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Saquinavir

A Review of its Pharmacology and Clinical Potential in the Management of HIV Infection

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Abstract

Synopsis

Saquinavir is a peptide derivative which inhibits the HIV protease enzyme, preventing post-translational processing of viral polyproteins. It was the first agent of its class to become available for the treatment of HIV infection.

Well controlled studies have assessed the effects of saquinavir, when used alone or in combination with reverse transcriptase inhibitors, in patients with advanced HIV infection. Analysis of CD4+ cell counts and measures of viral load in the ACTG 229 study suggest that triple therapy with saquinavir, zidovudine and zalcitabine is more effective than double therapy with saquinavir plus zidovudine or zidovudine plus zalcitabine in patients who have previously received long term treatment with zidovudine. Similar assessments from a small study in previously untreated patients suggest that double therapy with saquinavir plus zidovudine is more effective than monotherapy with either agent. Combination therapy with saquinavir and zalcitabine significantly reduced the time to the first AIDS-defining event or death, and the time to death, compared with zalcitabine alone, according to data from a large, long term study (NV 14256) in patients with advanced HIV infection who had previously received zidovudine.

Saquinavir is generally well tolerated, either as monotherapy or in combination with reverse transcriptase inhibitors; no change in tolerability profile was reported when saquinavir was added to treatment with nucleoside analogues. In vitro and clinical studies have documented the emergence of saquinavir-resistant HIV strains. Although the possible impact of resistance on the clinical efficacy of saquinavir has yet to be fully characterised, genotypic and phenotypic resistance appear to develop slowly during treatment with saquinavir, and the drug does not appear to have a significant effect on the incidence of mutations associated with cross-resistance to other protease inhibitors.

Thus, laboratory and clinical results suggest that saquinavir in combination with reverse transcriptase inhibitors is effective in the treatment of advanced HIV infection. Initial data on the effects of saquinavir on disease progression and mortality are promising, and the apparent absence of mutations conferring cross-resistance to other protease inhibitors is a potentially valuable clinical feature. Additional data on disease progression, mortality and viral resistance, together with information on relative efficacy (in comparison with other protease inhibitors), will need to be assessed before the clinical value of saquinavir can be fully determined. Nevertheless, saquinavir represents a valuable new pharmacological option for the treatment of HIV infection and is likely to be a useful component of combined therapy with reverse transcriptase inhibitors and/or other protease inhibitors.

Pharmacodynamic Properties

Saquinavir is an HIV protease inhibitor which is a transition-state mimetic of the phenylalanine-proline (Phe-Pro) peptide bond. It competitively inhibits HIV-1 and HIV-2 protease-mediated cleavage of the HIV gag and pol polyproteins. Proteolytic processing at Phe-Pro is rare in mammalian systems and saquinavir is therefore unlikely to inhibit mammalian proteases.

In vitro studies have shown that saquinavir inhibits processing of HIV poly-proteins, thus preventing the formation of mature viral particles and reducing subsequent viral replication as assessed by p24 antigen levels, culturable viral titre, polymerase chain reaction analysis of proviral DNA, syncytium formation and cell death. The concentration of saquinavir required to produce 50% inhibition of HIV-1 ranged from about 2 to 7 nmol/L (≈1.5 to 5.4 μg/L) in most studies. Combination of saquinavir with nucleoside analogue inhibitors of HIV reverse transcriptase and/or other anti-HIV compounds produced synergistic inhibition of HIV replication.

Two common mutations conferring resistance to saquinavir have been identified in vitro and in vivo. One or both of these mutations were identified in 45% of patients receiving saquinavir as monotherapy and in 31% of those receiving the drug as part of combination therapy (mean treatment duration ≈1 year). In general, viral resistance appears to develop slowly during saquinavir treatment. Analysis of HIV protease sequences from clinical HIV isolates suggests that saquinavir as monotherapy or in combination regimens has little or no effect on the incidence of mutations associated with resistance to other protease inhibitors. Such mutations occurred infrequently (2 to 9%) and/or at a frequency similar to or lower than that seen at baseline (sequences from patients treated for up to 147 weeks).

