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New drugs for the treatment of HIV infection

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Abstract

Despite the availability of 15 approved drugs for the treatment of HIV infection, issues of convenience, tolerability, and antiretroviral activity make the continued development of newer drugs important. New drugs in clinical development represent both existing classes of antiretroviral agents—reverse transcriptase inhibitors (eg, diaminopurine dioxolane), nonnucleoside reverse transcriptase inhibitors (eg, capravirine), and protease inhibitors (eg, tipranavir and BMS-232632)—and newer classes of antiretroviral agents, such as nucleotide analogue reverse transcriptase inhibitors (eg, tenofovir) and fusion inhibitors (eg, pentafuside). Newer drugs may offer improvements over existing agents by having simpler dosing schedules (once or twice daily), better tolerability, or improved virologic activity against wild-type or resistant virus. Continued advancements in HIV treatment will stem from ongoing development of antiretroviral drugs.

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References and Recommended Reading

  1. Gu Z, Wainberg MA, Nguyen-Ba N, et al.: Mechanism of action and in vitro activity of 1′,3′-dioxolanylpurine nucleoside analogues against sensitive and drug-resistant human immunodeficiency virus type 1 variants. Antimicrob Agents Chemother 1999, 43:2376–2382.

    PubMed  CAS  Google Scholar 

  2. Wang LH, Bigley JW, St. Claire RL, et al.: Preliminary assessments of the pharmacokinetics of DAPD and its active metabolite DXG in HIV-infected subjects [abstract]. In 7th Conference on Retroviruses and Opportunistic Infections. San Francisco: January 30–February 2, 2000.

  3. Mewshaw J, Borroto-Esoda K, Wakefield D, et al.: DAPD: A novel nucleoside inhibitor of HIV-1 replication is active against drug-resistant isolates of HIV-1 from patients failing standard nucleoside therapy [abstract]. In 39th Interscience Conference on Antimicrobial Agents and Chemotherapy. San Francisco: September 26–29, 1999.

  4. Ussery MA, Wood OL, Kunder SC, et al.: Anti-HIV activity in the HuPBMC SCID mouse model of six novel nucleoside analogs: (-)-FTC, (+/-)-FTC, D-DAPD, D-D4FC, CS-92 and CS-87 [abstract]. In 11th International Conference on Antiviral Research. San Diego: March 1998.

  5. Richman DD, Kessler H, Eron J, et al.: Anti-HIV activity and tolerability of DAPD, a novel dioxolane guanosine RT inhibitor: initial results of a phase I/II 14-day monotherapy clinical trial [abstract]. In 7th Conference on Retroviruses and Opportunistic Infections. San Francisco: January 30–February 2, 2000. First presented clinical trial of DAPD/DXG in HIV-infected patients

  6. Potts KE, Fujiwara T, Sato A, et al.: Antiviral activity and resistance profile of AG1549, a novel HIV-1 nonnucleoside reverse transcriptase inhibitor [abstract]. In 6th Conference on Retroviruses and Opportunistic Infections. Chicago: January 31–February 4, 1999.

  7. Hernandez J, Amador L, Amantea M, et al.: Short-course monotherapy with AG1549, a novel nonnucleoside reverse transcriptase inhibitor (NNRTI), in antiretroviral-naïve patients [abstract]. In 7th Conference on Retroviruses and Opportunistic Infections. San Francisco: January 30–February 2, 2000. First presented clinical trial of capravirine in HIV-infected patients.

  8. Tsai C-C, Follis KE, Sabo A, et al.: Prevention of SIV infection in macaques by (R)-9-(2-phosphonylmethoxypropyl)adenine. Science 1995, 270:1197–1199.

    Article  PubMed  CAS  Google Scholar 

  9. Tsai C-C, Follis KE, Beck TW, et al.: Effects of (R)-9-(2-phosphonylmethoxypropyl)adenine monotherapy in chronic SIV infection in macaques. AIDS Res Hum Retroviruses 1997, 13:707–711.

