Mother to child transmission of HIV among Zimbabwean women who seroconverted postnatally: prospective cohort study

Abstract

Objectives: To estimate the rates and timing of mother to infant transmission of HIV associated with breast feeding in mothers who seroconvert postnatally, and their breast milk and plasma HIV loads during and following seroconversion, compared with women who tested HIV positive at delivery.

Design: Prospective cohort study.

Setting: Urban Zimbabwe.

Participants: 14 110 women and infants enrolled in the Zimbabwe Vitamin A for Mothers and Babies (ZVITAMBO) trial (1997-2001).

Main outcome measures: Mother to child transmission of HIV, and breast milk and maternal plasma HIV load during the postpartum period.

Results: Among mothers who tested HIV positive at baseline and whose infant tested HIV negative with polymerase chain reaction (PCR) at six weeks (n=2870), breastfeeding associated transmission was responsible for an average of 8.96 infant infections per 100 child years of breast feeding (95% CI 7.92 to 10.14) and varied little over the breastfeeding period. Breastfeeding associated transmission for mothers who seroconverted postnatally (n=334) averaged 34.56 infant infections per 100 child years (95% CI 26.60 to 44.91) during the first nine months after maternal infection, declined to 9.50 (95% CI 3.07 to 29.47) during the next three months, and was zero thereafter. Among women who seroconverted postnatally and in whom the precise timing of infection was known (≤90 days between last negative and first positive test; n=51), 62% (8/13) of transmissions occurred in the first three months after maternal infection and breastfeeding associated transmission was 4.6 times higher than in mothers who tested HIV positive at baseline and whose infant tested HIV negative with PCR at six weeks. Median plasma HIV concentration in all mothers who seroconverted postnatally declined from 5.0 log(10) copies/mL at the last negative enzyme linked immunosorbent assay (ELISA) to 4.1 log(10) copies/mL at 9-12 months after infection. Breast milk HIV load in this group was 4.3 log(10) copies/mL 0-30 days after infection, but rapidly declined to 2.0 log(10) copies/mL and <1.5 log(10) copies/mL by 31-90 days and more than 90 days, respectively. Among women whose plasma sample collected soon after delivery tested negative for HIV with ELISA but positive with PCR (n=17), 75% of their infants were infected or had died by 12 months. An estimated 18.6% to 20.4% of all breastfeeding associated transmission observed in the ZVITAMBO trial occurred among mothers who seroconverted postnatally.

Conclusions: Breastfeeding associated transmission is high during primary maternal HIV infection and is mirrored by a high but transient peak in breast milk HIV load. Around two thirds of breastfeeding associated transmission by women who seroconvert postnatally may occur while the mother is still in the "window period" of an antibody based test, when she would test HIV negative using one of these tests. Trial registration Clinical trials.gov NCT00198718.

Conflict of interest statement

Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous 3 years; no other relationships or activities that could appear to have influenced the submitted work.

Figures

Fig 1 Classification of HIV infected mothers according to mother to child risk of transmission. ELISA, enzyme linked immunosorbent assay; PCR, polymerase chain reaction

Fig 2 Cumulative (top panel) and instantaneous (one day; bottom panel) probability of breastfeeding associated transmission of HIV for three groups of women: those who were positive at baseline and at risk of breastfeeding associated transmission (baseline positive at risk of breastfeeding associated transmission); all women who seroconverted postnatally; and a subgroup of women who seroconverted postnatally and had a seroconversion interval of less than or equal to 90 days. Time line in the x axis is the time (in days) since HIV exposure began for the infants in each group: six weeks post partum for women who were baseline positive and at risk of breastfeeding associated transmission; and time of maternal HIV infection (defined as the midpoint of the mother’s last negative and first positive ELISA tests) for postnatal seroconverter mothers

Fig 3 Plasma (blue) and breast milk supernatant (open) HIV RNA concentration according to estimated time since HIV infection among women who seroconverted to HIV positive postnatally. Box plots show median, interquartile range, 95% confidence limits, and outliers. Only samples with detectable HIV RNA load are represented

Fig 4 Plasma (blue) and breast milk supernatant (open) HIV RNA concentration according to estimated time since delivery among women who tested HIV positive at baseline. Box plots show median, interquartile range, 95% confidence limits, and outliers. Only samples with detectable HIV RNA load are represented

Fig 5 Cumulative (top panel) and instantaneous (one day; bottom panel) probability of HIV transmission and HIV transmission or death among baseline positive women and baseline seroconverter women