The rate of viral rebound after attainment of an HIV load <50 copies/mL according to specific antiretroviral drugs in use: results from a multicenter cohort study.

BACKGROUND Relatively few data are available on the association between the use of specific antiretroviral drugs and the rate of viral rebound in those attaining a viral load (VL) <50 copies/mL while receiving highly active antiretroviral therapy (HAART). METHODS Patients achieving a VL <50 copies/mL for the first time while receiving HAART were followed until viral rebound (2 consecutive VLs >500 copies/mL). Pre-HAART antiretroviral-naive patients were analyzed separately from those with nucleoside reverse transcriptase inhibitor (NRTI) experience. RESULTS Of 3565 suppressed antiretroviral-naive patients, 381 experienced viral rebound (rate, 6.26 events/100 person-years of follow-up [pyrs] [95% confidence interval {CI}, 5.63-6.89 events/100 pyrs]). For those receiving efavirenz, the rate was 4.08 (95% CI, 3.16-5.01) events/pyrs. Compared with this, the rebound rate for those receiving indinavir was 1.52 times higher (rate ratio [RR], 1.52 [95% CI, 0.82-2.84]). RRs (95% CIs) for other drugs were: soft-gel saquinavir, 0.54 (0.07-3.97); nelfinavir, 2.44 (1.68-3.54); indinavir/ritonavir, 1.96 (1.02-3.77); saquinavir/ritonavir, 1.12 (0.48-2.61); lopinavir/ritonavir, 1.23 (0.58-2.59); nevirapine, 1.53 (1.11-2.10); and abacavir, 2.03 (1.26-3.25). Of 810 NRTI-exposed patients, 145 experienced viral rebound (rate, 8.29 [95% CI, 6.94-9.64] events/pyrs). For those receiving efavirenz, the rate was 5.25 (95% CI, 3.11-8.30) events/pyrs. Compared with this, the RRs (95% CIs) were: indinavir, 1.75 (0.82-3.73); hard-gel saquinavir, 3.48 (0.36-33.37); nelfinavir, 2.64 (1.37-5.08); indinavir/ritonavir, 0.32 (0.04-2.49); saquinavir/ritonavir, 0.64 (0.23-1.80); nevirapine, 1.65 (0.90-3.02); and abacavir, 1.82 (0.73-4.52). CONCLUSIONS We must make comparisons of antiretroviral outcomes in observational data with caution; however, our results suggest that, in those with VLs <50 copies/mL, certain drugs may be associated with higher rebound rates than others.

[1]  O. Kirk,et al.  Rate of viral rebound according to specific drugs in the regimen in 2120 patients with HIV suppression , 2004, AIDS.

[2]  Christopher D Pilcher,et al.  Triple-nucleoside regimens versus efavirenz-containing regimens for the initial treatment of HIV-1 infection. , 2004, The New England journal of medicine.

[3]  B. Gazzard,et al.  Comparison of first-line antiretroviral therapy with regimens including nevirapine, efavirenz, or both drugs, plus stavudine and lamivudine: a randomised open-label trial, the 2NN Study , 2004, The Lancet.

[4]  Kholoud Porter,et al.  The creation of a large UK‐based multicentre cohort of HIV‐infected individuals: The UK Collaborative HIV Cohort (UK CHIC) Study , 2004, HIV medicine.

[5]  Victor De Gruttola,et al.  Comparison of sequential three-drug regimens as initial therapy for HIV-1 infection. , 2003, The New England journal of medicine.

[6]  M. Battegay,et al.  Meta-analysis of randomized controlled trials of simplified versus continued protease inhibitor-based antiretroviral therapy in HIV-1-infected patients , 2003, AIDS.

[7]  B. Yip,et al.  Adherence and plasma HIV RNA responses to highly active antiretroviral therapy among HIV-1 infected injection drug users. , 2003, CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.

[8]  D. Podzamczer,et al.  Substitution of nevirapine, efavirenz, or abacavir for protease inhibitors in patients with human immunodeficiency virus infection. , 2003, The New England journal of medicine.

[9]  A. Mocroft,et al.  Virological rebound after suppression on highly active antiretroviral therapy , 2003, AIDS.

[10]  I. Escobar,et al.  Factors Affecting Patient Adherence to Highly Active Antiretroviral Therapy , 2003, The Annals of pharmacotherapy.

[11]  C. Mussini,et al.  Simplification of Protease Inhibitor-Containing Regimens with Efavirenz, Nevirapine or Abacavir: Safety and Efficacy Outcomes , 2003, Antiviral therapy.

[12]  Loren G. Miller,et al.  A prospective study of predictors of adherence to combination antiretroviral medication , 2002, Journal of General Internal Medicine.

