Estimates of the virological benefit of antiretroviral therapy are both assay- and analysis-dependent

被引:6
作者
Rae, S
Raboud, JM
Conway, B
Reiss, P
Vella, S
Cooper, D
Lange, J
Harris, M
Wainberg, MA
Robinson, P
Myers, M
Hall, D
Montaner, JSG
机构
[1] Univ British Columbia, St Pauls Hosp, Canadian HIV Trials Network, Vancouver, BC V6Z 1Y6, Canada
[2] Univ British Columbia, St Pauls Hosp, Ctr Excellence HIV AIDS, Vancouver, BC V6Z 1Y6, Canada
[3] Univ Amsterdam, Acad Med Ctr, Trop Med Ctr, Dept Infect Dis, NL-1105 AZ Amsterdam, Netherlands
[4] Ist Super Sanita, Virol Lab, I-00161 Rome, Italy
[5] St Vincents Hosp, Med Ctr, Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW 2010, Australia
[6] Univ Amsterdam, Acad Med Ctr, Dept Internal Med, NL-1105 AZ Amsterdam, Netherlands
[7] Univ Amsterdam, Acad Med Ctr, Human Retrovirus Lab, NL-1105 AZ Amsterdam, Netherlands
[8] McGill Univ, Jewish Gen Hosp, AIDS Ctr, Montreal, PQ H3T 1E2, Canada
[9] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA
关键词
HIV; plasma viral load; statistical analysis;
D O I
10.1097/00002030-199816000-00014
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Objective: To assess the potential discrepancies in reported changes in plasma viral load (PVL) depending on how values below the detection limit of the assay are handled in the data analysis phase of a randomized controlled clinical trial. Design: Data from a recently completed clinical trial comparing combinations of zidovudine, didanosine and nevirapine were analysed. In this trial, PVL was measured using an assay with a lower quantification limit of 400 HIV-1 RNA copies/ml initially. All PVL values less than 500 copies/ml were retested with a more sensitive assay with a lower quantification limit of 20 copies/ml. Methods: Several summary measures for assessing change in PVL were calculated using three different methods to adjust for PVL values less than the quantification limit of the assay. The differences between these measures were evaluated. Results: We found that the magnitude of the discrepancy between summary measures used to report changes in PVL depended on the proportion of subjects with PVL less than the quantification limit of the assay, how those observations were handled in the data analysis, and the relative difference between the quantification limits of the conventional and more sensitive assay. Conclusion: The lack of consensus in reporting of PVL data in the literature makes the interpretation of published trial results difficult In the absence of agreement on the most appropriate summary measure of PVL data, we recommend that all summaries include information on the quantification limit of the assay used, the proportion of observations at or below the quantification limit and how these observations were handled in the data analysis. (C) 1998 Lippincott Williams & Wilkins
引用
收藏
页码:2185 / 2192
页数:8
相关论文
共 19 条
[1]  
[Anonymous], DRUG INF J
[2]   Antiretroviral therapy for HIV infection in 1998 - Updated recommendations of the International AIDS Society USA panel [J].
Carpenter, CCJ ;
Fischl, MA ;
Hammer, SM ;
Hirsch, MS ;
Jacobsen, DM ;
Katzenstein, DA ;
Montaner, JSG ;
Richman, DD ;
Saag, MS ;
Schooley, RT ;
Thompson, MA ;
Vella, S ;
Yeni, PG ;
Volberding, PA .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1998, 280 (01) :78-86
[3]   Association of plasma human immunodeficiency virus type 1 RNA level with risk of clinical progression in patients with advanced infection [J].
Coombs, RW ;
Welles, SL ;
Hooper, C ;
Reichelderfer, PS ;
DAquila, RT ;
Japour, AJ ;
Johnson, VA ;
Kuritzkes, DR ;
Richman, DD ;
Kwok, S ;
Todd, J ;
Jackson, JB ;
DeGruttola, V ;
Crumpacker, CS ;
Kahn, J .
JOURNAL OF INFECTIOUS DISEASES, 1996, 174 (04) :704-712
[4]  
GILLINGS D, 1991, DRUG INF J, V25, P411, DOI DOI 10.1177/009286159102500311
[5]   Correlation of virus load in plasma and lymph node tissue in human immunodeficiency virus infection [J].
Harris, M ;
Patenaude, P ;
Cooperberg, P ;
Filipenko, D ;
Thorne, A ;
Raboud, J ;
Rae, S ;
Dailey, P ;
Chernoff, D ;
Todd, J ;
Conway, B ;
Montaner, JSG .
JOURNAL OF INFECTIOUS DISEASES, 1997, 176 (05) :1388-1392
[6]   A pilot study of nevirapine, indinavir, and lamivudine among patients with advanced human immunodeficiency virus disease who have had failure of combination nucleoside therapy [J].
Harris, M ;
Durakovic, C ;
Rae, S ;
Raboud, J ;
Fransen, S ;
Shillington, A ;
Conway, B ;
Montaner, JSG .
JOURNAL OF INFECTIOUS DISEASES, 1998, 177 (06) :1514-1520
[7]  
Hollander M., 1973, Nonparametric Statistical Methods
[8]  
Hornung R., 1989, Appl. Occupat. Environ. Hygiene, V5, P46, DOI DOI 10.1080/1047322X.1990.10389587
[9]   Monitoring plasma HIV-1 RNA levels in addition to CD4(+) lymphocyte count improves assessment of antiretroviral therapeutic response [J].
Hughes, MD ;
Johnson, VA ;
Hirsch, MS ;
Bremer, JW ;
Elbeik, T ;
Erice, A ;
Kuritzkes, DR ;
Scott, WA ;
Spector, SA ;
Basgoz, N ;
Fischl, MA ;
DAquila, RT .
ANNALS OF INTERNAL MEDICINE, 1997, 126 (12) :929-938
[10]   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 [J].
Katzenstein, DA ;
Hammer, SM ;
Hughes, MD ;
Gundacker, H ;
Jackson, JB ;
Fiscus, S ;
Rasheed, S ;
Elbeik, T ;
Reichman, R ;
Japour, A ;
Merigan, TC ;
Hirsch, MS .
NEW ENGLAND JOURNAL OF MEDICINE, 1996, 335 (15) :1091-1098