Drugs

, Volume 65, Issue 15, pp 2209–2244 | Cite as

Nelfinavir

A Review of its Use in the Management of HIV Infection
  • Caroline M. Perry
  • James E. Frampton
  • Paul L. McCormack
  • M. Asif A. Siddiqui
  • Risto S. Cvetković
Adis Drug Evaluation

Summary

Abstract

Nelfinavir (Viracept®) is an orally administered protease inhibitor. In combination with other antiretroviral drugs (usually nucleoside reverse transcriptase inhibitors [NRTIs]), nelfinavir produces substantial and sustained reductions in viral load in patients with HIV infection. Nelfinavir may be used in the treatment of adults, adolescents and children aged ≥2 years with HIV infection. It can also be used in pregnancy. Resistance to nelfinavir may develop, but the most common mutation (D30N, appearing mainly in HIV-1 subtype B) does not confer resistance to other protease inhibitors, thereby conserving these agents for later use. Although less effective than lopinavir/ritonavir, the preferred first-line treatment in US guidelines, nelfinavir is positioned as an alternative agent for the treatment of adults and adolescents with HIV infection and is an option for those unable to tolerate other protease inhibitors. Nelfinavir also has a role in the management of pregnant patients as well as paediatric patients with HIV infection.

Pharmacological Properties

Nelfinavir is a selective, nonpeptidic competitive inhibitor of the HIV-1 protease. The drug shows good in vitro activity against HIV-1 strains, including strains resistant to zidovudine or non-nucleoside reverse transcriptase inhibitors. The activity of the major metabolite of nelfinavir (M8) against HIV-1 in vitro is similar to that of the parent drug. Additive activity against HIV-1 is observed with nelfinavir in combination with stavudine, didanosine or saquinavir; synergistic activity against HIV-1 is observed with nelfinavir in combination with zidovudine, lamivudine or zalcitabine.

Resistance to nelfinavir is mediated most commonly via a substitution at residue 30 (D30N) in HIV protease and has been identified in clinical isolates of HIV from patients receiving treatment with the drug in combination with other agents. This mutation appears to be unique to nelfinavir. Less commonly, a substitution at residue 90 (L90M) may occur during treatment with nelfinavir; this mutation can confer resistance to several other protease inhibitors.

Nelfinavir produces beneficial effects on immune function with increases in CD4+ cell counts observed in patients treated with nelfinavir-containing combination regimens. Treatment with nelfinavir was associated with a decrease in Fas expression and Fas-mediated apoptosis and an increase in CD4+ cell counts in patients with HIV infection.

The absorption of nelfinavir from the currently available oral formulations is increased when the drug is administered after food, compared with the fasted state. Both nelfinavir and its active metabolite M8 are highly bound to serum proteins and nelfinavir shows extensive tissue distribution. Transplacental passage of the drug appears limited. Nelfinavir is metabolised in the liver by multiple cytochrome P450 (CYP) enzymes. M8 is its major metabolite. The plasma terminal half-life of nelfinavir ranges from 3.7 to 5.3 hours. Almost 90% of the drug is eliminated via the faeces; 1–2% is recovered in urine mostly as unchanged drug. In children, systemic exposure to nelfinavir is highly variable. Clearance in this population is increased by ≈2–3 times compared with that in adults. However, in children aged 2–13 years, adequate systemic exposure to the drug is achieved at recommended dosages.

Plasma concentrations of nelfinavir are markedly lower in pregnant women with HIV infection during the third trimester than concentrations in nonpregnant patients. A dosage of 1250mg twice daily produces adequate plasma concentrations in pregnant women, whereas plasma concentrations in recipients of 750mg three times daily may be lower and more variable. Nelfinavir interacts with a number of other drugs via induction or inhibition of CYP isoenzymes in the liver.

Therapeutic Efficacy

The efficacy of oral nelfinavir has been investigated in HIV-infected, antiretroviral therapy (ART)-naive or -experienced patients, including adults, adolescents, children and pregnant women. Key clinical trials were ≤48 weeks in duration and measured plasma HIV RNA levels as a virological surrogate marker of disease progression.

ART-naive adults and adolescents: In randomised, double-blind or open-label, multicentre studies, nelfinavir demonstrated similar virological efficacy at both recommended dosage levels (750mg three times daily or 1250mg twice daily) when administered as a component of triple therapy (with zidovudine and lamivudine). Treatment with the regimen containing nelfinavir 750mg three times daily resulted in significantly better virological and/or immunological outcomes compared with the placebo-containing regimen.

Administered as part of triple therapy in randomised, double-blind, partially blind or open-label, multicentre studies, nelfinavir 750mg three times daily or 1250mg twice daily showed virological efficacy similar to that of atazanavir 200–600mg and was noninferior to fosamprenavir/ritonavir 1400mg/200mg once daily in the SOLO trial. In the NEAT trial, which was also a noninferiority trial, a larger proportion of fosamprenavir than nelfinavir recipients achieved HIV RNA levels of <400 copies/mL at the end of treatment. Nelfinavir was less effective than lopinavir/ritonavir 400mg/100mg twice daily, each given in combination with lamivudine and stavudine.

Approximately one-half to two-thirds of the nelfinavir-treated patients in these studies had undetectable viral loads (<400 copies/mL) after 48 weeks of treatment (various intent-to-treat analyses). Immunological responses were similar for each of these protease inhibitor-based regimens. Quadruple regimens containing nelfinavir have also shown efficacy in therapy-naive patients with HIV infection. Triple therapy with efavirenz, zidovudine and lamivudine was the optimal regimen in a study comparing three- and four-drug regimens containing nelfinavir and/or efavirenz in combination with either stavudine and didanosine or zidovudine and lamivudine.

ART-experienced adults and adolescents: Quadruple therapy containing nelfinavir 750mg three times daily plus efavirenz 600mg once daily and triple therapy containing efavirenz 600mg once daily generally resulted in higher rates of viral suppression than triple therapy containing nelfinavir 750mg three times daily in a randomised, partially blinded, multicentre study. Quadruple therapy produced the most durable virological response. In other randomised studies in ART-experienced patients, nelfinavir 750mg three times daily or 1250mg twice daily demonstrated similar virological efficacy to ritonavir 400mg twice daily, indinavir 800mg three times daily and delavirdine 400mg twice daily, when each drug was administered as a component of triple therapy, and similar long-term clinical efficacy (expressed in terms of the incidence of AIDS-defining conditions/death) to ritonavir 600mg twice daily.

