Dolutegravir may be more effective in pregnant women starting HIV treatment late
When starting treatment in the third trimester, pregnant women taking dolutegravir are more likely to achieve undetectable viral loads at the time of giving birth compared with those taking efavirenz.
A trial involving pregnant women with untreated HIV in South Africa and Uganda found dolutegravir- (DTG) based antiretroviral therapy (ART) was associated with higher rates of viral load reduction compared with efavirenz- (EFV) based regimes, when treatment was started late in pregnancy.
Delayed initiation of ART in pregnancy is linked to an increased risk of mother-to-child transmission and infant mortality, and is common in many settings with a high HIV prevalence. Although the causes of this are many, one factor put forward by the study may be that conventional EFV-based ART regimes do not work fast enough to suppress a mother’s viral load in the later stages of pregnancy and at birth, when transmission risk is highest.
Newer, DTG-based regimes are associated with faster declines in HIV viral load in non-pregnant adults and are less susceptible to drug resistance. However, less is known about the safety and efficacy of this type of treatment in pregnancy, particularly when initiated in late pregnancy.
In this study, known as DolPHIN-2, investigators sought to understand the benefits of providing DTG for women starting ART in the third trimester. Pregnant women (n=269) were randomly assigned to receive either treatment – 135 on DTG-based and 133 on efavirenz-based regimes between January and August 2018. The women were all over 18 years with untreated but confirmed HIV, in their third trimester of pregnancy and starting ART for the first time.
Participants’ viral loads were measured at 7 days and 28 days after ART initiation, at 36 weeks’ gestation and at a post-partum visit 0-14 days after birth. Women on DTG-based therapy were more likely to achieve undetectable viral loads at the time of birth compared with those taking EFV-based regimes when initiated in the third trimester. In total, 89 (74%) of 120 women in the DTG group had viral loads of less than 50 copies per mL, compared with 50 (43%) of 117 in efavirenz group at birth.
In total, three infant HIV infections were detected, all in the DTG group. These were likely to be in-utero transmissions based on the early PCR-positivity of the infants, and the low viral loads of their mothers at birth. However as the infants were not tested within two days of birth, peripartum transmission could not be excluded.
The findings support the revision to WHO guidelines in 2019 recommending DTG as the preferred first- and second-line HIV treatment for all populations, including pregnant women, in lower- and middle-income countries. Safety concerns had previously been raised about the use of DTG in women of childbearing age after it was linked to neural tube defects in infants, but later evidence found this link was much smaller than initially suggested.
Although both types of treatment were generally well tolerated by participants, more mothers reported serious adverse events in the DTG group (22%) than in the efavirenz group (11%). However, the study notes this incidence is similar to previous large randomised trials in non-pregnant adults. Congenital disorders did not differ between groups, and no neural tube defects were reported.
The study addresses an important knowledge gap around mother-to-child transmission of HIV in women initiating treatment late in pregnancy, and the results can be taken to support the global transition to DTG use in first-line ART. Longer-term follow-up is currently underway to detect transmissions during breastfeeding.