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

L. M. Demeter, M. D. Hughes, D. W. Coombs, J. B. Jackson, J. M. Grimes, R. J. Bosch, S. A. Fiscus, S. A. Spector, K. E. Squires, Margaret A Fischl, S. M. Hammer

Research output: Contribution to journalArticle

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Abstract

Background: A substantial proportion of patients with HIV infection will not respond to antiretroviral therapy. Early predictors of response to treatment are needed to identify patients who are at risk for treatment failure. Objective: To determine predictors of virologic and clinical response to indinavir, zidovudine, and lamivudine therapy. Design: Observational analysis of one treatment group in a phase III trial. Setting: 40 AIDS Clinical Trials units. Patients: 489 patients receiving indinavir, zidovudine, and lamivudine who had 1) a CD4 count of 0.200 × 109 cells/L or less after 8 or more weeks of study therapy and 2) plasma HIV-1 RNA measurements obtained at baseline and week 8. Measurements: HIV-1 RNA level and CD4 cell count at weeks 0, 4, 8, 24, and 40. Clinical progression was defined as a new AIDS-defining illness or death. Results: Patients' levels of HIV-1 RNA at the 8th study week of therapy predicted whether patients would achieve virologic suppression to below 500 (or 50) copies/mL at study week 24. An HIV-1 RNA level less than 500 copies/mL at week 24 was achieved in 71% of patients whose level at week 8 had been less than 500 copies/mL, 53% of those with a level of 500 copies/mL or more and at least 2-log10 copies/mL reduction since baseline, 29% of those with a level of 500 copies/mL or more with a 1- to 1.99-log10 copies/mL reduction, and 9% of those with a level of 500 copies/mL or greater and less than 1-log10 copies/mL reduction since baseline (P < 0.001). HIV-1 RNA level at week 8 also predicted clinical progression. HIV-1 disease progressed in 2.2% of the patients with a week-8 HIV-1 RNA level less than 500 copies/mL, 2.3% of patients with 500 copies/mL or greater and at least 2-log10 copies/mL reduction since baseline, 4.9% of patients with 500 copies/mL or greater and 1- to 1.99-log10 copies/mL reduction since baseline, and 10.6% of patients with 500 copies/mL or greater and less than 1-log10 copies/mL, decrease since baseline (P = 0.009). After adjustment for HIV-1 RNA level, patients with a higher week-8 CD4 cell count were more likely to have a week-24 HIV-1 RNA level less than 500 copies/mL (relative risk for patients with a week-8 CD4 count ≥ 0.10 × 109 cells/L, 1.47 [95% Cl, 1.00 to 2.16] compared with <0.050 × 109 cells/L; relative risk for patients with a week-8 CD4 count of 0.05 to 0.099 × 109 cells/L, 0.98 [Cl, 0.61 to 1.57] compared with <0.050 × 109 cells/L). After adjustment for HIV-1 RNA level, patients with a week-8 CD4 count of 0.05 × 109 cells/L or greater (compared with <0.05 × 109 cells/L) had a decreased hazard for clinical progression (hazard ratio, 0.25 [Cl, 0.09 to 0.67]). Conclusions: The HIV-1 RNA level and CD4 cell count achieved at 8 weeks of treatment are important predictors of subsequent virologic and clinical outcomes.

Original languageEnglish
Pages (from-to)954-964
Number of pages11
JournalAnnals of Internal Medicine
Volume135
Issue number11
StatePublished - Dec 4 2001
Externally publishedYes

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Indinavir
Lamivudine
Zidovudine
Clinical Protocols
HIV-1
Clinical Trials
CD4 Lymphocyte Count
RNA
Therapeutics
Acquired Immunodeficiency Syndrome

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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. / Demeter, L. M.; Hughes, M. D.; Coombs, D. W.; Jackson, J. B.; Grimes, J. M.; Bosch, R. J.; Fiscus, S. A.; Spector, S. A.; Squires, K. E.; Fischl, Margaret A; Hammer, S. M.

In: Annals of Internal Medicine, Vol. 135, No. 11, 04.12.2001, p. 954-964.

