Skip to main content
SpringerLink
Log in

Tipranavir

A Review of its Use in the Management of HIV Infection

  • Adis Drug Evaluation
  • Published:
Drugs Aims and scope Submit manuscript

Summary

Abstract

Tipranavir (Aptivus®) is a selective nonpeptidic HIV-1 protease inhibitor (PI) that is used in the treatment of treatment-experienced adults with HIV-1 infection. Tipranavir is administered orally twice daily and must be given in combination with low-dose ritonavir, which is used to boost its bioavailability.

The durable efficacy of tipranavir, in combination with low-dose ritonavir (tipranavir/ritonavir 500 mg/200 mg twice daily), has been demonstrated in well designed trials in treatment-experienced adults infected with multidrug-resistant strains of HIV-1. In treatment-experienced adults with HIV-1 infection receiving an optimized background regimen, viral suppression was greater and immunological responses were better with regimens containing tipranavir/ritonavir than with comparator ritonavir-boosted PI-containing regimens. The efficacy benefit appeared to be more marked in patients receiving two fully active drugs in the regimen, with the combination of tipranavir/ritonavir and enfuvirtide (for the first time) appearing to be the most successful. Although tipranavir is generally well tolerated, clinical hepatitis and hepatic decompensation, and intracranial haemorrhage have been associated with the drug. Tipranavir also has a complex drug-interaction profile. Thus, tipranavir, administered with ritonavir, is an effective treatment option for use in the combination therapy of adults with HIV-1 infection who have been previously treated with other antiretroviral drugs.

Pharmacological Properties

Tipranavir is a highly potent and selective nonpeptidic sulfonamide-containing dihydropyrone HIV-1 PI with good in vitro activity against a broad range of laboratory strains and clinical isolates of HIV-1. In vitro, resistance to tipranavir is slow to develop and the process is complex. On-treatment genotyping of viral isolates from treatment-experienced patients in clinical trials indicate that the mutations predominantly emerging with tipranavir treatment are L33F/I/V, V82T/ L and I84V. In vitro, mutations of the HIV-1 wild-type virus that confer resistance to tipranavir also confer resistance to most other commonly used PIs, with the exception of saquinavir and darunavir. The activity of tipranavir is reduced in the presence of human plasma proteins. Synergistic, additive and antagonistic effects have been observed with tipranavir and various other antiretroviral drugs in vitro.

Tipranavir is administered in combination with low-dose ritonavir (tipranavir/ ritonavir), which boosts its bioavailability resulting in the achievement of effective plasma/serum concentrations of tipranavir with a twice-daily regimen. Depending on the dose of tipranavir/ritonavir administered, maximum plasma tipranavir concentrations are reached within 1–5 hours and, in the majority of individuals, steady state is reached after approximately 7 days of twice-daily administration. At steady state, tipranavir pharmacokinetics are linear when tipranavir is boosted by low-dose ritonavir. The effect of tipranavir/ritonavir on cytochrome P450 (CYP) isoenzymes, particularly CYP3A, and on P-glycoprotein (P-gp) results in numerous pharmacokinetic interactions between tipranavir/ ritonavir and other drugs. At steady state, tipranavir/ritonavir shows moderate inhibitory effects on hepatic CYP3A4/5, strong inhibitory effects on intestinal CYP3A4/5 and a minimal effect on the activity of P-gp, according to preliminary results of a well designed drug interaction study in healthy volunteers.

Therapeutic Efficacy

The therapeutic efficacy of oral tipranavir/ritonavir 500 mg/200 mg twice daily versus that of a ritonavir-boosted comparator PI (CPI) [lopinavir, indinavir, saquinavir or amprenavir] has been evaluated in the similarly designed randomized, nonblind, multicentre RESIST (Randomized Evaluation of Strategic Intervention in multidrug reSistant patients with Tipranavir)-1 and RESIST-2 trials in highly antiretroviral-experienced, HIV-1-infected adult patients. All patients also received concurrent treatment with an optimized background regimen (with or without enfuvirtide).

Study participants were HIV-1-infected adult patients who had received ≥3 months of previous treatment with a nucleoside reverse transcriptase inhibitor, a non-nucleoside reverse transcriptase inhibitor and a PI. Included patients had also previously received at least two PI-based regimens. At baseline, all patients had a plasma HIV-1 RNA level of ≥1000 copies/mL.

