MATERNAL CELL-FREE VIREMIA IN THE NATURAL-HISTORY OF PERINATAL HIV-1 TRANSMISSION - A METAANALYSIS

We performed a meta-analysis of the predictive value of maternal cell- free viral load in vertical HIV-1 transmission, including 9 cohorts wi th 1115 mother-infant pairs (696 untreated and 419 treated women). The pooled rate of transmission in untreated women was 21.3% (95% confide nce interval [CI], 18.3%-24.5%). The rates of transmission for untreat ed women in the <1000 copies/ml, 1000 to 9999 copies/ml, and greater t han or equal to 10,000 copies/ml categories were 5% (95% CI, 2%-11%), 15% (95% CI, 11%-20%) and 37% (95% CI, 29%-46% by random effects), res pectively. The area under the receiver operating characteristic (ROC) curve in individual studies ranged from 0.67 to 1.00. The predictive p erformance of RNA differed between cohorts in which different percenta ges of transmitters had RNA values >10,000 copies/ml. When 95% of tran smitters have RNA values >1000 copies/ml, 77% of nontransmitters would also have values above this cutoff Transmission rates for treated wom en in the 1000 to 9999 copies/ml category (7%; 95% CI, 4%-11%,) and gr eater than or equal to 10,000 copies/ml category (18%; 95% CI, 12%-27% ) were probably lower than those for untreated women, whereas the tran smission rate for treated women with <1000 copies/ml was 5% (95% CI, 2 %-11%). Thus, the risk gradient between RNA categories seems attenuate d in treated women. Several aspects of the design, analysis, and repor ting of research in this area may be improved in the future with atten tion to selection and observer biases, multivariate adjustment, and te chnical consistency. Maternal HIV-1 RNA is a modest predictor of trans mission for individual mothers, but a strong predictor of the average risk in groups of untreated mothers. Its discriminatory power is bette r in untreated than in treated populations and is better in cohorts wi th a high prevalence of elevated viral load values than in cohorts wit h generally low levels of viremia.