Background: HIV lipodystrophy (HIVLD) is a heterogeneous syndrome. Both protease inhibitors (PIs) and nucleoside analogues (NRTIs) contribute to pathogenesis. The contribution of non-nucleoside analogues (NNRTIs) to HIVLD has not been demonstrated. In this study we assessed the effect on lipodystrophy of ceasing combination NRTI therapy and switching to a ritonavir boosted PI and NNRTI.

Methods: Assessment was by standardized questionnaire (maximally thin -3 and maximally fat +3), physical examination, fasted laboratory measurements, DEXA scan, and CT scan of mid-abdomen and thigh at weeks 0 and 48. Results were compared by Student’s t-test.

Results: The study enrolled 61 patients (38 male, 23 female). The median duration of prior NRTI therapy was 4.1 years. Strong correlation between patient and physician based assessments was seen (all correlation coefficients were statistically significant).

Conclusions: The results suggest that ceasing NRTIs and switching to a PI and NNRTI regimen leads to an improvement of lipoatrophy. This is consistent with the hypothesis that lipoatrophy is predominantly mediated through NRTIs. In addition, the observed concomitant increases in central abdominal fat support that PIs, through a separate mechanism, may lead to lipoaccumulation.

Study Parameter, Mean (SD)	Week 0 (n = 60)	Week 48 (n = 60)	Change	p-value
Weight (kg)	56.6 [9.7]	56.5 [10.5]	-0.1 [4.0]	0.25
HIV RNA (c/ml)	15,528 [13,918]	1,564 [7,750]	-13,964 [14,907]	*
CD4+	176 [126]	297 [136]	121 [108]	*
Lactate (mmol/L)	1.41 [0.74]	1.62 [0.64]	0.20 [0.97]	0.11
Total Cholesterol (mg/dl)	172.2 [36.7]	265.3 [74.6]	93.2 [60.9]	*
Triglycerides (mg/dl)	147.3 [83.6]	383.8 [247.5]	236.5 [212.7]	*
Glucose (mg/dl)	91.8 [11.5]	94.8 [12.0]	3.1 [13]	0.07
Body Composition, sq. cm. (CT)
Mid-abdomen (visceral fat)	86.3 [49.7]	94.2 [54.3]	8.0 [30.8]	0.05
Mid-abdomen (subcutaneous fat)	95.8 [51.0]	104.5 [54.1]	8.6 [31.7]	0.04
Mid-thigh (subcutaneous fat)	33.1 [23.9]	36.6 [25.3]	3.5 [7.6]	*
Body Fat as % of Mass (DEXA)
Fat in trunk	21 [7.0]	22.8 [6.8]	1.8 [3.6]	*
Fat in legs	17.5 [9.8]	19.2 [10.0]	1.7 [2.5]	*
Fat in arms	18.2 [8.9]	21.0 [10.1]	2.8 [3.8]	*
Body Lean as % of Mass (DEXA)
Lean in trunk	77.1 [6.9]	75.4 [6.7]	-1.7 [3.6]	*
Lean in legs	78.4 [9.3]	76.7 [9.6]	-1.7 [3.6]	*
Lean in arms	77.1 [8.6]	73.8 [11.3]	-3.4 [6.0]	*
Patient Assessment of body –3 to +3
Abdomen score (p-value)	0.33 [1.34] (0.12)	1.49 [1.60] (*)	1.15 [1.72]	*
Thighs score (p-value)	-0.68 [1.28] (*)	-0.88 [1.32] (*)	-0.20 [1.37]	0.26
Arms score (p-value)	-0.88 [1.33] (*)	-1.07 [1.49] (*)	-0.18 [1.53]	0.36

* p < 0.001