Table 2

Cohort studies and randomised controlled trials of lipodystrophy with NRTIs

Study	No	Rx	LD assessment	Overall LD prevalence	Analysis	Factors associated with increased risk of LD
Cohort studies
Bernasconi et al¹²² Swiss HIV cohort	1359	NRTI PI	Physician and patient assessment	Any LD: 578/1359 (43%), Fat loss (FL): 382/1359 (28%), Fat acc (FA): 412/1359 (30%)	Multivariate logistic regression	Fat loss—age, greater NRTI exposure, d4T, ABC, elevated lactate Fat gain—age
Goujard et al¹²³ Liposud	646	NRTI PI	Physician assessment	Any LD: 374/646 (58%), LD (PI group): 316/498 (64%), LD (NRTI group): 58/148 (39%)	Unadjusted comparison of LD+ with LD−	Duration of treatment overall, duration of PI treatment, d4T therapy
Galli et al¹²⁴	188	Only NRTI	Physician and patient assessment	Any LD: 31/188 (16%), Any LD (Female): 25/96 (26%), Any LD (Male): 6/92 (7%)	Multivariate analysis	Female sex, d4T
Saint Marc et al¹²⁵ LIPOCO study	154	NRTI PI	Physician assessment, BIA, CT	Any LD: 82/154 (53%), FL (PI group): 58/100 (58%), FL (NRTI group): 15/39 (38%), FA (PI group): 45/100 (45%), FA (NRTI group): 3/39 (8%)	Multivariate logistic regression	d4T therapy
Carr et al¹²⁶	220	NRTI PI	Physician and patient assessment, DEXA, CT	NA—case-control study, 116 LD cases, 104 controls	Multivariate analysis	FL: age, greater NRTI exposure, d4T therapy, elevated lactate FA: age, PI duration, 3TC
Gervasoni et al¹²⁷	306	NRTI PI	Physician assessment, DEXA	Any LD: 32/306 (11%), LD (NRTI group): 12/162 (7%)	Multivarate logistic regression	Duration of ART, viral load >10 000 copies
Wolf et al¹²⁸	93	NRTI PI	Physician assessment	Any LD: 49/93 (53%)	Multivariate logistic regression	Elevated oestradiol, triglyceride >500 mg/dl, d4T
Mauss et al¹²⁹ LipART	221	NRTI PI	Physician and patient assessment at 3 years	Any LD: 76/221 (34%)	Multivariate analysis	CD4 nadir <200 cells, d4T treatment
Lichtenstein et al¹³⁰ HOPS	1077	NRTI PI	Physician and patient assessment	Any LD: 529/1077 (49%), Moderate/severe LD: 18%	Multivariate logistic regression	Age, white race, change in BMI, nadir CD4, study site, d4T, indinavir
Mallal et al¹³¹ W Australia cohort	277	NRTI PI	Physician assessment, longitudinal DEXA	Overall FL: 121/277 (44%), FL (PI group): 112/201 (54%), FL (NRTI gp.): 9/71 (13%)	Cox proportional hazards, multivariate linear regression	FL—age, white race, dual NRTI therapy duration, d4T duration, PI duration
Carmena et al¹³²	232	NRTI PI	Physician assessment	Overall LD: 24/232 (10%)	Multivariate logistic regression	Undetectable viral load, d4T therapy
Galli et al¹³³ LipoICONA	704	NRTI PI	Physician assessment	FL: 43/704 (10%), FA: 62/704 (11%), Mixed: 29/704 (6%)	Cox proportional hazards model	FL: d4T, HCV negative FA: weight, Mixed: Female sex, indinavir
Saves et al¹³⁴ APROCO	670	All NRTI +PI	Physician and patient assessment	Any LD 12 months: 188/304 (62%), Any LD 20 months: 212/336 (63%)	Multivariate analysis	Age, BMI, duration of ART before initiation of PI
Martinez et al¹³⁵	506	All NRTI +PI	Physician and patient assessment	Any LD: 82/506 (17%), FL alone: 25/506 (31%), Both FL+FA: 42/506 (8%)	Multivariate regression	Age, sexual transmission of HIV, d4T therapy
Galli et al¹³⁶ LIMS	2258	NRTI PI	Physician and patient assessment	Any LD: 750/2258 (33%), FA: 435/2258 (19%)	Multivariate analysis	Age, ART duration and no of drugs. Female sex
Schwenk et al¹⁶⁷	278	HAART	Physician and patient assessment	Any LD: 88/278 (32%), FL 18/278 (21%),FA 10/278 (11%), Mixed: 59/278 (67%)	Multivariate logistic regression	Age, PI duration, low CD4
Bogner et al¹³⁷	115	HAART	Physician and patient assessment	FL: 39/115 (34%), FA: 33/115 (29%)	Backward logistic regression	All: HAART duration, white race. FL: age and viral load

Study	No	Rx	LD assessment	Findings
Randomised, controlled trials
Molina et al¹³⁸ ALBI study	151	ZDV/3TC v d4T/ddI v d4T/ddI for 3 months then ZDV/3TC	Physician assessment at 30 months (120/151)	Overall LD: 37/120 (31%). LD (NRTIs alone): 20/61 (33%). LD significantly more frequent on d4T/ddI than ZDV/3TC (p=0.001)
Law et al¹¹⁵ OZCOMBO I + II	178	ZDV/3TC v d4T/3TC v d4T/ddI, plus NVP or IDV	Physician and patient assessment plus DEXA and CT (84/178)	Peripheral fat wasting significantly more common with d4T/ddI relative to d4T/3TC relative to ZDV/3TC (p<0.05)
Joly et al¹³⁹ NOVAVIR	100	ZDV v d4T, plus 3TC and IDV	Physician assessment at 30 months (120/151)	Peripheral fat wasting significantly more common in d4T arm v ZDV arm (70% v 43%, p=0.018)
Dale et al¹⁴⁰ START I + II	406	ZDV/3TC v d4T/3TC v d4T/ddI plus IDV	Post-study analysis of adverse event database, no LD assessment	Lack of LD assessment limits analysis. At 12 months, one case of LD was recorded. Including other terms such as weight changes and GI disorder: 26/406 (6%)