Pharmacokinetic Properties

Peak plasma concentrations (Cmax) of saquinavir are reached about 3 to 4 hours after single- or multiple-dose oral administration of capsules with food in healthy volunteers. The bioavailability of a single dose of saquinavir under these conditions is 4%, 18 times greater than the value obtained when the drug is administered in the fasting state. Mean Cmax values ranged from 35.5 to 127.0 μg/L after single-dose administration of saquinavir 600mg with food in healthy volunteers; multiple administration of the same dose produced a mean Cmax of 90.4 μg/L. A Cmax of 242.3 μg/L was reached 2 hours after administration in patients receiving saquinavir 600mg 3 times daily under steady-state conditions.

Saquinavir is metabolised by the cytochrome P4503A4 isozyme to a number of inactive derivatives. The terminal elimination half-life of saquinavir after intravenous administration was 13.2 hours. 88% of a 600mg oral dose was detected in the faeces, with 1 % found in the urine. The relative bioavailability of saquinavir was increased when it was coadministered with ketoconazole or ranitidine and decreased when it was given with rifampicin (rifampin) or rifabutin.

Clinical Potential

The ACTG 229 study compared the efficacy of triple therapy with saquinavir 600mg, zidovudine 200mg and zalcitabine 0.75mg 3 times daily with that of 2 double therapy combinations in 297 zidovudine-experienced patients with advanced HIV infection who were treated for 24 weeks or more [median duration of prior zidovudine treatment was 27 months; median CD4+ cell count was 156 (range 25 to 394) cells/μl at baseline]. Triple therapy produced a larger and more sustained increase in CD4+ cell counts than treatment with saquinavir plus zidovudine or zidovudine plus zalcitabine. Similarly, measurement of HIV-1 titres in peripheral blood mononuclear cells (PBMCs) and plasma HIV-1 RNA titres indicated that triple therapy was significantly more effective than either of the double therapies. Although the mean CD4+ cell count after 48 weeks was below that seen at baseline in patients receiving triple therapy, viral suppression was still evident (39% decrease in mean PBMC HIV-1 titre compared with baseline).

Saquinavir 600mg plus zidovudine 200mg 3 times daily produced a greater increase in CD4+ cell counts and a larger reduction in plasma HIV-1 RNA titres than monotherapy with either saquinavir 600mg or zidovudine 200mg 3 times daily in a small group of previously untreated patients (n = 71; study V13330).

Final disease progression/mortality data are available from the NV 14256 study, which assessed the effects of saquinavir and zalcitabine, either alone or in combination, in 940 evaluable patients with advanced HIV infection who had previously received zidovudine for at least 16 weeks. The median initial treatment duration was 56 weeks for combination therapy (n = 308), 48 weeks for zalcitab-ine monotherapy (n = 314) and 56 weeks for saquinavir monotherapy (n = 318). Median follow-up in all groups was 73 to 74 weeks. When compared with zalcitabine monotherapy, treatment with saquinavir plus zalcitabine significantly increased the time to first AIDS-defining event or death (p = 0.0002, risk ratio 0.47), and the time to death (p = 0.002, risk ratio 0.28), according to an intent-to-treat log-rank analysis of event rates. The number of first AIDS-defining events or deaths was reduced by about 46%, and the number of deaths by about 68%, for combination therapy compared with zalcitabine monotherapy. There were no significant differences between the 2 monotherapies (statistical analysis not provided for combination therapy vs saquinavir).

Tolerability

Saquinavir was generally well tolerated when given as monotherapy or as part of combination antiretroviral regimens. Gastrointestinal disturbances were the most common adverse events in 159 patients who received saquinavir monotherapy as part of a double-blind study (median duration 42 weeks); diarrhoea was the most common single event, occurring with moderate or greater severity in 3.8% of patients. Fatigue, diarrhoea and nausea were the most common clinical adverse events considered possibly related to treatment in patients receiving saquinavir plus zidovudine plus zalcitabine as part of study ACTG 229 (17, 5 and 9% incidence, respectively, for moderate events; 2, 1 and 0%, respectively, for severe events). The addition of saquinavir to zidovudine and/or zalcitabine did not produce any significant change in clinical or laboratory-assessed tolerability profiles.

