ABSTRACT For those pregnant and positive for the HIV infection, the first-line antiretroviral therapy (ART) is a dolutegravir-based regimen. This regimen is more effective among nonpregnant adults when compared with other types of ART (it has a high barrier of resistance and fewer drug interactions than other types and is less likely to be discontinued due to adverse effects). Whereas the effectiveness, efficacy, and safety of dolutegravir in pregnancy have been compared with efavirenz in randomized trials, data comparing dolutegravir to protease inhibitor–based, integrase strand-transform inhibitor (INSTI)–based, and nonnucleoside reverse transcriptase inhibitor (NNRTI)–based ART regimens commonly used in pregnancy within the United States are limited. Since April 2007, some 22 sites in the United States and Puerto Rico enrolled HIV-infected pregnant persons and their infants within 72 hours following birth into the SMARTT Dynamic cohort. The current analysis entailed using the Pediatric HIV/AIDS Cohort Study SMARTT (Surveillance and Monitoring for ART Toxicities) protocol for evaluation of participants enrolled in the SMARTT Dynamic cohort through January 1, 2020, whose initial ART in pregnancy included oral rilpivirine, atazanavir-ritonavir, darunavir-ritonavir, raltegravir, and elvitegravir-cobicistat, in combination with dolutegravir, abacavir-lamivudine, tenofovir disoproxil fumarate–emtricitabine, tenofovir disoproxil fumarate–lamivudine, or tenofovir alafenamide fumarate–emtricitabine. Definition of the initial ART was the first ART regimen recorded in pregnancy, whether initiated before conception or during pregnancy. Outcomes included viral suppression at delivery, low birth weight and very low birth weight (<2500 and <1500 g), preterm and very preterm birth (at <37 and <32 weeks' gestation, respectively), small for gestational age (SGA), and neonatal death within 14 days after birth. Composite outcomes evaluated included any adverse birth outcome and any severe adverse birth outcome. The authors evaluated viral suppression at delivery, along with adverse birth outcomes in persons with an initial treatment regimen of dolutegravir for HIV infection when compared with those whose initial regimen included other contemporary ART drugs commonly prescribed in the Europe and the United States. In those participants who received dolutegravir, viral suppression was present at delivery in 96.7%; corresponding rates were 84.0% for atazanavir-ritonavir, 89.2% for raltegravir, and 89.8% for elvitegravir-cobicistat (adjusted risk differences vs dolutegravir were −13.0 percentage points [95% confidence interval {CI}, −17.0 to −6.1], −17.0 percentage points [95% CI, −27.0 to −2.4], and −7.0 percentage points [95% CI, −13.3 to −0.0], respectively). The observed risks of preterm birth were 13.6% to 17.6%. Adjusted risks of infants being born preterm, having low birth weight, or being SGA did not differ substantially between dolutegravir and other, non–dolutegravir-based ART. Although these contribute important information to the literature, the study has some limitations. There was limited information on some preterm birth variables, such as important predictors of low birth weight and preterm birth (ie, previous preterm birth, parity, and prepregnancy body mass index). Furthermore, the analysis involved participants from a large multisite cohort study, but samples of participants receiving INSTIs were small, thereby limiting both the ability to detect small differences in adverse birth outcomes and the ability to conduct stratified analyses in accordance to ART initiation timing. The authors of the study note that their results provide evidence suggesting lower levels of effectiveness in suppression at delivery using atazanavir-ritonavir and raltegravir than dolutegravir. Therefore, they suggest that darunavir-ritonavir is a reasonable alternative when dolutegravir use is not feasible.