Skip to main content
SpringerLink
Log in

Novel Targets for Antiretroviral Therapy

Clinical Progress to Date

  • Leading Article
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

The advent of HIV-1 resistance to antiretroviral medications, the need for lifelong antiretroviral therapy (ART) for HIV-infected individuals, and the goal of minimizing ART-related adverse effects and toxicity all drive the need for new antiretroviral drugs. Two new classes of antiretroviral medications for HIV treatment, the CCR5 and integrase inhibitors, have recently been approved for use in patients in whom previous HIV treatment regimens have failed. These new agent classes are a welcome addition to other antiretroviral classes, which include nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors and fusion inhibitors.

Maraviroc is a CCR5 co-receptor antagonist that blocks HIV binding to the CCR5 receptor, which is a CD4 co-receptor necessary for cell entry. It is approved for use in ART-experienced patients with CCR5-tropic HIV, and was found to significantly reduce HIV viral load and increase CD4+ cell count when combined with an optimized background ART regimen (OBR). Treatment failure with maraviroc has been described and is primarily associated with the presence of CXCR4-tropic virus. Vicriviroc is another CCR5 co-receptor antagonist that is in late clinical trials.

Raltegravir is the first US FDA-approved HIV-1 integrase inhibitor. It is approved for use in ART-experienced patients and was found to significantly reduce HIV viral load and increase CD4+ cell counts compared with placebo in combination with an OBR. Raltegravir has also been studied in treatment-naive patients and was found to be non-inferior to an efavirenz-based regimen. Elvitegravir is another HIV-1 integrase inhibitor in clinical development.

Other new antiretroviral agents in clinical development include PRO140, a monoclonal antibody against CCR5, and bevirimat, a maturation inhibitor that prevents late-stage gag polyprotein processing. A number of other drug targets, such as CCR5 co-receptor agonists, CXCR4 co-receptor antagonists, novel fusion inhibitors, and alternative antiretroviral strategies, such as immune stimulation and gene therapy, are under investigation.

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
Table IV

Similar content being viewed by others

References

  1. Antiretroviral Therapy Cohort Collaboration. Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies. Lancet 2008 Jul 26; 372(9635): 293–9

    Google Scholar 

  2. Mocroft A, Vella S, Benfield TL, et al. Changing patterns of mortality across Europe in patients infected with HIV-1. EuroSIDA Study Group. Lancet 1998 Nov 28; 352(9142): 1725–30

    CAS  PubMed  Google Scholar 

  3. El-Sadr WM, Lundgren JD, Neaton JD, et al. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med 2006 Nov 30; 355(22): 2283–96

    CAS  PubMed  Google Scholar 

  4. Jacobson JM, Turner BJ, Abrutyn E. Trials that matter: CD4+ T-lymphocyte count-guided interruption of antiretroviral therapy in HIV-infected patients. Ann Intern Med 2007 May 1; 146(9): 682–3

    PubMed  Google Scholar 

  5. Ruiz L, Paredes R, Gomez G, et al. Antiretroviral therapy interruption guided by CD4 cell counts and plasma HIV-1 RNA levels in chronically HIV-1-infected patients. AIDS 2007 Jan 11; 21(2): 169–78

    CAS  PubMed  Google Scholar 

  6. Richman DD, Morton SC, Wrin T, et al. The prevalence of antiretroviral drug resistance in the United States. AIDS 2004 Jul 2; 18(10): 1393–401

    PubMed  Google Scholar 

  7. Tozzi V, Zaccarelli M, Bonfigli S, et al. Drug-class-wide resistance to antiretrovirals in HIV-infected patients failing therapy: prevalence, risk factors and virological outcome. Antivir Ther 2006; 11(5): 553–60

    CAS  PubMed  Google Scholar 

  8. Truong HM, Grant RM, McFarland W, et al. Routine surveillance for the detection of acute and recent HIV infections and transmission of antiretroviral resistance. AIDS 2006 Nov 14; 20(17): 2193–7

    PubMed  Google Scholar 

  9. Turner D, Wainberg MA. HIV transmission and primary drug resistance. AIDS Rev 2006 Jan–Mar; 8(1): 17–23

    PubMed  Google Scholar 

  10. Briz V, Poveda E, Soriano V. HIV entry inhibitors: mechanisms of action and resistance pathways. J Antimicrob Chemother 2006 Apr; 57(4): 619–27

    CAS  PubMed  Google Scholar 

  11. Lewis M, Mori J, Simpson P, et al. Changes in V3 loop sequence associated with failure of maraviroc treatment in patients enrolled in the MOTIVATE 1 and 2 trials [abstract no. 871]. 15th Conference on Retroviruses and Opportunistic Infections; 2008 Feb 8–11; Boston (MA)

  12. Este JA, Telenti A. HIV entry inhibitors. Lancet 2007 Jul 7; 370(9581): 81–8

    CAS  PubMed  Google Scholar 

  13. Al-Mawsawi LQ, Neamati N. Blocking interactions between HIV-1 integrase and cellular cofactors: an emerging anti-retroviral strategy. Trends Pharmacol Sci 2007 Oct; 28(10): 526–35

    CAS  PubMed  Google Scholar 

  14. Savarino A. A historical sketch of the discovery and development of HIV-1 integrase inhibitors. Expert Opin Investig Drugs 2006 Dec; 15(12): 1507–22

    CAS  PubMed  Google Scholar 

  15. McNicholl IR, McNicholl JJ. On the horizon: promising investigational antiretroviral agents. Curr Pharm Des 2006; 12(9): 1091–03

    CAS  PubMed  Google Scholar 

  16. Daar ES, Kesler KL, Petropoulos CJ, et al. Baseline HIV type 1 coreceptor tropism predicts disease progression. Clin Infect Dis 2007 Sep 1; 45(5): 643–9

    PubMed  Google Scholar 

  17. Goetz MB, Leduc R, Kostman JR, et al. Predictions of disease progression by HIV co-receptor tropism (CRT) in persons (P) with untreated chronic HIV infection [abstract no. H-1027]. 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2007 Sep 17–20; Chicago (IL)