Dosage and Administration

Saquinavir is currently recommended, in combination with nucleoside analogues, for the treatment of advanced HIV infection in selected patients. The drug should be administered within 2 hours of a full meal at a dosage of 600mg 3 times daily.

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References

  1. Levy JA. Pathogenesis of human immunodeficiency virus infection. Microbiol Rev 1993; 57(1): 183–289

    PubMed  CAS  Google Scholar 

  2. Pantaleo G, Graziosi Fauci AS. The immunopathogenesis of human immunodeficiency virus infection. N Engl J Med 1993 Feb 4; 328(5): 327–35

    Article  PubMed  CAS  Google Scholar 

  3. Kohl NE, Emini EA, Schlief WA, et al. Active human immunodeficiency virus protease is required for viral infectivity. Proc Natl Acad Sci USA 1988; 85: 4686–90

    Article  PubMed  CAS  Google Scholar 

  4. Redshaw S. Inhibitors of HIV proteinase. Expert Opin Invest Drugs 1994; 3(3): 273–86

    Article  CAS  Google Scholar 

  5. Pettit SC, Michael SF, Swanstrom R. The specificity of the HIV-1 protease. Perspect Drug Discov Des 1993; 1: 69–83

    Article  CAS  Google Scholar 

  6. Velia S. Update on a proteinase inhibitor. AIDS 1994 Sep; 8 Suppl.3: 25–9

    Article  Google Scholar 

  7. Kramer RA, Schaber MD, Skalka AM, et al. HTLV-III gag protein is processed in yeast cells by the virus pol-protease. Science 1986 Mar 28; 231: 1580–4

    Article  PubMed  CAS  Google Scholar 

  8. Göttlinger HG, Sodroski JG, Haseltine WA. Role of capsid precursor processing and myristoylation in morphogenesis and infectivity of human immunodeficiency virus type 1. Proc Natl Acad Sci USA 1989; 86: 5781–5

    Article  PubMed  Google Scholar 

  9. Roberts NA, Martin JA, Kinchington D, et al. Rational design of peptide-based HIV proteinase inhibitors. Science 1990 Apr 20; 248: 358–61

    Article  PubMed  CAS  Google Scholar 

  10. Craig JC, Grief C, Mills JS, et al. Effects of a specific inhibitor of HIV proteinase (Ro 31-8959) on virus maturation in a chronically infected promonocytic cell line (U1). Antiviral Chem Chemother 1991; 2(3): 181–6

    CAS  Google Scholar 

  11. Craig JC, Duncan IB, Hockley D, et al. Antiviral properties of Ro 31-8959, an inhibitor of human immunodeficiency virus (HIV) proteinase. Antiviral Res 1991 Dec; 16: 295–305

    Article  PubMed  CAS  Google Scholar 

  12. Jacobsen H, Ahlborn-Laake L, Gugel R, et al. Progression of early steps of human immunodeficiency virus type 1 replication in the presence of an inhibitor of viral protease. J Virol 1992 Aug; 66: 5087–91

    PubMed  CAS  Google Scholar 

  13. Craig JC, Duncan IB, Whittaker L, et al. Antiviral synergy between inhibitors of HIV proteinase and reverse transcriptase. Antiviral Chem Chemother 1993; 4(3): 161–6

    CAS  Google Scholar 

  14. Galpin S, Roberts NA, O’Connor T, et al. Antiviral properties of the HIV-1 proteinase inhibitor Ro-8959. Antiviral Chem Chemother 1994; 5(1): 43–5

    CAS  Google Scholar 

  15. Johnson VA, Merrill DP, Chou TC et al. Human immunodeficiency virus type 1 (HIV-1) inhibitory interactions between protease inhibitor Ro 31-8959 and zidovudine, 2’,3’-dideoxycytidine, or recombinant interferon-αA against zidovudine-sensitive or -resistant HIV-1 in vitro. J Infect Dis 1992 Nov; 166: 1143–6