Paediatric patients: Triple therapy with nelfinavir, administered twice or three times daily, plus zidovudine and stavudine (all dosages unspecified) was more effective than placebo in children aged ≥2 years (but not in those aged <2 years) in a randomised, double-blind trial. Approximately one-quarter of the nelfinavir-treated patients in this study had an undetectable viral load (<400 copies/mL) after 48 weeks of treatment, compared with around one-third to one-half of the children who received three- and four-drug regimens containing nelfinavir in an open-label study.

Tolerability

Nelfinavir, as part of combination therapy, was generally well tolerated by adults and adolescents with HIV infection in clinical trials; a small proportion of patients (4%) discontinued treatment due to adverse events. Diarrhoea, generally of mild to moderate intensity and manageable, was the most common adverse event (incidence 20% in two randomised trials) in ART-naive adults and adolescents who received recommended dosages of nelfinavir (750mg three times daily or 1250mg twice daily).

In 48-week, randomised, comparative trials in ART-naive patients, recommended dosages of nelfinavir were usually as well tolerated as atazanavir 200–600mg once daily, fosamprenavir 1400mg twice daily, fosamprenavir/ ritonavir 1400mg/200mg once daily, lopinavir/ritonavir 400mg/100mg twice daily, nevirapine 200mg twice daily and abacavir 300mg twice daily, when each of these agents was administered as a component of a three-drug regimen. Likewise, quadruple and triple therapies containing nelfinavir and/or efavirenz had similar adverse event profiles when evaluated in HIV-infected, ART-experienced patients. However, nelfinavir was better tolerated than indinavir 800mg three times daily and ritonavir 600mg twice daily in terms of the treatment discontinuation rate, when each of these protease inhibitors was assessed as part of combination therapy in ART-experienced patients. A retrospective meta-analysis indicated that nelfinavir was associated with the lowest rate of occurrence of hepatotoxicity relative to indinavir, saquinavir, ritonavir and saquinavir/ ritonavir.

The tolerability profile of nelfinavir in paediatric patients was similar to that in adults. Diarrhoea was the most common, drug-related adverse event. A postmarketing adverse event review did not reveal any unexpected safety concerns relating to the use of nelfinavir in paediatric patients.

The first study with sufficient power to detect a two-fold increase in the risk of overall birth defects with nelfinavir found no such increase. Triple therapy containing nelfinavir was well tolerated by HIV-infected, pregnant women.