Recipients of tipranavir/ritonavir experienced a sustained response to treatment, with a significantly larger proportion of patients achieving a confirmed viral load reduction of ≥1 log10 copies/mL at 48 weeks than recipients of CPIs (primary endpoint; pooled data). In addition, the tipranavir/ritonavir treatment group had a longer time to treatment failure than did patients treated with the CPIs (primary endpoint). Immunological responses, a secondary efficacy measure, were also significantly better in the tipranavir/ritonavir group than in the recipients of CPIs. Preliminary data indicate that the efficacy of tipranavir/ritonavir is sustained for up to 156 weeks.

Tolerability

In the RESIST trials, adverse events with tipranavir/ritonavir were typical of those seen with the ritonavir-boosted CPIs, despite the higher dosage of ritonavir received by patients in the tipranavir/ritonavir group. Gastrointestinal adverse events were the most common treatment-emergent events with tipranavir/ritonavir and were usually mild. The adverse event rate per 100 patient-exposure years of any adverse event was similar among patients receiving tipranavir/ritonavir and those receiving a CPI/ritonavir. Exposure-adjusted total rates of grade 3 or 4 laboratory abnormalities were also similar in the the two treatment groups. Grade 3 or 4 elevations in triglyceride levels, cholesterol levels and liver enzymes occurred significantly more frequently among patients receiving tipranavir/ritonavir than in the CPI/ritonavir recipients. However, the most highly treatment-experienced patients did not experience grade 3 or 4 AST or ALT elevations during 96 weeks of treatment with tipranavir/ritonavir in five phase IIb/III trials. When reported, grade 3 or 4 AST or ALT elevations were were asymptomatic in the majority of patients.

Reports of clinical hepatitis and hepatic decompensation, including some fatalities, have been associated with tipranavir/ritonavir treatment, usually in patients receiving multiple medications and with advanced HIV-1-infection. Caution is recommended and increased liver enzyme monitoring should be considered in patients with liver enzyme abnormalities or hepatitis receiving tipranavir. In addition, tipranavir has been associated with fatal and nonfatal intracranial haemorrhage and should be administered with caution in patients with an increased bleeding risk (see boxed warning in the manufacturer’s prescribing information). However, rates of intracranial haemorrage in a large cohort of US Medi-Cal recipients not taking tipranavir were similar to those observed in premarketing trials of tipranavir. Rashes have been reported in patients receiving tipranavir/ritonavir.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Table II
Table III
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Notes

  1. The use of trade names is for identification purposes only and does not imply endorsement.

References

  1. Hammer SM, Saag MS, Schechter M, et al. Treatment for adult HIV infection: 2006 Recommendations of the International AIDS Society-USA panel. JAMA 2006; 296(7): 827–43

    Article  PubMed  CAS  Google Scholar 

  2. Temesgen Z, Cainelli F, Poeschla EM, et al. Approach to salvage antiretroviral therapy in heavily antiretroviral-experienced HIV-positive adults. Lancet Infect Dis 2006; 6(8): 496–507

    Article  PubMed  CAS  Google Scholar 

  3. DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents: a working group of the Office of AIDS Research Advisory Council (OARAC) Jan 29 2008. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents [online]. Available from URL: http://aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL.pdf [Accessed 2008 May 2]

  4. Clumeck N, Pozniak A, Raffi F, et al. European AIDS Clinical Society (EACS) guidelines for the clinical management and treatment of HIV-infected adults in Europe [online]. Available from URL: http://www.eacs.eu/guide/index.htm [Accessed 2008 May 16]

  5. Gazzard B, Bernard AJ, Boffito M, et al. British HIV Association (BHIVA) guidelines for the treatment of HIV-infected adults with antiretroviral therapy (2006). HIV Med 2006 Nov; 7(8): 487–503

    Article  PubMed  CAS  Google Scholar 

  6. Youle M. Overview of boosted protease inhibitors in treatment-experienced HIV-infected patients. J Antimicrob Chemother 2007 Sep 25; 60: 1195–205

    Article  PubMed  CAS  Google Scholar 

  7. Deeks SG. Antiretroviral treatment of HIV-infected adults. Br Med J 2006; 332(7556): 1489–93

    Article  Google Scholar 

  8. Hicks CB, Cahn P, Cooper DA, et al. Durable efficacy of tipranavir-ritonavir in combination with an optimised background regimen of antiretroviral drugs for treatment-experienced HIV-1-infected patients at 48 weeks in the Randomized Evaluation of Strategic Intervention in multi-drug reSistant patients with Tipranavir (RESIST) studies: an analysis of combined data from two randomised open-label trials. Lancet 2006 Aug 5; 368(9534): 466–75

