Mallal and colleagues investigated subcutaneous (SC) fat wasting among 277 patients receiving antiretroviral therapy. The researchers performed a cross-sectional analysis of the Western Australian Cohort, analyzing 161 patients using dual energy

x-ray absorptiometry scans and 77 patients with sequential scans in 6 month intervals between March 1998 and February 1999. Forty-seven patients were not receiving antiretroviral therapy during the course of the study. For the remainder of the patients, current therapy was as follows:

SC fat wasting was observed in 112 of 201 (54%) patients receiving protease inhibitors (PIs) and 9 of 71 (13%) of patients receiving dual NRTIs. SC fat wasting was associated with age, white race, or cumulative time on PI, d4T, or AZT. The rate of SC fat wasting was higher among patients receiving a PI-containing regimen compared with patients on a dual NRTI regimen. Among patients exclusively on triple drug therapy, shorter time to wasting was associated with age, white race, and cumulative time on dual NRTIs prior to highly active antiretroviral therapy and nevirapine. In addition, patients on PI-containing regimens using d4T appeared to have a shorter time to wasting compared with patients receiving AZT.

Among the 9 patients on dual NRTI therapy who showed SC fat wasting, 6 were receiving d4T and 3 were receiving AZT at the time of the study, however, the 6 patients on d4T were all heavily AZT experienced. The average duration of AZT experience among all 9 patients was 45 months, while the average d4T experience among the 6 patients receiving the drug was 14 months.

The investigators concluded that d4T increases SC fat wasting, but the data are limited. There are concerns due to inconsistencies about the sample sizes in this study; the researchers report varying group numbers for both the dual NRTI group and the PI-treated group (49 versus 71, 181 versus 201, respectively). Furthermore, it is unclear where the 47 patients receiving no therapy fit into the study. In addition, no baseline demographics were reported; therefore, it cannot be determined if other clinical characteristics independent of antiretroviral use were involved. While antiretroviral history was provided for the 9 patients with SC fat loss among the dual NRTI group, no history was provided for PI-treated patients. The data, therefore, may only show that NRTI use is associated with lipodystrophy, and that d4T use increases with duration of therapy.