Skip to main content

Advertisement

Log in

Antiretroviral therapy: When and what to start—an American perspective

  • Published:
Current Infectious Disease Reports Aims and scope Submit manuscript

Abstract

The major US treatment guidelines recently recommended starting antiretroviral therapy (ART) later in the course of HIV infection due to an increasing awareness of the difficulties associated with these regimens. Most of the data to support this change come from observational cohort studies. When deciding to start ART, a number of patient-specific factors and other issues should be considered. Given the many choices for initial ART, one should individualize the choice, taking into account antiretroviral regimen potency, durability, side effects, toxicities, and convenience to ensure a sustained clinical benefit for the patient.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. Yeni PG, Hammer SM, Carpenter CC, et al.: Antiretroviral treatment for adult HIV infection in 2002: updated recommendations of the International AIDS Society-USA Panel. JAMA 2002, 288:222–235. Concise antiretroviral treatment recommendations from an expert panel, updated every year or two. Also available at www.ias-usa.org

    Article  PubMed  CAS  Google Scholar 

  2. Panel on Clinical Practices for Treatment of HIV Infection: US Department of Health and Human Services Guidelines for the use of antiretrovirals in HIV-infected adults and adolescents. www.aidsinfo.nih.gov. Accessed January 6, 2003. Comprehensive ART guidelines that are updated in real-time. Provides an extensive review of all aspects of ART.

  3. Cozzi Lepri A, Phillips AN, d’Arminio Monforte A, et al.: When to start highly active antiretroviral therapy in chronically HIV-infected patients: evidence from the ICONA study. AIDS 2001, 15:983–990.

    Article  Google Scholar 

  4. Phillips AN, Staszewski A, Weber R, et al.: HIV Viral load response to antiretroviral therapy according to the baseline CD4 cell count and viral load. JAMA 2001;286:2560–2567.

    Article  PubMed  CAS  Google Scholar 

  5. Kaplan LD, Northfelt DW: Malignancies associated with AIDS. In The Medical Management of AIDS. Edited by Sande M, Volberding P. Philadelphia: WB Saunders Company; 1999:467–496.

    Google Scholar 

  6. Phair J, Munoz A, Detels R, et al.: The risk of Pneumocystis carinii pneumonia among men infected with human immunodeficiency virus type 1. N Engl J Med 1990, 322:161–165.

    Article  PubMed  CAS  Google Scholar 

  7. Ellerbrock TV, Chiasson MA, Bush TJ et al.: Incidence of cervical squamous intraepithelial lesions in HIV-infected women. JAMA 2000, 283:1031–1037.

    Article  PubMed  CAS  Google Scholar 

  8. Palefsky JM, Holly EA, Hogeboom CJ, et al.: Virologic, immunologic, and clinical parameters in the incidence and progression of anal squamous intraepithelial lesions in HIV-positive and HIV-negative homosexual men. J Acquir Immune Defic Syndr Hum Retrovirol 1998, 17:314–319.

    PubMed  CAS  Google Scholar 

  9. Sieg SF, Mitchem JB, Bazdar DA, Lederman MM: Close link between CD4+ and CD8+ t cell proliferation defects in patients with human immunodeficiency virus disease and relationship to extend periods of CD4+ lymphopenia. J Infect Dis 2002, 185:1401–1408.

    Article  PubMed  Google Scholar 

  10. Chouquet C, Autran B, Gomerd E et al.: Correlation between breadth of memory HIV-specific cytotoxic T cells, viral load and disease progression in HIV infection. AIDS 2002, 16:2399–2407.

    Article  PubMed  CAS  Google Scholar 

  11. Quinn TC, Wawer MJ, Sewankambo N, et al.: Viral load and heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group. N Engl J Med 2000, 342:921–929.