[13]  P. Keiser,et al.  Comparison of Nevirapine- and Efavirenz-Containing Antiretroviral Regimens in Antiretroviral-Naïve Patients: A Cohort Study , 2002, HIV clinical trials.

[14]  K. Ariyoshi,et al.  Comparative response of African HIV-1-infected individuals to highly active antiretroviral therapy , 2002, AIDS.

[15]  B. Gazzard,et al.  Switching to zidovudine plus lamivudine plus abacavir maintains viral suppression in patients with high viral load before antiretroviral therapy: a retrospective clinical cohort analysis. , 2002, AIDS.

[16]  B. Stricker,et al.  Low risk of treatment failure after substitution of nevirapine for protease inhibitors among human immunodeficiency virus-infected patients with virus suppression. , 2002, The Journal of infectious diseases.

[17]  H. Günthard,et al.  A randomized trial of simplified maintenance therapy with abacavir, lamivudine, and zidovudine in human immunodeficiency virus infection. , 2002, The Journal of infectious diseases.

[18]  M. Moroni,et al.  Virologic and immunologic response to regimens containing nevirapine or efavirenz in combination with 2 nucleoside analogues in the Italian Cohort Naive Antiretrovirals (I.Co.N.A.) study. , 2002, The Journal of infectious diseases.

[19]  T. Wall,et al.  Prevalence, predictors, and outcomes of early adherence after starting or changing antiretroviral therapy. , 2002, AIDS patient care and STDs.

[20]  R. Paredes,et al.  Virological, immunological, and clinical impact of switching from protease inhibitors to nevirapine or to efavirenz in patients with human immunodeficiency virus infection and long-lasting viral suppression. , 2002, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[21]  A. Telenti,et al.  Switching from protease inhibitors to efavirenz: differences in efficacy and tolerance among risk groups: a case–control study from the Swiss HIV Cohort , 2002, AIDS (London).

[22]  F. Brun-Vézinet,et al.  Predictors of virological rebound in HIV-1-infected patients initiating a protease inhibitor-containing regimen , 2002, AIDS.

[23]  B. Gazzard,et al.  Virological suppression at 6 months is related to choice of initial regimen in antiretroviral-naive patients: a cohort study , 2002, AIDS.

[24]  C. Sabin,et al.  Durability of HIV-1 viral suppression over 3.3 years with multi-drug antiretroviral therapy in previously drug-naive individuals , 2001, AIDS.

[25]  O. Kirk,et al.  Viral load outcome of non-nucleoside reverse transcriptase inhibitor regimens for 2203 mainly antiretroviral-experienced patients , 2001, AIDS.

[26]  B. Gazzard,et al.  Simplification with abacavir-based triple nucleoside therapy versus continued protease inhibitor-based highly active antiretroviral therapy in HIV-1-infected patients with undetectable plasma HIV-1 RNA , 2001, AIDS.

[27]  S. Hammer,et al.  Nelfinavir, efavirenz, or both after the failure of nucleoside treatment of HIV infection. , 2001, The New England journal of medicine.

[28]  R. Paredes,et al.  Antiretroviral treatment simplification with nevirapine in protease inhibitor-experienced patients with hiv-associated lipodystrophy: 1-year prospective follow-up of a multicenter, randomized, controlled study. , 2001 .

[29]  W. Henley,et al.  Comparison of the effectiveness of non-nucleoside reverse transcriptase inhibitor-containing and protease inhibitor-containing regimens using observational databases , 2001, AIDS.

[30]  C. Petropoulos,et al.  Loss of antiretroviral drug susceptibility at low viral load during early virological failure in treatment-experienced patients , 2000, AIDS.

[31]  V. Soriano,et al.  Risks and benefits of replacing protease inhibitors by nevirapine in HIV-infected subjects under long-term successful triple combination therapy , 2000, AIDS.

[32]  A. Mocroft,et al.  Predictors of virological success and ensuing failure in HIV-positive patients starting highly active antiretroviral therapy in Europe: results from the EuroSIDA study. , 2000, Archives of internal medicine.

[33]  D. Costagliola,et al.  Factors associated with clinical and virological failure in patients receiving a triple therapy including a protease inhibitor , 2000, AIDS.

[34]  C. Sabin,et al.  Determinants of sustainable CD4 lymphocyte count increases in response to antiretroviral therapy. , 1999, AIDS.

[35]  A. Telenti,et al.  Clinical progression and virological failure on highly active antiretroviral therapy in HIV-1 patients: a prospective cohort study , 1999, The Lancet.

[36]  C. Sabin,et al.  Virological response to protease inhibitor therapy in an HIV clinic cohort. , 1999, AIDS.

[37]  R. Hogg,et al.  Nucleoside analogue use before and during highly active antiretroviral therapy and virus load rebound. , 2004, The Journal of infectious diseases.