  18. Daar ES, Eron Jr J, Schapiro JM. Clinical care options HIV. Answering the questions: HIV tropism in clinical practice. 2008 Sep 18 [online]. Available from URL: http://www.clinicaloptions.com/hiv [Accessed 2008 Dec 4]

  19. Moyle GJ, Wildfire A, Mandalia S, et al. Epidemiology and predictive factors for chemokine receptor use in HIV-1 infection. J Infect Dis 2005 Mar 15; 191(6): 866–72

    PubMed  Google Scholar 

  20. Demarest J, Bonny T, Vavro C, et al. HIV-1 co-receptor tropism in treatment naive and experienced subjects [abstract no. H-1136]. 44th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); 2004 Oct 30–Nov 2; Washington, DC

  21. Coakley E, Benhamida J, Chappey C, et al. An evaluation of tropism profiles and other characteristics among 3988 individuals screened from A4001026, A4001027 (MOTIVATE 1) and A4001028 (MOTIVATE 2) studies for maraviroc [abstract no. 8]. Second International Workshop on Targeting HIV Entry; 2006 Oct 20–21; Boston (MA)

  22. Melby T, Despirito M, Demasi R, et al. HIV-1 coreceptor use in triple-class treatment-experienced patients: baseline prevalence, correlates, and relationship to enfuvirtide response. J Infect Dis 2006 Jul 15; 194(2): 238–46

    CAS  PubMed  Google Scholar 

  23. Wilkin TJ, Su Z, Kuritzkes DR, et al. HIV type 1 chemokine coreceptor use among antiretroviral-experienced patients screened for a clinical trial of a CCR5 inhibitor: AIDS Clinical Trial Group A5211. Clin Infect Dis 2007 Feb 15; 44(4): 591–5

    CAS  PubMed  Google Scholar 

  24. Brumme ZL, Goodrich J, Mayer HB, et al. Molecular and clinical epidemiology of CXCR4-using HIV-1 in a large population of antiretroviral-naive individuals. J Infect Dis 2005 Aug 1; 192(3): 466–74

    CAS  PubMed  Google Scholar 

  25. Tressler R, Valdez H, van der Ryst E, et al. Comparison of results from the SensiTrop™ vs Trofile™ assays on 100 samples from the maraviroc expanded access program [abstract no. 920a]. 15th Conference on Retroviruses and Opportunistic Infections; 2008 Feb 8–11; Boston (MA)

  26. Reeves J, Han D, Wilkin T, et al. An enhanced version of the Trofile HIV co-receptor tropism assay predicts emergence of cxcr4 use in ACTG5211 vicriviroc trial samples [abstract no. 869]. 15th Conference on Retroviruses and Opportunistic Infections; 2008 Feb 8–11; Boston (MA)

  27. Reeves JD, Han D, Lui Y, et al. Enhancements to the Trofile HIV coreceiptor tropism assay enable reliable detection of CXCR4-using subpopulations at less than 1% [abstract no. H-1026]. Program and abstracts of the 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); 2007 Sep 17–20; Chicago (IL)

  28. Trinh L, Han D, Huang W, et al. Validation of an enhanced sensitivity Trofile HIV-1 co-receptor tropism assay [abstract no. H-1219]. 48th Annual ICAAC/IDSA Meeting; 2008 Oct 25–28; Washington, DC

  29. Li WL, Webb E, Reposar T, et al. Adaptation and validation of the SensiTrop II molecular co-receptor tropism assay on international clades of HIV virus [abstract no. H-1220]. 48th Annual ICAAC/IDSA Meeting; 2008 Oct 25–28; Washington, DC

  30. Moores A, Dong W, Wynhoven B, et al. Improved detection of X4 HIV-1 by V3 genotyping: application to plasma RNA and proviral DNA [abstract no. H-1217]. 48th Annual ICAAC/IDSA Meeting; 2008 Oct 25–28; Washington, DC

  31. Soulie C, Malet I, Lambert-Niclot S, et al. Primary genotypic resistance of HIV-1 to CCR5 antagonists in CCR5 antagonist treatment-naive patients. AIDS 2008 Oct 18; 22(16): 2212–4

    CAS  PubMed  Google Scholar 

  32. Gulick RM, Lalezari J, Goodrich J, et al. Maraviroc for previously treated patients with R5 HIV infection. N Engl J Med 2008 Oct 2; 359(14): 1429–41

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Saag M, Ive P, Heera J, et al. A multicenter, randomized, double-blind, comparative trial of a novel CCR5 antagonist, maraviroc vs efavirenz, both in combination with Combivir (zidovudine [ZDV]/lamivudine [3TC], for the treatment of antiretroviral naive patients infected with R5 HIV 1: week 48 results of the MERIT study [abstract no. WESS104]. 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention; 2007 Jul 22–25; Sydney

  34. Saag M, Heera J, Goodrich J, et al. Reanalysis of the MERIT study with the enhanced Trofile assay (MERIT-ES) [abstract no. H1232a]. 48th Annual ICCAC/IDSA Meeting; 2008 Oct 25–28; Washington, DC

  35. Gulick RM, Su Z, Flexner C, et al. Phase 2 study of the safety and efficacy of vicriviroc, a CCR5 inhibitor, in HIV-1-infected, treatment-experienced patients: AIDS clinical trials group 5211. J Infect Dis 2007 Jul 15; 196(2): 304–12

    CAS  PubMed  Google Scholar 

  36. Gulick R, Su Z, Flexner C, et al. ACTG 5211: phase II study of the safety and efficacy of vicriviroc (VCV) in HIV-infected treatment-experienced subjects: 48 week results [abstract no. TUAB102]. 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention; 2007 Jul 22–25; Sydney

  37. Zingman B, Suleiman J, DeJesus E, et al. Vicriviroc, a next generation CCR5 antagonist, exhibits potent, sustained suppression of viral replication in treatment-experienced adults: VICTOR-E1 48-week results [abstract no. 39LB]. 15th Conference on Retroviruses and Opportunistic Infections; 2008 Feb 8–11; Boston (MA)