    Article  PubMed  CAS  Google Scholar 

  12. Egger M, May M, Chene G, et al.: Prognosis of HIV-1-infected patients starting highly active antiretroviral therapy: a collaborative analysis of prospective studies. Lancet 2002; 360:119–129. A large collaboration of 13 cohorts examining patients beginning an initial ART regimen. This study provides important prognostic information for patients beginning ART, similar to that which Mellors et al. [17] provided for patients not on ART.

    Article  PubMed  Google Scholar 

  13. Hogg RS, Yip B, Chan KJ, et al.: Rates of disease progression by baseline CD4 cell count and viral load after initiating triple-drug therapy. JAMA 2001, 286:2568–2577.

    Article  PubMed  CAS  Google Scholar 

  14. Sterling TR, Chaisson RE, Moore RD: HIV-1 RNA, CD4 Tlymphocytes, and clinical response to highly active antiretroviral therapy. AIDS 2001, 15:2251–2257.

    Article  PubMed  CAS  Google Scholar 

  15. Palella FJ Jr, Deloria-Knoll M, Chmiel JS, et al.: Survival benefit of initiating antiretroviral therapy in HIV-infected persons in different CD4+ cell strata. Ann Intern Med 2003, 138:620–626.

    PubMed  Google Scholar 

  16. Opravil M, Ledergerber B, Furrer H, et al.: Clinical efficacy of early initiation of HAART in patients with asymptomatic HIV infection and CD4 cell count > 350 X 106/l. AIDS 2002, 16:1371–1381. Case control study that found a benefit to starting ART at a CD4 cell count of 350 to 500 cells/mm3.

    Article  PubMed  CAS  Google Scholar 

  17. Mellors JW, Munoz A, Giorgi JV, et al.: Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV infection. Ann Intern Med 1997, 126:946–954.

    PubMed  CAS  Google Scholar 

  18. Van Leuwen R, Katlama C, Murphy RL, et al.: A randomized trial to study first-line combination therapy with or without a protease inhibitor in HIV-1-infected patients. AIDS 2003, 17:987–999.

    Article  Google Scholar 

  19. Van Leuwen R: The Atlantic Study: a randomized, open-label trial comparing two protease inhibitor (PI)-sparing antiretroviral strategies versus a standard PI-containing regimen, 2 year follow-up data [abstract #MoPeB3089]. In Abstracts of the XIV International AIDS Conference. Barcelona. July 7-12, 2002.

  20. Bartlett JA, Johnson J, Herrera G, et al.: Abacavir/lamivudine (ABC/3TC) in combination with efavirenz (NNRTI), amprenavir/ritonavir (PI) or stavudine (NRTI): ESS40001 (CLASS) preliminary 48 week results [abstract #TuOrB1189]. In Abstracts of the XIV International AIDS Conference. Barcelona. July 7-12, 2002.

  21. Bartlett JA, DeMasi R, Quinn J, et al.: Overview of the effectiveness of triple combination therapy in antiretroviral-naïve HIV-1 infected adults. AIDS 2001, 15:1369–1377. Meta-analysis of 23 antiretroviral studies that found comparable virologic suppression rates between a PI, NNRTI, and three-NRTI regimen.

    Article  PubMed  CAS  Google Scholar 

  22. Staszewski S, Morales-Ramirez J, Tashima KT, et al.: Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir, and indinavir plus zidovudine and lamivudine in the treatment of HIV-1 infection in adults. N Engl J Med 1999, 341:1865–1873. Large comparative study that showed efavirenz was superior to indinavir as part of a combination antiretroviral regimen.

    Article  PubMed  CAS  Google Scholar 

  23. Podzamczer D, Ferrer E, Consiglio E, et al.: A randomized clinical trial comparing nelfinavir or nevirapine associated to zidovudine/lamivudine in HIV-infected naïve patients (the Combine Study). Antiviral Ther 2002, 7:81–90.

    CAS  Google Scholar 

  24. Montaner JSG, Saag MS, Barylski C, et al.: FOCUS study: saquinavir qd regimen versus efavirenz qd regimen week 48 analysis in HIV infected patients [abstract #H-167]. In Abstracts of the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy. San Diego. September 27–30, 2002.