    Article  PubMed  CAS  Google Scholar 

  16. Rusconi S, Merrill DP, Hirsch MS. Inhibition of human immunodeficiency virus type 1 replication in cytokine-stimulated monocytes/macrophages by combination therapy. J Infect Dis 1994 Dec; 170: 1361–6

    Article  PubMed  CAS  Google Scholar 

  17. Taylor DL, Brennan TM, Bridges CG, et al. Synergistic inhibition of human immunodeficiency virus type 1 in vitro by 6-0-butanoylcastanospermine (MDL 28 574) in combination with inhibitors of the virus-encoded reverse transcriptase and proteinase. Antiviral Chem Chemother 1995 May; 6: 143–52

    CAS  Google Scholar 

  18. Feorino PM, Butera ST, Folks TM, et al. Activity of the protease inhibitor Ro 31-8959 on acute, chronic and latent HIV infection [abtract no. PO-A25-0601]. IXth International Conference on AIDS; 1993 Jun 6–11; Berlin, Vol. 1, 235

    Google Scholar 

  19. Nitschko H, Lindhofer H, Schätzl H, et al. Long-term treatment of HIV-infected MT-4 cells in culture with HIV proteinase inhibitor Ro 31-8959 leads to complete cure of infection. Antiviral Chem Chemother 1994; 5(4): 236–42

    CAS  Google Scholar 

  20. Macatonia SE, Duncan IB, Knight SC. Improved function of dendritic cells exposed in vitro to human immunodeficiency virus type I (HIV-1) on treatment with the proteinase inhibitor Ro 31-8959 [abstract no. PO-A25-0601]. IXth International Conference on AIDS; 1993 Jun 6–11; Berlin, Vol. I, 235

    Google Scholar 

  21. Craig JC, Whittaker L, Duncan IB, et al. In vitro anti-HIV and cytotoxicological evaluation of the triple combination: AZT and ddC with HIV proteinase inhibitor saquinavir (Ro 31-8959). Antiviral Chem Chemother 1994 Nov; 5: 380–6

    CAS  Google Scholar 

  22. Connell EV, Hsu MC, Richman DD. Combinative interactions of a human immunodeficiency virus (HIV) Tat antagonist with HIV reverse transcriptase inhibitors and an HIV protease inhibitor. Antimicrob Agents Chemother 1994 Feb; 38: 348–52

    Article  PubMed  CAS  Google Scholar 

  23. Merril DP, Moonis M, Chou T-C, et al. Lamivudine or stavudine in two- and three-drug combinations against human immunodeficiency virus type I replication in vitro. J Infect Dis 1996; 173: 355–64

    Article  Google Scholar 

  24. Brennan TM, Taylor DL, Bridges CG. The inhibition of human immunodeficiency virus type 1 in vitro by a non-nucleoside reverse transcriptase inhibitor MKC-442, alone and in combination with other anti-HIV compounds. Antiviral Res 1995 Mar; 26: 173–87

    Article  PubMed  CAS  Google Scholar 

  25. Craig JC, Whittaker L, Duncan IB, et al. In vitro resistance to an inhibitor of HIV proteinase (Ro 31-8959) relative to inhibitors of reverse transcriptase (AZT and TIBO). Antiviral Chem Chemother 1993; 4(6): 335–9

    CAS  Google Scholar 

  26. Dianzani F, Antonelli G, Turriziani O, et al. In vitro selection of human immunodeficiency virus type 1 resistant to Ro 31-8959 proteinase inhibitor. Antiviral Chem Chemother 1993; 4(6): 329–33

    CAS  Google Scholar 

  27. Jacobsen H, Craig CJ, Duncan IB, et al. Molecular characterization of HIV-variants with reduced sensitivity to Ro 31-8959, a viral proteinase inhibitor [abstract]. AIDS Res Hum Retroviruses 1994 Aug; 10 Suppl.1: S24

    Google Scholar 

  28. Turriziani O, Antonelli G, Jacobsen H, et al. Identification of an amino acid substitution involved in the reduction of sensitivity of HIV-1 to an inhibitor of viral proteinase. Acta Virol 1994; 38: 297–8