    Article  PubMed  CAS  Google Scholar 

  9. European Medicines Agency. Aptivus 250mg soft capsules: summary of product characteristics [online]. Available from URL: http://www.emea.europa.eu.humandocs/PDFs/EPAR/aptivus/H-631-PI-en.pdf [Accessed 2008 May 2]

  10. Plosker GL, Figgitt DP. Tipranavir. Drugs 2003; 63(15): 1611–8

    Article  PubMed  CAS  Google Scholar 

  11. Croom KF, Keam SJ. Tipranavir: a ritonavir-boosted protease inhibitor. Drugs 2005; 65(12): 1669–77

    Article  PubMed  CAS  Google Scholar 

  12. Muzammil S, Armstrong AA, Kang LW, et al. Unique thermodynamic response of tipranavir to HIV-1 protease drug resistance mutations. J Virol 2007 Mar 14; 81(10): 5144–54

    Article  PubMed  CAS  Google Scholar 

  13. Poppe SM, Slade DE, Chong KT, et al. Antiviral activity of the dihydropyrone PNU-140690, a new nonpeptidic human immunodeficiency virus protease inhibitor. Antimicrob Agents Chemother 1997 May; 41(5): 1058–63

    PubMed  CAS  Google Scholar 

  14. Boehringer Ingelheim. Aptivus® (tipranavir) capsules, 250mg: US prescribing information [online]. Available from URL: http://bidocs.boehringer-ingelheim.com/BIWebAccess/View-Servlet.ser?docBase=renetnt=/Prescribing+Information/PIs/Aptivus/10003515+US+01.pdf [Accessed 2008 June 9]

  15. Committee for Medicinal Products for Human Use (CHMP). Scientific discussion (of aptivus) [online]. Available from URL: http://www.emea.int [Accessed 2007 Apr 17]

  16. Abecasis AB, Deforche K, Bacheler LT, et al. Investigation of baseline susceptibility to protease inhibitors in HIV-1 subtypes C, F, G and CRF02 AG. Antivir Ther 2006; 11(5): 581–9

    PubMed  CAS  Google Scholar 

  17. de Requena DG, Bonora S, Calcagno A, et al. Tipranavir (TPV) genotypic inhibitory quotient (gIQ) predicts virological response at 48 weeks to TPV-based salvage regimens. Antimicrob Agents Chemother 2007 Dec 26; 52(3): 1066–71

    Article  PubMed  Google Scholar 

  18. Doyon L, Tremblay S, Bourgon L, et al. Selection and characterization of HIV-1 showing reduced susceptibility to the nonpeptidic protease inhibitor tipranavir. Antiviral Res 2005 Oct; 68(1): 27–35

    Article  PubMed  CAS  Google Scholar 

  19. Baxter JD, Schapiro JM, Boucher CA, et al. Genotypic changes in human immunodeficiency virus type 1 protease associated with reduced susceptibility and virologic response to the protease inhibitor tipranavir. J Virol 2006 Nov; 80(21): 10794–801

    Article  PubMed  CAS  Google Scholar 

  20. Naeger LK, Strahle KA. Food and Drug Administration analysis of tipranavir clinical resistance in HIV-1-infected treatment-experienced patients. AIDS 2007 Jan 11; 21(2): 179–85

    Article  PubMed  CAS  Google Scholar 

  21. Marcelin AG, Masquelier B, Descamps D, et al. Mutations associated with response to boosted tipranavir in HIV-1-infected PI-experienced patients [abstract no. 612]. 14th Conference on Retroviruses and Opportunistic Infections; 2007 Feb 25–28; Los Angeles (CA)

  22. Scherer J, Boucher CA, Baxter JD, et al. Improving the prediction of virologie response to tipranavir: the development of a tipranavir weighted score [poster no. P3.4/07]. 11th European AIDS Conference (EACS); 2007 Oct 24–27; Madrid

  23. Chen L, Sabo JP, Philip E, et al. Steady state disposition of the nonpeptidic protease inhibitor tipranavir when coadministered with ritonavir. Antimicrob Agents Chemother 2007 July 7; 51(7): 2436–44

