Recommendations for the Use of Antiretroviral Drugs in Pregnant Women with HIV Infection and Interventions to Reduce Perinatal HIV Transmission in the United States

The information in the brief version is excerpted directly from the full-text guidelines. The brief version is a compilation of the tables and boxed recommendations.

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Nucleoside and Nucleotide Analogue Reverse Transcriptase Inhibitors

Tenofovir Alafenamide (Vemlidy, TAF)

Last Updated: December 7, 2018; Last Reviewed: December 7, 2018

Tenofovir alafenamide (TAF) is an orally bioavailable form of tenofovir. Data on its use in human pregnancy is insufficient to inform a drug-associated risk determination for birth defects or miscarriage.

Animal Studies

Carcinogenicity
Because TAF is rapidly converted to tenofovir, and tenofovir exposure in rats and mice is lower after TAF administration than after tenofovir disoproxil fumarate (TDF) administration, carcinogenicity studies were performed with TDF. Long-term oral carcinogenicity studies of tenofovir in mice and rats were carried out at 167 times (mice) and 55 times (rats) tenofovir exposure than that seen after TAF administration at recommended doses in humans. In female mice, liver adenomas were increased. In rats, no carcinogenic findings were observed.1,2

Reproduction/Fertility
Reproduction studies have been performed in rats and rabbits at TAF exposures similar to and 53 times higher than human exposure, respectively, and revealed no evidence of impaired fertility or mating performance associated with TAF administration.1-3

Teratogenicity/Adverse Pregnancy Outcomes
No effects on early embryonic development were seen when TAF was administered to male or female rats at 62 times the human therapeutic exposure.1-3

Placental and Breast Milk Passage
Rat studies demonstrated secretion of tenofovir in breast milk after administration of TDF; whether TAF is present in animal milk is unknown.1,3

Human Studies in Pregnancy

Pharmacokinetics
Pharmacokinetics (PKs) of TAF have been reported in 31 women taking TAF 25 mg without any pharmaco-enhancer, and in 27 women taking TAF 10 mg boosted with cobicistat 150 mg.4 This study evaluated plasma TAF exposures with and without boosting in pregnant and postpartum women relative to those in non-pregnant adults. No significant differences in PKs were seen between pregnant and postpartum women taking boosted TAF. Among women taking unboosted TAF, the significantly different plasma exposures during pregnancy and postpartum were driven by higher exposures postpartum.

Placental and Breast Milk Passage
TAF was below the assay limit of quantification (<3.9 ng/mL) in 15 of 15 cord blood samples tested.4 Maternal plasma TAF at delivery was measurable in 2 of the 15 paired samples.

Teratogenicity/Adverse Pregnancy Outcomes
In the Antiretroviral Pregnancy Registry, the number of reported cases of TAF exposures is insufficient to draw any conclusions about risk of birth defects.5

Excerpt from Table 10a

Note: When using FDCs, refer to other sections in Appendix B and Table 10 for information about the dosing and safety of individual drug components of the FDC during pregnancy.

Generic Name
(Abbreviation)
Trade Name
Formulation Dosing Recommendations Use in Pregnancy
Tenofovir Alafenamide
(TAF)
Vemlidy

(TAF/BIC/FTC)
Biktarvy

(TAF/FTC)
Descovy

(TAF/EVG/COBI/FTC)
Genvoya

(TAF/FTC/RPV)
Odefsey

(TAF/DRV/COBI/FTC)
Symtuza

Note: Generic available for some formulations.
TAF (Vemlidy)d
Tablet:
  • 25 mg
TAF/BIC/FTC (Biktarvy):
  • TAF 25 mg plus BIC 50 mg plus FTC 200 mg tablet
TAF/FTC (Descovy):
  • TAF 25 mg plus FTC 200 mg tablet
TAF/EVG/COBI/FTC (Genvoya):
  • TAF 10 mg plus EVG 150 mg plus COBI 150 mg plus FTC 200 mg tablet
TAF/FTC/RPV (Odefsey):
  • TAF 25 mg plus FTC 200 mg plus RPV 25 mg tablet
TAF/DRV/COBI/FTC (Symtuza):
  • TAF 10 mg plus DRV 800 mg plus COBI 150 mg plus FTC 200 mg tablet
Standard Adult Dose
TAF (Vemlidy):
  • 1 tablet once daily with food
TAF/BIC/FTC (Biktarvy):
  • 1 tablet once daily with or without food
TAF/FTC (Descovy):
  • 1 tablet once daily with or without food
  • Same dose (TAF 25 mg) can be used with or without pharmaco-enhancers.
TAF/EVG/COBI/FTC (Genvoya):
  • 1 tablet once daily with food
TAF/FTC/RPV (Odefsey):
  • 1 tablet once daily with food
TAF/DRV/COBI/FTC (Symtuza):
  • 1 tablet once daily with food
PK in Pregnancy:
  • Plasma PK not significantly altered in pregnancy.
Dosing in Pregnancy:
  • No change in dose indicated.
  • For guidance about use of combination products in pregnancy, please see the specific sections on other components (i.e., BIC, COBI. DRV, EVG, FTC, RPV).
Low placental transfer to fetus.b

Insufficient data to assess for teratogenicity in humans. No evidence of teratogenicity in rats.

Renal function should be monitored because of potential for renal toxicity.
a Individual ARV drug doses may need to be adjusted in patients with renal or hepatic insufficiency (for details, see the Adult and Adolescent Guidelines Appendix B, Table 8).
b Placental transfer categories are determined by mean or median cord blood/maternal delivery plasma drug ratio:
          High: >0.6
          Moderate: 0.3–0.6
          Low: <0.3
d Generic formulation available

Key to Acronyms: COBI = cobicistat; BIC = bictegravir; DRV = darunavir; EVG = elvitegravir; FDC = fixed-dose combination; FTC = emtricitabine; PK = pharmacokinetic; RPV = rilpivirine; TAF = tenofovir alafenamide

References

  1. Emtricitabine/rilpivirine/tenofovir alafenamide (Odefsey) [package insert]. Food and Drug Administration. 2016. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208351s000lbl.pdf.
  2. Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (Genvoya) [package insert]. Food and Drug Administration. 2016. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207561s003lbl.pdf
  3. Emtricitabine/tenofovir alafenamide (Descovy) [package insert]. Food and Drug Administration. 2016. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208215s000lbl.pdf.
  4. Momper J, Best B, Wang J, et al. Tenofovir alafenamide pharmacokinetics with and without cobicistat in pregnancy. Presented at: 22nd International AIDS Conference. 2018. Amsterdam, Netherlands.
  5. Antiretroviral Pregnancy Registry Steering Committee. Antiretroviral pregnancy registry international interim report for 1 January 1989–31 January 2018. Wilmington, NC: Registry Coordinating Center. 2018. Available at: http://www.apregistry.com/.

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