Annals of internal medicine: Monitoring plasma HIV-1 RNA levels in addition to CD4+ lymphocyte count improves assessment of antiretroviral therapeutic response

Michael D. Hughes, Victoria A. Johnson, Martin S. Hirsch, James W. Bremer, Tarek Elbeik, Alejo Erice, Daniel R. Kuritzkes, Walter A. Scott, Stephen A. Spector, Nesli Basgoz, Margaret A Fischl, Richard T. D'Aquila

Research output: Contribution to journalArticle

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Abstract

Background: CD4+ lymphocyte counts and plasma HIV-1 RNA levels predict progression of HIV-related disease, but the relative importance of these and other virological factors in defining response to antiretroviral therapy is not yet clear. Objective: To determine the short-term variability of plasma HIV-1 RNA level during stable therapy; the relative importance of pretreatment values and early changes in CD4+ count, HIV-1 RNA levels, and infectious HIV-1 titers in mononuclear cells of peripheral blood and pretreatment syncytium-inducing phenotype of an HIV-1 isolate for prediction of disease progression and decline in CD4+ counts during therapy. Design: Data were collected prospectively in a randomized, clinical trial comparing two combination regimens (ACTG [AIDS Clinical Trials Group] Protocol 241) and pooled across treatments. Setting: 8 AIDS Clinical Trials Units. Patients: 198 adults with HIV-1 infection and no more than 350 CD4+ lymphocytes/mm3 who had received at least 6 months of nucleoside therapy. Interventions: All patients received zidovudine and didanosine; 100 received nevirapine and 98 received placebo. Measurements: CD4+ lymphocyte counts, plasma HIV-1 RNA levels, and infectious HIV-1 titers in cells were measured before and 8 and 48 weeks after study treatment. Assay for the syncytium-inducing viral phenotype was done at baseline. Progression was defined as occurrence of opportunistic infection, malignancy, or death during the 48 weeks after treatment began. Results: The difference between two measurements of HIV-1 RNA levels at baseline was within ±0.39 log10 copies/mL (2.5-fold) for 90% of 167 patients receiving stable therapy. In a multivariate model, risk for disease progression was reduced by 56% (95% CI, 8% to 79% [P 0.028]) for every 10-fold lower HIV-1 RNA level at baseline, by 52% (CI, 6% increase to 79% reduction [P - 0.071]) for every 10-fold reduction in HIV-1 RNA level at 8 weeks after-treatment initiation, and by 67% (CI, 42% to 81% [P< 0.001]) for every 2-fold higher CD4+ count at baseline. These risk factors and syncytium-inducing vital phenotype at baseline, but not infectious HIV-1 titers in circulating cells, were associated with change in CD4 counts over 48 weeks. Conclusions: For an individual patient, a change in plasma HIV-1 RNA level of 2.5-fold or more probably indicates a true biological change. Monitoring HIV-1 RNA levels and CD4+ lymphocytes before a change in antiretroviral treatment and monitoring HIV-1 RNA levels shortly thereafter improves prediction of disease progression and decline in CD4+ counts for 1 year compared with monitoring CD4+ counts or HIV-1 RNA levels alone. Additional monitoring of infectious HIV-1 titers in mononuclear cells of peripheral blood is not useful.

Original languageEnglish
Pages (from-to)929-938
Number of pages10
JournalAnnals of Internal Medicine
Volume126
Issue number12
StatePublished - Jun 15 1997

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CD4 Lymphocyte Count
Internal Medicine
HIV-1
RNA
Therapeutics
Giant Cells
Disease Progression
Phenotype
Blood Cells
Acquired Immunodeficiency Syndrome
Clinical Trials
Lymphocytes
Didanosine
Nevirapine
Aftercare
Zidovudine
Opportunistic Infections
Clinical Protocols
Nucleosides
HIV Infections

ASJC Scopus subject areas

  • Medicine(all)

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Hughes, M. D., Johnson, V. A., Hirsch, M. S., Bremer, J. W., Elbeik, T., Erice, A., ... D'Aquila, R. T. (1997). Annals of internal medicine: Monitoring plasma HIV-1 RNA levels in addition to CD4+ lymphocyte count improves assessment of antiretroviral therapeutic response. Annals of Internal Medicine, 126(12), 929-938.

Annals of internal medicine : Monitoring plasma HIV-1 RNA levels in addition to CD4+ lymphocyte count improves assessment of antiretroviral therapeutic response. / Hughes, Michael D.; Johnson, Victoria A.; Hirsch, Martin S.; Bremer, James W.; Elbeik, Tarek; Erice, Alejo; Kuritzkes, Daniel R.; Scott, Walter A.; Spector, Stephen A.; Basgoz, Nesli; Fischl, Margaret A; D'Aquila, Richard T.

In: Annals of Internal Medicine, Vol. 126, No. 12, 15.06.1997, p. 929-938.

