Monitoring plasma HIV-1 RNA levels in addition to CD4(+) lymphocyte count improves assessment of antiretroviral therapeutic response

被引:225
作者
Hughes, MD
Johnson, VA
Hirsch, MS
Bremer, JW
Elbeik, T
Erice, A
Kuritzkes, DR
Scott, WA
Spector, SA
Basgoz, N
Fischl, MA
DAquila, RT
机构
[1] HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH PUBL HLTH, CAMBRIDGE, MA 02138 USA
[2] HARVARD UNIV, SCH MED, CAMBRIDGE, MA 02138 USA
[3] VET AFFAIRS MED CTR, BIRMINGHAM, AL 35294 USA
[4] UNIV ALABAMA, SCH MED, BIRMINGHAM, AL 35294 USA
[5] RUSH MED COLL, CHICAGO, IL 60612 USA
[6] UNIV CALIF SAN FRANCISCO, SAN FRANCISCO, CA 94143 USA
[7] UNIV MINNESOTA, SCH MED, CTR HLTH, MINNEAPOLIS, MN 55455 USA
[8] UNIV COLORADO, HLTH SCI CTR, DENVER, CO 80262 USA
[9] UNIV MIAMI, SCH MED, DEPT BIOCHEM & MOL BIOL, MIAMI, FL 33101 USA
[10] UNIV CALIF SAN DIEGO, LA JOLLA, CA 92093 USA
[11] VET AFFAIRS MED CTR, DENVER, CO USA
关键词
D O I
10.7326/0003-4819-126-12-199706150-00001
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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/mm(3) 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 log(10) 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 viral 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-I RNA levels and CD4(+) lymphocytes before a change in antiretroviral treatment and monitoring HIV-1 RNA levers 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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收藏
页码:929 / 938
页数:10
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