  38. Markowitz M, Nguyen BY, Gotuzzo E, et al, for the Protocol 004 Part II Study Team. Rapid onset and durable antiretroviral effect of raltegravir (MK-0518), a novel HIV-1 integrase inhibitor, as part of combination ART in treatment HIV-1 infected patients: 48-week data [abstract no. TUAB104]. 4th IAS Conference on HIV Pathogenesis, Treatment, and Prevention; 2007 Jul 22–25; Sydney

  39. Murray JM, Emery S, Kelleher A, et al. The integrase inhibitor raltegravir alters viral decay kinetics of HIV, significantly reducing the second phase and challenging current hypotheses of viral replication [abstract no. TUAB103]. 4th IAS Conference on HIV Pathogenesis, Treatment, and Prevention; 2007 Jul 22–25; Sydney

  40. Lennox J, DeJesus E, Lazzarin A, et al. Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive HIV-1 infected patients: STARTMRK protocol 021 [abstract no. H-896a]. 48th Annual ICAAC/IDSA Meeting; 2008 Oct 25–28; Washington, DC

  41. Jacobson JM, Thomson M, Saag MS, et al. Antiretroviral activity and pharmacodynamics of PRO 140, a CCR5 monoclonal antibody, in HIV-infected individuals [abstract no. H-716]. 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2007 Sep 17–20; Chicago (IL)

  42. Steigbigel RT, Cooper DA, Kumar PN, et al. Raltegravir with optimized background therapy for resistant HIV-1 infection. N Engl J Med 2008 Jul 24; 359(4): 339–54

    PubMed  Google Scholar 

  43. Cooper D, Gatell J, Rockstroh J, et al, for the BENCHMRK-1 Study Group 48-week results from BENCHMRK-1, a phase III study of raltegravir in patients failing ART with triple-class resistant HIV-1 [abstract no. 788]. 15th Conference on Retroviruses and Opportunistic Infections; 2008 Feb 8–11; Boston (MA)

  44. Steigbigel R, Kumar P, Eron J, et al., for the BENCHMRK-2 Study Group. 48-Week results from BENCHMRK-2, a phase III study of raltegravir in patients failing ART with triple-class resistant HIV [abstract no. 789]. 15th Conference on Retroviruses and Opportunistic Infections; 2008 Feb 8–11; Boston (MA)

  45. Zolopa AR, Mullen M, Berger D, et al. The HIV integrase inhibitor GS-9137 demonstrates potent antiretroviral activity in treatment-experienced patients [abstract no. 143LB]. 14th Conference on Retroviruses and Opportunistic Infections; 2007 Feb 25–28; Los Angeles (CA)

  46. Lalezari J, Goodrich J, DeJesus E, et al. Efficacy and safety of maraviroc plus optimized background therapy in viremic ART-experienced patients infected with CCR5-tropic HIV-1: 24-week results of a phase 2b/3 study in the US and Canada [abstract no. 104bLB]. 14th Conference on Retroviruses and Opportunistic Infections; 2007 Feb 25–28; Los Angeles (CA)

    Google Scholar 

  47. Nelson M, Fätkenhever G, Konourina I, et al. Efficacy and safety of maraviroc plus optimized background therapy in viremic, ART-experienced patients infected with CCR5-tropic HIV-1 in Europe, Australia, and North America: 24-week results [abstract no. 104aLB]. 14th Conference on Retroviruses and Opportunistic Infections; 2007 Feb 25–28; Los Angeles (CA)

  48. Hardy D, Reynes J, Konourina I, et al. Efficacy and safety of maraviroc plus optimized background therapy in treatment-experienced patients infected with CCR5-tropic HIV-1: 48-week combined analysis of the MOTIVATE studies [abstract no. 792]. 15th Conference on Retroviruses and Opportunistic Infections; 2008 Feb 8–11; Boston (MA)

  49. Ayoub A, Goodrich J, van der Ryst E, et al. Adverse event profile of maraviroc in treatment-experienced patients infected wtih R5 HIV-1 [abstract no. H-1264]. 48th Annual ICAAC/IDSA Meeting; 2008 Oct 25–28; Washington, DC

  50. van der Ryst E, Westby M. Changes in HIV-1 co-receptor tropism for patients participating in the maraviroc MOTIVATE 1 and 2 clinical trials [abstract no. H-715]. Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); 2007 Sep 17–20; Chicago (IL)

  51. Heera J, Saag M, Ive P, et al. Virological correlates associated with treatment failure at week 48 in the phase 3 study of maraviroc in treatment-naive patients [abstract no. 40LB]. 15th Conference on Retroviruses and Opportunistic Infections; 2008 Feb 8–11; Boston (MA)

  52. Valdez H, Lewis M, Delogne C, et al. Weighted OBT susceptibility scor (wOBTSS) is a stronger predictor of virologic response at 48 weeks than baseline tropism result in MOTIVATE 1 and 2 [abstract no. H-1221]. 48th Annual ICAAC/IDSA Meeting; 2008 Oct 25–28; Washington, DC

  53. Sansone A, Keung A, Tetteh E, et al. Pharmacokinetics of vicriviroc are not affected in combination with five different protease inhibitors boosted by ritonavir [abstract no. 582]. 15th Conference on Retroviruses and Opportunistic Infections; 2008 Feb 8–11; Boston (MA)

  54. Sansone A, Seiberling M, Kraan M, et al. Similar increase in SCH 417690 exposure with coadministration of varying doses of ritonavir in healthy volunteers [abstract no. 78]. 6th International Workshop on Clinical Pharmacology of HIV Therapy; 2005 Apr 28–30; Quebec City (QC)

  55. Su Z, Reeves JD, Krambrink A, et al. Response to vicriviroc (VCV) in HIV-infected treatment-experienced subjects using an enhanced Trofile HIV co-receptor tropism assay: reanalysis of ACTC 5211 results [abstract no. H-895]. 48th Annual ICAAC/IDSA Meeting; 2008 Oct 25–28; Washington, DC