Research output: Contribution to journalArticle

Hughes, MD, Johnson, VA, Hirsch, MS, Bremer, JW, Elbeik, T, Erice, A, Kuritzkes, DR, Scott, WA, Spector, SA, Basgoz, N, Fischl, MA & D'Aquila, RT 1997, 'Annals of internal medicine: Monitoring plasma HIV-1 RNA levels in addition to CD4+ lymphocyte count improves assessment of antiretroviral therapeutic response', Annals of Internal Medicine, vol. 126, no. 12, pp. 929-938.
Hughes, Michael D. ; Johnson, Victoria A. ; Hirsch, Martin S. ; Bremer, James W. ; Elbeik, Tarek ; Erice, Alejo ; Kuritzkes, Daniel R. ; Scott, Walter A. ; Spector, Stephen A. ; Basgoz, Nesli ; Fischl, Margaret A ; D'Aquila, Richard T. / Annals of internal medicine : Monitoring plasma HIV-1 RNA levels in addition to CD4+ lymphocyte count improves assessment of antiretroviral therapeutic response. In: Annals of Internal Medicine. 1997 ; Vol. 126, No. 12. pp. 929-938.
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abstract = "Background: CD4+ lymphocyte counts and plasma HIV-1 RNA levels predict progression of HIV-related disease, but the relative importance of these and other virological factors in defining response to antiretroviral therapy is not yet clear. Objective: To determine the short-term variability of plasma HIV-1 RNA level during stable therapy; the relative importance of pretreatment values and early changes in CD4+ count, HIV-1 RNA levels, and infectious HIV-1 titers in mononuclear cells of peripheral blood and pretreatment syncytium-inducing phenotype of an HIV-1 isolate for prediction of disease progression and decline in CD4+ counts during therapy. Design: Data were collected prospectively in a randomized, clinical trial comparing two combination regimens (ACTG [AIDS Clinical Trials Group] Protocol 241) and pooled across treatments. Setting: 8 AIDS Clinical Trials Units. Patients: 198 adults with HIV-1 infection and no more than 350 CD4+ lymphocytes/mm3 who had received at least 6 months of nucleoside therapy. Interventions: All patients received zidovudine and didanosine; 100 received nevirapine and 98 received placebo. Measurements: CD4+ lymphocyte counts, plasma HIV-1 RNA levels, and infectious HIV-1 titers in cells were measured before and 8 and 48 weeks after study treatment. Assay for the syncytium-inducing viral phenotype was done at baseline. Progression was defined as occurrence of opportunistic infection, malignancy, or death during the 48 weeks after treatment began. Results: The difference between two measurements of HIV-1 RNA levels at baseline was within ±0.39 log10 copies/mL (2.5-fold) for 90{\%} of 167 patients receiving stable therapy. In a multivariate model, risk for disease progression was reduced by 56{\%} (95{\%} CI, 8{\%} to 79{\%} [P 0.028]) for every 10-fold lower HIV-1 RNA level at baseline, by 52{\%} (CI, 6{\%} increase to 79{\%} reduction [P - 0.071]) for every 10-fold reduction in HIV-1 RNA level at 8 weeks after-treatment initiation, and by 67{\%} (CI, 42{\%} to 81{\%} [P< 0.001]) for every 2-fold higher CD4+ count at baseline. These risk factors and syncytium-inducing vital phenotype at baseline, but not infectious HIV-1 titers in circulating cells, were associated with change in CD4 counts over 48 weeks. Conclusions: For an individual patient, a change in plasma HIV-1 RNA level of 2.5-fold or more probably indicates a true biological change. Monitoring HIV-1 RNA levels and CD4+ lymphocytes before a change in antiretroviral treatment and monitoring HIV-1 RNA levels shortly thereafter improves prediction of disease progression and decline in CD4+ counts for 1 year compared with monitoring CD4+ counts or HIV-1 RNA levels alone. Additional monitoring of infectious HIV-1 titers in mononuclear cells of peripheral blood is not useful.",
author = "Hughes, {Michael D.} and Johnson, {Victoria A.} and Hirsch, {Martin S.} and Bremer, {James W.} and Tarek Elbeik and Alejo Erice and Kuritzkes, {Daniel R.} and Scott, {Walter A.} and Spector, {Stephen A.} and Nesli Basgoz and Fischl, {Margaret A} and D'Aquila, {Richard T.}",
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T2 - Monitoring plasma HIV-1 RNA levels in addition to CD4+ lymphocyte count improves assessment of antiretroviral therapeutic response

AU - Hughes, Michael D.

AU - Johnson, Victoria A.

AU - Hirsch, Martin S.

AU - Bremer, James W.

AU - Elbeik, Tarek

AU - Erice, Alejo

AU - Kuritzkes, Daniel R.

AU - Scott, Walter A.

AU - Spector, Stephen A.

AU - Basgoz, Nesli

AU - Fischl, Margaret A

AU - D'Aquila, Richard T.

