Two cases of HIV transmission through breastfeeding in mothers with undetectable viral load reported

Two cases of HIV transmission from mother to infant during the breastfeeding period when mothers had an undetectable viral load have been reported by PROMISE, a large international study of the effectiveness of antiretroviral treatment in preventing vertical HIV transmission.

The findings were presented in a poster at the 22nd International AIDS Conference in Amsterdam in July.

Earlier this year an international group of researchers called for more research to determine if HIV can be transmitted through breast milk even if the breastfeeding mother has an undetectable viral load in blood. Swiss doctors have argued that pregnant women with HIV should be informed of the uncertain evidence about the risk of transmission during breastfeeding, and rather than being prohibited from breastfeeding while taking antiretroviral drugs, should be supported to breastfeed safely through regular viral load testing and education about factors that might increase the risk of transmission, such as mastitis.

Glossary

deoxyribonucleic acid (DNA)

The material in the nucleus of a cell where genetic information is stored.

middle income countries

The World Bank classifies countries according to their income: low, lower-middle, upper-middle and high. There are around 50 lower-middle income countries (mostly in Africa and Asia) and around 60 upper-middle income countries (in Africa, Eastern Europe, Asia, Latin America and the Caribbean).

low income countries

The World Bank classifies countries according to their income: low, lower-middle, upper-middle and high. While the majority of the approximately 30 countries that are ranked as low income are in sub-Saharan Africa, many African countries including Kenya, Nigeria, South Africa and Zambia are in the middle-income brackets. 

The PROMISE study was a large international study conducted in 14 low- and middle-income countries, investigating the effectiveness of maternal antiretroviral therapy in preventing HIV transmission and its impact on maternal health. The study recruited women with CD4 cell counts above 350 cells/mm3 and randomised participants at three time-points: before delivery, after delivery during the breastfeeding period (postpartum), or after breastfeeding was discontinued.

In the postpartum randomisation, 2431 mother-infant pairs were randomised to either maternal antiretroviral therapy or infant prophylaxis with nevirapine during the breastfeeding period, beginning 6-14 days after delivery. All infants in the antiretroviral therapy arm also received daily nevirapine prophylaxis for six weeks after delivery, as recommended in World Health Organization guidelines. Mothers randomised to the infant prophylaxis arm were offered antiretroviral therapy after the results of the START study were announced in 2015.

Maternal viral load was tested at study entry and at weeks 6, 14, 26 and 50 weeks postpartum. Infant specimens for nucleic acid testing were collected at study entry, week 6 and every four weeks subsequently to detect HIV DNA. (HIV diagnosis in infants must be established by testing for HIV DNA as infant antibodies do not appear until around 18 months of age.) Infants were classified as infected with HIV if they had two positive nucleic acid test results.

Seven infants in the antiretroviral therapy arm and seven infants in the infant prophylaxis arm tested positive for HIV DNA in the primary analysis, which covered the period up to 56 days after the end of the breastfeeding period or 18 months postpartum, whichever came first.

These data were reported previously in a 2018 publication of the study findings in the Journal of Acquired Immune Deficiency Syndromes. (A secondary analysis, which included all infections reported up to 24 months postpartum, reported eight infections in mother-infant pairs randomised to antiretroviral therapy.)

New data from the study, presented in Amsterdam, show that two infants tested positive for HIV DNA either at the same time as their mothers had an undetectable viral load or viral load < 40 copies/ml, or shortly afterwards.

In one case, an infant tested positive for HIV DNA at a week 14 postpartum visit while its mother had an undetectable viral load. However, at the preceding baseline and week 6 visits, the mother had a detectable viral load above 40 copies/ml but below 1000 copies/ml.

In the second case, an infant tested positive for HIV DNA at around week 36 postpartum and the positive status was confirmed at another visit shortly afterwards (unspecified interval) and again at week 50. The infant’s mother had an undetectable viral load at weeks 14, 26 and at each of the visits at which the infant tested positive for HIV DNA.

There are several possible explanations for these cases. One possibility is that even when HIV is undetectable in blood, it may still be transmitted in breast milk through cell-associated virus. The volume of breast milk consumed during the breastfeeding period and the amount of potentially infected cells in breast milk mean that the risk differs from sexual transmission and may be much higher, despite undetectable viral load in blood.

Another possibility is that, in the first case, viral suppression was too slow to prevent HIV transmission, and that infection had taken place at some point after week 6 when viral load might still have been detectable. If that were the case, it suggests that HIV transmission through breast milk might occur when viral load measured in blood is below 1000 copies/ml.

In the second case, poor adherence might explain transmission, but it is hard to see how viral load could have rebounded after week 26 but returned to undetectable levels by week 36.

Taken together, these cases of transmission suggest that undetectable does not mean untransmittable in the case of breastfeeding.

References

Flynn PM et al. Association of maternal viral load and the CD4 count with perinatal HIV-1 transmission risk during breastfeeding in the PROMISE postpartum component. 22nd International AIDS Conference, Amsterdam, abstract THPEB115. (download poster).

Flynn PM et al. Prevention of HIV-1 transmission through breastfeeding: efficacy and safety of maternal antiretroviral therapy versus infant nevirapine prophylaxis for duration of breastfeeding in HIV-1-infected women with high CD4 count (IMPAACT PROMISE): a randomised, open-label, clinical trial. J Acquir Immune Defic Syndr, 77(4): 383-392, 2018.