Differences in antiretroviral safety and efficacy by sex in a multinational randomized clinical trial

Figures & data

Table 1. Entry participant characteristics by sex.

		Sex
Variable	Description	Female (n = 739)	Male (n = 832)	p-value^*
Age, years^†		33 (30, 41)	35 (28, 39)	< 0.001
Race (%)	Asian	166 (22.5%)	192 (23.1%)	< 0.001
	Black/African American	458 (62.0%)	329 (39.5%)
	White	58 (7.8%)	193 (23.2%)
	Other/unknown	57 (7.7%)	118 (14.2%)
Ethnicity (%)	Hispanic	90 (12.2%)	232 (27.9%)	< 0.001
Site location; country (%)	Brazil	82 (11.1%)	149 (17.9%)	< 0.001
	Haiti	48 (6.5%)	52 (6.3%)
	India	111 (15.0%)	144 (17.3%)
	Malawi	149 (20.2%)	72 (8.7%)
	Peru	45 (6.1%)	89 (10.7%)
	South Africa	141 (19.4%)	69 (8.3%)
	Thailand	55 (7.4%)	45 (5.4%)
	United States	38 (5.1%)	172 (20.7%)
	Zimbabwe	70 (9.5%)	40 (4.8%)
Weight; kg^‡		58.5 (13.3)	66.3 (13.6)	< 0.001
Body mass index (BMI);kg/m^2^‡		23.6 (5.0)	22.7 (3.7)	0.002
Anthropometric measurements^†	Mid arm (cm)	27.2 (25.0, 30.0)	27.8 (25.7, 30.0)	0.013
	Mid thigh (cm)	48.0 (44.0, 53.2)	46.5 (43.0, 50.6)	< 0.001
	Waist/hip ratio	0.8 (0.8, 0.9)	0.9 (0.9, 0.9)	< 0.001
Karnofsky score median		90 (90, 100)	90 (90, 100)	0.080
Any prior/current binge drinking		80 (10.8%)	249 (29.9%)	< 0.001
CD4+ lymphocyte count (mm^− 3)^†		182 (113, 232)	165 (81, 230)	< 0.001
Plasma human immunodeficiency virus type 1 (HIV-1) RNA (log10 copies/ml)^†		4.9 (4.5, 5.4)	5.2 (4.7, 5.5)	< 0.001
Screening plasma HIV RNA stratum	< 100 000 c/ml	382 (51.7%)	339 (40.7%)	< 0.001
	>100 000 c/mL	357 (48.3%)	493 (59.3%)
Prior or current AIDS diagnosis		46 (6.6%)	121 (14.5%)	< 0.001
Prior or current tuberculosis		129 (17.2%)	150 (17.6%)	0.690
Hepatitis B surface antigen positive		35 (4.7%)	55 (6.6%)	0.110
Liver transaminases^†	AST, IU/l	28 (23, 38)	31 (24, 41)	< 0.001
	ALT, IU/l	22 (16, 32)	29 (20, 45)	< 0.001
Creatinine clearance,mL/min^†,^‖		94 (78, 117)	101 (84, 123)	< 0.001
Randomized treatment assignment	EFV+3TC/ZDV	241 (32.6%)	278 (33.4%)	0.65
	ATV+FTC+DDI-EC	256 (34.6%)	270 (32.5%)
	EFV+FTC/TDF	242 (32.7%)	284 (34.1%)

* Wilcoxon Rank Sum test for continuous variables; Chi-square test for categorical variables

† Median (25th and 75th percentiles)

‡ Mean (standard deviation)

§ Antiretroviral drugs were Efavirenz (EFV), lamivudine (3TC), zidovudine (ZDV), atazanavir (ATV), emtricitabine (FTC), and tenofovir-DF (TDF)

‖ Crockoft-Gault calculation.

Figure 1. Distribution of study participants and reasons for premature discontinuation from study before treatment failure.

Table 2. Efficacy and safety outcomes by sex and treatment arm.