  56. Suleiman J, Sobhie DR, DeJesus E, et al. HIV viral tropism in vicriviroc VICTOR-E1 tials: correlations with clinical variables [abstract no. WEPEA107]. 4th IAS Conference on HIV Pathogenesis, Treatment, and Prevention; 2007 Jul 22–25; Sydney

  57. Dunkle LM, Greaves WL, McCarthy MC, et al. Long-term safety of vicriviroc [abstract no. A-954]. 48th Annual ICAAC/IDSA Meeting; 2008 Oct 25–28; Washington, DC

  58. Lalezari J, Yadavalli GK, Para M, et al. Safety, pharmacokinetics, and antiviral activity of HGS004, a novel fully human IgG4 monoclonal antibody against CCR5, in HIV-1-infected patients. J Infect Dis 2008 Mar 1; 197(5): 721–7

    CAS  PubMed  Google Scholar 

  59. Currier J, Lazzarin A, Sloan L, et al. Antiviral activity and safety of aplaviroc with lamivudine/zidovudine in HIV-infected, therapy-naive patients: the ASCENT (CCR102881) study. Antivir Ther 2008; 13(2): 297–306

    CAS  PubMed  Google Scholar 

  60. Nichols WG, Steel HM, Bonny T, et al. Hepatotoxicity observed in clinical trials of aplaviroc (GW873140). Antimicrob Agents Chemother 2008 Mar; 52(3): 858–65

    CAS  PubMed  Google Scholar 

  61. Cohen C, DeJesus E, Mills A, et al. Potent antiretroviral activity of the once-daily CCR5 antagonist INCB009471 over 14 days of monotherapy [abstract no TUAB106]. 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention; 2007 July 22–25; Sydney

  62. Pett S, Emery S, MacRae K, et al. Safety and activity of SCH532706, a Small molecule chemokine receptor 5 antagonist in HIV-1-infected individuals [abstract no. 38]. 15th Conference on Retroviruses and Opportunistic Infections; 2008 Feb 8–11; Boston (MA)

  63. Dorr P, Westby M, McFadyen L, et al. PF-232798, a second generation oral CCR5 antagonist [abstract no. 738]. 15th Conference on Retroviruses and Opportunistic Infections; 2008 Feb 3–6; Boston (MA)

  64. Biswas P, Tambussi G, Lazzarin A. Access denied? The status of co-receptor inhibition to counter HIV entry. Expert Opin Pharmacother 2007 May; 8(7): 923–33

    CAS  PubMed  Google Scholar 

  65. Antiviral briefs. AIDS Patient Care STDs 2008 Jun; 22 (6): 535–7

  66. Progenics Pharmaceuticals. PRO 140 by IV administration in adults with HIV-1 infection [ClinicalTrials.gov identifier NCT00613379]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2008 Nov 19]

  67. Murga JD, Franti M, Pevear DC, et al. Potent antiviral synergy between monoclonal antibody and small-molecule CCR5 inhibitors of human immunodeficiency virus type 1. Antimicrob Agents Chemother 2006 Oct; 50(10): 3289–96

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Pugach P, Ketas TJ, Michael E, et al. Neutralizing antibody and anti-retroviral drug sensitivities of HIV-1 isolates resistant to small molecule CCR5 inhibitors. Virology 2008 Aug 1; 377(2): 401–7

    CAS  PubMed  Google Scholar 

  69. Olson WC, Doshan H, Zhan C, et al. First-in-humans trial of PRO 140, a humanized CCR5 monoclonal antibody for HIV-1 therapy [abstract no. WePe62C04]. 3rd IAS Conference on HIV Pathogenesis and Treatment; 2005 Jul 24–27; Rio de Janeiro

  70. Marozsan AJ, Parsons T, Huang W, et al. Clonal analysis of HIV-1 co-receptor tropism change following treatment with PRO 140, a CCR5 monoclonal antibody [abstract no. H-1218]. 48th Annual ICAAC/IDSA Meeting; 2008 Oct 25–28; Washington, DC

  71. Jacobson J, Thompson M, Fischi M. Antiviral activity and tolerability of 5mg/kg and 10mg/kg doses of PRO 140, a humanized monoclonal antibody to CCR5 [abstract no. H1269a]. 48th Annual ICCAC/IDSA Meeting; 2008 Oct 25–28; Washington, DC

  72. Wang X, Douglas SD, Lai JP, et al. Neurokinin-1 receptor antagonist (aprepitant) inhibits drug-resistant HIV-1 infection of macrophages in vitro. J Neuroimmune Pharmacol 2007 Mar; 2(1): 42–8

    PubMed  Google Scholar 

  73. University of Pennsylvania. Effects of treatment with aprepitant (Emend®) in HIV infected individuals [ClinicalTrials.gov identifier NCT00428519]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2008 Nov 19]

  74. Fatkenheuer G, Nelson M, Lazzarin A, et al. Subgroup analyses of maraviroc in previously treated R5 HIV-1 infection. N Engl J Med 2008 Oct 2; 359(14): 1442–55

    PubMed  Google Scholar 

  75. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents [online]. Available from URL: http://www.aidsinfo.nih.gov/Guidelines [Accessed 2008 Nov 20]

  76. Selzentry (maraviroc) tablets [online]. Available from URL: http://www.fda.gov/cder/foi/label/2007/022128lbl.pdf [Accessed 2008 Dec 19]

  77. Pommier Y, Johnson AA, Marchand C. Integrase inhibitors to treat HIV/AIDS. Nat Rev Drug Discov 2005 Mar; 4(3): 236–48

    CAS  PubMed  Google Scholar 

  78. Yuji Matsuzaki WW, Yamataka K, Sato1 M, et al. JTK-303/GS 9137, a novel small-molecule inhibitor of HIV-1 integrase: anti-HIV activity profile and pharmacokinetics in animals [abstract no. 508]. 13th Conference on Retroviruses and Opportunistic Infections; 2006 Feb 5–8; Denver (CO)