    PubMed  CAS  Google Scholar 

  29. Tisdale M, Myers RE, Maschera B. et al. Cross-resistance analysis of human immunodeficiency virus type 1 variants individually selected for resistance to five different protease inhibitors. Antimicrob Agents Chemother 1995 Aug; 39: 1704–10

    Article  PubMed  CAS  Google Scholar 

  30. Eberle J, Bechowsky B, Rose D, et al. Resistance of HIV type 1 to proteinase inhibitor Ro 31-8959. AIDS Res Hum Retro-viruses 1995 Jun; 11: 671–6

    Article  CAS  Google Scholar 

  31. Jacobsen H, Yasargil K, Winslow DL, et al. Characterization of human immunodeficiency virus type 1 mutants with decreased sensitivity to proteinase inhibitor Ro 31-8959. Virology 1995; 206(1): 527–34

    Article  PubMed  CAS  Google Scholar 

  32. Roberts NA. Drug-resistance patterns of saquinavir and other HIV proteinase inhibitors. AIDS 1995; 9 Suppl.2: S27–32

    CAS  Google Scholar 

  33. Hoffmann-La Roche (Basel). Resistance and cross resistance to inhibitors of HIV proteinase — studies with saquinavir (In-virase™). 1996. (Data on file)

  34. Partaledis JA, Yamaguchi K, Tisdale M, et al. In vitro selection and characterization of human immunodeficiency virus type 1 (HIV-1) isolates with reduced sensitivity to hydroxy-ethylamino sulfonamide inhibitors of HIV-1 aspartyl protease. J Virol 1995; 69(9): 5228–35

    PubMed  CAS  Google Scholar 

  35. Hoffmann-La Roche Inc. Invirase™(saquinavir mesylate) capsules prescribing information. Nutley, New Jersey, USA, 1996

  36. Schapiro JM, Winters MA, Kozal MJ, et al. Saquinavir monotherapy trial: prolonged suppression of viral load and resistance mutations with higher dosage [abstract no. LB-5]. 35th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1995 Sep 17–20; San Francisco, 8

    Google Scholar 

  37. Jacobsen H, Haenggi M, Ott M, et al. Reduced sensitivity to saquinavir: an update on genotyping from phase I/II trials. Antiviral Res 1996; 29: 95–7

    Article  PubMed  CAS  Google Scholar 

  38. Velia S, Galluzzo Giannini G, et al. Saquinavir/zidovudine combination in patients with advanced HIV infection and no prior antiretroviral therapy: CD4+ lymphocyte/plasma RNA changes, and emergence of HIV strains with reduced phenotypic sensitivity. Antiviral Res 1996; 29: 91–3

    Article  Google Scholar 

  39. Condra JH, Schleif WA, Blahy OM et al. In vivo emergence of HIV-1 variants resistant to multiple protease inhibitors. Nature 1995 Apr 6; 374: 569–71

    Article  PubMed  CAS  Google Scholar 

  40. Williams PEO, Sampson AP, Green CP, et al. Disposition and bioavailability of the HIV-proteinase inhibitor, Ro 31-8959, after single doses in healthy volunteers. Br J Clin Pharmacol 1992 Aug; 34: 155P–6P

    Google Scholar 

  41. Hoffmann-La Roche. Ro 31-8959 Saquinavir Invirase™. In-vestigational Drug Brochure, W-144’962. 1996. (Data on file)

  42. Shaw TM, Muirhead GJ, Parish N, et al. Tolerability and pharmacokinetics of single oral doses of Ro 31-8959, an HIV proteinase inhibitor. Br J Clin Pharmacol 1994 Aug; 34: 166P–7P

    Google Scholar 

  43. Muirhead GJ, Shaw T, Williams PEO, et al. Pharmacokinetics of the HIV-proteinase inhibitor, Ro 318959, after single and multiple oral doses in healthy volunteers. Br J Clin Pharmacol 1992 Aug; 34: 170P–1P