    Article  PubMed  CAS  Google Scholar 

  24. Cooper C, van Heeswijk K, Bilodeau M. The pharmacokinetics (PK) of single-dose and steady-state tipranavir/ritonavir (TPV/ r) 500 mg/200 mg in subjects with mild or moderate hepatic impairment. [poster Tu Pe3. 1B07]. 3rd International AIDS Society Conference on HIV Pathogenesis and Treatment; 2005 Jul 24–27; Rio de Janeiro

  25. Sabo JP, Cahn P, Delia Negra M, et al. Population pharmacokinetic assessment of systemic steady-state tipranavir concentrations for HIV+ pediatrie patients administered tipranavir/ritonavir: BI 1182.14 and PACTG 1051 Study Team [abstract no. 687]. 13th Conference on Retroviruses and Opportunistic Infections; dy2006 Feb 5; Denver (CO)

  26. MacGregor TR, Sabo JP, Norris SH, et al. Pharmacokinetic characterization of different dose combinations of coadministered tipranavir and ritonavir in healthy volunteers. HIV Clin Trials 2004 Nov; 5(6): 371–82

    Article  PubMed  Google Scholar 

  27. Baldwin JR, Borin MT, Wang Y, et al. Effects of food and antacid on bioavailability of the protease inhibitor PNU-140690 in healthy volunteers [abstract no. 649]. 5th Conference on Retroviruses and Opportunistic Infections; 1998 Feb 1–5; Chicago (IL)

  28. La Porte C, Cameron D, Sabo J, et al. The effect of omeprazole, food and formulation on the pharmacokinetics of tipranavir coadministered with ritonavir [poster no. 59]. 8th International Workshop on Clinical Pharmacology of HIV Therapy; 2007 Apr 16–18; Budapest

  29. Vourvahis M, Kashuba AD. Mechanisms of pharmacokinetic and pharmacodynamic drug interactions associated with ritonavir-enhanced tipranavir. Pharmacotherapy 2007 Jun; 27(6): 888–909

    Article  PubMed  CAS  Google Scholar 

  30. Vourvahis M, Dumond J, Patterson K, et al. Effects of tipranavir/ritonavir on the activity of hepatic and intestinal cytochrome P450 3A4/5 and P-glycoprotein: implications for drug interactions [abstract no. 563, plus poster]. 14th Conference on Retroviruses and Opportunistic Infections; 2007 Feb 25–28; Los Angeles (CA)

  31. Walmsley SL, Katlama C, Lazzarin A, et al. Pharmacokinetics, safety, and efficacy of tipranavir boosted with ritonavir alone or in combination with other boosted protease inhibitors as part of optimized combination antiretroviral therapy in highly treatment-experience dp Patients (BI Study 1182.51). J Acquir Immune Defic Syndr 2008 Apr 1; 47(4): 429–40

    Article  PubMed  CAS  Google Scholar 

  32. Sabo JP, Elgadi M, Wrack J, et al. The pharmacokinetic interaction between atazanavir/ritonavir (ATV/r) and steady state tipranavir/ritonavir (TPV/r) in healthy volunteers [abstract no.48]. 7th International Workshop on Clinical Pharmacology of HIV Therapy; 2006 Apr 20–22; Lisbon

  33. Goebel FD, Sabo JP, MacGregor TR, et al. Pharmacokinetic drug interaction screen of three doses of tipranavir/ritonavir (TPV/r) in HIV-infected patients on stable highly active antiretroviral therapy (HAART) [abstract plus poster].HIV-1 DART Frontiers in Drug Development for Antiretroviral Therapies; 2002 Dec 15–19; Naples (FL)

  34. Scholler M, Kraft M, Hoetelmans R, et al. Significant decrease in TMC125 exposures when co-administered with tipranavir boosted with ritonavir in healthy subjects [abstract no. 583, plus poster]. 13th Conference on Retroviruses and Opportunistic Infections; 2006 Feb 5–9; Denver (CO)

  35. van Heeswijk R, Sabo J, MacGregor T, et al. The effect of tipranavir/ritonavir 500/200mg bid (TPV/r) on the pharmacokinetics (PK) of clarithromycin (CLR) in healthy volunteers [abstract no. A-457]. 44th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2004 Oct 30–Nov 2; Washington, DC [online]. Available from URL: http://www.abstractsonline.com [Accessed 2005 Mar 3]