References

  1. 1.
    Yazdanpanah Y, Sissoko D, Egger M, et al. Clinical efficacy of antiretroviral combination therapy based on protease inhibitors or non-nucleoside analogue reverse transcriptase inhibitors: indirect comparison of controlled trials. BMJ 2004 Jan; 328(7434): 249–53PubMedCrossRefGoogle Scholar
  2. 2.
    Department of Health and Human Services (US). Guidelines for the use of antiretroviral agents in HIV infected agents in HIV-1 infected adults and adolescents [online]. Available from URL: http://aidsinfo.nih.gov/guidelines/adult/AA_040705.pdf [Accessed 2005 Aug 19]Google Scholar
  3. 3.
    Agouron Pharmaceuticals Inc. Viracept® (nelfinavir mesylate) tablets and oral powder: US prescribing information [online]. Available from URL: http://www.pfizer.com/pfizer/download/ uspi_viracept.pdf [Accessed 2005 Aug 1]Google Scholar
  4. 4.
    Bardsley-Elliot A, Plosker GL. Nelfinavir: an update on its use in HIV infection. Drugs 2000 Mar; 59(3): 581–620PubMedCrossRefGoogle Scholar
  5. 5.
    Speck RR, Flexner C, Tian C-J, et al. Comparison of human immunodeficiency virus type 1 Pr55Gag and Prl60Gag-Pol processing intermediates that accumulate in primary and transformed cells treated with peptidic and nonpeptidic protease inhibitors. Antimicrob Agents Chemother 2000 May; 44(5): 1397–403PubMedCrossRefGoogle Scholar
  6. 6.
    Kohl NE, Emini EA, Schleif WA, et al. Active human immunodeficiency virus protease is required for viral infectivity. Proc Natl Acad Sci U S A 1988 Jul; 85: 4686–90PubMedCrossRefGoogle Scholar
  7. 7.
    Patick AK, Mo H, Markowitz M, et al. Antiviral and resistance studies of AG1343, an orally bioavailable inhibitor of human immunodeficiency virus protease. Antimicrob Agents Chemother 1996 Feb; 40(2): 292–7PubMedGoogle Scholar
  8. 8.
    Zhang KE, Wu E, Patick AK, et al. Circulating metabolites of the human immunodeficiency virus protease inhibitor nelfinavir in humans: structural identification, levels in plasma, and antiviral activities. Antimicrob Agents Chemother 2001 Apr; 45: 1086–93PubMedCrossRefGoogle Scholar
  9. 9.
    Patick AK, Boritzki TJ, Bloom LA. Activities of human immunodeficiency virus type 1 (HIV-1) protease inhibitor nelfinavir mesylate in combination with reverse transcriptase and protease inhibitors against acute HIV-1 infection in vitro. Antimicrob Agents Chemother 1997 Oct; 41(10): 2159–64PubMedGoogle Scholar
  10. 10.
    Flexner C. HIV-protease inhibitors. N Engl J Med 1998 Apr 30; 338(18): 1281–92PubMedCrossRefGoogle Scholar
  11. 11.
    Pellegrin I, Breilh D, Montestruc F, et al. Virologic response to nelfinavir-based regimens: pharmacokinetics and drug resistance mutations (VIRAPHAR study). AIDS 2002 Jul 5; 16(10): 1331–40PubMedCrossRefGoogle Scholar
  12. 12.
    Kemper CA, Witt MD, Keiser PH, et al. Sequencing of protease inhibitor therapy: insights from an analysis of HIV phenotypic resistance in patients failing protease inhibitors. AIDS 2001 Mar 30; 15: 609–15PubMedCrossRefGoogle Scholar
  13. 13.
    Hirsch MS, Brun-Vézinet F, D’Aquila RT, et al. Antiretroviral drug resistance testing in adult HIV-1 infection: recommendations of an International AIDS Society-USA panel. JAMA 2000 May 10; 283(18): 2417–26PubMedCrossRefGoogle Scholar
  14. 14.
    Nunez M, de Mendoza C, Valer L, et al. Resistance mutations in HIV-infected patients experiencing early failure with nelfinavir-containing triple combinations. Med Sci Monit 2002 Sep; 8(9): CR620–3PubMedGoogle Scholar
  15. 15.
    Clotet B, Ruiz L, Martinez-Picado J, et al. Prevalence of HIV protease mutations on failure of nelfinavir-containing HAART: a retrospective analysis of four clinical studies and two observational cohorts. HIV Clin Trials 2002 Jul; 3(4): 316–23PubMedCrossRefGoogle Scholar
  16. 16.
    Kempf DJ, King MS, Bernstein B, et al. Incidence of resistance in a double-blind study comparing lopinavir/ritonavir plus stavudine and lamivudine to nelfinavir plus stavudine and lamivudine. J Infect Dis 2004 Jan 1; 189(1): 51–60PubMedCrossRefGoogle Scholar
  17. 17.
    Patick AK, Duran M, Cao Y, et al. Genotypic and phenotypic characterization of human immunodeficiencey virus type 1 variants isolated from patients treated with the protease inihibitor nelfinavir. Antimicrob Agents Chemother 1998 Oct; 42(10): 2637–44PubMedGoogle Scholar
  18. 18.
    Manfredi R, Calza L. HIV genotype mutations evoked by nelfinavir-based regimens: frequency, background, and consequences on subsequent treatment options [letter]. J Acquir Immune Defic Syndr 2002 Jun 1; 30(2): 258–60PubMedGoogle Scholar
  19. 19.
    Eshleman SH, Krogstad P, Brooks Jackson JB, et al. Analysis of human immunodeficiency virus type 1 drug resistance in children receiving nucleoside analogue reverse-transcriptase inhibitors plus nevirapine, nelfinavir, or ritonavir (Pediatric AIDS Clinical Trials Group 377). J Infect Dis 2001 Jun 15; 183: 1732–8PubMedCrossRefGoogle Scholar
  20. 20.
    Grossman Z, Paxinos EE, Averbuch D, et al. Mutation D30N is not preferentially selected by human immunodeficiency virus type 1 subtype C in the development of resistance to nelfinavir. Antimicrob Agents Chemother 2004 Jun; 48(6): 2159–65PubMedCrossRefGoogle Scholar
  21. 21.
    Gonzalez LM, Brindeiro RM, Aguiar RS, et al. Impact of nelfinavir resistance mutations on in vitro phenotype, fitness, and replication capacity of human immunodeficiency virus type 1 with subtype B and C proteases. Antimicrob Agents Chemother 2004 Sep; 48(9): 3552–5PubMedCrossRefGoogle Scholar
  22. 22.
    Masquelier B, Droz C, Dary M, et al. R57K polymorphism in the human immunodeficiency virus type 1 protease as predictor of early virological failure in a cohort of antiretroviral-naive patients treated mostly with a nelfinavir-containing regimen. Antimicrob Agents Chemother 2003 Nov; 47(11): 3623–6PubMedCrossRefGoogle Scholar
  23. 23.
