XVI International AIDS Conference Abstract # ThABO101

1. Long-Term Changes in Lipids and Glucose/Insulin among HIV-Infected Antiretroviral Naïve Persons Randomized to PI vs. NNRTI vs. PI+NNRTI-based strategies: Results of the CPCRA 061 Metabolic Study J. Shlay, G. Bartsch, G. Peng, J. Wang, C. Gibert, F. Visnegarwala, S. Raghavan, Y Xiang, M. Farrough, H. Perry, D. Kotler, C. Grunfeld, W. El-Sadr for the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA) XVI International AIDS Conference Abstract # ThABO101

2. Background • Morphologic changes (lipoatrophy and lipohypertrophy), insulin resistance, and dyslipidemia are important metabolic consequences of antiretroviral therapy in patients with HIV/AIDS • However, long-term comparative data on the metabolic effects of initiating different ART strategies in ART-naïve patients are limited

3. Objectives • To assess long-term changes in metabolic parameters and body composition among antiretroviral-naïve patients randomized to three highly active antiretroviral therapy (ART) strategies

4. Patient meets eligibility requirements Randomized to 3 strategy arms (1:1:1) N=1,397 PI + NRTIs N=470 NNRTI + NRTIsN=463 PI + NNRTI + NRTI(s) N=464 PI Strategy N=141 in Metabolic substudy NNRTI StrategyN=141in Metabolic substudy PI + NNRTI Strategy N=140 in Metabolic substudy C•P•C•R•A

5. Baseline Characteristics – 1* PI (N=141) NNRTI (N=141) PI + NNRTI (N=140) Age (years) 37 38 39 Female (%) 26 23 17 RaceAfrican American (%) 61 62 59 Prior AIDS (%) 38 39 32 CD4 (cells/mm3) 235 206 204 RNA (log10 copies/mL) 4.9 5.0 5.0 * No significant differences among treatment strategies

6. Baseline Characteristics - 2 PI (N=141) NNRTI (N=141) PI + NNRTI (N=140) P-Value Triglycerides (mg/dL) 122.9 129.3 146.4 NS Total Cholesterol (mg/dL) 160.0 157.1 168.7 *HDL Cholesterol (mg/dL) 39.0 36.8 35.3 NSLDL Cholesterol (mg/dL) 96.7 94.1 105.3 * Glucose (mg/dL) 86.1 88.6 86.4 NS Insulin (µ/mL) 8.5 9.9 10.4 NS * Significant differences among treatment strategies: p < 0.05

7. ART Prescribed after Randomization PI(N=141) NNRTI(N=140) PI + NNRTI(N=140) PI (%)NFV 58 0 64 IDV 12 0 11RTV-boosted 26 0 22Other 4 0 2 NNRTI (%)EFV 0 63 50NVP 1 37 49Other 0 0 1 NRTI (%)ZDV + 3TC 53 53 38d4T + 3TC 19 19 10ABC + 3TC 11 12 16ddI + d4T 12 12 14Single NRTI 0 0 19Other 6 4 2

8. Change in LDL Cholesterol* * If triglycerides ≥ 400, direct LDL, otherwise calculated LDL

9. Change in HDL Cholesterol

10. Change in Triglycerides

11. Change in Insulin

12. Conclusions - I • PI+NNRTI strategy associated with a greater increase in LDL-C and triglycerides compared to the PI or NNRTI strategies; no significant differences noted between PI and NNRTI strategies • LDL-C levels increased primarily within the first few months after initiation of ART, followed by a decline during the remainder of follow-up

13. Conclusions - II • Unlike LDL-C, triglyceride levels did not decline with continued therapy • Significantly greater increases in mean HDL-C seen with the NNRTI strategy compared to the PI strategy • PI+NNRTI strategy should be avoided unless no other options are available

14. Conclusions - III • Increases in insulin and glucose were noted during follow-up, with no differences by ART strategy • Increases in insulin and glucose were gradual and continued throughout follow-up, unlike the pattern of changes noted with the lipids • Findings support the need for ongoing monitoring of glucose levels as well as for the development of diabetes, irrespective of ART regimen used