    Google Scholar 

  44. Stewart F, Williams PEO, Delfraissy JF, et al. Modelling of a concentration-response relationship during monotherapy with the proteinase inhibitor Ro 31-8959 in HIV infected patients [abstract no. PI-90]. 95th Annual Meeting of the American Society for Clinical Pharmacology and Therapeutics; 1994 Mar 30-Apr 1; New Orleans, 145

    Google Scholar 

  45. Farrar G, Mitchell AM, Hooper H, et al. Prediction of potential drug interactions of saquinavir (Ro 31-8959) from in vitro data. Br J Clin Pharmacol 1994 Aug; 38: 162P

    Google Scholar 

  46. Norbeck D, Kumar G, Marsh K, et al. Ritonavir and saquinavir: potential for two-dimensional synergy between HIV protease inhibitors [abstract no. LB-7]. 35th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1995 Sep 17–20; San Francisco, 9

    Google Scholar 

  47. Kitchen VS, Skinner C, Ariyoshi K, et al. Safety and activity of saquinavir in HIV infection. Lancet 1995 Apr 15; 345: 952–5

    Article  PubMed  CAS  Google Scholar 

  48. Collier AC, Coombs RW, Schoenfeld DA, et al. Treatment of human immunodeficiency virus infection with saquinavir, zidovudine, and zalcitabine. N Engl J Med 1996; 334: 1011–7

    Article  PubMed  CAS  Google Scholar 

  49. Lagakos SW, Hoth DF. Surrogate markers in AIDS: Where are we? Where are we going? Ann Intern Med 1992; 116(7): 599–601

    PubMed  CAS  Google Scholar 

  50. Yarchoan R, Venzon DJ, Pluda JM, et al. CD4 count and the risk for death in patients infected with HIV receiving anti-retroviral therapy. Ann Intern Med 1991; 115(3): 184–9

    PubMed  CAS  Google Scholar 

  51. De Gruttola V, Wulfsohn M, Fischi MA, et al. Modeling the relationship between survival and CD4 lymphocytes in patients with AIDS and AIDS-related complex. J Acquir Immune Defic Syndr 1993; 6: 359–65

    PubMed  Google Scholar 

  52. Choi S, Lagakos SW, Schooley RT, et al. CD4p+ lymphocytes are an incomplete surrogate marker for clinical progression in persons with asymptomatic HIV infection taking zidovudine. Ann Intern Med 1993; 118: 674–80

    PubMed  CAS  Google Scholar 

  53. Hoffmann-La Roche (Nutley). 1996. (Data on file)

  54. Roche Invirase clears FDA in 97 days as first approved protease inhibitor: new formulation in study; international confirmatory trial size, power increased. FDC Rep Pink Sheet 1995; Dec 11: 3-4

  55. Roche Invirase combined with nucleosides shows greater surrogate marker activity in AZT-naive patients; confirmatory trials may need more patients. FDC Rep Pink Sheet 1995; Nov 13: 14-6

  56. Evaluation and management of early HIV infection: guideline overview. J NatlMed Assoc 1994; 86 (3): 173-6

  57. Whittington R, Brogden RN. Zalcitabine: a review of its pharmacology and clinical potential in Acquired Immunodeficiency Syndrome (AIDS). Drugs 1992 Apr; 44(4): 656–83

    Article  PubMed  CAS  Google Scholar 

  58. Faulds D, Brogden RN. Didanosine: a review of its antiviral activity, pharmacokinetic properties and therapeutic potential in Human Immunodeficiency Virus infection. Drugs 1992 Jan; 44(1): 94–116

    Article  PubMed  CAS  Google Scholar 

  59. Abrams DI. Treatment options in zidovudine intolerance or failure. AIDS 1994; 8 Suppl.3: S3–7

    Article  PubMed  Google Scholar 

  60. Cooper DA. Early antiretroviral therapy. AIDS 1994; 8 Suppl.3: S9–S14

    Article  PubMed  Google Scholar 

  61. Hirsch MS, Yeni P. A bend in the road — implications of ACTG 175 and Delta trials [editorial]. Antiviral Ther 1996; 1(1): 6–8

