Factors Related to In-Utero HIV Mother to Child Transmission

In developing nations, most interventions to prevent HIV-1 MTCT target the transmission that occurs either at the time of delivery or during the infant breast-feeding period. In-utero transmission (transmission that occurs before the baby has been born) accounts for 20-30% of HIV-1 infected infants in developing countries such as Kenya. As more strategies are adopted to decrease the MTCT at the time of delivery and during the breast-feeding period, the contribution of in-utero MTCT to the number of infants infected will likely increase. Several factors are already known to be associated with in-utero transmission. These include maternal HIV-1 viral load, antenatal antiretroviral therapy (ART), infant sex, low birthweight, and ascending infections like chorioamnionitis. The goal of this study was to attempt to identify additional risk factors that place HIV-1 positive mothers at risk for in-utero MTCT.

The study took place in Kenya between 1999 and 2002. Through widespread screening, 4512 women were identified as HIV-1 positive. Four-hundred sixty-three women consented to participate in the study. These women were followed over time. All women started oral AZT (the best studied antiretroviral to treat HIV) between 34-36 weeks and continued it through delivery. Sexually transmitted diseases were treated in accordance with Kenyan guidelines. Slides collected at 32 weeks gestation were evaluated for evidence of bacterial vaginosis (a non-sexually transmitted disease), and serum viral loads were also determined from 32 week blood samples. All newborns had PCR tests within 48 hours of birth. Twenty-nine women gave birth to an HIV-positive infant with a positive HIV-1 PCR within 48 hours of birth, evidence of in-utero MTCT.

Pregnancies of the 29 infants infected in-utero (termed “cases”) were compared to those of the 422 infants that were not infected at birth, but either remained HIV-1 negative, or who were infected during the first 12 months of life (termed “controls”). When analyses were performed which controlled for other factors related to MTCT –such as plasma and cervical viral load, maternal CD4 percentage at 32 weeks gestation, and duration of AZT—several risk factors emerged for in-utero MTCT. These included plasma and cervical HIV-1 RNA levels, failure to receive AZT for at least 3 weeks before delivery, illness during pregnancy (defined as fever, diarrhea, or cough), and bacterial vaginosis. Newborns born to mothers having any one of these risk factors were anywhere from 1 and a half times to 3 times as likely to experience MTCT during the in-utero period than newborns born to mothers who did not have these factors.

This is the first article to identify illness during pregnancy and bacterial vaginosis as risk factors for in-utero MTCT of HIV-1. A strength of the article is that some of the other risk factors found to be associated with in-utero MTCT—such as plasma and cervical HIV-1 RNA levels and not receiving AZT for an adequate duration—lend validity to the novel findings, as HIV-1 viral load and AZT have been found by other investigators to be associated with in-utero HIV-1 MTCT. Additionally, bacterial vaginosis is a condition that may be modifiable, and thus further research in this area may hold potential promise for intervention. The other novel risk factor of illness during pregnancy—while potentially just a marker of disease severity-- could aid in identifying HIV-1 positive women in developing nations for whom earlier ART initiation should be considered. An argument can be made that a better control group could have been only the infants who were HIV-1 negative after one year of life, but given that in-utero transmission was the event of interest, the selected control group served that purpose. The small size of the number of cases and the retrospective nature of the study are additional recognizable weaknesses which may limit the strength of the findings. Ultimately, however, this study may help to identify areas which warrant additional investigation when attempting to learn about risk factors for in-utero MTCT.

--Summarized by Barrett Robinson, MD, MPH

Barrett Robinson is a Maternal-Fetal Medicine Fellow at Northwestern Memorial Hospital, where he participates in the ongoing care of one of Illinois’ largest clinics exclusively servicing HIV-positive pregnant patients.

Citation:
Farquhar, Carey, et al. “Illness during pregnancy and bacterial vaginosis are associated with in-utero HIV-1 transmission.” AIDS 2010;24: 153-55.

Original Article (Subscription may be required)

Abstract