Background:  Although peripheral fat loss is a consistent feature of HIV-associated lipodystrophy, less is known about whether changes in central and peripheral fat occur in tandem or independently—a question that can be addressed only in longitudinal studies. Accordingly, we examined intra-individual changes in DEXA and anthropometry data before and 64 weeks after initiation of ART in A5005S, the metabolic substudy of ACTG 384.

Methods:  On ACTG 384, ART-naive subjects were randomized to receive didanosine (ddI)/stavudine (d4T) or zidovudine (ZDV)/lamivudine (3TC) in combination with efavirenz (EFV), nelfinavir (NFV), or both. In the subset on A5005S, waist and hip circumferences were measured in triplicate using NHANES guidelines. DEXA scanning with standardized regional analysis was performed in a subset of these subjects. Paired circumference data (baseline to week 64) are available in 220 subjects, 95 of whom have paired DEXA data. 

Results:  Equal proportions of subjects had an increase in waist circumference or decrease in hip circumference of > 2.54 cm (41 and 40%, respectively). The proportion of subjects with waist/hip ratio  >0.95 in men and > 0.90 in women (levels associated with increased risk of cardiovascular disease) increased from 35% at baseline to 47% at week 64, with 50 subjects increasing (23%), while only 24 subjects decreased (11%; p = 0.003, McNemar’s test). In those who developed increased waist-to-hip ratio, 24% had both increased waist circumference and decreased hip circumference; waist circumference increased with no decrease in hip circumference in 52%, whereas hip circumference decreased with no increase in waist circumference in only 22%. DEXA results show a similarly mixed pattern of regional gain and loss. Equal proportions of subjects had directionally similar changes in limb and trunk fat (35% gained in both regions, 34% lost in both regions), 26% had an increase in trunk fat with a decrease in limb fat, while only 5% gained limb fat and lost trunk fat (p < 0.001, McNemar's test). Analysis by treatment arms produced similar results.

Conclusions:  Individual results obtained by both anthropometry and DEXA show diverse patterns of fat gain and loss over 64 weeks after initiation of ART. In one quarter of subjects, DEXA trunk fat increased while limb fat decreased, but in 69% the changes were in the same direction. In the majority of cases, increases in waist-to-hip ratio were associated with increases in waist circumference without a concomitant decrease in hip circumference. Increases in waist-to-hip ratio that were a result of decreased hip circumference without a concomitant increase in waist circumference also occurred but were less common.

Keywords: lipodystrophy; lipoatrophy; metabolic complications