    Dronda F, Casado JL, Moreno S, et al. Phenotypic cross-resistance to nelfinavir: the role of prior antiretroviral therapy and the number of mutations in the protease gene. AIDS Res Hum Retroviruses 2001 Feb 10; 17(3): 211–5PubMedCrossRefGoogle Scholar
  24. 24.
    Tebas P, Patick AK, Kane EM, et al. Virologic responses to a ritonavir-saquinavir-containing regimen in patients who had previously failed nelfinavir. AIDS 1999; 13(2): F23–8PubMedCrossRefGoogle Scholar
  25. 25.
    MacManus S, Yates P, Elsten R, et al. GW433908/ritonavir once daily in antiretroviral therapy-naive HIV-infected patients: absence of protease resistance at 48 weeks. AIDS 2004; 18: 651–5PubMedCrossRefGoogle Scholar
  26. 26.
    MacManus S, Yates P, White S, et al. GW433908 in ART-naive subjects: absence of resistance at 48 weeks with boosted regimen and APV-like resistance profile with unboosted regimen [abstract no. 598 plus poster]. 10th Conference on Retroviruses and Opportunistic Infections; 2003 Feb 10–14; Boston (MA)Google Scholar
  27. 27.
    Yerly S, Rickenbach M, Popescu M, et al. Drug resistance mutations in HIV-1-infected subjects during protease inhibitor-containing highly active antiretroviral therapy with nelfinavir or indinavir. Antivir Ther 2001 Sep; 6: 185–9PubMedGoogle Scholar
  28. 28.
    De Luca A, Di Giambenedetto S, Bacarelli A, et al. Genotypic resistance to boosted (fos)amprenavir and lopinavir in clinical isolates from patients failing protease inhibitors-containing HAART regimens: prevalence and predictors [abstract no. P99]. 7th International Congress on Drug Therapy in HIV Infection; 2004 Nov 14–18; GlasgowGoogle Scholar
  29. 29.
    Elston R, Yates P, Tisdale M, et al. GW433908 (908)/ritonavir (r): 48 week results in PI-experienced subjects: a retrospective analysis of virological response based on baseline genotype and phenotype [abstract no. MoOrB1055]. 15th International AIDS Conference; 2004 Jul 11–16; BangkokGoogle Scholar
  30. 30.
    Bristol-Myers Squibb Company. Reyataz® (atazanavir sulfate) capsules prescribing information, 2005 Jun [online]. Available from URL: http://www.bms.com [Accessed 2005 Sep 30]Google Scholar
  31. 31.
    Hoetelmans RMW, Reijers MHE, Weverling GJ, et al. The effect of plasma drug concentrations on HIV-1 clearance rate during quadruple drug therapy. AIDS 1998; 12(11): F111–5PubMedCrossRefGoogle Scholar
  32. 32.
    Duval X, Peytavin G, Albert I, et al. Determination of indinavir and nelfinavir trough plasma concentration efficacy thresholds according to virological response in HIV-infected patients. HIV Med 2004 Jul; 5(4): 307–13PubMedCrossRefGoogle Scholar
  33. 33.
    Saitoh A, Singh KK, Powell CA, et al. An MDR1-3435 variant is associated with higher plasma nelfinavir levels and more rapid virologie response in HIV-1 infected children. AIDS 2005 Mar 4; 19(4): 371–80PubMedCrossRefGoogle Scholar
  34. 34.
    Dockrell DH, Badley AD, Villacian JS, et al. The expression of Fas ligand by macrophages and its upregulation by human immunodeficiency virus infection. J Clin Invest 1998 Jun; 101(11): 2394–405PubMedCrossRefGoogle Scholar
  35. 35.
    Phenix BN, Angel JB, Mandy F, et al. Decreased HIV-associated T cell apoptosis by HIV protease inhibitors. AIDS Res Hum Retroviruses 2000; 16(6): 559–67PubMedCrossRefGoogle Scholar
  36. 36.
    Victorino R, Sousa A, Chaves AF. Effects of triple antiretroviral therapy on the expression of Fas antigen in patients with HIV1 infection [abstract no. 31178]. 12th World AIDS Conference; 1998 Jun 28–Jul 3; GenevaGoogle Scholar
  37. 37.
    Badley AD, Parato K, Cameron DW, et al. Dynamic correlation of apoptosis and immune activation during treatment of HIV infection. Cell Death Differ 1999 May; 6(5): 420–32PubMedCrossRefGoogle Scholar
  38. 38.
    Chavan SJ, Tamma SL, Kaplan M, et al. Reduction in T cell apoptosis in patients with HIV disease following antiretroviral therapy. Clin Immunol 1999 Oct; 93(1): 24–33PubMedCrossRefGoogle Scholar
  39. 39.
    Kaufmann G, Zaunders J, Cunningham P, et al. Comparison of immune reconstitution in subjects treated with HAART during primary and chronic HIV-1 infection [abstract no. 345]. 7th Conference Retroviruses and Opportunistic Infections; 2000 Jan 30–Feb 2; San Francisco (CA)Google Scholar
  40. 40.
    Smith DE, Kaufmann GR, Kahn JO, et al. Greater reversal of CD4+ cell abnormalities and viral load reduction after initiation of antiretroviral therapy with zidovudine, lamivudine, and nelfinavir before complete HIV type 1 seroconversion. AIDS Res Hum Retroviruses 2003 Mar; 19: 189–99PubMedCrossRefGoogle Scholar
  41. 41.
    Roche Products Limited. UK Summary of product characteristics: Viracept (nelfinavir) 250mg film-coated tablets [online]. Available from URL: http://emc.medicines.org.uk/ [Accessed 2005 Aug 5]Google Scholar
  42. 42.
    Kaeser B, Charoin JE, Gerber M, et al. Assessment of the bioequivalence of two nelfinavir tablet formulations under fed and fasted conditions in healthy subjects. Int J Clin Pharmacol Ther 2005 Mar; 43(3): 154–62PubMedGoogle Scholar
  43. 43.
    Regazzi MB, Seminari E, Villani P, et al. Nelfinavir suspension obtained from nelfinavir tablets has equivalent pharmacokinetic profile. J Chemother 2001 Oct; 13: 569–74PubMedGoogle Scholar
  44. 44.
    Hsyu P, Petersen C, Pun E, et al. Increased bioavailability of nelfinavir 625 mg tablet and the potential impact on adverse experiences [abstract no. 116 plus poster]. Antivir Ther 2003 Aug 4; 8: L77–8Google Scholar
  45. 45.
    Marzolini C, Rudin C, Decosterd LA, et al. Transplacental passage of protease inhibitors at delivery. AIDS 2002 Apr 12; 16: 889–93PubMedCrossRefGoogle Scholar
  46. 46.
    Ford J, Cornforth D, Hoggard PG, et al. Intracellular and plasma pharmacokinetics of nelfinavir and M8 in HIV-infected patients: relationship with P-glycoprotein expression. Antivir Ther 2004 Feb; 9(1): 77–84PubMedGoogle Scholar
  47. 47.
    Hennessy M, Clarke S, Spiers JP, et al. Intracellular accumulation of nelfinavir and its relationship to P-glycoprotein expression and function in HIV-infected patients. Antivir Ther 2004 Feb; 9(1): 115–22PubMedGoogle Scholar
