Background:  A recently completed 6-year RTV/SQV study with and without NRTI intensification provides the opportunity to partition the effect of NRTI therapy from PI therapy on the prevalence and risk factors of MoAs.

Methods:  A standardized questionnaire and directed physical exam for MoAs were administered from year 3 to year 5.  Potential risk factors evaluated using logistic regression models included NRTI intensification, duration of prior RTIs, baseline
HIV RNA, baseline CD4+ cell count, lipid measurements during the study, age, and gender.

Results:   66 subjects remain on study at the end of year 5. Of these, 32 intensified therapy with NRTI(s) at some time prior to this time point. The prevalence of the most common MoAs at year 5 for NRTI-intensified vs NRTI-sparing regimens was: buttock wasting (9/32[28%] vs 2/34[6%], p<0.05) and thinning of cheeks (11/32[34%] vs 2/34[6%]. p<0.01), respectively.  Using logistic regression models, NRTI intensification was a statistically significant risk factor both for buttock wasting (odds ratio [OR] 6.3; 95% CI 1.24-31.7) and for thinning of cheeks (OR 8.4; 95% CI 1.7-41.7).  Comparison of the most prevalent MoAs observed for subjects ongoing at year 5 with those of the same subjects at baseline (year 3) found increases over time: NRTI–intensified subjects (n = 32): thinning of cheeks (25.0% - 34.4%), buttock wasting 25.0% - 28.1%), wasting in upper extremities (6.3% - 21.9%), and wasting in lower extremities (6.3% - 21.9%); NRTI-sparing subjects (n = 34): thinning of cheeks (2.9% - 5.9%), buttock wasting (0% - 5.9%), and wasting in lower extremities (0% - 8.8%). Self-reported, exam-confirmed presence of at least 3 MoAs at year 5 for NRTI-intensified vs NRTI-sparing regimens was 10/32 (31%) vs 2/34 (6%), respectively (p<0.01).

Conclusions:  Final results in this study demonstrate that NRTI intensification was associated with an increased risk of morphologic abnormalities. Morphologic abnormalities were more frequent in subjects on an NRTI-intensified regimen with a greater number of abnormalities increasing with time.  The pathophysiology of MoAs needs to be further evaluated in order to develop regimens that may not contribute to development of this syndrome.