.

^a Measured from fasting samples.

Figure 2 Clamp analyses at baseline, week 12, and week 48: (A) glucose disposal rate and (B) insulin sensitivity.^a

DRV, darunavir; r, low-dose ritonavir; ATV, atazanavir; W12, week 12; W48, week 48; IQR, interquartile range. ^aThe boxes and horizontal lines reflect the IQR and median values, respectively. The vertical lines reflect the 5th and 95th percentiles. There is one outlier in the DRV/r group at the week 48 time point. The week 12 insulin sensitivity value of 174.8 mg/kg*min per μIU/mL × 100 in the ATV/r group is not displayed (outlier).