Research output: Contribution to journalArticle

Demeter, LM, Hughes, MD, Coombs, DW, Jackson, JB, Grimes, JM, Bosch, RJ, Fiscus, SA, Spector, SA, Squires, KE, Fischl, MA & Hammer, SM 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', Annals of Internal Medicine, vol. 135, no. 11, pp. 954-964.
Demeter, L. M. ; Hughes, M. D. ; Coombs, D. W. ; Jackson, J. B. ; Grimes, J. M. ; Bosch, R. J. ; Fiscus, S. A. ; Spector, S. A. ; Squires, K. E. ; Fischl, Margaret A ; Hammer, S. M. / 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. In: Annals of Internal Medicine. 2001 ; Vol. 135, No. 11. pp. 954-964.
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abstract = "Background: A substantial proportion of patients with HIV infection will not respond to antiretroviral therapy. Early predictors of response to treatment are needed to identify patients who are at risk for treatment failure. Objective: To determine predictors of virologic and clinical response to indinavir, zidovudine, and lamivudine therapy. Design: Observational analysis of one treatment group in a phase III trial. Setting: 40 AIDS Clinical Trials units. Patients: 489 patients receiving indinavir, zidovudine, and lamivudine who had 1) a CD4 count of 0.200 × 109 cells/L or less after 8 or more weeks of study therapy and 2) plasma HIV-1 RNA measurements obtained at baseline and week 8. Measurements: HIV-1 RNA level and CD4 cell count at weeks 0, 4, 8, 24, and 40. Clinical progression was defined as a new AIDS-defining illness or death. Results: Patients' levels of HIV-1 RNA at the 8th study week of therapy predicted whether patients would achieve virologic suppression to below 500 (or 50) copies/mL at study week 24. An HIV-1 RNA level less than 500 copies/mL at week 24 was achieved in 71{\%} of patients whose level at week 8 had been less than 500 copies/mL, 53{\%} of those with a level of 500 copies/mL or more and at least 2-log10 copies/mL reduction since baseline, 29{\%} of those with a level of 500 copies/mL or more with a 1- to 1.99-log10 copies/mL reduction, and 9{\%} of those with a level of 500 copies/mL or greater and less than 1-log10 copies/mL reduction since baseline (P < 0.001). HIV-1 RNA level at week 8 also predicted clinical progression. HIV-1 disease progressed in 2.2{\%} of the patients with a week-8 HIV-1 RNA level less than 500 copies/mL, 2.3{\%} of patients with 500 copies/mL or greater and at least 2-log10 copies/mL reduction since baseline, 4.9{\%} of patients with 500 copies/mL or greater and 1- to 1.99-log10 copies/mL reduction since baseline, and 10.6{\%} of patients with 500 copies/mL or greater and less than 1-log10 copies/mL, decrease since baseline (P = 0.009). After adjustment for HIV-1 RNA level, patients with a higher week-8 CD4 cell count were more likely to have a week-24 HIV-1 RNA level less than 500 copies/mL (relative risk for patients with a week-8 CD4 count ≥ 0.10 × 109 cells/L, 1.47 [95{\%} Cl, 1.00 to 2.16] compared with <0.050 × 109 cells/L; relative risk for patients with a week-8 CD4 count of 0.05 to 0.099 × 109 cells/L, 0.98 [Cl, 0.61 to 1.57] compared with <0.050 × 109 cells/L). After adjustment for HIV-1 RNA level, patients with a week-8 CD4 count of 0.05 × 109 cells/L or greater (compared with <0.05 × 109 cells/L) had a decreased hazard for clinical progression (hazard ratio, 0.25 [Cl, 0.09 to 0.67]). Conclusions: The HIV-1 RNA level and CD4 cell count achieved at 8 weeks of treatment are important predictors of subsequent virologic and clinical outcomes.",
author = "Demeter, {L. M.} and Hughes, {M. D.} and Coombs, {D. W.} and Jackson, {J. B.} and Grimes, {J. M.} and Bosch, {R. J.} and Fiscus, {S. A.} and Spector, {S. A.} and Squires, {K. E.} and Fischl, {Margaret A} and Hammer, {S. M.}",
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TY - JOUR

T1 - 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

AU - Demeter, L. M.

AU - Hughes, M. D.

AU - Coombs, D. W.

AU - Jackson, J. B.

AU - Grimes, J. M.

AU - Bosch, R. J.

AU - Fiscus, S. A.

AU - Spector, S. A.

AU - Squires, K. E.

AU - Fischl, Margaret A

AU - Hammer, S. M.

