A timely objective common to many HIV studies involves assessing the correlation between two different measures of viral load obtained from each of a sample of patients. This correlation has scientific utility in a number of contexts, including those aimed at a comparison of competing assays for quantifying virus and those aimed at determining the level of association between viral loads in two different reservoirs using the same assay. A complication for the analyst seeking valid point and interval estimates of such a correlation is the fact that both variables may be subject to left censoring due to values below assay detection limits. We address this problem using a bivariate normal likelihood that accounts for left censoring of two variables that may have different detection limits. We provide simulation results to evaluate sampling properties of the resulting correlation estimator and compare it with ad hoc estimators in the presence of nondetects. In an effort to obtain improved confidence interval properties relative to the Wald approach, we evaluate and compare profile likelihood-based intervals. We apply the methods to HIV viral load data on women and infants from a trial in Bangkok, Thailand, and we discuss an extension of the original model to accommodate interval censoring arising due to the study design.
Human immunodeficiency virus (HIV) levels in cervicovaginal lavage (CVL) and plasma samples were evaluated in relation to perinatal transmission in a randomized placebo-controlled trial of brief antenatal zidovudine treatment. Samples were collected at 38 weeks' gestation from 310 women and more frequently from a subset of 74 women. At 38 weeks, after a 2-week treatment period, CVL HIV-1 was quantifiable in 23% and 52% of samples in the zidovudine and placebo groups, respectively (P<.001). The perinatal transmission rate was 28.7% among women with quantifiable CVL HIV-1 and high plasma virus levels (>10,000 copies/mL) and 1% among women without quantifiable CVL HIV-1 and with low plasma virus levels (P<.001). A 1-log increase in plasma HIV-1 increased the transmission odds 1.8 and 6.1 times (95% confidence interval, 0.9-3.5 vs. 2.4-15.4) for women with and without quantifiable CVL HIV-1, respectively (P=.03). CVL HIV-1 is an independent risk factor for perinatal HIV-1 transmission.
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