Flandre P, Alcais A, Descamps D, Morand-Joubert L, Joly V; International Conference on AIDS (15th : 2004 : Bangkok, Thailand).

Int Conf AIDS. 2004 Jul 11-16; 15: abstract no. MoPeC3598.

INSERM U 472, Villejuif, France

Background: Magnitude of reduction in HIV-1 RNA levels provides an important complement to endpoint based on percentage of patients achieving HIV-1 RNA below a threshold value. Analyses and interpretation of this endpoint, however, is difficult due to the lower limit of quantification (LLQ). Methods: Crude method that defines all HIV-1 RNA levels below the LLQ as equal to the LQ provide biased estimates of the HIV-1 RNA reduction. Censored methods that takes into account the censoring of HIV-1 RNA measurements by the LLQ may overestimate HIV-1 RNA reduction. We suggest to consider that such reduction are left-censored by the LLQ and right-bounded by baseline HIV-1 RNA levels. We suggest to use non-parametric and parametric methods introduced for interval-censored data to analyse such data. These methods are discussed and applied with data of two clinical trials: NOVAVIR (ANRS protocol 073) and TRIANON (ANRS protocol 081) study. Results: In the TRIANON study, crude methods indicated not statistical difference in HIV-1 RNA reduction at week 72 between 3TC/D4T/IDV and NVP/D4T/IDV (p=0.40). Censored method shown a statistical difference in reduction between the two groups (p=0.02). In the 3TC group, however, median reduction in HIV-1 RNA was larger than the maximum upper bound indicating the shortcoming of that method. The use of interval-censored method provide reliable estimate of such reduction and non-parametric method show no statistical difference between the two groups (p=0.16). In the NOVAVIR (d4T/3TC/IDV vs. ZDV/3TC/IDV) study there was no statistical difference in reduction at week 80 whatever the method used. Graphical procedures indicated that the log10 transformation to compute HIV-1 RNA reduction was not appropriate to both data. Conclusion Interval-censored methods provide reliable estimate and comparison of HIV-1 RNA reduction between different treatment groups when HIV-1 RNA levels are subject to censoring by the LLQ.

Publication Types:

• Meeting Abstracts

Keywords:

• Clinical Trials as Topic
• Humans
• Lamivudine
• RNA
• RNA, Viral
• Stavudine
• Zidovudine
• methods

Other ID:

• GWAIDS0035676

UI: 102279892

From Meeting Abstracts