  25. Robbins G, Shafer R, Smeaton L, et al.: Antiretroviral strategies in naïve HIV+ subjects: comparison of sequential 3-drug regimens (ACTG 384) [abstract #LbOr20A]. In Abstracts of the XIV International AIDS Conference. Barcelona. July 7-12, 2002.

  26. Squires KE, Thiry A, Giordano M, et al.: Atazanavir (ATV) qd and efavirenz (EFV) qd with fixed-dose ZDV + 3TC: Comparison of antiviral efficacy and safety through week 24 (AI424-034) [abstract #H-1076]. In Abstracts of the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy. San Diego. September 27–30, 2002.

  27. Staszewski S, Keiser P, Montaner J, et al.: Abacavir-lamivudinezidovudine vs. indinavir-lamivudine-zidovudine in antiretroviral-naïve HIV-infected adults. JAMA 2001, 285:1155–1163.

    Article  PubMed  CAS  Google Scholar 

  28. Vibhagool A, Cahn P, Schechter M, et al.: Abacavir/Combivir (ABC/COM) is comparable to indinavir/Combivir in HIV-1 infected antiretroviral therapy naïve adults: preliminary results of a 48-week open label study (CNA3014) [abstract #63]. In Abstracts of the 1st International AIDS Society Conference on HIV Pathogenesis and Treatment. Buenos Aires. July 8-11, 2001.

  29. Division of AIDS (DAIDS), National Institute of Allergy and Infectious Diseases, National Institutes of Health: Notice to physicians: important interim results from a phase III, randomized, double-blind comparison of three protease inhibitor-sparing regimens for the initial treatment of HIV infection (AACTG Protocol A5095). http://www.AIDSinfo. nih.gov/clinical_trials/>, March 10, 2003. Accessed June 10, 2003.

  30. Gulick RM, Meibohm A, Havlir D, et al.: Six-year follow-up of HIV-1-infected adults in a clinial trial of antiretroviral therapy with indinavir, zidovudine, and lamivudine. AIDS 2003, In press.

  31. Cameron DW, Angel J, Ryan J, et al.: Durability of ritonavir (RTV) plus saquinavir (SQV) dual protease inhibitor therapy in HIV infection: 5-year follow-up [abstract #550-T]. In Abstracts of the 9th Conference on Retroviruses and Opportunistic Infections. Seattle. February 24–28, 2002.

  32. Murphy R, Brun S, King M, et al.: Lopinavir/ritonavir (Kaletra) in antiretroviral naïve HIV+ patients: 4 year follow-up [abstract #H165]. In Abstracts of the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy. San Diego. September 27–30, 2002.

  33. Tashima K, Staszewski S, Morales-Ramirez J, et al.: 3-year durability of response with an efavirenz (EFV)-containing regimen: 144-week follow-up of study 006 [abstract #224]. In Abstracts of the 1st International AIDS Society Conference on HIV Pathogenesis and Treatment. Buenos Aires. July 8-11, 2001.

  34. Squires KE, Gulick R, Tebas P, et al.: A comparison of stavudine plus lamivudine versus zidovudine plus lamivudine in combination with indinavir in antiretroviral naïve individuals with HIV infections: selection of thymidine analog regimen therapy (START 1). AIDS 2000, 14:1591–1600.

    Article  PubMed  CAS  Google Scholar 

  35. Eron JJ, Murphy RL, Peterson D, et al.: A comparison of stavudine, didanosine and indinavir with zidovudine, lamivudine and indinavir for the initial treatment of HIV-1 infected individuals: selection of thymidine analog regimen therapy (START II). AIDS 2000, 14:1601–1610.

    Article  PubMed  CAS  Google Scholar 

  36. Carr A, Chuah J, Hudson J, et al.: A randomized, open-label comparison of three highly active antiretroviral therapy regimens including two nucleoside analogues and indinavir for previously untreated HIV-1 infection: the OzCombo1 Study. AIDS 2000, 14:1171–1180.

