The risk of mother-to-child HIV transmission associated with breast-feeding may be especially high if the woman has only recently become infected, according to a prospective cohort study conducted in Zimbabwe.1 Among women who had been HIV-negative at delivery but became infected while breast-feeding, the transmission rate was 35 per 100 child-years of breast-feeding during the first nine months after infection—substantially higher than the rate among mothers who had been HIV-positive prior to delivery (nine infections per 100 child-years of breast-feeding). The transmission rate eventually plummeted among newly infected women: None of their infants became infected 12–24 months after their mothers had. Overall, 24% of mothers who had become infected while breast- feeding and 14% of those who had been infected at delivery transmitted the virus to their infants during the 24-month study.
The data come from a trial conducted in clinics and hospitals in Harare, Zimbabwe, from November 1997 to January 2000. The trial was designed to examine whether vitamin A supplements reduced the risk of mother-to-child HIV transmission during breast-feeding (they did not); the investigators subsequently performed this secondary analysis because few data are available on the risk of transmission during breast-feeding among mothers who become infected after delivery. Researchers have suspected that the risk of transmission through breast-feeding is particularly high in the period following infection but prior to seroconversion (when the individual has developed antibodies against the virus), because blood levels of HIV are extremely high during this interval.
Women who gave birth in the participating facilities were eligible for the trial if they resided in the city and did not have an acutely life-threatening illness, and if their infants were singletons who weighed at least 1.5 kg. At enrollment, women provided information about their social and demographic characteristics; in addition, the investigators collected blood samples from mothers and infants, along with breast milk samples, for HIV testing. Further samples were taken at follow-up visits at six weeks and three months and then every three months afterward, for up to two years. Mothers who had not been infected with HIV at enrollment but tested positive at three months or later were classified as having been infected postpartum; infection was assumed to have occurred halfway between the mother's last negative and first positive tests. The researchers used Kaplan-Meier analyses to compare transmission rates between the 334 mothers whose infections had occurred postpartum and the 2,870 mothers who had been HIV-positive at delivery. In both groups, all infants were HIV-negative six weeks after birth.
Mean age at enrollment was 26 for women who were HIV-positive at delivery and 23 for those who seroconverted during the study. Both groups had an average of 10 years of schooling and a median monthly household income of about US$75. Almost all women were married or in union. The vast majority (>90%) did not exclusively breast-feed their infant beyond the first three months.
During the first two years after delivery, the rate of mother-to-child HIV transmission was higher among mothers who acquired the virus during the breast-feeding period than among those who tested positive at delivery (26 vs. nine infections per 100 child-years of breast-feeding). Among mothers who had been HIV-positive at baseline, the transmission rate hovered around 8–9 infections per 100 child- years of breast-feeding throughout the study. However, among mothers who seroconverted after giving birth, the rate varied substantially: It was very high during the first nine months after infection (35 per 100 child-years), then declined substantially during the next three months (10 per 100 child-years); no infections occurred during the second year. Overall, the odds of mother-to-infant transmission were about three times as high among mothers who had been infected postnatally as among those who had been HIV-positive at delivery (rate ratio, 2.9); by the end of the study, 24% of infants whose mothers seroconverted during breast-feeding had tested positive, compared with 14% of those whose mothers had been infected at baseline.
Among women who became infected during the breast-feeding period, the interval between their last negative test and first positive test ranged from a few weeks to nearly a year. Because the timing of the maternal infection could be estimated more precisely for mothers with shorter intervals than for those with longer intervals, the researchers conducted a subgroup analysis of the 51 women for whom the timing of seroconversion could be determined with relative precision (i.e., the interval between the last negative and first positive tests was less than 90 days). Among these women, the rate of breast-feeding–related transmission was strikingly high during the first three months after infection (78 infections per 100 child-years of breast-feeding); it was about half as high during the next six months (38 per 100), and no infections occurred after the ninth month following infection. By the study's end, 30% of infants born to these mothers were infected; nearly two-thirds of these transmissions occurred within three months of the mother's infection, a period when the mother may have tested negative on an antibody-based HIV test.
Finally, analyses of breast milk from seroconverters revealed that 50% of samples collected within 31 days of infection had detectable levels of HIV RNA; the proportion declined to 35–38% during months 2–9 and 25% during months 10–12. Among samples with detectable HIV levels, virus loads during the month after infection were more than 100 times those during the ensuing 11 months, indicating that HIV levels spiked following infection and then declined sharply.
The study's limitations, according to the researchers, include the small sample sizes for the breast milk analyses (ranging from 56 to as few as eight during the year following infection) and the study's inability to identify breast-feeding–related HIV transmissions that occurred before infants were six weeks old. Nonetheless, they note that the findings suggest that the risk of passing on the virus is "very high" if a mother is newly infected with HIV, "but only for a relatively brief period of time." Because the majority of transmissions occurred before newly infected mothers were likely to test positive, the researchers believe that offering women multiple postnatal HIV tests "would have only a modest effect" on reducing transmission during breast-feeding; instead, the investigators recommend a "renewed focus on prevention of primary HIV, particularly among pregnant and breast-feeding women."
1. Humphrey JH et al., Mother to child transmission of HIV among Zimbabwean women who seroconverted postnatally: prospective cohort study, BMJ, 2010, doi:10.1136/bmj.c6580, accessed Jan. 5, 2011.