skip navigation

Skip Nav

Clinical Guidelines Portal

Clinical Guidelines Portal

Table of Contents

Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States

Integrase Inhibitors

Dolutegravir (Tivicay, DTG)

(Last updated: June 7, 2016; last reviewed: June 7, 2016)

Dolutegravir is classified as Food and Drug Administration Pregnancy Category B.

Animal Carcinogenicity Studies 

Dolutegravir was not genotoxic or mutagenic in vitro. No carcinogenicity was detected in 2-year long-term studies in mice at exposures up to 14-fold higher than that achieved with human systemic exposure at the recommended dose, or in rats at exposures up to 10-fold higher in males and 15-fold higher in females than human exposure at the recommended dose.

Reproduction/Fertility
Dolutegravir did not affect fertility in male and female rats and rabbits at exposures approximately 27-fold higher than human clinical exposure, based on area under the curve, at the recommended dose.

Animal Teratogenicity/Developmental Toxicity
Studies in rats and rabbits have shown no evidence of developmental toxicity, teratogenicity or effect on reproductive function with dolutegravir.

Placental and Breast Milk Passage
Studies in rats have demonstrated that dolutegravir crosses the placenta in animal studies and is excreted into breast milk in rats.

Human Studies in Pregnancy 

Pharmacokinetics
Human reports of dolutegravir use in human pregnancy are limited to two published case reports of dolutegravir use in single pregnant women and one presentation of dolutegravir safety, pharmacokinetic, and efficacy data from 21 pregnant women.1-3 In both case reports, dolutegravir was used safely and effectively in pregnancy.1,2 In the series of 21 pregnant women, dolutegravir plasma concentrations were lower during pregnancy than postpartum but HIV-1 RNA in the third trimester was below 50 copies/mL in all 15 women for whom third-trimester data were available. Dolutegravir was well tolerated by these pregnant women.3

Placental and Breast Milk Passage
No human data on placental passage or breast milk excretion are available.

Teratogenicity Data
In the Antiretroviral Pregnancy Registry, insufficient numbers of first-trimester exposures to dolutegravir in humans have been monitored to be able to make a risk determination.4 In the series of pregnant women discussed above, congenital anomalies were reported in 4 infants: total anomalous pulmonary venous return, cystic fibrosis and polycystic right kidney, congenital chin tremor, and sacral dimple with filum terminale fibrolipoma.

Excerpt from Table 7a
Generic Name
(Abbreviation)
Trade Name
Formulation  Dosing Recommendations Use in Pregnancy
Dolutegravir
(DTG)
Tivicay

(DTG/ABC/3TC)
Triumeq
Tablets:
  • 50 mg
Triumeq:
  • DTG 50 mg plus ABC 600 mg plus 300-mg 3TC tablet
Standard Adult Dose
ARV-Naive or ARV-Experienced (but Integrase Inhibitor-Naive Patients)
DTG (Tivicay):
  • 1 tablet once daily, without regard to food.
DTG/ABC/3TC (Triumeq):
  • 1 tablet once daily, without regard to food.
ARV-Naive or ARV-Experienced but Integrase Inhibitor-Naive if Given with EFV, FPV/r, TPV/r, or Rifampin; or Integrase Inhibitor-Experienced
DTG (Tivicay):
  • 1 tablet twice daily, without regard to food.
PK in Pregnancy:
  • Limited PK data in human pregnancy.
Dosing in Pregnancy:
  • Insufficient data to make dosing recommendation.
Unknown placental transfer to fetus.

Insufficient data to assess for teratogenicity in humans. No evidence of teratogenicity in mice, rats, or rabbits.

a Individual antiretroviral drug dosages may need to be adjusted in renal or hepatic insufficiency (for details, see Adult Guidelines, Appendix B, Table 7).

Key to Abbreviations: 3TC = lamivudine; ABC = abacavir; ARV = antiretroviral; DTG = dolutegravir EFV = efavirenz; FPV/r = fosamprenavir/ritonavir; PK = pharmacokinetic; TPV/r = tipranavir/ritonavir


References

  1. Pain JB, Le MP, Caseris M, et al. Pharmacokinetics of dolutegravir in a premature neonate after HIV treatment intensification during pregnancy. Antimicrob Agents Chemother. 2015;59(6):3660-3662. Available at http://www.ncbi.nlm.nih.gov/pubmed/25845873.
  2. Pinnetti C, Tintoni M, Ammassari A, et al. Successful prevention of HIV mother-to-child transmission with dolutegravir-based combination antiretroviral therapy in a vertically infected pregnant woman with multiclass highly drug-resistant HIV-1. AIDS. 2015;29(18):2534-2537. Available at http://www.ncbi.nlm.nih.gov/pubmed/26372490.
  3. Mulligan N, Best B, Capparelli E, et al. Dolutegravir pharmacokinetics in HIV-infected pregnant and postpartum women. Presented at: Conference on Retroviruses and Opportunistic Infections. 2016. Boston, MA.
  4. Antiretroviral Pregnancy Registry Steering Committee. Antiretroviral Pregnancy Registry international interim report for 1 Jan 1989–31 July 2015. Wilmington, NC: Registry Coordinating Center. 2015. Available at http://www.apregistry.com/.

Back to Top