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N2 - Background: CD4+ lymphocyte counts and plasma HIV-1 RNA levels predict progression of HIV-related disease, but the relative importance of these and other virological factors in defining response to antiretroviral therapy is not yet clear. Objective: To determine the short-term variability of plasma HIV-1 RNA level during stable therapy; the relative importance of pretreatment values and early changes in CD4+ count, HIV-1 RNA levels, and infectious HIV-1 titers in mononuclear cells of peripheral blood and pretreatment syncytium-inducing phenotype of an HIV-1 isolate for prediction of disease progression and decline in CD4+ counts during therapy. Design: Data were collected prospectively in a randomized, clinical trial comparing two combination regimens (ACTG [AIDS Clinical Trials Group] Protocol 241) and pooled across treatments. Setting: 8 AIDS Clinical Trials Units. Patients: 198 adults with HIV-1 infection and no more than 350 CD4+ lymphocytes/mm3 who had received at least 6 months of nucleoside therapy. Interventions: All patients received zidovudine and didanosine; 100 received nevirapine and 98 received placebo. Measurements: CD4+ lymphocyte counts, plasma HIV-1 RNA levels, and infectious HIV-1 titers in cells were measured before and 8 and 48 weeks after study treatment. Assay for the syncytium-inducing viral phenotype was done at baseline. Progression was defined as occurrence of opportunistic infection, malignancy, or death during the 48 weeks after treatment began. Results: The difference between two measurements of HIV-1 RNA levels at baseline was within ±0.39 log10 copies/mL (2.5-fold) for 90% of 167 patients receiving stable therapy. In a multivariate model, risk for disease progression was reduced by 56% (95% CI, 8% to 79% [P 0.028]) for every 10-fold lower HIV-1 RNA level at baseline, by 52% (CI, 6% increase to 79% reduction [P - 0.071]) for every 10-fold reduction in HIV-1 RNA level at 8 weeks after-treatment initiation, and by 67% (CI, 42% to 81% [P< 0.001]) for every 2-fold higher CD4+ count at baseline. These risk factors and syncytium-inducing vital phenotype at baseline, but not infectious HIV-1 titers in circulating cells, were associated with change in CD4 counts over 48 weeks. Conclusions: For an individual patient, a change in plasma HIV-1 RNA level of 2.5-fold or more probably indicates a true biological change. Monitoring HIV-1 RNA levels and CD4+ lymphocytes before a change in antiretroviral treatment and monitoring HIV-1 RNA levels shortly thereafter improves prediction of disease progression and decline in CD4+ counts for 1 year compared with monitoring CD4+ counts or HIV-1 RNA levels alone. Additional monitoring of infectious HIV-1 titers in mononuclear cells of peripheral blood is not useful.

AB - Background: CD4+ lymphocyte counts and plasma HIV-1 RNA levels predict progression of HIV-related disease, but the relative importance of these and other virological factors in defining response to antiretroviral therapy is not yet clear. Objective: To determine the short-term variability of plasma HIV-1 RNA level during stable therapy; the relative importance of pretreatment values and early changes in CD4+ count, HIV-1 RNA levels, and infectious HIV-1 titers in mononuclear cells of peripheral blood and pretreatment syncytium-inducing phenotype of an HIV-1 isolate for prediction of disease progression and decline in CD4+ counts during therapy. Design: Data were collected prospectively in a randomized, clinical trial comparing two combination regimens (ACTG [AIDS Clinical Trials Group] Protocol 241) and pooled across treatments. Setting: 8 AIDS Clinical Trials Units. Patients: 198 adults with HIV-1 infection and no more than 350 CD4+ lymphocytes/mm3 who had received at least 6 months of nucleoside therapy. Interventions: All patients received zidovudine and didanosine; 100 received nevirapine and 98 received placebo. Measurements: CD4+ lymphocyte counts, plasma HIV-1 RNA levels, and infectious HIV-1 titers in cells were measured before and 8 and 48 weeks after study treatment. Assay for the syncytium-inducing viral phenotype was done at baseline. Progression was defined as occurrence of opportunistic infection, malignancy, or death during the 48 weeks after treatment began. Results: The difference between two measurements of HIV-1 RNA levels at baseline was within ±0.39 log10 copies/mL (2.5-fold) for 90% of 167 patients receiving stable therapy. In a multivariate model, risk for disease progression was reduced by 56% (95% CI, 8% to 79% [P 0.028]) for every 10-fold lower HIV-1 RNA level at baseline, by 52% (CI, 6% increase to 79% reduction [P - 0.071]) for every 10-fold reduction in HIV-1 RNA level at 8 weeks after-treatment initiation, and by 67% (CI, 42% to 81% [P< 0.001]) for every 2-fold higher CD4+ count at baseline. These risk factors and syncytium-inducing vital phenotype at baseline, but not infectious HIV-1 titers in circulating cells, were associated with change in CD4 counts over 48 weeks. Conclusions: For an individual patient, a change in plasma HIV-1 RNA level of 2.5-fold or more probably indicates a true biological change. Monitoring HIV-1 RNA levels and CD4+ lymphocytes before a change in antiretroviral treatment and monitoring HIV-1 RNA levels shortly thereafter improves prediction of disease progression and decline in CD4+ counts for 1 year compared with monitoring CD4+ counts or HIV-1 RNA levels alone. Additional monitoring of infectious HIV-1 titers in mononuclear cells of peripheral blood is not useful.

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