  48. 48.
    Hsyu PH, Lillibridge JH, Beeby S, et al. Pharmacokinetics of nelfinavir and metabolite M8 in patients with liver impairment after a single oral 750mg dose of viracept. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, 337Google Scholar
  49. 49.
    Regazzi M, Maserati R, Villani P, et al. Clinical pharmacokinetics of nelfinavir and its metabolite M8 in human immunodeficiency virus (HIV)-positive and HIV-hepatitis C virus-coinfected subjects. Antimicrob Agents Chemother 2005 Feb; 49(2): 643–9PubMedCrossRefGoogle Scholar
  50. 50.
    Mirochnick M, Stek A, Acevedo M, et al. Safety and pharmacokinetics of nelfinavir coadministered with zidovudine and lamivudine in infants during the first 6 weeks of life. J Acquir Immune Defic Syndr 2005 Jun 1; 39(2): 189–94PubMedGoogle Scholar
  51. 51.
    Bergshoeff AS, Fraaij PLA, van Rossum AMMC, et al. Pharmacokinetics of nelfinavir in chidren: influencing factors and dose implications. Antivir Ther 2003 Jun; 8(3): 215–22PubMedGoogle Scholar
  52. 52.
    Nellen JF, Schillevoort I, Wit FW, et al. Nelfinavir plasma concentrations are low during pregnancy. Clin Infect Dis 2004 Sep 1; 39(5): 736–40PubMedCrossRefGoogle Scholar
  53. 53.
    Mirochnick M, Bryson Y, Stek A, et al. Pharmacokinetics of nelfinavir and its M8 metabolite in pregnant HIV-infected women and their infants: PACTG 353 [abstract no. 1891]. Pediatr Res 2003 Apr; 53 (Pt 2): 331Google Scholar
  54. 54.
    van Heeswijk RPG, Khaliq Y, Gallicano KD, et al. The pharmacokinetics of nelfinavir and M8 during pregnancy and post partum. Clin Pharmacol Ther 2004 Dec; 76(6): 588–97PubMedCrossRefGoogle Scholar
  55. 55.
    Kruse G, Esser S, Stocker H, et al. The steady-state pharmacokinetics of nelfinavir in combination with tenofovir in HIV-infected patients. Antivir Ther 2005; 10(2): 349–55PubMedGoogle Scholar
  56. 56.
    Kruse G, Esser S, Stocker H, et al. Tenofovir (TDF) does not impair the steady-state pharmacokinetics of nelfinavir (NFV) in HIV-infected patients [poster A-446]. 44th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); 2004 Oct 30–Nov 2; Washington, DCGoogle Scholar
  57. 57.
    Boffito M, Pozniak A, Kearney B, et al. Lack of a drug interaction between tenofovir DF and nelfinavir [poster]. 7th International Conference on Drug Therapy in HIV; 2004 Nov 14–18; GlasgowGoogle Scholar
  58. 58.
    Schippers EF, Hugen PWH, den Hartigh J, et al. No drug-drug interaction between nelfinavir or indinavir and mefloquine in HIV-1-infected patients. AIDS 2000 Dec 1; 14: 2794–5PubMedCrossRefGoogle Scholar
  59. 59.
    Park-Wyllie LY, Antoniou T. Concurrent use of bupropion with CYP2B6 inhibitors, nelfinavir, ritonavir and efavirenz: a case series. AIDS 2003 Mar 7; 17: 638–40PubMedCrossRefGoogle Scholar
  60. 60.
    Kosel BW, Aweeka FT, Benowitz NL, et al. The effects of cannabinoids on the pharmacokinetics of indinavir and nelfinavir. AIDS 2002 Mar 8; 16: 543–50PubMedCrossRefGoogle Scholar
  61. 61.
    Stone JA, Migoya EM, Hickey L, et al. Potential for interactions between caspofungin and nelfinavir or rifampin. Antimicrob Agents Chemother 2004 Nov; 48(11): 4306–14PubMedCrossRefGoogle Scholar
  62. 62.
    Amsden GW, Nafziger AN, Foulds G, et al. A study of the pharmacokinetics of azithromycin and nelfinavir when coadministered in healthy volunteers. J Clin Pharmacol 2000 Dec; 40 (Pt 2): 1522–7PubMedGoogle Scholar
  63. 63.
    Kurowski M, Molto J, Breske A, et al. Atazanavir (ATV) enhances trough concentrations of nelfinavir (NFV) and its M8 metabolite in a treatment regimen without ritonavir (RTV) [poster 8.2]. 6th International Workshop of Clinical Pharmacology of HIV Therapy; 2005 Apr 28–30; QuebecGoogle Scholar
  64. 64.
    Stocker H, Kruse G, Arasteh K, et al. Pharmacokinetic interaction between saquinavir/r and nelfinavir in HIV-infected patients [poster A-454]. 44th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); 2004 Oct 30–Nov 2; Washington, DCGoogle Scholar
  65. 65.
    Saag MS, Tebas P, Sension M, et al. Randomized, double-blind comparison of two nelfinavir doses plus nucleosides in HIV-infected patients (Agouron study 511). AIDS 2001 Oct 19; 15: 1971–8PubMedCrossRefGoogle Scholar
  66. 66.
    Walmsley S, Bernistein B, King M, et al. Lopinavir-ritonavir versus nelfinavir for the initial treatment of HIV infection. N Engl J Med 2002 Jun 27; 346: 2039–46PubMedCrossRefGoogle Scholar
  67. 67.
    Rodriguez-French A, Boghossian J, Gray GE, et al. The NEAT Study: a 48-week open-label study to compare the antiviral efficacy and safety of GW433908 versus nelfinavir in antire-troviral therapy-naive HIV-1-infected patients. J Acquir Immune Defic Syndr 2004 Jan 1; 35(1): 22–32PubMedCrossRefGoogle Scholar
  68. 68.
    Moyle G, Pozniak A, Opravil M, et al. The SPICE Study: 48-week activity of combinations of saquinavir soft gelatin and nelfinavir with and without nucleoside analogues. J Acquir Immune Defic Syndr 2000 Feb 1; 23: 128–37PubMedGoogle Scholar
  69. 69.
    Perez G, MacArthur RD, Walmsley S, et al. A randomized clinical trial comparing nelfinavir and ritonavir in patients with advanced HIV disease (CPCRA 042/CTN 102). HIV Clin Trials 2004 Jan 28; 5(1): 7–18PubMedCrossRefGoogle Scholar
  70. 70.
    Kirk O, Lundgren JD, Pedersen C, et al. A randomized trial comparing initial HAART regimens of nelfinavir/nevirapine and ritonavir/saquinavir in combination with two nucleoside reverse transcriptase inhibitors. Antivir Ther 2003 Dec; 8(6): 595–602PubMedGoogle Scholar
  71. 71.
    Murphy RL, Sanne I, Chan P, et al. Dose-ranging, randomized, clinical trial of atazanavir with lamivudine and stavudine in antiretroviral-naive subjects: 48-week results. AIDS 2003; 17: 2603–14PubMedCrossRefGoogle Scholar
  72. 72.
    Matheron S, Descamps D, Boue F, et al. Triple nucleoside combination zidovudine/lamivudine/abacavir versus zidovudine/lamivudine/nelfinavir as first-line therapy in HIV-1-infected adults: a randomized trial. Antivir Ther 2003 Apr; 8: 163–71PubMedGoogle Scholar