  79. Grinsztejn B, Nguyen BY, Katlama C, et al. Safety and efficacy of the HIV-1 integrase inhibitor raltegravir (MK0518) in treatment-experienced patients with multidrug-resistant virus: a phase II randomised controlled trial. Lancet 2007 Apr 14; 369(9569): 1261–9

    CAS  PubMed  Google Scholar 

  80. Eron JD, Nguyen BY, Steigbigel RT, et al. AIDS defining conditions (ADCs) in the BENCHMRK-1 and −2 trials: 48 week analysis [abstract no. H-1249]. 48th Annual ICAAC/IDSA Meeting; 2008 Oct 25–28; Washington, DC

  81. DeJesus E, Berger D, Markowitz M, et al. for the 183-0101 Study Team. The HIV integrase inhibitor GS-9137 (JTK-303) exhibits potent antiviral activity in treatment-naive and experienced patients [abstract no. 160LB]. 13th Conference on Retroviruses and Opportunistic Infections; 2006 Feb 5–8; Denver (CO)

  82. Ceecherini-Silberstein F, Malet I, Perno CF, et al. Specific mutations related to HIV-1 integrase inhibitors are associated with reverse transcriptase mutations in HAART-treated patients [abstract no. 4]. Antivir Ther 2007; 12: S6

  83. Hazuda DJ, Miller MD, Nguyen BY, et al. Resistance to the HIV-integrase inhibitor raltegravir: analysis of protocol 005, a phase II study in patients with triple-class resistant HIV-1 infection [abstract no. 8]. Antivir Ther 2007; 12: S10

  84. McColl DJ, Fransen S, Gupta S, et al. Resistance analysis of a phase 2 study of the integrase inhibitor elvitegravir (GS-9137) [poster no. P71/03]. 11th European AIDS Conference; 2007 Oct 24–27; Madrid

  85. Witmer M, Danovich R, Day A, et al. Cross resistance between HIV-1 integrase strand transfer inhibitors (In-STIs) raltegravir, elvitegravir and second generation In-STIs [abstract no. H-1232]. 48th Annual ICAAC/IDSA Meeting; 2008 Oct 25–28; Washington, DC

  86. Cooper DA, Steigbigel RT, Gatell JM, et al. Subgroup and resistance analyses of raltegravir for resistant HIV-1 infection. N Engl J Med 2008 Jul 24; 359(4): 355–65

    CAS  PubMed  Google Scholar 

  87. Myers RE, Pillay D. HIV-1 integrase sequence variation and covariation [abstract no. 3]. Antivir Ther 2007; 12: S65

    Google Scholar 

  88. Van Baelen K, Clynhens M, Rondelez E et al. Low level of baseline resistance to integrase inhibitors L731,988 and L870,810 in randomly selected subtype B and non-B HIV-1 strains [abstract no. 5]. Antivir Ther 2007; 12: S7

    Google Scholar 

  89. Roquebert B, Damond F, Descamps D, et al. Polymorphism of HIV-2 integrase gene and in vitro phenotypic susceptibility of HIV-2 clinical isolates to integrase inhibitors: raltegravir and elvitegravir [abstract no. 83]. Antivir Ther 2007; 12: S92

    Google Scholar 

  90. Miller M, Danovich R, Fransen S, et al. Analysis of resistance to the HIV-1 integrase inihibitor raltegravir: results from BENCHMRK 1 and 2 [abstract no. H-898]. 48th Annual ICAAC/IDSA Meeting; 2008 Oct 25–28; Washington, DC

  91. DeJesus E, Cohen C, Elion R, et al. First report of raltegravir (RAL, MK-0518) use after virologic rebound on elvitegravir (EVT, GS 9137) [abstract no. TUPEB032]. 4th IAS Conference on HIV Pathogenesis, Treatment, and Prevention; 2007 Jul 22–25; Sydney

  92. Fransen S, Gupta W, Huarg W, et al. Preformance characteristics and validation of the phenosense integrase assay [abstract no. H-1214]. 48th Annual ICAAC/IDSA Meeting; 2008 Oct 25–28; Washington, DC

  93. Pearce-Pratt R, Phillips DM. Sulfated polysaccharides inhibit lymphocyte-to-epithelial transmission of human immunodeficiency virus-1. Biol Reprod 1996 Jan; 54(1): 173–82

    CAS  PubMed  Google Scholar 

  94. Perotti ME, Pirovano A, Phillips DM. Carrageenan formulation prevents macrophage trafficking from vagina: implications for microbicide development. Biol Reprod 2003 Sep; 69(3): 933–9

    CAS  PubMed  Google Scholar 

  95. Zappe H, Snell ME, Bossard MJ. PEGylation of cyanovirin-N, an entry inhibitor of HIV. Adv Drug Deliv Rev 2008 Jan 3; 60(1): 79–87

    CAS  PubMed  Google Scholar 

  96. Madan RP, Mesquita PM, Cheshenko N, et al. Molecular umbrellas: a novel class of candidate topical microbicides to prevent human immunodeficiency virus and herpes simplex virus infections. J Virol 2007 Jul; 81(14): 7636–46

    CAS  PubMed  PubMed Central  Google Scholar 

  97. McLean C, Jones H, McNicholl J, et al. Evaluation of the safety of carraguard for vaginal use by HIV-infected women: results from a phase I, randomized, placebo-controlled, 3-treatment cross-over study [abstract no. 566]. 15th Conference on Retroviruses and Opportunistic Infections; 2008 Feb 8–11; Boston (MA)

  98. Vermeire K, Bell TW, Choi HJ, et al. The anti-HIV potency of cyclotriazadisulfonamide analogs is directly correlated with their ability to down-modulate the CD4 receptor. Mol Pharmacol 2003 Jan; 63(1): 203–10

    CAS  PubMed  Google Scholar 

  99. Vermeire K, Princen K, Hatse S, et al. CADA, a novel CD4-targeted HIV inhibitor, is synergistic with various anti-HIV drugs in vitro. AIDS 2004 Nov 5; 18(16): 2115–25

