Maternal illness during pregnancy is associated with In utero mother to child transmission

In utero transmission accounts for 20-30% of mother to child transmissions among breastfeeding populations. As interventions to reduce intrapartum transmission risk become more accessible in sub-Saharan Africa, In utero transmission will account for a greater proportion of paediatric HIV infections.

Carey Farquar from the University of Washington and University of Nairobi Collaborative Research Group presented findings from a prospective cohort study to determine correlates of In utero HIV transmission.

In this study of 463 infants born to HIV positive mothers, women were enrolled before 32 weeks gestation and received AZT from week 34. At 32 weeks, mothers were interviewed for medical history during pregnancy, and tested for STIs (syphilis, gonorrhea, chlamydia and trichomonas), bacterial vaginosis, CD4 count and viral load in plasma and cervical secretions.

Study visits were every two weeks and then weekly after starting AZT. Mother and infant visits were then monthly for one year. Infants were tested at birth for HIV-1 DNA (filter paper) and RNA (plasma) within 48 hours of delivery. Infant HIV status was then assessed every 3 months. Seventy seven infants died and 48 were lost to follow up.

Of the 88 infants infected during the study period, the investigators found that 29 infants (6%) had detectable HIV-1 DNA or RNA within 48 hours of birth and were defined as infected In utero (33% of the HIV infected infants). Additionally, 37 infants (42%) were negative at birth and positive at month 1; 12 (14%) had no sample at birth and were positive at month 1; and 10 were HIV-negative at month 1 and positive at a later time point. The infected In utero infants were compared to those uninfected or infected at a later time point (n=422).

In multivariate analysis, higher maternal plasma HIV-1 RNA (log 10 copies/mL) OR 1.9 (95% CI: 1.1-3.1, p=0.02); maternal AZT >/= 3 weeks, OR 0.4 (95% CI: 0.2-1.0, p=0.04); history of cough, fever or diarrhea during pregnancy, OR 2.6 (95% CI: 1.2-5.8, p=0.02) and bacterial vaginosis at 32 weeks were significantly associated with In utero transmission.

Speculating on the mechanism Professor Faquar suggested that illness during pregnancy could cause a transient increase in viral load or immune activation, or that In utero transmitting women were infected with HIV during pregnancy.

Comment

Various studies have suggested that most transmission occurs at the time of delivery and that In utero transmission probably occurs late in pregnancy.

Interventions which effectively reduce transmission to < 1- 2% have generally been initiated late in the second trimester which supports the presumption that In utero transmission is a late event. This study importantly identifies non-specific markers of infection during pregnancy with risk of In utero transmission.

More information is required to know whether these represent preventable events and whether short course AZT commenced at 28-32 weeks is protective. Also, particularly given the data from CROI on cotrimoxazole reducing chorioamnionitis etc (Walker et al), this also may well be a valuable intervention.

Farquhar C., Mbori-Ngacha D, Harris J et al. Illness during pregnancy is associated with In utero human immunodeficiency virus type-1 (HIV-1) transmission. XVI International AIDS Conference, Toronto, Canada. 13-18 August 2006. Oral abstract THACO102.