Maternal Cell-Free Viremia in the Natural History of Perinatal HIV-1 Transmission

We performed a meta-analysis of the predictive value of maternal cell-free viral load in vertical HIV-1 transmission, including 9 cohorts with 1115 mother-infant pairs (696 untreated and 419 treated women). The pooled rate of transmission in untreated women was 21.3% (95% confidence interval [CI], 18.3%-24.5%). The rates of transmission for untreated women in the <1000 copies/ml, 1000 to 9999 copies/ml, and > or = 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), respectively. The area under the receiver operating characteristic (ROC) curve in individual studies ranged from 0.67 to 1.00. The predictive performance of RNA differed between cohorts in which different percentages of transmitters had RNA values >10,000 copies/ml. When 95% of transmitters have RNA values >1000 copies/ml, 77% of nontransmitters would also have values above this cutoff. Transmission rates for treated women in the 1000 to 9999 copies/ml category (7%; 95% CI, 4%-11%,) and > or = 10,000 copies/ml category (18%; 95% CI, 12%-27%) were probably lower than those for untreated women, whereas the transmission rate for treated women with <1000 copies/ml was 5% (95% CI, 2%-11 %). Thus, the risk gradient between RNA categories seems attenuated in treated women. Several aspects of the design, analysis, and reporting of research in this area may be improved in the future with attention to selection and observer biases, multivariate adjustment, and technical consistency. Maternal HIV-1 RNA is a modest predictor of transmission for individual mothers, but a strong predictor of the average risk in groups of untreated mothers. Its discriminatory power is better in untreated than in treated populations and is better in cohorts with a high prevalence of elevated viral load values than in cohorts with generally low levels of viremia.