Zero transmission in France for mothers on ART from conception with undetectable viral load at delivery

1 February 2023. Related: Pregnancy.

Polly Clayden, HIV i-Base

In France – a setting with free access to ART, monthly viral load testing, infant ART prophylaxis, and formula feeding – suppressive ART, started before pregnancy, reduced vertical HIV transmission to almost zero.

These findings were reported ahead of print in Clinical Infectious Diseases, August 2022.

The analysis included 14,630 women living with HIV, delivering from 2000 to 2017 at facilities participating in the national prospective French Perinatal Cohort (ANRS-EPF). At least 95% of pregnant women at each participating centre are included in this cohort (exclusions are those less than 18 years and voluntary).

Vertical transmission was analysed according to time period, timing of ART initiation, maternal viral load and gestational age at birth. No infants were breastfed and all received neonatal prophylaxis.

Women in the last time period (2011–2017) were older, more often from sub-Saharan Africa, and less likely to be diagnosed with HIV during the current pregnancy than women enrolled during 2000–2010.

The proportion of women receiving ART at conception increased: from 28.3% (1434/5067) in 2000–2005 to 46.3% (2055/4441) in 2006–2010 and to 65.8% (3117/4738) in 2011–2017, p<0.001.

Transmission rates dropped steadily over the three time periods: from 1.1% in 2000–2005 (58/5123), to 0.7% in 2006–2010 (30/4600) and 0.2% in 2011–2017 (10/4907), p<0.001.

When the analysis was restricted to the 6316/14,630 (43%) women on ART at conception, transmission decreased from 0.42% (6/1434) in 2000–2005 to 0.03% (1/3117) in 2011–2017, p=0.007.

For women on ART at conception, if maternal viral load was undetectable near delivery, there were no transmissions whatever the ART regimen (95% CI 0 to 0.07; 0/5482). See Table 1.

For those starting ART during pregnancy and with undetectable viral load near delivery, transmission was 0.57% (95% CI 0.37 to 0.83; 26/4596).

And for women treated at conception but with detectable viral load near delivery, transmission was 1.08% (95% CI 0.49 to 2.04; 9/834).

Irrespective when ART was started, the transmission rate was higher with severe preterm birth (<32 weeks’ gestation) 2.06% (95% CI, 0.83 to 4.21; 7/339) than moderate preterm (32–36 weeks’ gestation) 1.34% (95% CI, 0.86 to 1.98; 24/1796) than in term births 0.54% (95% CI 42 to 0.68; 67/12 465), p< 0.001.

The authors noted that this association was not found in the last period. And it was reduced although still significant when the analysis was restricted to women on ART at conception, across the three time periods.

There were 10 cases of vertical transmission 2011–2017.

• Only one woman was on ART at conception. She had herself been perinatally infected at birth but was poorly adherent to ART and her viral load was >400 copies/mL during pregnancy.
• One woman received no ART during pregnancy because of difficulties in antenatal care.
• The remaining women started ART during pregnancy. In two cases this was very late (>37 weeks’ gestation) and the other five women started ART between 9 and 22 weeks’ gestation. Two did not achieve viral suppression. There was only one transmission with an undetectable viral load at delivery. No breastfeeding was reported.

The authors commented that the main finding from this study was confirmation of zero HIV transmission among women who start ART before conception and have an undetectable viral load at delivery, with formula feeding and routine neonatal prophylaxis.

They also suggested that preconception maternal ART and undetectable viral load at delivery may mitigate the effect of preterm birth on vertical transmission.

Table 1: Risk of transmission by timing of ART and VL near delivery (2000–2017)

comment

The overall vertical transmission rate during the most recent period in this cohort was extremely low (0.2%). The authors noted that this is lower than recently reported in other high-income countries, which range from 0.46% to 1.6%.

In the UK and Ireland, the steady decline across time periods is similar to these results.

As guidelines in high-income countries become more permissive about breastfeeding among women who fulfil other criteria associated with no transmission – mainly early ART start, undetectable viral load with regular monitoring – it will be important to see whether these results remain similar.   

Reference

Sibiude J et al. Update of Perinatal HIV-1 Transmission in France: zero transmission for 5482 mothers on continuous ART from conception and with undetectable viral load at delivery. Clin Infect Dis. August 2022. Online ahead of print.
https://academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciac703/6678600