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Comparative Study
. 2022 Sep 1;387(9):799-809.
doi: 10.1056/NEJMoa2200600.

Dolutegravir in Pregnancy as Compared with Current HIV Regimens in the United States

Kunjal Patel  1 , Yanling Huo  1 , Jennifer Jao  1 , Kathleen M Powis  1 , Paige L Williams  1 , Deborah Kacanek  1 , Lynn M Yee  1 , Ellen G Chadwick  1 , Stephanie Shiau  1 , Denise L Jacobson  1 , Sean S Brummel  1 , Leila Sultan-Beyer  1 , Christian R Kahlert  1 , Rebecca Zash  1 , George R Seage 3rd  1 ; Pediatric HIV/AIDS Cohort Study; Swiss Mother and Child HIV Cohort Study
Collaborators, Affiliations
Comparative Study

Dolutegravir in Pregnancy as Compared with Current HIV Regimens in the United States

Kunjal Patel et al. N Engl J Med. .

Abstract

Background: Data on the effectiveness and safety of dolutegravir-based antiretroviral therapy (ART) for human immunodeficiency virus type 1 (HIV-1) infection in pregnancy as compared with other ART regimens commonly used in the United States and Europe, particularly when initiated before conception, are limited.

Methods: We conducted a study involving pregnancies in persons with HIV-1 infection in the Pediatric HIV/AIDS Cohort Study whose initial ART in pregnancy included dolutegravir, atazanavir-ritonavir, darunavir-ritonavir, oral rilpivirine, raltegravir, or elvitegravir-cobicistat. Viral suppression at delivery and the risks of infants being born preterm, having low birth weight, and being small for gestational age were compared between each non-dolutegravir-based ART regimen and dolutegravir-based ART. Supplementary analyses that included participants in the Swiss Mother and Child HIV Cohort Study were conducted to improve the precision of our results.

Results: Of the pregnancies in the study, 120 were in participants who received dolutegravir, 464 in those who received atazanavir-ritonavir, 185 in those who received darunavir-ritonavir, 243 in those who received rilpivirine, 86 in those who received raltegravir, and 159 in those who received elvitegravir-cobicistat. The median age at conception was 29 years; 51% of the pregnancies were in participants who started ART before conception. Viral suppression was present at delivery in 96.7% of the pregnancies in participants who received dolutegravir; corresponding percentages were 84.0% for atazanavir-ritonavir, 89.2% for raltegravir, and 89.8% for elvitegravir-cobicistat (adjusted risk differences vs. dolutegravir, -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 small for gestational age did not differ substantially between non-dolutegravir-based ART and dolutegravir. Results of supplementary analyses were similar.

Conclusions: Atazanavir-ritonavir and raltegravir were associated with less frequent viral suppression at delivery than dolutegravir. No clear differences in adverse birth outcomes were observed with dolutegravir-based ART as compared with non-dolutegravir-based ART, although samples were small. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others.).

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Figures

Figure 1.
Figure 1.. Selection of the Study Population.
The analysis of rilpivirine (RPV) as compared with dolutegravir (DTG) included only pregnancies in which the earliest human immunodeficiency virus (HIV) viral load was no greater than 100,000 copies per milliliter and the earliest CD4 cell count was at least 200 cells per cubic millimeter. 3TC denotes lamivudine, ABC abacavir, ART antiretroviral therapy, ATV/r atazanavir–ritonavir, DRV/r darunavir–ritonavir, EVG/c elvitegravir–cobicistat, FTC emtricitabine, RAL raltegravir, TAF tenofovir alafenamide fumarate, and TDF tenofovir disoproxil fumarate.
Figure 2.
Figure 2.. Differences as Compared with Dolutegravir in the Probability of Viral Suppression.
Differences above the dashed reference line indicate a lower probability of viral suppression at delivery (i.e., a viral load of <200 copies per milliliter) with dolutegravirbased ART, and differences below the dashed reference line indicate a higher probability of viral suppression at delivery with dolutegravir-based ART. I bars indicate the 95% confidence interval.
Figure 3.
Figure 3.. Differences as Compared with Dolutegravir in the Risks of Adverse Birth Outcomes.
Differences above the dashed reference line indicate a lower risk with dolutegravir-based ART, and differences below the dashed reference line indicate a higher risk with dolutegravir-based ART. Preterm birth was defined as birth before 37 weeks’ gestation. Low birth weight was defined as a birth weight of less than 2500 g. Small for gestational age was defined as a birth weight below the 10th percentile for gestational age. An adverse birth outcome was defined as preterm birth, low birth weight, status of being small for gestational age, or neonatal death within 14 days after delivery. I bars indicate the 95% confidence interval.
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References

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