All Title Author
Keywords Abstract

PLOS ONE  2006 

Clinical Outcome of HIV-Infected Patients with Sustained Virologic Response to Antiretroviral Therapy: Long-Term Follow-Up of a Multicenter Cohort

DOI: 10.1371/journal.pone.0000089

Full-Text   Cite this paper   Add to My Lib


Background Limited information exists on long-term prognosis of patients with sustained virologic response to antiretroviral therapy. We aimed to assess predictors of unfavorable clinical outcome in patients who maintain viral suppression with HAART. Methods Using data collected from ten clinic-based cohorts in Spain, we selected all antiretroviral-naive adults who initiated HAART and maintained plasma HIV-1 RNA levels <500 copies/mL throughout follow-up. Factors associated with disease progression were determined by Cox proportional-hazards models. Results Of 2,613 patients who started HAART, 757 fulfilled the inclusion criteria. 61% of them initiated a protease inhibitor-based HAART regimen, 29.7% a nonnucleoside reverse-transcriptase inhibitor-based regimen, and 7.8% a triple-nucleoside regimen. During 2,556 person-years of follow-up, 22 (2.9%) patients died (mortality rate 0.86 per 100 person-years), and 40 (5.3%) died or developed a new AIDS-defining event. The most common causes of death were neoplasias and liver failure. Mortality was independently associated with a CD4-T cell response <50 cells/L after 12 months of HAART (adjusted hazard ratio [AHR], 4.26 [95% confidence interval {CI}, 1.68–10.83]; P = .002), and age at initiation of HAART (AHR, 1.06 per year; 95% CI, 1.02–1.09; P = .001). Initial antiretroviral regimen chosen was not associated with different risk of clinical progression. Conclusions Patients with sustained virologic response on HAART have a low mortality rate over time. Long-term outcome of these patients is driven by immunologic response at the end of the first year of therapy and age at the time of HAART initiation, but not by the initial antiretroviral regimen selected.


