Background:  The use of ritanovir-boosted tipranavir (TPV/r) is indicated in treatment-experienced patients. Elevation of lipid levels have been observed more frequently after use of TPV/r (500 mg/200 mg twice daily) than after use of other low-dose ritonavir-boosted protease inhibitors (PI). It is of interest to estimate the potential added risk for coronary heart disease (CHD) associated with TPV/r use compared with conventional ritonavir-boosted PI (CPI/r).

Methods:  In treatment-experienced patients, mean 5-year CHD risk was modelled according to metabolic factors observed at baseline and week 8 of the RESIST trials. The CHD risk estimates were calculated using the Framingham risk equation, a parametric statistical model controlling for multiple cardiovascular risk factors (including age, sex, diabetes, prior cardiovascular disease, the ratio of serum total cholesterol to HDL cholesterol [TC:HDL]); and imputed average values of blood pressure (120 mmHg) and smoking (45%). Different average values were considered in sensitivity analyses. The numbers needed to treat to harm one person (NNTH) were calculated from the absolute CHD risk difference between the study arms.

Results:  In the RESIST trials, 746 (median age 43 years, IQR 38 to 49; 15.7% women) and 737 (42 years, 38 to 48;11.7% women) individuals were randomized to TPV/r and CPI/r, respectively. Week-8 data were available for 630 and 613 individuals. Over the first 8 weeks of exposure, the TC:HDL ratio increased from 5.1(4.1 to 6.3) to 6.0 (4.7 to 7.6) in the TPV/r arm, while from 5.0 (4.1 to 6.2) to 5.2 (4.1 to 6.5) in the CPI/r arm (difference between arms, p <0.0001). At baseline, the predicted CHD risk was quite similar for both arms. However, at 8 weeks of exposure the modelled CHD risk differed (see the figure). The mean predicted average risk of CHD over a 5-year period is 1.75% overall in the TPV/r arm versus 1.32% in the CPI/r arm, for an attributable NNTH estimate of 234 (1/[0.0175 to 0.0132]).

Conclusions:  In summary, these findings suggest that in highly treatment-experienced patients requiring a boosted PI regimen, the potential added harm on risk of CVD induced by TPV/r (500 mg/200 mg twice daily) versus CPI/r is present, but limited in absolute terms in most patients. The differences in predicted absolute risks between the TPV/r and CPI/r arms results in estimated NNTH in the range of 150 to 300 for the men in the study over a 5-year period; the NNTH is considerably higher for women.