    CAS  PubMed  Google Scholar 

  100. Vermeire K, Brouwers J, Van Herrewege Y, et al. CADA, a potential anti-HIV microbicide that specifically targets the cellular CD4 receptor. Curr HIV Res 2008 May; 6(3): 246–56

    CAS  PubMed  Google Scholar 

  101. Rusconi S, Moonis M, Merrill DP, et al. Naphthalene sulfonate polymers with CD4-blocking and anti-human immunodeficiency virus type 1 activities. Antimicrob Agents Chemother 1996 Jan; 40(1): 234–6

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Cummins Jr JE, Guarner J, Flowers L, et al. Preclinical testing of candidate topical microbicides for anti-human immunodeficiency virus type 1 activity and tissue toxicity in a human cervical explant culture. Antimicrob Agents Chemother 2007 May; 51(5): 1770–9

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Mayer KH, Karim SA, Kelly C, et al. Safety and tolerability of vaginal PRO 2000 gel in sexually active HIV-uninfected and abstinent HIV-infected women. AIDS 2003 Feb 14; 17(3): 321–9

    CAS  PubMed  Google Scholar 

  104. Tabet SR, Callahan MM, Mauck CK, et al. Safety and acceptability of penile application of 2 candidate topical microbicides: BufferGel and PRO 2000 Gel: 3 randomized trials in healthy low-risk men and HIV-positive men. J Acquir Immune Defic Syndr 2003 Aug 1; 33(4): 476–83

    CAS  PubMed  Google Scholar 

  105. National Institute of Allergy and Infectious Diseases (NIAID). BufferGel and PRO 2000/5: vaginal gels to prevent HIV infection in women [ClinicalTrials.gov identifier NCT00074425]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2008 Nov 20]

  106. Godofsky E, Zhang X, Sorensen M, et al. In vitro antiretroviral activity of the humanized anti-CD4 monodlonal antibody, TNX-355, against CCR5, CXCR4, and dual-tropic isolates and synergy with enfuvirtide [abstract no. LB-26]. 45th Conference on Antimicrobial Agents and Chemotherapy; 2005 Dec 16–19; Washington, DC

  107. Norris D, Morales J, Godofsky E, et al. TNX-355, in combination with optimized background regimen (OBR), achieves statistically significant viral load reduction and CD4 cell count increase when compared with OBR alone in phase II study at 48 weeks [abstract no. THLB0218]. 16th International AIDS Conference; 2006 Aug 13–18; Toronto (ON)

  108. Zhang XQ, Sorensen M, Fung M, et al. Synergistic in vitro antiretroviral activity of a humanized monoclonal anti-CD4 antibody (TNX-355) and enfuvirtide (T-20). Antimicrob Agents Chemother 2006 Jun; 50(6): 2231–3

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Dimitrov A. Ibalizumab, a CD4-specific mAb to inhibit HIV-1 infection. Curr Opin Investig Drugs 2007 Aug; 8(8): 653–61

    CAS  PubMed  Google Scholar 

  110. Starpharma Pty Ltd. SPL7013 gel: male tolerance study [ClinicalTrials.gov identifier NCT00370357]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2008 Nov 20]

  111. Starpharma Pty Ltd. Safety and acceptability of SPL7013 Gel (VivaGel™) in sexually active women [ClinicalTrials.gov identifier NCT00442910]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2008 Nov 20]

  112. Progenics Pharmaceuticals, Inc. Safety and efficacy of PRO 542 in the treatment of HIV-infected patients [ClinicalTrials.gov identifier NCT00055185]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2008 Nov 20]

  113. Shearer WT, Israel RJ, Starr S, et al. Recombinant CD4-IgG2 in human immunodeficiency virus type 1-infected children: phase 1/2 study. The Pediatric AIDS Clinical Trials Group Protocol 351 Study Team. J Infect Dis 2000 Dec; 182(6): 1774–9

    CAS  PubMed  Google Scholar 

  114. Jacobson JM, Lowy I, Fletcher CV, et al. Single-dose safety, pharmacology and antiviral activity of the human immunodeficiency virus (HIV) type 1 entry inhibitor PRO 542 in HIV-infected adults. J Infect Dis 2000 Jul; 182(1): 326–329

    CAS  PubMed  Google Scholar 

  115. Jacobson JM, Israel RJ, Lowy I, et al. Treatment of advanced human immunodeficiency virus type 1 disease with the viral entry inhibitor PRO 542. Antimicrob Agents Chemother 2004 Feb; 48(2): 423–9

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Kadow J, Wang HG, Lin PF. Small-molecule HIV-1 gp120 inhibitors to prevent HIV-1 entry: an emerging opportunity for drug development. Curr Opin Investig Drugs 2006 Aug; 7(8): 721–6

    CAS  PubMed  Google Scholar 

  117. Veazey RS, Klasse PJ, Schader SM, et al. Protection of macaques from vaginal SHIV challenge by vaginally delivered inhibitors of virus-cell fusion. Nature 2005 Nov 3; 438(7064): 99–102

    CAS  PubMed  Google Scholar 

  118. Hanna G, Lalezari J, Hellinger J, et al. Antiviral activity, safety, and tolerability of a novel, oral small-molecule HIV-1 attachment inhibitor, BMS-488043, in HIV-1-infected subjects [abstract no. 141]. 11th Conference on Retroviruses and Opportunistic Infections; 2004 Feb 8–11; San Francisco (CA)

  119. Hanna G, Yan J-H, Fiske W, et al. Safety, tolerability, and pharmacokinetics of a novel, small molecule HIV-1 attachment inhibitor, BMS-488043, after single and multiple oral doses in healthy subjects [abstract no. 535]. 11th Conference on Retroviruses and Opportunistic Infections; 2004 Feb 8–11; San Francisco (CA)

  120. Ferain O, Schols D, Bernard J, et al. ESN-196, a novel, small-molecule CCR5 agonist inhibits R5 HIV infection [abstract no. 738]. 15th Conference on Retroviruses and Opportunistic Infections; 2008 Feb 3–6; Boston (MA)