    CAS  Google Scholar 

  62. Stephenson J. Other AIDS drug regimens beat AZT alone, reduce clinical progression and mortality. JAMA 1995; 274(15): 1183–4

    Article  PubMed  CAS  Google Scholar 

  63. Videx & Hivid cleared for wider use. Scrip 1996; No. 2109 Mar 8: 19

  64. Bristol Videx initial HIV therapy recommended based on 50% death risk reduction over AZT; DDI/AZT combination should be in labeling, committee says. FDC Rep Pink Sheet 1996; Mar 4: 9-10

  65. Pinching AJ. Managing HIV disease after Delta: questions remain about how to manage patients already on nucleoside monotherapy. BMJ 1996 Mar 2; 312: 521–2

    Article  PubMed  CAS  Google Scholar 

  66. Abbot Norvir for HIV reduces death risk 40%, reduces disease progression risk 55% in advanced HIV; FDA approves ritonavir March 1 in record 72 days. FDC Rep Pink Sheet 1996; Mar 4: 7-8

  67. Merck Crixivan should not be limited to specific sub-populations, FDA committee says; combo therapy may have advantage in viral load. FDC Rep Pink Sheet 1996; Mar 11: 15-6

  68. Abbot’s ritonavir survival advantage. Scrip 1996; No. 2101 Feb 9: 21

    Google Scholar 

  69. Protease inhibitor cocktails set new standards for HIV therapy. Scrip 1996; No. 2100 Feb 6: 17

  70. Moyle G, Gazzard B. Current knowledge and future prospects for the use of HIV protease inhibitors. Drugs 1996 May; 51(5): 701–12

    Article  PubMed  CAS  Google Scholar 

  71. FDA recommends new AIDS drug. Press release, The Associated Press, 29 Feb 1996.

  72. New drugs for HIV infection. Med Lett Drugs Ther 1996; 38 (972): 35-7

    Google Scholar 

  73. Hoffmann-La Roche (Basel). Saquinavir: ongoing trials. 1996. (Data on file)

  74. Soo W, Nauss-Karol C, Elkins M, et al. Inter-company collaboration combination trials. J Acquir Immune Defic Syndr 1995; 10 Suppl.2: S92–96

    Google Scholar 

  75. Combination AIDS trial starts. Scrip 1996; No. 2126 May 7: 18

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    Stuart Noble & Diana Faulds

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Various sections of the manuscript reviewed by: W.R. Bowie, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; A. Collier, University of Washington School of Medicine, University of Washington, Seattle, Washington, USA; E. De Clerq, Rega Institute, Katholieke Universiteit Leuven, Leuven, Belgium; M. Floridia, Laboratory of Virology, Istituto Superiore di Sanita, Rome, Italy; M. Hirsch, Infectious Disease Unit, Massachusetts General Hospital, Boston, Massachusetts, USA; D.J. Jefferies, Department of Virology, St Bartholomew’s and the Royal London School of Medicine and Dentistry, London, England; D. Kinchington, Department of Virology, Medical College of St Bartholomew’s Hospital, London, England; D.J. Lancaster, Medical Education Department, Methodist Hospitals of Memphis, Memphis, Tennessee, USA; M.H. Markowitz, The Aaron Diamond AIDS Research Center, New York, New York, USA; H. Mitsuya, Experimental Retrovirology Section, National Cancer Institute, Bethesda, Maryland, USA; L. Naesens, Rega Institute, Katholieke Universiteit Leuven, Leuven, Belgium; R.B. Pollard, Division of Infectious Diseases, University of Texas Medical Branch, Galveston, Texas, USA; E. Sandström, Department of Dermatovenereology, Södersjukhuset, Stockholm, Sweden; S. Velia, Laboratory of Virology, Istituto Superiore di Sanita, Rome, Italy; K. von der Helm, Max-von-Pettenkofer Institut, University of Munich, Munich, Germany.

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Noble, S., Faulds, D. Saquinavir. Drugs 52, 93–112 (1996). https://doi.org/10.2165/00003495-199652010-00007

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