    Article  PubMed  CAS  Google Scholar 

  10. Deeks SG, Barditch-Crovo P, Lietman PS: Safety, pharmacokinetics, and antiretroviral activity of intravenous 9-[2-(R)-(Phosphonomethoxy) propyl]adenine, a novel anti-human immunodeficiency virus (HIV) therapy, in HIV-infected adults. Antimicrob Agents Chemother 1998, 42:2380–2384. First report demonstrating data to support once-daily dosing and the virologic activity of tenofovir in HIV-infected patients.

    PubMed  CAS  Google Scholar 

  11. Wainberg M, Miller MD, Quan Y, et al.: The M184V substitution in reverse transcriptase increases sensitivity of HIV-1 to PMPA [abstract]. In 5th Conference on Retroviruses and Opportunistic Infections. Chicago: February 1–5, 1998.

  12. Thompson M: 48-Week phase II safety and efficacy results for once-daily anti-HIV agent, Tenofovir DF [abstract]. In International Conference for Antiviral Research. Baltimore: April 2000. Abstract report demonstrating the activity of tenofovir in a treatmentexperienced patient sample.

  13. Miller MD, Margot MA, Robison M, et al.: HIV-1 RT mutations in patients after 24 weeks of tenofovir disoproxil fumarate (formerly PMPA prodrug) therapy added to stable background ART [abstract]. In 7th Conference on Retroviruses and Opportunistic Infections. San Francisco: January 30–February 2, 2000.

  14. Sham HL, Kempf DJ, Molla A, et al.: ABT-378, a highly potent inhibitor of the human immunodeficiency virus protease. Antimicrob Agents Chemother 1998, 42:3218–3224.

    PubMed  CAS  Google Scholar 

  15. Murphy RL, Brun S, Hicks C, et al.: ABT-378/ritonavir plus stavudine and lamivudine for the treatment of antiretroviral-naïve adults with HIV-1 infection: 48 week results. AIDS 2001, 15:1–9. First report demonstrating safety, tolerability, and antiretroviral activity of lopinavir/ritonavir, stavudine, and lamivudine in treatment-naïve patients.

    Article  Google Scholar 

  16. Gulick R, King M, Brun S, et al.: ABT-378/Ritonavir (ABT-378/ r) in antiretroviral-naïve HIV + patients: 72 Weeks [abstract]. In 7th Conference on Retroviruses and Opportunistic Infections. San Francisco: January 30–February 2, 2000. Abstract report demonstrating virologic activity of lopinavir/ritonavirbased combination therapy in a naïve patient sample over 72 weeks.

  17. Deeks S, Brun S, Xu Y, et al.: ABT-378/Ritonavir (ABT-378/r) suppresses HIV RNA to < 400 copies/ml in 84% of PI-experienced patients at 48 weeks [abstract]. In 7th Conference on Retroviruses and Opportunistic Infections. San Francisco: January 30–February 2, 2000. Abstract report demonstrating virologic activity of lopinavir/ritonavirbased combination therapy in a selected cohort of protease inhibitorexperienced patients over 48 weeks

  18. Turner SR, Strohbach JW, Tommasi RA, et al.: Tipranavir (PNU-140690): a potent, orally bioavailable nonpeptidic HIV protease inhibitor of the 5,6-dihydro-4-hydroxy-2-pyrone sulfonamide class. J Med Chem 1998, 41:3467–3476.

    Article  PubMed  CAS  Google Scholar 

  19. Larder B, Hertogs K, Bloor S, et al.: Tipranavir inhibits broadly protease inhibitor-resistant HIV-1 clinical samples. AIDS 2000, 14:1943–1948. Phenotyping of large panel of clinical isolates demonstrates activity of tipranavir against viruses that are resistant to currently available protease inhibitors.

    Article  PubMed  CAS  Google Scholar 

  20. Rusconi S, La Seta Catamancio S, Citterio P, et al.: Susceptibility to PNU-140690 (tipranavir) of human immunodeficiency virus type 1 isolates derived from patients with multidrug resistance to other protease inhibitors. Antimicrob Agents Chemother 2000, 44:1328–1332.

    Article  PubMed  CAS  Google Scholar 

  21. Poppe SM, Slade DE, Chong K-T, et al.: Antiviral activity of the dihydropyrone PNU-140690, a new nonpeptidic human immunodeficiency virus protease inhibitor. Antimicrob Agents Chemother 1997, 41:1058–1063.