  121. Vangelista L, Secchi M, Lusso P. Rational design of novel HIV-1 entry inhibitors by RANTES engineering. Vaccine 2008 Jun 6; 26(24): 3008–15

    CAS  PubMed  PubMed Central  Google Scholar 

  122. Kish-Catalone TM, Lu W, Gallo RC, et al. Preclinical evaluation of synthetic-2 RANTES as a candidate vaginal microbicide to target CCR5. Antimicrob Agents Chemother 2006 Apr; 50(4): 1497–509

    CAS  PubMed  PubMed Central  Google Scholar 

  123. Abayneh SA, Ellmark P, Karlsson U, et al. Sensitivity of HIV type 1 primary isolates to human anti-CD40 antibody-mediated suppression is related to coreceptor use. AIDS Res Hum Retroviruses 2008 Mar; 24(3): 447–52

    CAS  PubMed  Google Scholar 

  124. Hendrix CW, Collier AC, Lederman MM, et al. Safety, pharmacokinetics, and antiviral activity of AMD3100, a selective CXCR4 receptor inhibitor, in HIV-1 infection. J Acquir Immune Defic Syndr 2004 Oct 1; 37(2): 1253–62

    CAS  PubMed  Google Scholar 

  125. Saag M, Rosenkranz S, Becker K, et al. Proof of concept of antireetroviral activity of AMD11070 (an orally administered CXCR4 entry inhibitor): results of the first dosing cohort A studied in ACTG protocol A5210 [abstract no. 512]. 14th Conference on Retroviruses and Opportunistic Infections; 2007 Feb 25–28; Los Angeles (CA)

  126. Moyle GJ, DeJesus E, Boffito M, et al. CXCR4 antagonism: proof of activity with AMD11070 [abstract no. 511]. 14th Conference on Retroviruses and Opportunistic Infections; 2007 Feb 25–28; Los Angeles (CA)

  127. Blanco J, Clotet-Codina I, Bosch B, et al. Multiparametric assay to screen and dissect the mode of action of antihuman immunodeficiency virus envelope drugs. Antimicrob Agents Chemother 2005 Sep; 49(9): 3926–9

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Moncunill G, Armand-Ugon M, Clotet-Codina I, et al. Anti-HIV activity and resistance profile of the CXC chemokine receptor 4 antagonist POL3026. Mol Pharmacol 2008 Apr; 73(4): 1264–73

    CAS  PubMed  Google Scholar 

  129. Yi Y, Shaheen F, Collman RG. Preferential use of CXCR4 by R5×4 human immunodeficiency virus type 1 isolates for infection of primary lymphocytes. J Virol 2005 Feb; 79(3): 1480–6

    CAS  PubMed  PubMed Central  Google Scholar 

  130. Munch J, Standker L, Adermann K, et al. Discovery and optimization of a natural HIV-1 entry inhibitor targeting the gp41 fusion peptide. Cell 2007 Apr 20; 129(2): 263–75

    PubMed  Google Scholar 

  131. He Y, Cheng J, Lu H, et al. Potent HIV fusion inhibitors against enfuvirtide-resistant HIV-1 strains. Proc Natl Acad Sci U S A 2008 Oct 21; 105(42): 16332–7

    PubMed  PubMed Central  Google Scholar 

  132. Delmedico M, Bray B, Cammack N, et al. Next generation HIV peptide fusion inhibitor candidates achieve potent, durable suppression of virus replication in vitro and improved pharmacokinetic properties [abstract no. 48]. 13th Conference on Retroviruses and Opportunistic Infections; 2006 Feb 5–8; Denver (CO)

  133. Trimeris. Next generation fusion inhibitor program: TRI-1144 (TR-0291144) [online]. Available from URL: http://www.trimeris.com/300Pipeline.aspx [Accessed 2008 Nov 20]

  134. He Y, Xiao Y, Song H, et al. Design and evaluation of sifuvirtide, a novel HIV-1 fusion inhibitor. J Biol Chem 2008 Apr 25; 283(17): 11126–34

    CAS  PubMed  Google Scholar 

  135. Li F, Goila-Gaur R, Salzwedel K, et al. PA-457: a potent HIV inhibitor that disrupts core condensation by targeting a late step in Gag processing. Proc Natl Acad Sci U S A 2003 Nov 11; 100(23): 13555–60

    CAS  PubMed  PubMed Central  Google Scholar 

  136. Adamson C, Salzwedel K, Castillo A, et al. Viral resistance to PA-457, a novel inhibitor of HIV-1 maturation [abstract no. 156]. 13th Conference on Retroviruses and Opportunistic Infections; 2006 Feb 5–8; Denver (CO)

  137. Adamson C, Waki K, Ablan S, et al. Viral resistance to the HIV-1 maturation inhibitor bevirimat in the context of a protease that confers resistance to protease inhibitors [abstract no. 859]. 15th Conference on Retroviruses and Opportunistic Infections; 2008 Feb 3–6; Boston (MA)

  138. Stoddart CA, Joshi P, Sloan B, et al. Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice. PLoS ONE 2007; 2(11): e1251

    PubMed  PubMed Central  Google Scholar 

  139. Martin D, Ballow C, Doto J, et al. The safety, tolerability, and pharmacokinetics of multiple oral doses of PA-457, the first-in-class hiv maturation inhibitor, in healthy volunteers [abstract no. 551]. 12th Conference on Retroviruses and Opportunistic Infections; 2005 Feb 22–25; Boston (MA)

  140. Martin D, Jacobson J, Schurmann D, et al. PA-457, the first-in-class maturation inhibitor, exhibits antiviral activity following a single oral dose in HIV-1-infected patients [abstract no. 159]. 12th Conference on Retroviruses and Opportunistic Infections; 2005 Feb 22–25; Boston (MA)

  141. Kilgore N, Reddick M, Zuiderhof M, et al. The first-in-class maturation inhibitor, PA-457, is a potent inhibitor of HIV-1 drug-resistant isolates and acts synergistically with approved HIV drugs in vitro [abstract no. 509]. 13th Conference on Retroviruses and Opportunistic Infections; 2006 Feb 5–8; Denver (CO)