Outcome	Assigned treatment group^γ	Female, N (%)	Male, N (%)	Hazard ratio (HR) [95% confidence interval (CI)]^* comparing females to males	P Value^†	Adjusted hazard ratio (aHR) (95% CI)
Efficacy endpoints
Treatment failure	Overall	142 (19.2)	169 (20.3)		0.018
	ZDV/3TC+EFV	49 (20.3)	49 (17.6)	1.14 (0.76, 1.72)		1.13 (0.75, 1.71)^‡
	ATV+FTC+DDI-EC	45 (17.6)	73 (27.0)	0.60 (0.41, 0.87)		0.59 (0.40, 0.87)^‡
	EFV+TDF/FTC	48 (19.8)	47 (16.5)	1.21 (0.80, 1.83)		1.25 (0.82, 1.92)^‡
Virologic failure	Overall	113 (15.2)	137 (16.5)		0.013
	ZDV/3TC+EFV	39 (16.2)	39 (14.0)	1.18 (0.75, 1.86)		1.10 (0.69, 1.74)^§
	ATV+FTC+DDI-EC	34 (13.2)	60 (22.2)	0.57 (0.37, 0.88)		0.56 (0.36, 0.86)^§
	EFV+TDF/FTC	40 (16.5)	38 (13.3)	1.33 (0.84, 2.11)		1.38 (0.86, 2.21)^§
Disease progression	Overall	19 (2.6)	27 (3.2)	0.78 (0.42, 1.47)	0.45	0.84 (0.44, 1.58)^‖
Death	Overall	22 (3.0)	34 (4.1)	0.59 (0.34, 1.04)	0.600	0.85 (0.47, 1.54)^¶
Safety endpoints
Primary safety	Overall	393 (53.4)	444 (53.6)		0.002
	EFV+ZDV/3TC	160 (66.4)	153 (55.2)	1.4 (1.1, 1.8)		1.49 (1.18, 1.88)***
	ATV+FTC+DDI-EC	126 (49.6)	155 (57.8)	0.82 (0.64, 1.04)		0.82 (0.64, 1.05)***
	EFV+TDF/FTC	107(44.4)	136 (47.9)	0.88 (0.68, 1.14)		0.91 (0.70, 1.19)***
Sign/symptom	Overall	147 (20.0)	184 (22.2)	0.95 (0.75, 1.19)	0.50	1.05 (0.82, 1.35)
****Abnormal laboratory	Overall	164 (22.3)	181 (21.8)	0.84 (0.67, 1.06)	0.090
	ZDV/3TC+EFV	56 (23.2)	61 (22.0)			1.28 (0.89, 1.83)
	ATV+FTC+DDI-EC	56 (22.0)	60 (22.4)			0.90 (0.61, 1.33)
	EFV+TDF/FTC	35 (14.5)	54 (19.0)			0.66 (0.43, 1.04)
Initial regimen change	Overall	249 (33.8)	299 (36.1)	1.03 (0.86, 1.24)	0.060
	ZDV/3TC+EFV	109 (45.2)	113 (40.8)			1.35 (1.03, 1.79)
	ATV+FTC+DDI-EC	79 (31.1)	107 (39.9)			0.84 (0.62, 1.14)
	EFV+TDF/FTC	61 (25.3)	79 (27.8)			0.96 (0.68, 1.35)

* Basic model adjusted for country and plasma HIV-1 RNA stratification factors, and treatment arm

† P value for interaction term between sex and treatment arm

‡ Adjusted model included age, race, pretreatment CD4+ lymphocytes and body measurements

§ Adjusted model included age, race and pretreatment CD4+lymphocytes

‖ Adjusted model included pretreatment CD4+lymphocytes and body measurements

¶ Adjusted model race, pretreatment CD4+ lymphocytes, body measurements, prior AIDS diagnosis, and serum ALT

*** Adjusted model included serum AST, body measurements, and ethnicity

**** Adjusted model included baseline weight, body measurement, and serum AST

γ Antiretroviral drugs were Efavirenz (EFV), lamivudine (3TC), zidovudine (ZDV), atazanavir (ATV), emtricitabine (FTC), and tenofovir-DF (TDF).

Figure 2. Comparison of CD4 change from pretreatment between men and women.