PY - 2001/12/4

Y1 - 2001/12/4

N2 - Background: A substantial proportion of patients with HIV infection will not respond to antiretroviral therapy. Early predictors of response to treatment are needed to identify patients who are at risk for treatment failure. Objective: To determine predictors of virologic and clinical response to indinavir, zidovudine, and lamivudine therapy. Design: Observational analysis of one treatment group in a phase III trial. Setting: 40 AIDS Clinical Trials units. Patients: 489 patients receiving indinavir, zidovudine, and lamivudine who had 1) a CD4 count of 0.200 × 109 cells/L or less after 8 or more weeks of study therapy and 2) plasma HIV-1 RNA measurements obtained at baseline and week 8. Measurements: HIV-1 RNA level and CD4 cell count at weeks 0, 4, 8, 24, and 40. Clinical progression was defined as a new AIDS-defining illness or death. Results: Patients' levels of HIV-1 RNA at the 8th study week of therapy predicted whether patients would achieve virologic suppression to below 500 (or 50) copies/mL at study week 24. An HIV-1 RNA level less than 500 copies/mL at week 24 was achieved in 71% of patients whose level at week 8 had been less than 500 copies/mL, 53% of those with a level of 500 copies/mL or more and at least 2-log10 copies/mL reduction since baseline, 29% of those with a level of 500 copies/mL or more with a 1- to 1.99-log10 copies/mL reduction, and 9% of those with a level of 500 copies/mL or greater and less than 1-log10 copies/mL reduction since baseline (P < 0.001). HIV-1 RNA level at week 8 also predicted clinical progression. HIV-1 disease progressed in 2.2% of the patients with a week-8 HIV-1 RNA level less than 500 copies/mL, 2.3% of patients with 500 copies/mL or greater and at least 2-log10 copies/mL reduction since baseline, 4.9% of patients with 500 copies/mL or greater and 1- to 1.99-log10 copies/mL reduction since baseline, and 10.6% of patients with 500 copies/mL or greater and less than 1-log10 copies/mL, decrease since baseline (P = 0.009). After adjustment for HIV-1 RNA level, patients with a higher week-8 CD4 cell count were more likely to have a week-24 HIV-1 RNA level less than 500 copies/mL (relative risk for patients with a week-8 CD4 count ≥ 0.10 × 109 cells/L, 1.47 [95% Cl, 1.00 to 2.16] compared with <0.050 × 109 cells/L; relative risk for patients with a week-8 CD4 count of 0.05 to 0.099 × 109 cells/L, 0.98 [Cl, 0.61 to 1.57] compared with <0.050 × 109 cells/L). After adjustment for HIV-1 RNA level, patients with a week-8 CD4 count of 0.05 × 109 cells/L or greater (compared with <0.05 × 109 cells/L) had a decreased hazard for clinical progression (hazard ratio, 0.25 [Cl, 0.09 to 0.67]). Conclusions: The HIV-1 RNA level and CD4 cell count achieved at 8 weeks of treatment are important predictors of subsequent virologic and clinical outcomes.

AB - Background: A substantial proportion of patients with HIV infection will not respond to antiretroviral therapy. Early predictors of response to treatment are needed to identify patients who are at risk for treatment failure. Objective: To determine predictors of virologic and clinical response to indinavir, zidovudine, and lamivudine therapy. Design: Observational analysis of one treatment group in a phase III trial. Setting: 40 AIDS Clinical Trials units. Patients: 489 patients receiving indinavir, zidovudine, and lamivudine who had 1) a CD4 count of 0.200 × 109 cells/L or less after 8 or more weeks of study therapy and 2) plasma HIV-1 RNA measurements obtained at baseline and week 8. Measurements: HIV-1 RNA level and CD4 cell count at weeks 0, 4, 8, 24, and 40. Clinical progression was defined as a new AIDS-defining illness or death. Results: Patients' levels of HIV-1 RNA at the 8th study week of therapy predicted whether patients would achieve virologic suppression to below 500 (or 50) copies/mL at study week 24. An HIV-1 RNA level less than 500 copies/mL at week 24 was achieved in 71% of patients whose level at week 8 had been less than 500 copies/mL, 53% of those with a level of 500 copies/mL or more and at least 2-log10 copies/mL reduction since baseline, 29% of those with a level of 500 copies/mL or more with a 1- to 1.99-log10 copies/mL reduction, and 9% of those with a level of 500 copies/mL or greater and less than 1-log10 copies/mL reduction since baseline (P < 0.001). HIV-1 RNA level at week 8 also predicted clinical progression. HIV-1 disease progressed in 2.2% of the patients with a week-8 HIV-1 RNA level less than 500 copies/mL, 2.3% of patients with 500 copies/mL or greater and at least 2-log10 copies/mL reduction since baseline, 4.9% of patients with 500 copies/mL or greater and 1- to 1.99-log10 copies/mL reduction since baseline, and 10.6% of patients with 500 copies/mL or greater and less than 1-log10 copies/mL, decrease since baseline (P = 0.009). After adjustment for HIV-1 RNA level, patients with a higher week-8 CD4 cell count were more likely to have a week-24 HIV-1 RNA level less than 500 copies/mL (relative risk for patients with a week-8 CD4 count ≥ 0.10 × 109 cells/L, 1.47 [95% Cl, 1.00 to 2.16] compared with <0.050 × 109 cells/L; relative risk for patients with a week-8 CD4 count of 0.05 to 0.099 × 109 cells/L, 0.98 [Cl, 0.61 to 1.57] compared with <0.050 × 109 cells/L). After adjustment for HIV-1 RNA level, patients with a week-8 CD4 count of 0.05 × 109 cells/L or greater (compared with <0.05 × 109 cells/L) had a decreased hazard for clinical progression (hazard ratio, 0.25 [Cl, 0.09 to 0.67]). Conclusions: The HIV-1 RNA level and CD4 cell count achieved at 8 weeks of treatment are important predictors of subsequent virologic and clinical outcomes.

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