  142. Lalezari J, McCallister S, Gigliotti M, et al. A phase 2 safety and efficacy study of bevirimat (BVM) in heavily treatment experienced HIV+ patients identifies the target phase 3 study profile [abstract no. H-891]. 48th Annual ICAAC/IDSA Meeting; 2008 Oct 25–28; Washington, DC

  143. Martin DE, Wang-Smith L, Acosta EP, et al. Pharmacokinetics/pharmacodynamics of bevirimat (BVM) in a 14-day functional monotherapy trial in HIV-infected patients [abstract no. A-954]. 48th Annual ICAAC/IDSA Meeting; 2008 Oct 25–28; Washington, DC

  144. Herzmann C, Cuthbertson Z, Fosdick L, et al. Long-term clinical and surrogate marker effects of subcutaneous intermittent interleukin-2 without antiretroviral therapy in HIV-infected patients. J Antimicrob Chemother 2008 Sep; 62(3): 583–6

    CAS  PubMed  Google Scholar 

  145. Molina JM, Levy Y, Fournier I, et al, for the ANRS 119-Interstart study team. Predictors of slow disease progression in ART-naive HIV-1-infected patients treated with IL-2: 3 year extended follow-up of the Interstart ANRS 119 trial [abstract no. 702]. 15th Conference on Retroviruses and Opportunistic Infections; 2008 Feb 8–11; Boston (MA)

  146. Sanchez-Conde M, Lopez J, Rodriguez C, et al. Response to IL-2 in patients with immunodiscordant response to HAART is associated with long-term clinical benefit [abstract no. 705]. 15th Conference on Retroviruses and Opportunistic Infections; 2008 Feb 8–11; Boston (MA)

  147. Copenhagen HIV Program. The ESPRIT trial [online]. Available from URL: http://www.cphiv.dk/ESPRIT/About/tabid/120/Default.aspx [Accessed 2008 Nov 21]

  148. ESPRIT. Copenhagen ICC regional newsletter. ESPRIT No 14/SILCAAT No 8. Copenhagen: University of Copenhagen, 2008 Feb 22

  149. National Institutes of Health Clinical Center. Interluekin-7 to treat HIV-infected people receiving antiretroviral treatment [ClinicalTrials.gov identifier NCT00105417]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2008 Nov 20]

  150. Dropulic B, MacGregor RR, Humeau L, et al. Phase I clinical trial demonstrates safety and feasibility of autologous cellular therapy with lentiviral vector modified CD4 T cells expressing anti-HIV antisense in patients with HAART-resistant HIV-1 infection [abstract no. 552]. 12th Conference on Retroviruses and Opportunistic Infections; 2005 Feb 22–25; Boston (MA)

  151. MacGregor RR. Clinical protocol: a phase 1 open-label clinical trial of the safety and tolerability of single escalating doses of autologous CD4 T cells transduced with VRX496 in HIV-positive subjects. Hum Gene Ther 2001 Nov 1; 12(16): 2028–9

    CAS  PubMed  Google Scholar 

  152. Lukashov V, Quinanes-Mateu M, McGarrity G, et al. Lentiviral delivered VRX496 long antisense sequences exerts molecular pressure on HIV-1 in human subjects [abstract no. 753a]. 15th Conference on Retroviruses and Opportunistic Infections; 2008 Feb 8–11; Boston (MA)

  153. Johnson & Johnson Pharmaceutical Research & Development, L.L.C. Trial of an anti-HIV-1 gene transfer product [ClinicalTrials.gov identifier NCT00074997]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2008 Nov 20]

  154. Levine BL, Humeau LM, Boyer J, et al. Gene transfer in humans using a conditionally replicating lentiviral vector. Proc Natl Acad Sci U S A 2006 Nov 14; 103(46): 17372–7

    CAS  PubMed  PubMed Central  Google Scholar 

  155. VIRxSYS Corporation. A rollover study for subjects who completed participation in the VRX496-USA-05-002 trial [ClinicalTrials.gov identifier NCT00622232]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2008 Nov 20]

  156. University of Pennsylvania. Evaluate the tolerability and therapeutic effects of repeated doses of autologous T cells with VRX496 in HIV [ClinicalTrials.gov identifier NCT00295477]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2008 Nov 20]

  157. VIRxSYS Corporation. Safety and efficacy of T cell genetic immunotherapy for HIV [ClinicalTrials.gov identifier NCT00131560]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2008 Nov 20]

  158. Dayton AI. Within you, without you: HIV-1 Rev and RNA export [letter]. Retrovirology 2004; 1: 35

    PubMed  PubMed Central  Google Scholar 

  159. Ishaq M, Hu J, Wu X, et al. Knockdown of cellular RNA helicase DDX3 by short hairpin RNAs suppresses HIV-1 viral replication without inducing apoptosis. Mol Biotechnol 2008 Jul; 39(3): 231–8

    CAS  PubMed  Google Scholar 

  160. Rossi JJ, June CH, Kohn DB. Genetic therapies against HIV. Nat Biotechnol 2007 Dec; 25(12): 1444–54

    CAS  PubMed  PubMed Central  Google Scholar 

  161. Perez EE, Wang J, Miller JC, et al. Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases. Nat Biotechnol 2008 Jul; 26(7): 808-16

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

No sources of funding were used to assist in the preparation of this manuscript. The authors have no conflicts of interest that are directly relevant to the content of this review.

Author information

Authors and Affiliations

  1. VA Palo Alto Health-Care System, 3801 Miranda Ave. (132), Palo Alto, California, 94304, USA

    Birgitt Dau &  Mark Holodniy

  2. Division of Infectious Diseases & Geographic Medicine, Stanford University, Palo Alto, California, USA

    Birgitt Dau &  Mark Holodniy

Authors
  1. Birgitt Dau
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mark Holodniy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mark Holodniy.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dau, B., Holodniy, M. Novel Targets for Antiretroviral Therapy. Drugs 69, 31–50 (2009). https://doi.org/10.2165/00003495-200969010-00003

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-200969010-00003

Keywords

Search

Navigation