HIV Transmission from Mother to Child: Diagnosis and Treatment
Abstract & Commentary
Synopsis: A study of maternal HIV load demonstrates that transmission can occur even at relatively low levels of RNA.
Source: Sperling RS, et al. Maternal viral load, zidovudine treatment, and the risk of transmission of human immunodeficiency virus type 1 from mother to infant. N Engl J Med 1996;335:1621-1629.
Data from the pediatric actg 076 clinical trial demonstrating the protective effect of AZT on the vertical transmission of HIV was presented almost two years ago. Yet, correlates with virologic markers were lacking. Sperling et al have now examined the risk of HIV transmission based on maternal plasma HIV RNA levels.
A total of 402 women who had CD4 counts greater than 200/mm3 and who were 14-34 weeks pregnant were randomized to receive AZT or placebo before December 1993; their infants additionally received AZT for six weeks post-delivery. Fifteen (7.6%) infants in the AZT-treated group were HIV infected vs. 46 (22.6%0 of those in the placebo group (p < 0.001).
Maternal HIV RNA levels were available, either by bDNA or RT-PCR assay, or both, in 333 women at baseline, and paired measurements at both entry and at delivery were available in 286. In the highest viral load quartile (> 15,700 copies/mL by RT-PCR), the transmission rates were 13.3% for those who received AZT vs. 41.7% for those who did not. In the lowest quartile (< 17730 copies/mL) 2.5% vs 7.1%, respectively) were transmittors. Higher levels of plasma HIV RNA at the time of delivery also were statistically significantly associated with an increased transmission risk. A significant protective effect of AZT remained after adjusting for each predictive variable, although AZT treatment was associated with only a modest decrease in plasma HIV RNA (median reduction, 0.28 vs 0.04log copies/mL in the treated and untreated groups, respectively; P < 0.001).
COMMENT BY CAROL A. KEMPER, MD
While a greater risk for transmission exists for those moms with high levels of plasma HIV RNA, this study demonstrates that transmission can occur even at relatively low levels of RNA. Even at the second lowest quartile (1731-5660 HIV RNA copies/mL), transmission rates were 7.5% and 26.2% for those who did and did not receive AZT. These data suggest that aggressive antiviral treatment is indicated regardless of the absolute CD4 count or baseline plasma HIV RNA value, with the specific aim of lowering the plasma viral load to as little as possible. AZT monotherapy was not very effective in reducing viral burden in this study, nor would it be expected to be in women with extensive AZT use or those who are failing other therapies. Whether this means using antiretroviral agents other than AZT in pregnant women in advance of adequate safety data is a sticky question (Phase I pharmacokinetic/safety studies are ongoing with both 3TC and nevaripine), but the risk of transmission is non-trivial, even at lower copy numbers, and may outweigh the risk of administration of other antiretrovirals.
These data suggest that in order to effectively monitor pregnant women, more sensitive assays of plasma HIV RNA should be employed and should be used to optimize therapy.