  73. 73.
    Sanne I, Piliero P, Squires K, et al. Results of a phase 2 clinical trial at 48 weeks (AI424-007): a dose-ranging, safety, and efficacy comparative trial of atazanavir at three doses in combination with didanosine and stavudine in antiretroviral-naive subjects. J Acquir Immune Defic Syndr 2003; 32: 18–29PubMedCrossRefGoogle Scholar
  74. 74.
    Gartland M, AVANTI Study Group. AVANTI 3: a randomized, double-blind trial to compare the efficacy and safety of lamivudine plus zidovudine versus lamivudine plus zidovudine plus nelfinavir in HIV-1-infected antiretroviral-naive patients. Antivir Ther 2001 Jun; 6: 127–34PubMedGoogle Scholar
  75. 75.
    Gathe Jr JC, Ive P, Wood R, et al. SOLO: 48-week efficacy and safety comparison of once-daily fosamprenavir/ritonavir versus twice-daily nelfinavir in naive HIV-1-infected patients. AIDS 2004 Jul 23; 18(11): 1529–37PubMedCrossRefGoogle Scholar
  76. 76.
    Podzamczer D, Ferrer E, Consiglio E, et al. A randomized clinical trial comparing nelfinavir or nevirapine associated to zidovudine/lamivudine in HIV-infected naive patients (the Combine Study). Antivir Ther 2002 Jun; 7: 81–90PubMedGoogle Scholar
  77. 77.
    Bernstein B, Kempf D, Moseley M, et al. Lack of resistance to ABT-378/ritonavir (ABT-378/R) observed after 24 weeks of therapy in antiretroviral-naive subjects [abstract no. P325]. Int Cong Drug Therapy HIV. AIDS 2000; 14 Suppl. 4: S110Google Scholar
  78. 78.
    Albrecht MA, Bosch RJ, Hammer SM, et al. Nelfinavir, efavirenz, or both after the failure of nucleoside treatment of HIV infection. N Engl J Med 2001 Aug 9; 345: 398–407PubMedCrossRefGoogle Scholar
  79. 79.
    Robbins GK, De Gruttola V, Shafer RW, et al. Comparison of sequential three-drug regimens as initial therapy for HIV-1 infection. N Engl J Med 2003 Dec 11; 349(24): 2293–303PubMedCrossRefGoogle Scholar
  80. 80.
    Shafer RW, Smeaton LM, Robbins GK, et al. Comparison of four-drug regimens and pairs of sequential three-drug regimens as initial therapy for HIV-1 infection. N Engl J Med 2003 Dec 11; 349(24): 2304–15PubMedCrossRefGoogle Scholar
  81. 81.
    Cooper D, Yeni P. Virological and immunological outcomes at 3 years following initiation of ART with regimens containing a NNRTI or PI or both: the INITIO Trial [abstract no. 165LB]. 12th Conference on Retroviruses and Opportunistic Infections; 2005 Feb 22–25; Boston (MA)Google Scholar
  82. 82.
    Daniels E, Clotet B, Clax P, et al. Long-term efficacy of nelfinavir, impact on adverse events and lipodystrophy [poster 100]. Antivir Ther 2004; 9(6): L57Google Scholar
  83. 83.
    Fumaz C, Lopez Aldeguer J, Lozano F, et al. Clinical and psychological impact of prolonged nelfinavir-containing regimens. PSIRENE study [abstract no. P54]. 7th International Congress on Drug Therapy in HIV Infection; 2004 Nov 14–18; GlasgowGoogle Scholar
  84. 84.
    Gathe J, Chu A, Yuen N, et al. Durability of nelfinavir combination therapy after 4 years: 3-year extension data from Agouron Study 511 [poster LB10]. 8th European Conference on Clinical Aspects and Treatment of HIV-Infection; 2001 Oct 28–31; Athens, GreeceGoogle Scholar
  85. 85.
    Roca B, Gomez CJ, Arnedo A. A randomized, comparative study of lamivudine plus stavudine, with indinavir or nelfinavir, in treatment-experienced HIV-infected patients. AIDS 2000 Jan 28; 14: 157–61PubMedCrossRefGoogle Scholar
  86. 86.
    Smith D, Hales G, Roth N, et al. A randomized trial of nelfinavir, ritonavir, or delavirdine in combination with saquinavir-SGC and stavudine in treatment-experienced HIV-1-infected patients. HIV Clin Trials 2001 Mar 30; 2(2): 97–107PubMedCrossRefGoogle Scholar
  87. 87.
    Bahrani A, Oldfield IEC. Substitution of nelfinavir (NV) for indinavir (IV) in patients on combination therapy and the effect on viral loads [abstract no. I-241]. 38th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1998 Sep 24–27; San Diego (CA), 440Google Scholar
  88. 88.
    Trylesinski A, Dohin E, Delmas C, et al. Alleviating protease inhibitor constraints and for a viral load maintained below the limit of quantification for the long term efficacy, tolerance and compliance: the nelfinavir switch solution [abstract no. P114]. AIDS 1998 Nov; 12 Suppl. 4: S45Google Scholar
  89. 89.
    Lefebvre E, Shafran S. Maintenance of virological suppression in patients switched from indinavir (IDV) to nelfinavir (NFV) [abstract no. P62]. AIDS 2000 Oct; 14 Suppl. 4: S34Google Scholar
  90. 90.
    Wensing AMJ, Reedijk M, Richter C, et al. Replacing ritonavir by nelfinavir or nelfinavir/saquinavir as part of highly active antiretroviral therapy leads to an improvement of triglyceride levels. AIDS 2001 Nov 9; 15: 2191–3PubMedCrossRefGoogle Scholar
  91. 91.
    Starrett B, Connor S. Maintenance of viral suppression and improvement of metabolic parameters after replacing ritonavir with nelfinavir in a HAART regimen [abstract]. 7th Conference on Retroviruses and Opportunistic Infections; 2000 Jan 30–Feb 2; San Francisco (CA)Google Scholar
  92. 92.
    Knechten H, Lippok B, Knickmann M. Switch from indinavir (IDV) to nelfinavir (NFV) in patients on antiviral therapy with stavudine (d4T) and lamivudine (3TC) [abstract P123]. AIDS 1998 Nov; 12 Suppl. 4: S47Google Scholar
  93. 93.
    Hellinger JA, Cohen CJ, Stein AJ, et al. Efficacy of nelfinavir in patients switched from ritonavir/saquinavir combination antiretroviral therapy. HIV Clin Trials 2000; 1(2): 25–8PubMedCrossRefGoogle Scholar
  94. 94.
    Post J, Williams C. An open label, randomized trial switching nelfinavir dosing from tid to bid: 84 week report [abstract no. TuPeB3224]. 13th International AIDS Conference; 2000 Jul 9–14; Durban, 362Google Scholar
  95. 95.
    Dhingra R, Munsiff A. Twice daily nelfinavir results in greater durability and higher CD4 counts than TID dosing [abstract no. WePeB4118]. 13th International AIDS Conference; 2000 Jul 9–14; Durban, 59Google Scholar