[1]  Bartlett JA, DeMasi R, Quinn J, Moxham C, Rousseau F (2001) Overview of the effectiveness of triple combination therapy in antiretroviral-naive HIV-1 infected adults. AIDS 15: 1369–1377.
[2]  Mellors JW, Rinaldo CR Jr, Gupta P, et al. (1996) Prognosis in HIV-1 infection predicted by the quantity of virus in plasma. Science 272: 1167–1170.
[3]  Mellors JW, Munoz A, Giorgi JV, et al. (1997) Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection. Ann Intern Med 126: 946–954.
[4]  Staszewski S, DeMasi R, Hill AM, Dawson D (1998) HIV-1 RNA, CD4 cell count and the risk of progression to AIDS and death during treatment with HIV-1 reverse transcriptase inhibitors. AIDS 12: 1991–1997.
[5]  Demeter LM, Hughes MD, Coombs RW, et al. (2001) Predictors of virologic and clinical outcomes in HIV-1 infected patients receiving concurrent treatment with indinavir, zidovudine, and lamivudine. AIDS Clinical Trials Group protocol 320. Ann Intern Med 135: 954–964.
[6]  Panel on Clinical Practices for Treatment of HIV Infection convened by the Department of Health and Human Services (DHHS)May 04. 2006 Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. Available at: Accessed 6 September 2006.
[7]  Palella FJ Jr, Delaney KM, Moorman AC, et al. (1998) Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med 338: 853–860.
[8]  Gebhardt M, Rickenbach M, Egger M (1998) Impact of antiretroviral combination therapies on AIDS surveillance reports in Switzerland. Swiss HIV Cohort Study. AIDS 12: 1195–1201.
[9]  Mocroft A, Ledergerber B, Katlama C, et al. (2003) Decline in the AIDS and death rates in the EuroSIDA study: an observational study. Lancet 362: 22–29.
[10]  Perez-Hoyos S, del Amo J, Muga R, et al. (2003) Effectiveness of highly active antiretroviral therapy in Spanish cohorts of HIV seroconverters: differences by transmission category. AIDS 17: 353–359.
[11]  Sterne JA, Hernan MA, Ledergerber B, et al. (2005) Long-term effectiveness of potent antiretroviral therapy in preventing AIDS and death: a prospective cohort study. Lancet 366: 378–384.
[12]  Rodriguez-Arenas MA, Jarrin I, del Amo J, et al. (2006) Delay in the initiation of HAART, poorer virological response, and higher mortality among HIV-infected injecting drug users in Spain. AIDS Res Hum Retroviruses 22: 715–23.
[13]  Grabar S, Le Moing V, Goujard C, et al. (2000) Clinical outcome of patients with HIV-1 infection according to immunologic and virologic response after 6 months of highly active antiretroviral therapy. Ann Intern Med 133: 401–410.
[14]  Binquet C, Chene G, Jacqmin-Gadda H, et al. (2001) Modeling changes in CD4-positive T-lymphocyte counts after the start of highly active antiretroviral therapy and the relation with risk of opportunistic infections: the Aquitaine Cohort, 1996–1997. Am J Epidemiol 153: 386–393.
[15]  Moore DM, Hogg RS, Yip B, et al. (2005) Discordant immunologic and virologic responses to highly active antiretroviral therapy are associated with increased mortality and poor adherence to therapy. J Acquir Immune Defic Syndr 40: 288–293.
[16]  Schechter M, Tuboi SH (2006) Discordant immunological and virological responses to antiretroviral therapy. J Antimicrob Chemother 58: 506–510.
[17]  Grabar S, Kousignian I, Sobel A, et al. (2004) Immunologic and clinical responses to highly active antiretroviral therapy over 50 years of age. Results from the French Hospital Database on HIV. AIDS 18: 2029–2038.
[18]  Egger M, May M, Chene G, et al. (2002) Prognosis of HIV-1-infected patients starting highly active antiretroviral therapy: a collaborative analysis of prospective studies. Lancet 360: 119–129.
[19]  Marimoutou C, Chene G, Mercie P, et al. (2001) Prognostic factors of combined viral load and CD4+ cell count responses under triple antiretroviral therapy, Aquitaine Cohort, 1996–1998. J Acquir Immune Defic Syndr 27: 161–167.
[20]  Piketty C, Weiss L, Thomas F, et al. (2001) Long-term clinical outcome of human immunodeficiency virus-infected patients with discordant immunologic and virologic responses to a protease inhibitor-containing regimen. J Infect Dis 183: 1328–1335.
[21]  Grabar S, Le Moing V, Goujard C, et al. (2005) Response to highly active antiretroviral therapy at 6 months and long-term disease progression in HIV-1 infection. J Acquir Immune Defic Syndr 39: 284–292.
[22]  Moore D, Hogg R, Chan K, et al. (2006) Disease progression in patients with virological suppression in response to HAART is associated with the degree of immunological response. AIDS 20: 371–377.
[23]  Bonnet F, Thiebaut R, Chene G, et al. (2005) Determinants of clinical progression in antiretroviral-naive HIV-infected patients starting highly active antiretroviral therapy. Aquitaine Cohort, France, 1996–2002. HIV Med 6: 198–205.
[24]  De Gruttola V, Fleming T, Lin DY, Coombs R (1997) Perspective: validating surrogate markers–are we being naive? J Infect Dis 175: 237–246.
[25]  Li Q, Schacker T, Carlis J, et al. (2004) Functional genomic analysis of the response of HIV-1-infected lymphatic tissue to antiretroviral therapy. J Infect Dis 189: 572–582.
[26]  Olsen CH, Gatell J, Ledergerber B, et al. (2005) Risk of AIDS and death at given HIV-RNA and CD4 cell count, in relation to specific antiretroviral drugs in the regimen. AIDS 19: 319–330.
[27]  Mocroft A, Brettle R, Kirk O, et al. (2002) Changes in the cause of death among HIV positive subjects across Europe: results from the EuroSIDA study. AIDS 16: 1663–1671.
[28]  Escolano Hortelano CM, Ramos Rincon JM, Gutiérrez Rodero F, et al. (2004) Changes in the spectrum of morbidity and mortality in hospital admissions of HIV infected patients during the HAART era. Med Clin (Barc) 122: 1–5.
[29]  Valdez H, Chowdhry TK, Asaad R, et al. (2001) Changing spectrum of mortality due to HIV: analysis of 260 deaths during 1995–1999. Clin Infect Dis 32: 1487–1493.
[30]  Puoti M, Spinetti A, Ghezzi A, et al. (2001) Mortality from liver disease in patients with HIV infection: a cohort study. J Acquir Immune Defic Syndr 24: 211–217.
[31]  Welch K, Morse A (2002) The clinical profile of end-state AIDS in the era of highly active antiretroviral therapy. AIDS Patient Care STDs 16: 75–81.
[32]  Weber R, Friis-M?ller N, Sabin C, et al. on behalf of the D:A:D Study GroupHIV and non-HIV-related deaths and their relationship to immunodeficiency: The D:A:D Study [abstract] 12th Conference on Retroviruses and Opportunistic Infections;. Boston, Massachusetts, USA. 2005 22–25 February.
[33]  Braitstein P, Zala C, Yip B, et al. (2006) Immunologic response to antiretroviral therapy in hepatitis C virus-coinfected adults in a population-based HIV/AIDS treatment program. J Infect Dis 193: 259–268.
[34]  Rockstroh JK, Mocroft A, Soriano V, et al. (2005) Influence of hepatitis C virus infection on HIV-1 disease progression and response to highly active antiretroviral therapy. J Infect Dis 192: 992–1002.
[35]  Wood E, Hogg RS, Yip B, et al. (2003) Effect of medication adherence on survival of HIV-infected adults who start highly active antiretroviral therapy when the CD4+ cell count is 0.200 to 0.350×10(9) cells/L. Ann Intern Med 139: 810–816.
[36]  Hogg RS, Heath K, Bangsberg D, et al. (2002) Intermittent use of triple-combination therapy is predictive of mortality at baseline and after 1 year of follow-up. AIDS 16: 1051–1058.


comments powered by Disqus