  36. van Heeswijk R, Sabo J, MacGregor T, et al. The pharmacokinetic (PK) interaction between single-dose rifabutin (RFB) and steady-state tipranavir/ritonavir 500/200 mg bid (TPV/r) in healthy volunteers [abstract no. A-456]. 44th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2004 Oct 30–Nov 2; Washington, DC [online]. Available from URL: http://www.abstractsonline.com [Accessed 2005 Mar 4]

  37. van Heeswijk R, Sabo JP, Cooper C, et al. The pharmacokinetic interactions between tipranavir/ritonavir 500/200 mg bid (TPV/r) and atorvastatin, antacid, and CYP3A4 in healthy adult volunteers [abstract no. 5.2, plus poster]. 5th International Workshop on Clinical Pharmacology of HIV Therapy; 2004 Apr 1–3; Rome

  38. Mukwaya G, MacGregor T, Hoelscher D, et al. Interaction of ritonavir-boosted tipranavir with loperamide does not result in loperamide-associated neurologic side effects in healthy volunteers. Antimicrob Agents Chemother 2005 Dec; 49(12): 4903–10

    Article  PubMed  CAS  Google Scholar 

  39. Pham P, Lee L, Fuchs E, et al. Pharmacokinetic interaction between tipranavir/ritonavir and rosuvastatin [abstract no. 767]. 15th Conference on Retroviruses and Opportunistic Infections; 2008 Feb 3–6; Boston (MA)

  40. Durant J, Dellamonica P, Garraffo R, et al. The effect of tipranavir/ritonavir on the pharmacokinetics of tadalafil in healthy volunteers [abstract no. 61, plus poster]. 8th International Workshop on Clinical Pharmacology of HIV Therapy; 2007 Apr 16–18; Budapest

  41. van Heeswijk R, Sabo JP, MacGregor TR, et al. The effect of tipranavir/ritonavir 500/200 mg bid (TPV/r) on the pharmacokinetics of fluconazole in healthy volunteers [abstract no. 4.8, plus poster]. 5th International Workshop on Clinical Pharmacology of HIV Therapy; 2004 Apr 1–3; Rome

  42. Roszko PJ, Curry K, Brazina B, et al. Standard doses of efavirenz (EFV), zidovudine (ZDV), tenofovir (TDF) and didanoside (ddI) may be given with tipranavir/ritonavir (TPV/r) [abstract no. 865]. Antiviral Ther 2003; 8 Suppl. 1: S248. Plus poster presented at the 2nd International AIDS Society Conference on HIV Pathogenesis and Treatment; 2003 Jul 13–16; Paris

    Google Scholar 

  43. La Porte CJL, Sabo JP, Beique L, et al. Lack of effect of efavirenz (EFV) 600 mg QD on the pharmacokinetics of tipranavir/ritonavir 500/200 mg BID (TPV/r) in healthy volunteers [abstract no. A-1421, plus poster]. 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2007 Sep 17–20; Chicago, (IL)

  44. Gonzalez de Requena D, Calcagno A, Bonora S, et al. Unexpected drug-drug interaction between tipranavir/ritonavir and enfuvirtide. AIDS 2006 Oct 3; 20(15): 1977–9

    Article  PubMed  CAS  Google Scholar 

  45. Raffi F, Battegay M, Rusconi S, et al. Combined tipranavir and enfuvirtide use associated with higher plasma tipranavir concentrations but not with increased hepatotoxicity: subanalysis from RESIST. AIDS 2007 Sep 12; 21(14): 1977–80

    Article  PubMed  CAS  Google Scholar 

  46. Wenning LA, Hanley H, Stone J, et al. Effect of tipranavir + ritonavir on pharmacokinetics of MK-0518 [abstract no. A-374, plus poster]. 46th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2006 Sep 27–30; San Francisco (CA), 8

  47. Bonora S, Calcagno A, Fontana S, et al. Clinically significant drug interaction between tipranavir-ritonavir and phenobarbital in an HIV-infected subject [letter]. Clin Infect Dis 2007 Dec 15; 45(12): 1654–5

    Article  PubMed  Google Scholar 

  48. Pollard RB, Staszewski S, LeBlanc R, et al. Impact of prior PI usage on week 48 responses to tipranavir boosted with ritonavir [abstract no. TUPE0067, plus poster]. 16th International AIDS Conference; 2006 Aug 13–18; Toronto (ON)