  96. 96.
    Johnson M, Nieto-Cisneros L, Horban A, et al. Comparison of gastrointestinal tolerability and patient preference for treatment with the 625 mg and 250 mg nelfinavir tablet formulations. HIV Med 2005 Mar; 6(2): 107–13PubMedCrossRefGoogle Scholar
  97. 97.
    Gulick RM, Hu XJ, Fiscus SA, et al. Randomized study of saquinavir with ritonavir or nelfinavir together with delaviridine, adefovir, or both in human immunodeficiency virus-infected adults with virologic failure on indinavir: AIDS Clinical Trials Group Study 359. J Infect Dis 2000 Nov; 182: 1375–84PubMedCrossRefGoogle Scholar
  98. 98.
    Hammer SM, Bassett R, Squires KE, et al. A randomized trial of nelfinavir and abacavir in combination with efavirenz and adefovir dipivoxil in HIV-1-infected persons with virological failure receiving indinavir. Antivir Ther 2003 Dec; 8(6): 507–18PubMedGoogle Scholar
  99. 99.
    Perez-Molina JA, Perez Nr R, Miralles P, et al. Nelfinavir plus nevirapine plus two NRTIs as salvage therapy for HIV-infected patients receiving long-term antiretroviral treatment. HIV Clin Trials 2001 Jan 28; 2(1): 1–5PubMedCrossRefGoogle Scholar
  100. 100.
    Sullivan AK, Nelson MR, Shaw A, et al. Efficacy of a nelfinavir- and nevirapine-containing salvage regimen. HIV Clin Trials 2000 Jul 31; 1: 7–12PubMedCrossRefGoogle Scholar
  101. 101.
    Seminari E, Maggiolo F, Villani P, et al. Efavirenz, nelfinavir, and stavudine rescue combination therapy in HIV-1-positive patients heavily pretreated with nucleoside analogues and protease inhibitors. J Acquir Immune Defic Syndr 1999 Dec 15; 22(5): 453–60PubMedGoogle Scholar
  102. 102.
    Casado JL, Dronda F, Garcia-Aratia I, et al. Efficacy and tolerability of the combination of nevirapine, nelfinavir and saquinavir after ritonavir or indinavir failure [abstract no. 529]. 7th European Conference on Clinical Aspects and Treatment of HIV-Infection; 1999 Oct 23–27; Lisbon, 112Google Scholar
  103. 103.
    Arrizabalaga J, Iribarren JA, Rodriguez-Arrondo FJ, et al. Salvage therapy with ddI + hydroxyurea (HU) + efavirenz (EFV) + nelfinavir (NFV) in patients who had previously failed indinavir (IDV)/ritonavir (RIT) regimens. 24 weeks follow-up [abstract no. 2206]. 39th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1999 Sep 26–29; San Francisco (CA), 537Google Scholar
  104. 104.
    Santos J, Palacios R, Ruiz I, et al. Efficacy of nelfinavir as salvage therapy for protease inhibitors failures [abstract no. P65]. 8th European Conference on Clinical Aspects and Treatment of HIV-Infection; Athens 2001 Oct 28–31, 70Google Scholar
  105. 105.
    Viciana P, Perez R, Hernadez Quero J, et al. NNRTI salvage therapy with nelfinavir in PI naive patients [abstract plus poster 7.4/15]. 9th European AIDS Conference and 1st EACS Resistance and Pharmacology Workshop; 2003 Oct 25; Warsaw, 57Google Scholar
  106. 106.
    Hall CS, Raines CP, Barnett SH, et al. Efficacy of salvage therapy containing ritonavir and saquinavir after failure of single protease inhibitor-containing regimens. AIDS 1999; 13(10): 1207–12PubMedCrossRefGoogle Scholar
  107. 107.
    Zolopa A, Tebas P, Gallant J, et al. The efficacy of ritonavir (RTV)/saquinavir(SQV) antiretroviral therapy (ART) in patients who failed nelfinavir (NEV): a multicentre cohort study [abstract no. 2065]. 39th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1999 Sep 26–29; San Francisco (CA), 527Google Scholar
  108. 108.
    Cavorus A, Thompson CE, Salvato PD. Salvage therapy for antiretroviral failure in HIV+ patients [abstract no. 22402]. 12th World AIDS Conference; 1998 Jun 28–Jul 3; Geneva, 344Google Scholar
  109. 109.
    Center of Drug Evaluation and Research of the US Food and Drug Administration. Clinical review for NDA [online]. Available from URL: http://www.fda.gov/cder/foi/esum/2004/ 20778se5-022,20779se5-042,21503se5-001_viracept_clinical _bpca.pdf [Accessed 2005 Aug 19]Google Scholar
  110. 110.
    Krogstad P, Lee S, Johnson G, et al. Nucleoside-analogue reverse-transcriptase inhibitors plus nevirapine, nelfinavir, or ritonavir for pretreated children infected with human immunodeficiency virus type 1. Clin Infect Dis 2002 Apr 1; 34: 991–1001PubMedCrossRefGoogle Scholar
  111. 111.
    Luzuriaga K, McManus M, Mofenson L, et al. A trial of three antiretroviral regimens in HIV-1-infected children. N Engl J Med 2004 Jun 10; 350(24): 2471–2480PubMedCrossRefGoogle Scholar
  112. 112.
    Starr S, Courtney C, Spector S, et al. Combination therapy wtih efavirenz, nelfinavir, and nucleoside reverse-transcriptase inhibitors in children infected with human immunodeficiency virus type 1. N Engl J Med 1999 Dec 16; 341: 1874–81PubMedCrossRefGoogle Scholar
  113. 113.
    Starr S, Fletcher C, Spector S, et al. Efavirenz liquid formulations in human immunodeficiency virus-infected children. Pediatr Infect Dis J 2002 Jul; 21(7): 659–63PubMedCrossRefGoogle Scholar
  114. 114.
    Hoffmann F, Notheis G, Wintergerst U, et al. Comparison of ritonavir plus saquinavir- and nelfinavir plus saquinavir-containing regimens as salvage therapy in children with human immunodeficiency type 1 infection. Pediatr Infect Dis J 2000 Jan; 19: 47–51PubMedCrossRefGoogle Scholar
  115. 115.
    Resino S, Alvaro-Meca A, de Jose MI, et al. Lopinavir/r versus nelfinavir as salvage therapy [letter]. Pediatr Infect Dis J 2005 Apr; 24(4): 392–3PubMedCrossRefGoogle Scholar
  116. 116.
    Rachlis A, Gill M, Baril Jeal. Step-wise intervention for the management of nelfinavir (NFV)-associated diarrhoea [abstract plus poster no. 747]. Antivir Ther 2003; 8 Suppl. 1: S392Google Scholar
  117. 117.
    Heiser CR, Ernst JA, Barrett JT, et al. Probiotics, soluble fiber, and L-Glutamine (GLN) reduce nelfinavir (NFV)- or lopinavir/ritonavir (LPV/r)-related diarrhea. J Int Assoc Physicians AIDS Care (Chic Ill) 2004 Oct 31; 3(4): 121–9CrossRefGoogle Scholar
  118. 118.
    Huffman FG, Walgren ME. L-glutamine supplementation improves nelfinavir-associated diarrhea in HIV-infected individuals. HIV Clin Trials 2003 Sep 31; 4(5): 324–9PubMedCrossRefGoogle Scholar
