Desimplification to multi-tablet antiretroviral regimens in human immunodeficiency virus-type 1 infected adults: A cohort study

Table 1 Baseline characteristics

	FDC (n = 80)	MTR (n = 163)
Gender (female)	32.5% (26)	33.7% (55)	0.037 P = 0.8471
Italian origin	73.8% (59)	75.5% (123)	0.083 P = 0.7731
Comorbidities
HCV	12.5% (10)	8.6% (14)	0.918 P = 0.3381
HBV	2.5% (2)	1.2% (2)	0.535 P = 0.4651
Osteoporosis	1	0
Injecting drugs addiction	0	2
Diabetes	1	2
Kidney failure	1	0
Psychiatric disorders	6.2% (5)	4.9% (8)	0.190 P = 0.6631
Others diseases	18.7% (15)	27.0% (44)	1.976 P = 0.1601
Proportions of treated with
Atripla	37.5% (30)	28.2% (46)	2.141 P = 0.1431
Combivir	7.5% (6)	21.5% (35)	7.439 P = 0.0061
Kivexa	30.0% (24)	19.6% (32)	3.239 P = 0.0721
Truvada	25.0% (20)	30.7% (50)	0.839 P = 0.3601
Undetectable HIV-RNA at baseline	75.0% (60)	76.7% (125)	0.084 P = 0.7721
CD4 count at baseline	698.5 (SD 295.27)	671.6 (SD 268.87)	P = 0.4922
Mean age (yr)	47.3 (SD 10.77)	47.06 (SD 9.47)	P = 0.8392
Years of HAART	8.7 (SD 4.26)	8.7 (SD 4.85)	P = 0.9532
HAART pills number	2.4 (SD 1.35)	2.9 (SD 1.56)	P = 0.0162
Non HAART pills number	1.4 (SD 2.71)	1.1 (SD 1.95)	P = 0.4092
Total pills number	3.8 (SD 2.935)	4.0 (SD 2.63)	P = 0.5722

Proportions (n) or means (SD) as appropriate.

¹N-1 chi-square;

²T test for independent samples. HIV: Human immunodeficiency virus; HAART: Highly active antiretroviral therapy; HBV: Hepatitis B virus; HCV: Hepatitis C virus.

Table 2 Distribution of plasma human immunodeficiency virus-RNA levels

Weeks	HIV-RNA (copies/mL)	FDC	MTR	Total	Follow-up analysis	Overall analysis
	Total	80	163	243
0	NR	60	125	185	1P = 0.772
	< 20	20	38	58
24	NR	60	104	164	2P = 0.354; GOR 0.704 (95%CI: 0.403 to 1.229)	3P = 0.991; 4P = 0.366; GOR 0.956 (95%CI: 0.677 to 1.351); 5P = 0.298
	< 20	10	34	44
	20-50	8	15	23
	> 50	2	5	7
	Discontinued study drug	0	5	5
48	NR	56	100	156	2P = 0.828; GOR 0.996 (95%CI: 0.547 to 1.815)
	< 20	14	29	43
	20-50	5	7	12
	> 50	1	1	2
	Discontinued study drug	4	26	30
96	NR	53	92	145	2P = 0.310; GOR 1.385 (95%CI: 0.722 to 2.657)
	< 20	16	21	37
	20-50	4	4	8
	> 50	01	01	0
	Discontinued study drug	7	46	53

¹Pearson’s chi-square;

²Cochran-Armitage test for trend;

³Extended Mantel-Haenszel test for trend;

⁴Chi square test for heterogeneity;

⁵Chi square test for heterogeneity of GOR.¹Assumed 1 for Extended Mantel-Haenszel test for trend in overall analysis. GOR: Generalized odds ratio; HIV: Human immunodeficiency virus; MTR: Multi-tablet regimen; FDC: Fixed dose coformulation.

