Clinical progression of HIV-1 infection according to the viral response during the first year of antiretroviral treatment

ObjectiveTo compare HIV-disease progression according to changes of plasma HIV RNA observed in the year following initiation of a new antiretroviral treatment. DesignProspective cohort treated with two nucleoside analogues or a triple combination including a protease inhibitor. MethodsA Cox model was used to estimate the effect of viral response during the first year after initiation of treatment on the subsequent occurrence of new AIDS-defining events or death. Viral response was fitted either as HIV RNA reduction during the initial 4–12 months of treatment or reduction during the first month. ResultsAmong 773 patients (47% with triple drug combination) followed for a median period of 27 months, 62 patients experienced a clinical event. Poor viral responders (at least two measurements > 3.7 log10 copies/ml during 4–12 months of treatment) had a higher risk of disease progression than good responders (RNA < 2.7 log10 copies/ml) after adjustment [hazard ratio (HR), 2.24; 95% confidence interval (CI), 1.17–4.29]. Intermediate responders (2.7 ⩽ RNA ⩽ 3.7 log10 copies/ml) had a risk of progression comparable with that of good responders (HR, 1.43; 95% CI, 0.64–3.22). A large initial viral reduction was also a protective factor for clinical progression (HR, 0.51 for 1 log10 copies/ml increase of the reduction; 95% CI, 0.31–0.85) and was associated with the viral response during the subsequent 4–12 month period. No patient with a reduction < 0.5 log10 copies/ml in the first month was classified as a good responder in the subsequent 4–12 month period (P  < 0.01). ConclusionsA sustained HIV RNA > 3.7 log10 copies/ml should suggest a prompt change of treatment. When the reduction in HIV RNA is < 0.5 log10 after 1 month of treatment, this action should be anticipated. A sustained HIV RNA level between 2.7 and 3.7 log10 copies/ml may permit the deferral of a change of drug regimen according to the patient's history and therapeutic options.

[1]  J. Montaner,et al.  Estimates of the virological benefit of antiretroviral therapy are both assay‐ and analysis‐dependent , 1998, AIDS.

[2]  S. Hammer,et al.  Antiretroviral therapy for HIV infection in 1997. Updated recommendations of the International AIDS Society-USA panel. , 1998, JAMA.

[3]  D Commenges,et al.  Analysis of left-censored longitudinal data with application to viral load in HIV infection. , 2000, Biostatistics.

[4]  J. Leonard,et al.  The duration of viral suppression during protease inhibitor therapy for HIV‐1 infection is predicted by plasma HIV‐1 RNA at the nadir , 1998, AIDS.

[5]  M. Hughes,et al.  Monitoring Plasma HIV-1 RNA Levels in Addition to CD4+ Lymphocyte Count Improves Assessment of Antiretroviral Therapeutic Response , 1997, Annals of Internal Medicine.

[6]  S. Staszewski,et al.  HIV‐1 RNA, CD4 cell count and the risk of progression to AIDS and death during treatment with HIV‐1 reverse transcriptase inhibitors , 1998, AIDS.

[7]  R A Betensky,et al.  Clinical trials using HIV-1 RNA-based primary endpoints: statistical analysis and potential biases. , 1999, Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association.

[8]  P. Hartigan,et al.  Changes in plasma HIV-1 RNA and CD4+ lymphocyte counts and the risk of progression to AIDS. Veterans Affairs Cooperative Study Group on AIDS. , 1996, The New England journal of medicine.

[9]  John W. Mellors,et al.  Prognosis in HIV-1 Infection Predicted by the Quantity of Virus in Plasma , 1996, Science.

[10]  J. Kahn,et al.  Association of plasma human immunodeficiency virus type 1 RNA level with risk of clinical progression in patients with advanced infection. AIDS Clinical Trials Group (ACTG) 116B/117 Study Team. ACTG Virology Committee Resistance and HIV-1 RNA Working Groups. , 1996, The Journal of infectious diseases.

[11]  S. Hammer,et al.  The relation of virologic and immunologic markers to clinical outcomes after nucleoside therapy in HIV-infected adults with 200 to 500 CD4 cells per cubic millimeter. AIDS Clinical Trials Group Study 175 Virology Study Team. , 1996, The New England journal of medicine.

[12]  B. Walker,et al.  Report of the NIH Panel To Define Principles of Therapy of HIV Infection* , 1998, Annals of Internal Medicine.

[13]  D. Ho,et al.  Ordered accumulation of mutations in HIV protease confers resistance to ritonavir , 1996, Nature Medicine.

[14]  J. Schapiro,et al.  Drug-resistance genotyping in HIV-1 therapy: the VIRAD APT randomi sed controlled trial , 1999, The Lancet.

[15]  M A Fischl,et al.  A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. AIDS Clinical Trials Group 320 Study Team. , 1997, The New England journal of medicine.

[16]  J. Ioannidis,et al.  Predictive value of viral load measurements in asymptomatic untreated HIV‐1 infection: a mathematical model , 1996, AIDS.

[17]  D. Jeffries,et al.  HIV-1 RNA response to antiretroviral treatment in 1280 participants in the Delta Trial: an extended virology study. , 1999, AIDS.

[18]  R. Salamon,et al.  [Human immunodeficiency virus infection and AIDS in Aquitaine. 10 years' experience of a hospital information system, 1985-1995. Le Groupe d'Epidemiologie Clinique du SIDA en Aquitaine (GECSA)]. , 1997, Presse medicale.

[19]  J. Condra,et al.  In vivo emergence of HIV-1 variants resistant to multiple protease inhibitors , 1995, Nature.

[20]  Frank A. Ward,et al.  Data Management and Analysis , 2000 .

[21]  S. Hammer,et al.  Antiretroviral therapy for HIV infection in 1998: updated recommendations of the International AIDS Society-USA Panel. , 1997, JAMA.

[22]  B. Gazzard,et al.  1998 revision to the British HIV Association guidelines for antiretroviral treatment of HIV seropositive individuals , 1998, The Lancet.