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 language | English |
|---|---|
| Pages (from-to) | 929-938 |
| Number of pages | 10 |
| Journal | Annals of Internal Medicine |
| Volume | 126 |
| Issue number | 12 |
| State | Published - Jun 15 1997 |
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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 journal › Article
}
TY - JOUR
T1 - Annals of internal medicine
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.
PY - 1997/6/15
Y1 - 1997/6/15
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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M3 - Article
C2 - 9182469
AN - SCOPUS:0031570404
VL - 126
SP - 929
EP - 938
JO - Annals of Internal Medicine
JF - Annals of Internal Medicine
SN - 0003-4819
IS - 12
ER -