  49. Katlama C, Walmsley S, Hicks C, et al. Tipranavir achieves twice the rate of treatment response and prolongs durability of response vs comparator PI in ART-experienced patients, independent of baseline CD4 cell count or viral load: week 48 RESIST 1 and 2 combined analyses [abstract no. 520]. 13th Conference on Retroviruses and Opportunistic Infections; 2006 Feb 5–9; Denver (CO)

  50. Gazzard B, Antinori A, Cheli C. Combined analysis of RESIST 96 week data: durability and efficacy of tipranavir/r in treatment experienced patients [abstract no. P23]. 8th International Congress on Drug Therapy in HIV Infection; 2006 Nov 12–16; Glasgow

  51. Farthing C, Ward D, Hicks C, et al. Tipranavir/r demonstrates superior and durable treatment response compared with comparator PI/r in highly treatment-experienced patients: Weeks 96 RESIST 1 and 2 results [abstract no. H-1385, plus poster]. 46th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2006 Sep 27–30; San Francisco (CA), 284

  52. Hicks C, Cahn P, Ward D, et al. Tipranavir/r (TPV/r) maintains long term virological suppression: three year follow-up of RESIST [poster no. P7.3/25]. 11th European AIDS Conference (EACS); 2007 Oct 24–27; Madrid.

  53. Gathe J, Cooper DA, Farthing C, et al. Efficacy of the protease inhibitors tipranavir plus ritonavir in treatment-experienced patients: 24-week analysis from the RESIST-1 trial. Clin Infect Dis 2006 Nov 15; 43(10): 1337–46

    Article  PubMed  CAS  Google Scholar 

  54. Cahn P, Villacian J, Lazzarin A, et al. Ritonavir-boosted tipranavir demonstrates superior efficacy to ritonavir-boosted protease inhibitors in treatment-experienced HIV-infected patients: 24-week results of the RESIST-2 trial. Clin Infect Dis 2006 Nov 15; 43(10): 1347–56

    Article  PubMed  CAS  Google Scholar 

  55. Gathe JC, Pierone G, Piliero P, et al. Efficacy and safety of three doses of tipranavir boosted with ritonavir in treatment-experienced HIV type 1-infected patients. AIDS Res Hum Retroviruses 2007 Jan 1; 23(2): 216–23

    Article  PubMed  CAS  Google Scholar 

  56. Data on file, Boehringer Ingelheim, 2007

  57. Ernst J, Farthing C, Cooper D, et al. Week 8 response predicts week 48 virological responses to tipranavir/r in the RESIST studies [poster no. WEPEB037]. 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention; 2007 22–25 Jul; Sydney

  58. Mauss S, Stern J, Elgadi M, et al. Resist 24-week efficacy and safety of tipranavir boosted with ritonavir in hepatitis B or hepatitis C co-infected patient [abstract no. PE 13.3/4]. 10th European Aids Conference (EACS); 2005 Nov 17–20; Dublin

  59. Sulkowski M, Rockstroh J, Soriano V, et al. Clinical course of increased LFTs and hepatic events associated with tipranavir/ ritonavir based therapy in the RESIST trials [abstract no. poster]. 46th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2006 Sep 27–30; San Francisco (CA)

  60. Data on file, Boehringer Ingelheim, 2008

  61. Pierone G, Drulak M, Arasteh K, et al. A long-term open-label rollover trial assessing the safety and tolerability of combination tipranavir and ritonavir use in HIV-1-infected patients [abstract no. WePe6.2C05, plus poster]. 3rd International AIDS Society Conference on HIV Pathogenesis and Treatment; 2005 July 24–27; Rio de Janiero

  62. Friis-Moller N, Kraft M, Valdez H, et al. Predicted risk of coronary heart disease with tipranavir exposure compared to conventional PI in the RESIST trial [abstract no. 809, plus poster]. 14th Conference on Retroviruses and Opportunistic Infections; 2007 Feb 25–28; Los Angeles (CA)

  63. Pol S, Benhamou Y, Rockstroh J, et al. Hepatic profile of tipranavir in treatment experienced HIV-1 infected individuals [abstract and poster no. P4.5/03]. 11th European AIDS Conference (EACS); 2007 Oct 24–27; Madrid

