Pregnant women taking dolutegravir were significantly more likely to have a fully suppressed viral load at the time of delivery compared to women taking atazanavir/ritonavir or raltegravir, researchers in the United States report in the New England Journal of Medicine.
The researchers say that their findings support the use of dolutegravir in preference to atazanavir/ritonavir or raltegravir during pregnancy, with darunavir/ritonavir as an alternative where dolutegravir use is not feasible.
Several clinical trials have shown that dolutegravir treatment leads to superior viral suppression at the time of delivery - which minimises the risk of vertical HIV transmission - compared to efavirenz or to atazanavir/ritonavir. However, current guidelines for the use of antiretrovirals during pregnancy vary, partly due to the date they were last revised.
Uncertainty about the risk of neural tube defects associated with dolutegravir led some guidelines writing groups to be more cautious about the use of dolutegravir. Research presented at international conferences in 2020 and 2022 found no increased risk of neural tube defects in infants exposed to dolutegravir around the time of conception.
Current recommendations include:
- United Kingdom: Use efavirenz or atazanavir/ritonavir in preference to darunavir/ritonavir, rilpivirine or raltegravir. Dolutegravir may be considered as an alternative after six weeks of gestation. (2020)
- United States: Dolutegravir, raltegravir, darunavir/ritonavir or atazanavir/ritonavir are all preferred options if starting treatment during pregnancy. (2021)
- European AIDS Clinical Society: Use dolutegravir or raltegravir in preference to a boosted protease inhibitor, rilpivirine or efavirenz (2021)
- World Health Organization: As for all other people, dolutegravir is recommended during pregnancy (2021)
Dr Kunjal Patel of Harvard University and colleagues looked at viral suppression at the time of delivery in women with HIV who were already taking antiretroviral treatment at conception or started treatment during pregnancy, in the Pediatric HIV/AIDS Cohort Study, between 2007 and the end of 2019. They added data from the Swiss HIV Cohort in order to improve the precision of the analysis. They also assessed the incidence of pre-term birth and other adverse birth outcomes.
Data were available on 1257 pregnancies with observed birth outcomes. Of these, 120 were in participants who received dolutegravir, 464 in recipients of atazanavir/ritonavir, 185 in recipients of darunavir/ritonavir, 243 in recipients of rilpivirine, 86 in recipients of raltegravir and 153 in recipients of elvitegravir/cobicistat treatment.
Tenofovir disoproxil fumarate/emtricitabine was the nucleoside backbone for the vast majority of those taking atazanavir/ritonavir, darunavir/ritonavir, rilpivirine and raltegravir and in 32% of those taking dolutegravir. Abacavir/lamivudine was the backbone for 51% of those taking dolutegravir, while tenofovir alafenamide/emtricitabine was the backbone for 48% of those taking elvitegravir/cobicistat.
The majority of participants were non-Hispanic Black (66%).
Viral suppression at delivery differed substantially by treatment regimen. Whereas 96% of women taking dolutegravir had an undetectable viral load at the time of delivery, the percentage of women who were virally suppressed was lower for other regimens (atazanavir/ritonavir 84%, darunavir/ritonavir 90%, raltegravir 89%, elvitegravir/cobicistat 90%, rilpivirine 97%).
Analysis of the risk difference, adjusted for demographic factors, HIV care during pregnancy, substance use during pregnancy and sexually transmitted infections during pregnancy, showed that the difference in viral suppression between dolutegravir and each of atazanavir/ritonavir, raltegravir and elvitegravir/cobicistat was statistically significant.
The difference in viral suppression at delivery between dolutegravir and protease inhibitor-based regimens was especially marked in women who started antiretroviral treatment during pregnancy (atazanavir/ritonavir -21%, darunavir/ritonavir -14% versus dolutegravir). All other agents also showed inferior viral suppression compared to dolutegravir when treatment started in pregnancy, and this difference was statistically significant in each case.
When data from the Swiss HIV Cohort were included in the analysis, adding 170 pregnancies, there was no change in the results.
Although there was a clear trend towards a lower risk of adverse birth outcomes in women who were not taking dolutegravir, (preterm birth, low birth weight, being small for gestational age or neonatal death within 14 days of delivery), the difference between dolutegravir and any other agent was not statistically significant.
However, when the analysis was restricted to women who started treatment during pregnancy, starting treatment with dolutegravir, raltegravir, elvitegravir or rilpivirine was associated with a higher risk of an adverse birth outcome. Noting that previous studies have shown associations between use of specific drugs at conception and adverse birth outcomes, the study investigators say that “the association between the timing of ART initiation and the risk of adverse birth outcomes may differ according to specific ART.” Again, when data from the Swiss HIV Cohort were included in the analysis, adding 170 pregnancies, there was no change in the results.
The safety and efficacy of new antiretroviral agents in pregnancy should be evaluated in comparison with dolutegravir, they conclude.The study investigators say that US guidelines relied on data from small pharmacokinetic studies and voluntary reporting of pregnancy outcomes to the Antiretroviral Pregnancy Registry. They argue that their prospective study findings should be taken into account when updating guidelines or considering what to prescribe.
Patel K et al. Dolutegravir in pregnancy as compared to current HIV regimens in the United States. New England Journal of Medicine, 387: 799-809, 2022.