  119. 119.
    Nolan D, Upton R, McKinnon E, et al. Stable or increasing bone mineral density in HIV-infected patients treated with nelfinavir or indinavir. AIDS 2001 Jul 6; 15: 1275–80PubMedCrossRefGoogle Scholar
  120. 120.
    Guest JL, Ruffin C, Tschampa JM, et al. Differences in rates of diarrhea in patients with human immunodeficiency virus receiving lopinavir-ritonavir or nelfinavir. Pharmacotherapy 2004 Jun; 24(6): 727–35PubMedCrossRefGoogle Scholar
  121. 121.
    Bruno R, Sacchi P, Maiocchi L, et al. Hepatotoxicity and nelfinavir: a meta-analysis. Clin Gastroenterol Hepatol 2005 May; 3(5): 482–8PubMedCrossRefGoogle Scholar
  122. 122.
    Fontas E, van Leth F, Sabin CA, et al. Lipid profiles in HIV-infected patients receiving combination antiretroviral therapy: are different antiretroviral drugs associated with different lipid profiles? J Infect Dis 2004 Mar 15; 189(6): 1056–74PubMedCrossRefGoogle Scholar
  123. 123.
    Murphy R, Thiry A, Mancini M, et al. Switch to atazanavir from nelfinavir associated with cholesterol and triglyceride improvement: 12 wk results from BMS AI424-044 [abstract LBPEB9013 plus poster]. 14th International AIDS Conference; Barcelona 2002 Jul 7–12, 38Google Scholar
  124. 124.
    Duncombe C. Reversal of hyperlipidemia and lipodystrophy in patients switching therapy to nelfinavir. J Acquir Immune Defic Syndr 2000 May 1; 24: 78–9PubMedGoogle Scholar
  125. 125.
    Grover SA, Coupal L, Gilmore N, et al. Impact of dyslipidemia associated with Highly Active Antiretroviral Therapy (HAART) on cardiovascular risk and life expectancy. Am J Cardiol 2005 Mar 1; 95(5): 586–91PubMedCrossRefGoogle Scholar
  126. 126.
    da Silva B, ing M, Cernohous P, et al. Risk factors for body fat composition changes in patients treated with lopinavir/ ritonavir or nelfinavir [abstract no. 99]. Antivir Ther 2003 Aug 4; 8: L68Google Scholar
  127. 127.
    Treluyer JM, Morini JP, Dimet J, et al. High concentrations of nelfinavir as an independent risk factor for lipodystrophy in human immunodeficiency virus-infected patients. Antimicrob Agents Chemother 2002 Dec; 46: 4009–12PubMedCrossRefGoogle Scholar
  128. 128.
    Lewis RH, Popescu M. Lipodystrophy: results of a data evaluation of patients receiving nelfinavir-containing combination therapy. J Acquir Immune Defic Syndr 2000 Apr 1; 23: 355–6PubMedGoogle Scholar
  129. 129.
    Dube M, Zackin R, Parker R, et al. Prospective study of glucose and lipid metabolism in antiretroviral-naive subjects randomized to receive nelfinavir, efavirenz, or both combined with zidovudine+lamivudine or didanosine+stavudine: A5005s, a substudy of ACTG 384 [abstract no. 74]. 11th Conference on Retroviruses and Opportunistic Infections; 2004 Feb 8–11; San Francisco (CA), 2Google Scholar
  130. 130.
    Center for Drug Evaluation and Research for the US Food and Drug Administration. One year post-pediatric exclusivity post-marketing adverse event review: drug use data — nelfinavir mesylate [online]. Available from URL: http://www.fda.gov/ ohrms/dockets/ac/05/briefing/2005-4089bl_06_02_ Nelfinavir.pdf [Accessed 2005 Aug 19]Google Scholar
  131. 131.
    Covington DL, Conner SD, Doi PA, et al. Risk of birth defects associated with nelfinavir exposure during pregnancy. Obstet Gynecol 2004 Jun; 103(6): 1181–9PubMedCrossRefGoogle Scholar
  132. 132.
    Timmermans S, Tempelman C, Godfried MH, et al. Nelfinavir and nevirapine side effects during pregnancy. AIDS 2005 May 20; 19(8): 795–9PubMedCrossRefGoogle Scholar
  133. 133.
    Hitti J, Frenkel L, Stek A, et al. Maternal toxicity with continuous nevirapine in pregnancy: results from PACTG 1022. J Acquir Immune Defic Syndr 2004 Jul; 36(3): 772–6PubMedCrossRefGoogle Scholar
  134. 134.
    Baylor M, Gibbs N. Hepatotoxicity during pregnancy: a review of the FDA adverse event reporting system (AERS) database [abstract and poster 944]. 1 lth Conference on Retroviruses and Opportunistic Infections; 2004 Feb 8–11; San FranciscoGoogle Scholar
  135. 135.
    Yeni PG, Hammer SM, Hirsch MS, et al. Treatment for adult HIV infection 2004 recommendations of the International AIDS Society-USA Panel. JAMA 2004 Jul 14; 292(2): 251–65PubMedCrossRefGoogle Scholar
  136. 136.
    Aberg JA, Gallant JE, Anderson J, et al. Primary care guidelines for the management of persons infected with human immunodeficiency virus: recommendations of the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis 2004; 39: 609–29PubMedCrossRefGoogle Scholar
  137. 137.
    The British HIV Association. BHIVA guidelines for the treatment of HIV-infected adults with antiretroviral therapy 2005 [online]. Available from URL: http://www.bhiva.org/guidelines/2005/HIV/index.html [Accessed 2005 Aug 29]Google Scholar
  138. 138.
    The EACS Euroguidelines Group. European guidelines for the clinical management and treatment of HIV-infected adults in Europe. AIDS 2003 Jun; 17 Suppl. 2: S3–26CrossRefGoogle Scholar
  139. 139.
    Department of Health and Human Services (US). Guidelines for the use of antiretroviral agents in pediatric HIV infection [online]. Available from URL: http://aidsinfo.nih.gov/guidelines/pediatric/PED_032405 [Accessed 2005 Aug 01]Google Scholar
  140. 140.
    Hirsch MS. Antiretroviral drug resistance testing in adults infected with human immunodeficiency virus type 1: 2003 recommendations of an International AIDS Society-USA panel. Clin Infect Dis 2003; 37: 113–28PubMedCrossRefGoogle Scholar
  141. 141.
    Cvetković RS, Goa KL. Lopinavir/ritonavir: a review of its use in the management of HIV infection. Drugs 2003; 63(8): 769–802PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2005

Authors and Affiliations

  • Caroline M. Perry
    • 1
  • James E. Frampton
    • 1
  • Paul L. McCormack
    • 1
  • M. Asif A. Siddiqui
    • 1
  • Risto S. Cvetković
    • 1
  1. 1.Adis International LimitedAucklandNew Zealand

Personalised recommendations