Up to one third of mother-to-child HIV transmission is not being addressed by current interventions being implemented in resource-limited settings because no attempt is being made to prevent viral transmission whilst the infant is still in the womb, according to a study published in the journal AIDS and carried out by researchers from the University of Zimbabwe and various north American institutions.
The study examined the timing of HIV transmission from mother to child in 996 infants born to mothers participating in the ZVITAMBO trial, which studied the effects on transmission of vitamin A supplementation immediately after birth.
HIV DNA PCR testing was carried out in order to define the period of infection and the following assumptions were made:
- Intrauterine infection was assumed if an infant was found to be HIV DNA-positive in the first four days after birth and at a later stage (6 weeks, 3 or 6 months of age). If the infant was HIV DNA-positive at birth and died subsequently, this was also counted as a case of intrauterine infection.
- Infection during delivery or soon after birth (intrapartum or early postpartum) was assumed if the infant was HIV DNA-negative in the first four days after birth but positive by week 6 and again at a later date.
- Later infection through breastfeeding (late postpartum infection) was assumed if the infant was not HIV DNA-positive at week 6 but became HIV DNA-positive at a later stage.
Overall, 249 infants became infected with HIV within six months of birth, a rate of 30.7%. Eighty-nine were infected before delivery (in utero) (9.4%), 104 were infected during delivery or soon after (intrapartum or early postpartum) (16%) and 21 were infected late postpartum (5.3%). Thirty-five of the infected infants were excluded from the analysis of transmission timing because their last negative and first positive samples were too far apart to make a confident judgement about the timing of transmission.
One hundred and sixteen infants died within six months of birth, of which 69% were HIV DNA-positive by the time of death. Infants infected in utero were significantly more likely to die between eight weeks and six months after birth (hazard ratio 1.91, p=0.02), as were infants whose mothers had CD4 counts below 200 cells/mm3 (hazard ratio 1.84, p=0.04). However, these two factors did not interact. Although infants were more likely to contract HIV intrapartum or in the early postpartum period if their mother had a CD4 count below 200 cells/mm3, a low CD4 count did not increase the risk of intrauterine transmission.
Previous studies of risk factors for mother to child transmission have shown that high viral load is associated with a higher risk of mother to child transmission. Viral load data were not available in this study, so it is not possible to determine whether low CD4 count was a surrogate for high viral load.
The authors say that their findings show that a significant proportion of mother to child transmission is not being addressed by the most widely used prophylactic regimen, a single dose of nevirapine for the mother at delivery and a single dose for the infant in the first few days after birth. Approximately 30% of mother to child transmission occurs in the womb, they point out, and future studies need to be designed that will assess the impact of various regimens on transmission during this period.
Experts are increasingly persuaded that in resource-limited settings, regimens that can control the mother's viral load prior to delivery are preferable to regimens that only control viremia during delivery. A recent expert consensus meeting convened by the World Health Organisation concluded that, wherever possible, women should receive treatment with AZT (zidovudine) from week 28 of their pregnancy, together with nevirapine during delivery and a nevirapine dose for the infant (together with one week of AZT). Some experts would like to have gone further, recommending that mothers should receive a combination of AZT/3TC and nevirapine during pregnancy.
Further information on this website
Prevention of mother to child transmission with nevirapine: time for a rethink? - article from HIV & AIDS Treatment in Practice #24, published March 1 2004.
Reference
Zijenah LS et al. Timing of mother to child transmission of HIV-1 and infant mortality in the first 6 months of life in Harare, Zimbabwe. AIDS 18: 273-280, 2004.