  64. Fultz SL, Zingmond D, Gordon K.S., et al. Evaluation of intracranial hemorrhage in 49,610 HIV-infected veterans and California Medicaid recipients [poster no. 819]. 14th Conference on Retroviruses and Opportunistic Infections; 2007 Feb 25–28; Los Angeles (CA)

  65. Mocroft A, Phillips AN, Friis-Moller N, et al. Response to antiretroviral therapy among patients exposed to three classes of antiretrovirals: results from the EuroSIDA study. Antiviral Ther 2002; 7(1): 21–30

    CAS  Google Scholar 

  66. Richman D, Morton SC, Wrin T, et al. The prevalence of antiretroviral drug resistance in the United States. AIDS 2004; 18: 1393–401

    Article  PubMed  Google Scholar 

  67. Huang IC, Wu AW, Finnern HW, et al. Health-related quality of life and tolerability in treatment-experienced HIV-1-infected patients on tipranavir versus comparator regimens. Antivir Ther 2008; 13(1): 15–25

    PubMed  Google Scholar 

  68. Elston R, Kuritzkes D, Bethell R. An investigation into the influence of the tipranavir-associated V82L/T mutations on the susceptibility to darunavir and brecanavir [abstract no. M-174, plus poster]. 14th Conference on Retroviruses and Opportunistic Infections; Feb 25–28 2007; Los Angeles (CA)

  69. Simpson KN, Chumney ECG, Hicks CB, et al. Cost effectiveness of tipranavir in treatment-experienced HIV patients in the USA [abstract no. PIN10, plus poster]. Value Health 2006 May 30; 9(3): A156

    Article  Google Scholar 

  70. Boehringer Ingelheim. Boehringer Ingelheim initiates SPRING study of Aptivus® (tipranavir) in diverse group of highly treatment-experienced HIV-positive patients [online]. Available from URL: http://www.boehringer-ingelheim.com [Accessed 2007 Jun 28]

  71. Kumar PN, Cooper DA, Steigbigel RT. Efficacy of raltegravir, an HIV integrase inhibitor, in combination with regimens containing enfuvirtide, darunavir, or tipranavir in patients with triple-class resistant virus. Combined results from BENCHMRK-1 and BENCHMRK-2 [poster no. P7.2/06]. 11th European AIDS Conference (EACS); 2007 Oct 24–27; Madrid

Download references

Author information

Authors and Affiliations

  1. Wolters Kluwer Health ¦ Adis, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore 0754, Auckland, New Zealand

    Jennifer S. Orman & Caroline M. Perry

  2. Wolters Kluwer Health, Conshohocken, Pennsylvania, USA

    Jennifer S. Orman & Caroline M. Perry

Authors
  1. Jennifer S. Orman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Caroline M. Perry
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Caroline M. Perry.

Additional information

Various sections of the manuscript reviewed by: F. Cainelli, Infectious Diseases Unit, A. Pugliese Hospital, Catanzaro, Italy; B. Gazzard, St Stephen’s Centre, Chelsea and Westminster Hospital, London, England; C. Hicks, Department of Medicine, Division of Infectious Diseases and International Health, Duke University Medical Center, Durham, North Carolina, USA; C.J. La Porte, Division of Infectious Diseases, The Ottawa Hospital, Ottawa Health Research Institute, Ottawa, Ontario, Canada; A.G. Marcelin, Laboratoire de Virologie, Hôpital Pitié Salpêtrière, Paris, France; E. Seminari, Infectious Disease Department, San Raffaele Scientific Institute and Università Vita-Salute San Raffaele, Milan, Italy.

Data Selection

Sources: Medical literature published in any language since 1980 on ‘tipranavir’, identified using MEDLINE and EMBASE, supplemented by AdisBase (a proprietary database of Wolters Kluwer Health | Adis). Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug.

Search strategy: MEDLINE, EMBASE and AdisBase search terms were ‘tipranavir’ or ‘PNU-140690’. Searches were last updated 30 May 2008.

Selection: Studies in patients with HIV infection who received tipranavir. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.

Index terms: Tipranavir, HIV, pharmacodynamics, pharmacokinetics, therapeutic use, tolerability.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Orman, J.S., Perry, C.M. Tipranavir. Drugs 68, 1435–1463 (2008). https://doi.org/10.2165/00003495-200868100-00006

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-200868100-00006

Keywords

Search

Navigation