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My Take on Optimizing ART for Conception and Pregnancy

Brian Wood, MD

Associate Professor of Medicine
Division of Allergy and Infectious Diseases
University of Washington
Seattle, Washington

Brian Wood, MD, has no relevant conflicts of interest to report.

View ClinicalThoughts from this Author

Released: April 20, 2020

Guideline recommendations on preferred ART around the time of conception and during pregnancy have shifted multiple times during the past 2 years. As new data emerge and guidance evolves, which ART regimens should clinicians recommend to cisgender women and other persons living with HIV (PWH) who are trying to conceive or are pregnant?

ART at Conception
Prior to 2018, dolutegravir (DTG) had become the go-to anchor ARV for PWH trying to conceive. Then, an unplanned interim analysis from the Tsepamo birth surveillance study in Botswana raised serious concerns: DTG-based ART at time of conception was associated with a higher rate of infant neural tube defects (NTDs) compared with non–DTG-based ART, mostly incorporating efavirenz (EFV). This first analysis observed an NTD prevalence of 0.94% with DTG-containing regimens vs 0.12% with other ART regimens, prompting regulatory agencies to issue adverse event warnings for DTG. However, a 2019 update of the Tsepamo study reported an NTD prevalence of 0.30% with DTG vs 0.10% with other ART regimens at time of conception, corresponding to 3 NTDs per 1000 deliveries vs 1 NTD per 1000 deliveries, respectively. Furthermore, these findings may not be generalizable because Botswana does not fortify food with folate, and folate supplementation at the time of conception was rare in study participants. Data from countries that fortify food with folate are scant but reassuring, suggesting the possibility that the risk of NTDs with DTG may not be elevated in populations receiving folate supplementation. More data are needed to evaluate this hypothesis.

These updated results, combined with advocacy from PWH, led the WHO to continue recommending DTG in first-line and second-line ART, including for those of childbearing potential. In December 2019, the DHHS updated its guidelines to list DTG as a preferred option for PWH of childbearing potential who are using effective contraception and as an alternative option for PWH of childbearing potential not using effective contraception or PWH actively trying to conceive, with counseling on the risks and benefits. I would emphasize the importance of folate supplementation for PWH who may conceive. Recommended options for PWH who may conceive now include raltegravir (RAL) or a boosted PI, such as ritonavir-boosted atazanavir or ritonavir-boosted darunavir, plus 2 recommended NRTIs. There are insufficient data for tenofovir alafenamide (TAF) and for bictegravir at this time. In my practice, I most frequently recommend DTG or RAL plus emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) in this setting, with careful counseling about potential risks and benefits of various options.

ART in Pregnancy
What is the preferred ART regimen during pregnancy? DHHS perinatal guidelines have swung back to recommending DTG, RAL (BID option rather than QD high-dose option), or a boosted PI plus 2 NRTIs during all trimesters of pregnancy; similar to preconception ART, the NRTI combination is generally FTC/TDF rather than TAF based. There are important recommendations on ART to avoid during pregnancy, such as cobicistat-containing regimens, due to decreased plasma concentrations in pregnancy.

Recommendations regarding TAF may evolve as safety data accumulate. At CROI 2020, investigators presented results from the randomized phase III IMPAACT 2010 noninferiority trial comparing DTG plus FTC/TAF vs DTG plus FTC/TDF vs EFV/FTC/TDF in 643 ART-naive pregnant women initiated during gestational weeks 14-28. Of note, DTG-based ART demonstrated a statistically superior rate of virologic suppression at delivery (97.5% vs 91.0% with EFV/FTC/TDF; P = .005) as well as significantly shorter time to virologic suppression (P < .001). There were also significantly fewer adverse pregnancy outcomes with DTG plus FTC/TAF compared with the other 2 arms, and significantly fewer neonatal deaths with DTG plus FTC/TAF compared with EFV/FTC/TDF (all P < .05). Weight gain during pregnancy was significantly higher in the TAF-containing arm compared with the other 2 arms (both P < .05), but absolute differences were small and the clinical significance is unknown. I hope to see data for TAF in the first trimester of pregnancy in the near future as well as updated guidelines about considerations for TAF later in pregnancy.

Final Thoughts
Clinicians should follow guidelines for updates, understanding that optimal ART at conception and during pregnancy is a moving target. Furthermore, all PWH of childbearing potential should be asked about their plans for contraception and conception as a part of their routine care.

Join the Discussion
How are you prescribing DTG in PWH of childbearing potential? Are there situations in which you would recommend DTG for a patient not using effective contraception given that it is listed as an alternative option for this group in the DHHS guidelines? Please discuss your experiences in the comments section.

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