Table 3 Before-after (week 24 vs week 48/week 96) analysis of plasma viremia (4 levels and dichotomized)

	Crosstabulation (Week 48 vs week 24)						Crosstabulation (Week 96 vs week 24)						Pooled data
FDC
HIV-RNA (copies/mL)	NR	< 20	20-50	> 50	Discontinued study drug	Total	NR	< 20	20-50	> 50	Discontinued study drug	Total	3P = 0.972; GOR 1.00 (95%CI: 0.66 to 2.06)
NR	43	11	3	0	3	60	42	10	3	0	5	60
< 20	7	0	1	1	1	10	5	4	0	0	1	10
20-50	5	2	1	0	0	8	4	2	1	0	1	8
> 50	1	1	0	0	0	2	2	0	0	0	0	2
Total	56	14	5	1	4	80	53	16	4	0	7	80
	P = 0.8601; GOR = 1.00 (95%CI: 0.50 to 2.00)						P = 0.8451; GOR = 1.00 (95%CI: 0.46 to 2.16)
HIV-RNA (copies/mL)	≥ 20	< 20	Total					≥ 20	< 20	Total	(I-squared = 0.0%); 2P = 0.072; Odds ratio (odds A: odds B) = 0.471; Fisher’s 95%CI: 0.176 to 1.151
≥ 20	1	9	10					1	8	9
< 20	5	61	66					3	61	64
Total	6	70	76					4	69	73
	2P = 0.285						2P = 0.132
MTR
HIV-RNA (copies/mL)	NR	< 20	20-50	> 50	Discontinued study drug	Total	NR	< 20	20-50	> 50	Discontinued study drug	Total	3P = 0.036; GOR 1.65 (95%CI: 0.97 to 5.52)
NR	77	16	1	0	10	104	71	12	1	0	20	104
< 20	17	6	2	0	9	34	16	5	1	0	12	34
20-50	4	6	3	1	1	15	4	4	1	0	6	15
> 50	2	1	0	0	2	5	1	0	1	0	3	5
Discontinued study drug	0	0	1	0	4	5	0	0	0	0	5	5
Total	100	29	7	1	26	163	92	21	4	0	46	163
	P = 0.2031; GOR = 1.50 (95%CI: 0.85 to 2.64)						P = 0.0821; GOR = 1.86 (95%CI: 0.97 to 3.56)
HIV-RNA (copies/mL)	≥ 20	< 20	Total					≥ 20	< 20	Total	(I-squared = 0.0%); 2P = 0.001; Odds ratio (odds A: odds B) = 0.227; Fisher’s 95%CI: 0.067 to 0.615
≥ 20	4	13	17					2	9	11
< 20	3	116	119					2	104	106
Total	7	129	136					4	113	117
	2P = 0.012						2P = 0.035

¹McNemar test with continuity correction;

²McNemar test (two-tailed);

³Combination of the Mann-Whitney paired-data tests (weighting by sample sizes). I-squared: Higgins and Thompson’s heterogeneity test; GOR: Generalized odds ratio; HIV: Human immunodeficiency virus; MTR: Multi-tablet regimen; FDC: Fixed dose coformulation.

Table 4 Immunological responses to highly active antiretroviral therapy

	Baseline		24 wk			48 wk			96 wk
	n	mean CD4 (SD)	n	mean CD4 (SD)	P1 value	n	mean CD4 (SD)	P1 value	n	mean CD4 (SD)	P1 value
FDC	80	698.5 (295.3)	80	730.3 (339.7)	0.173	76	707.6 (281.9)	0.717	73	751.7 (289.9)	0.011
Atripla	30	649.7 (285.2)	30	666.3 (278.3)	0.549	29	709.9 (274.8)	0.032	26	715.0 (286.2)	0.02
Truvada	20	678.8 (261.3)	20	658.9 (263.3)	0.639	17	627.1 (224.8)	0.227	17	741.4 (279.2)	0.145
Kivexa	24	740.8 (356.4)	24	823.0 (460.2)	0.107	24	738.1 (341.0)	0.957	24	773.5 (317.2)	0.518
MTR	163	671.6 (268.9)	159	730.4 (282.0)	< 0.001	137	745.2 (281.0)	< 0.001	117	769.0 (269.0)	< 0.001
TDF/3TC/-EFV	46	665.6 (251.3)	43	742.9 (234.1)	0.003	34	746.0 (261.7)	0.002	30	759.9 (245.7)	< 0.001
TDF/3TC	50	665.7 (311.6)	50	735.7 (341.6)	0.003	44	751.8 (336.2)	< 0.001	40	766.8 (311.4)	< 0.001
ABC/3TC	32	675.4 (202.3)	32	733.7 (225.5)	0.06	29	740.7 (211.9)	0.036	28	810.5 (247.2)	< 0.001

¹Mean CD4 difference vs baseline (Fisher’s LSD test). MTR: Multi-tablet regimen; FDC: Fixed dose coformulation.