    Article  PubMed  CAS  Google Scholar 

  37. French M, Amin J, Roth N, et al.: Randomized, open-label, comparative trial to evaluate the efficacy and safety of three antiretroviral drug combinations including two nucleoside analogues and nevirapine for previously untreated HIV-1 infection: the OzCombo 2 Study. HIV Clin Trials 2002, 3:177–185.

    Article  PubMed  Google Scholar 

  38. van Leth F, Hassink E, Phanuphak P, et al.: Results of the 2NN study: a randomized comparative trial of first-line antiretroviral therapy with regimens containing either nevirapine alone, efavirenz alone, or both drugs combined, together with stavudine and lamivudine [abstract #176]. In Abstracts of the 10th Conference on Retroviruses and Opportunistic Infections. Boston. February 10–14, 2003.

  39. Katzenstein TL, Kirk O, Pedersen C, et al.: The Danish Protease Inhibitor Study: a randomized study comparing the virological efficacy of 3 protease inhibitor-containing regimens for the treatment of human immunodeficiency virus type 1 infection. J Infect Dis 2000, 182:744–750.

    Article  PubMed  CAS  Google Scholar 

  40. Walmsley S, Bernstein B, King M, et al.: Lopinavir-ritonavir versus nelfinavir for the initial treatment of HIV infection. N Engl J Med 2002, 346:2039–2046.

    Article  PubMed  CAS  Google Scholar 

  41. Rodriguez-French A, Nadler JP: The NEAT study: GW433908 efficacy and safety in anti-retroviral therapy (ART) naïve subjects, preliminary 24-week results [abstract #H166]. In Abstracts of the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy. San Diego. September 27–30, 2002.

  42. Schurmann D, Gathe J, Sanne I, et al.: Efficacy and safety of GW433908/ritonavir once daily in therapy-naïve subjects, 48 week results: the SOLO study [abstract #PL14.4]. In Abstracts of the Sixth International Congress on Drug Therapy in HIV Infection. Glasgow, Scotland, November 17–21, 2002.

  43. Sanne I, Cahn P, Percival L, et al.: Comparative results (phase II 48-week): BMS-232632, stavudine, lamivudine as HAART for treatment-naïve HIV+ patients (AI424-008) [abstract #I-668]. In Abstracts of the 41st Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago. September 22–25, 2001.

  44. Staszewski S, Gallant J, Pozniak A, et al.: Efficacy and safety of tenofovir disoproxil fumarate (TDF) versus stavudine (d4T) when used in combination with lamivudine (3TC) and efavirenz (EFV) in HIV-1 infected patients naïve to antiretroviral therapy (ART): 48-week interim results [abstract #LbOr17]. In Abstracts of the XIV International AIDS Conference. Barcelona. July 7–12, 2002.

  45. Saag M, Cahn P, Raffi F, et al.: A randomized, double-blind, multicenter comparison of emtricitabine qd to stavudine bid [abstract #LB-1]. In Abstracts of the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy. San Diego. September 27–30, 2002.

  46. Maggiolo F, Migliorino M, Maserati R, et al.: Virological and immunological responses to a once-a-day antiretroviral regimen with didanosine, lamivudine and efavirenz. Antivir Ther 2001, 6:249–253.

    PubMed  CAS  Google Scholar 

  47. Skowron G, Kuritzkes DR, Thompson MA, et al.: Once-daily quadruple-drug therapy with adefovir dipivoxil, lamivudine, didanosine, and efavirenz in treatment-naive human immunodeficiency virus type 1-infected patients. J Infect Dis 2002, 186:1028–1033.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wilkin, T.J., Gulick, R.M. Antiretroviral therapy: When and what to start—an American perspective. Curr Infect Dis Rep 5, 339–348 (2003). https://doi.org/10.1007/s11908-003-0012-z

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11908-003-0012-z

Keywords

Navigation