    PubMed  CAS  Google Scholar 

  22. Chong K-T, Pagano PJ: In vitro combination of PNU-140690, a human immunodeficiency virus type 1 protease inhibitor, with ritonavir against ritonavir-sensitive and -resistant clinical isolates. Antimicrob Agents Chemother 1997, 41:2367–2373.

    PubMed  CAS  Google Scholar 

  23. 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]. In 5th Conference on Retroviruses and Opportunistic Infections. Chicago: February 1–5, 1998.

  24. Borin MT, Wang Y, Schneck DW, et al.: Multiple-dose, safety, tolerance, and pharmacokinetics of the protease inhibitor PNU-140690 in healthy volunteers [abstract]. In 5th Conference on Retroviruses and Opportunistic Infections. Chicago: February 1–5, 1998.

  25. Wang Y, Tutton CM, Borin MT, et al.: The safety, tolerance, pharmacokinetics, and efficacy of PNU-140690, a new non-peptidic HIV protease inhibitor, in a phase I/II study [abstract]. In 12th World AIDS Conference. Geneva: June 28–July 3, 1998.

  26. Wang Y, Daenzer C, Wood R, et al.: The safety, efficacy, and viral dynamics analysis of tipranavir, a new-generation protease inhibitor, in a phase II study in antiretroviral-naïve HIV-1-infected patients [abstract]. In 7th Conference on Retroviruses and Opportunistic Infections. San Francisco: January 30–February 2, 2000. Abstract report demonstrating the benefits of combining tipranavir with ritonavir to improve the pharmacokinetic profile and virologic activity.

  27. O’Mara E, Mummaneni V, Randall D, et al.: BMS-232,632: A summary of multiple-dose pharmacokinetic, food Effect, and drug interaction studies in healthy subjects [abstract]. In 7th Conference on Retroviruses and Opportunistic Infections. San Francisco: January 30–February 2, 2000.

  28. Sanne I, Piliero P, Wood R, et al.: Safety and antiviral efficacy of a novel once-daily HIV-1 protease inhibitor, BMS-232632: Preliminary results from a phase II clinical trial [abstract]. In 7th Conference on Retroviruses and Opportunistic Infections. San Francisco: January 30–February 2, 2000. Abstract report of first extended clinical trial of BMS-232632.

  29. Black P, Wood O, Bacho M, et al.: T-20 and T-1052, novel inhibitors of HIV fusion, block infection of human macrophages by HIV-1 [abstract]. In 11th International Conference on AIDS. Vancouver, British Columbia, Canada: July 7–12, 1996.

  30. Hopkins S, Lambert DM, Recny MR, et al.: Pentafuside (T-20), a novel inhibitor of HIV-1 fusion: pharmacokinetics in rodents, monkeys and man [abstract]. In 4th Conference on Retroviruses and Opportunistic Infections. Washington, DC: January 22–26, 1997.

  31. Black PL, Wood OL, Broud DD, et al.: T-20, a novel inhibitor of HIV-1 fusion blocks HIV-1 infection in vitro in human PBMC and macrophages and in vivo in the HuPBMC-SCID mouse model [abstract]. In 4th Conference on Retroviruses and Opportunistic Infections. Washington, DC: January 22–26, 1997.

  32. Kilby JM, Hopkins S, Venetta TM, et al.: Potent suppression of HIV-1 replication in humans by T-20, a peptide inhibitor of gp41-mediated virus entry. Nat Med 1998, 4:1302–1307. This study supports the concept that fusion inhibitors have virologic activity in HIV-infected patients.

    Article  PubMed  CAS  Google Scholar 

  33. Lalezari J, Eron J, Carlson M, et al.: Safety, pharmacokinetics, and antiviral activity of T-20 as a single agent in heavily pre-treated patients [abstract]. In 6th Conference on Retroviruses and Opportunistic Infections. Chicago: January 31–February 4, 1999.

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Lee, K., Gulick, R.M. New drugs for the treatment of HIV infection. Curr Infect Dis Rep 3, 193–200 (2001). https://doi.org/10.1007/s11908-996-0058-9

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  • DOI: https://doi.org/10.1007/s11908-996-0058-9

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