Background:  Virological response to tipranavir (TPV)-based regimen showed to be associated with number of mutations of the protease gene, use of enfuvirtide (T20) and inhibitory quotient (gIQ). The role of the simpler to derive genotypic IQ (gIQ) has not yet been investigated. The aim of our study was to evaluate the relationship between TPV gIQ and early virological response to TPV-based salvage regimens.

Methods:  Patients placed on regimens containing 2 nucleoside reverse transcriptase inhibitors (NRTI) +TPV/ritonavir (RTV) 500/200 mg twice daily with or without T20 were prospectively studied. HIV RNA (viral load) and CD4⁺ cell count were recorded at baseline and at week 4, 8, and 12. TPV C_trough were measured at week 2, 4, 8, and 12 by a validated high-performance liquid chromatography (HPLC) system. Baseline genotypic resistance test and virtual phenotype were obtained. We used previously suggested TPV mutation score with 21 mutations at 16 protease codons. TPV gIQ was calculated as the ratio between mean concentration of all available TPV C_trough and number of TPV-associated mutations. Optimized background score (OBS) was calculated as the number of active drugs according to baseline virtual phenotype. Early virological response (HIV RNA<50 copies/mL) at week 12 was assessed. Values were given as median (IQR).

Results:  We included 27 multi-experienced patients. T20 was associated in 14 (51.8%) subjects. Baseline viral load and CD4⁺ cell count were 4.7 log (4.17 to 5.07) and 226 cells/mm³ (189 to 311), respectively. At week 12 viral load decrease was –2.15 (–3.07;–0.43), 11 patients (40.7%) had a viral load of <50 copies/mL, and CD4⁺ cell count increase was 8 cells/mm³ (–64; +61.5). Viral load decrease was correlated to TPV gIQ (R = 0.607, p = 0.001) and not to TPV C_trough (R = –0.338, p = 0.085), number of TPV mutations (R = 0.364, p = 0.062), optomized background score (R = –0.329, p = 0.094), and T20 use (R = 0.05, p = 0.97). TPV gIQ was the only predictor of viral load undetectability at week 12 by logistic regression analysis (p = 0.026). The TPV gIQ value associated with 50% probability of being undetectable at week 12 (EC₅₀) was 13,000. At this time point, 7 of 9 subjects with a TPV gIQ >13,000 had a viral load of <50 copies/mL, whereas only 4 of 18 subjects with TPV gIQ <13,000 had an undetectable viral load ( c² = 7.6, p = 0.011).

Conclusions:  TPV gIQ showed to predict EVR to TPV-containing salvage regimens better than TPV C_trough or TPV- associated mutations alone. A possible TPV gIQ cut-off value (13,000) for reaching and undectable viral load at week 12 was suggested. Further studies are needed to evaluate TPV gIQ as a new tool to optimize TPV-based salvage therapy.