Dolutegravir: A better choice for HIV viral suppression in pregnancy?

Among pregnant individuals on antiretroviral therapy (ART) for HIV-1 infection, those on dolutegravir had the greatest viral suppression rates at delivery, a recent US-based observational study showed. However, birth outcomes generally did not differ between dolutegravir recipients and those on various other ART regimens.

Participants were pregnant individuals (median age at conception 29 years) with HIV-1 infection enrolled in the Pediatric HIV/AIDS Cohort Study whose initial ART regimen in pregnancy (initiated before conception or during pregnancy) was dolutegravir (n=120), atazanavir–ritonavir (n=464), darunavir–ritonavir (n=185), oral rilpivirine (n=243), raltegravir (n=86), or elvitegravir–cobicistat (n=159) in combination with other regimens (abacavir–lamivudine, tenofovir disoproxil fumarate [TDF]–emtricitabine, TDF–lamivudine, or tenofovir alafenamide fumarate–emtricitabine). Fifty-one percent of pregnancies occurred in participants who were already on ART pre-conception.

At delivery, viral suppression (<200 copies/mL) was highest in patients on dolutegravir (96.7 percent), with lower levels observed in patients on atazanavir–ritonavir (84.0 percent; adjusted risk difference [ARD] vs dolutegravir, −13.0 percentage points), raltegravir (89.2 percent; ARD, −17.0 percentage points), and elvitegravir–cobicistat (89.8 percent; ARD, −7.0 percentage points). [N Engl J Med 2022;387:799-809]

“We think the observed differences are due to dolutegravir’s ability to rapidly decrease viral loads and its ease of use as part of a once-daily regimen that’s available as a fixed-dose combination,” said lead author Dr Kunjal Patel, senior research scientist at the Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, US.

The similar viral suppression rates at delivery between darunavir–ritonavir and dolutegravir suggest it may be a potential alternative to dolutegravir, the authors said. Viral suppression was also similar between patients on oral rilpivirine and dolutegravir (96.8 percent vs 96.3 percent)*.

Among patients already on ART at conception, viral suppression at delivery was higher with rilpivirine vs dolutegravir (risk difference, 7.3 percentage points) and lower with raltegravir vs dolutegravir (risk difference, –10.0 percentage points). Among those who initiated ART during pregnancy, viral suppression at delivery was lower among those on atazanavir–ritonavir (risk difference, –21.2 percentage points), darunavir–ritonavir (risk difference, –14.0 percentage points), rilpivirine (risk difference, –7.5 percentage points), raltegravir (risk difference, –7.4 percentage points), and elvitegravir–cobicistat (risk difference, –14.2 percentage points) vs dolutegravir.

The risk of preterm birth (<37 weeks gestation) ranged from 13.6–17.6 percent, low birth weight (LBW; <2,500 g) from 11.9–16.7 percent, and being born small for gestational age (SGA; <10^th percentile) from 9.1–12.5 percent across the treatment strategies. The risk of preterm birth was generally lower with the non–dolutegravir-based regimens vs dolutegravir, though with large variations observed. There were no significant differences observed between dolutegravir and non–dolutegravir-based regimens for other adverse birth outcomes, though sample sizes were small.  

The risk of the composite of any adverse birth outcome ranged from 22.6–27.9 percent and any severe adverse birth outcome from 0–4.2 percent across treatment regimens. Overall, there were 20 very preterm births (<32 weeks gestation), with 15 being born with very LBW (<1,500 g). There were no neonatal deaths within 14 days of birth. Three major congenital abnormalities occurred among patients who were on dolutegravir at conception or during the first trimester. Perinatal HIV transmission was documented in two pregnancies in the atazanavir–ritonavir group and one each in the elvitegravir–cobicistat and rilpivirine groups.

“We observed that among pregnancies in participants who took dolutegravir, oral rilpivirine, raltegravir, or elvitegravir–cobicistat, initiation of ART during pregnancy was associated with a higher risk of any adverse birth outcome than initiation of ART before pregnancy,” the authors noted, suggesting that the association between timing of ART initiation and adverse birth outcome risk may be regimen-dependent.

“Globally, a dolutegravir-based regimen is currently recommended for treating HIV, and this is the first study to directly compare regimens including dolutegravir to other antiretroviral regimens, such as raltegravir-based regimens, that are also listed as ‘Preferred’ in US perinatal guidelines,” remarked Patel.

“Our results highlight the continual need for systematic studies that compare new antiretroviral regimens with those already in clinical practice to help inform the evolution of guidelines and clinical practice over time,” she added.   

Among the limitations were the lack of information on pre-pregnancy BMI and previous history of preterm birth in the participants, both of which could have affected the outcomes.