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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

Nucleoside and Nucleotide Analogue Reverse Transcriptase Inhibitors

Tenofovir Disoproxil Fumarate (Viread, TDF)

(Last updated: August 6, 2015; last reviewed: August 6, 2015)

Tenofovir disoproxil fumarate, the orally bioavailable form of tenofovir, is classified as Food and Drug Administration Pregnancy Category B.

Animal Studies 

Tenofovir is mutagenic in one of two in vitro assays and has no evidence of clastogenic activity. Long-term oral carcinogenicity studies of tenofovir in mice and rats were carried out at 16 times (mice) and 5 times (rats) human exposure. In female mice, liver adenomas were increased at exposures 16 times that observed in humans at therapeutic doses. In rats, the study was negative for carcinogenic findings at exposures up to 5 times that observed in humans at the therapeutic dose.

Reproduction studies have been performed in rats and rabbits at doses up to 14 and 19 times the human dose, respectively, based on body surface area comparisons and revealed no evidence of impaired fertility or harm to the fetus associated with tenofovir. There were also no effects on fertility, mating performance, or early embryonic development when tenofovir was administered to male rats (600 mg/kg/day; equivalent to 10 times the human dose based on body surface area) for 28 days before mating and to female rats for 15 days before mating through Day 7 of gestation. There was, however, an alteration of the estrous cycle in female rats administered 600 mg/kg/day. 

Teratogenicity/Developmental Toxicity
Chronic exposure of fetal monkeys to tenofovir at high doses (exposure equivalent to 25 times the area under the curve (AUC) achieved with therapeutic dosing in humans) resulted in lower fetal circulating insulin-like growth factor (IGF)-1, higher IGF binding protein-3 levels, and lower body weights. A slight reduction in fetal bone porosity was also observed. Effects on these parameters were observed within 2 months of maternal treatment.

Placental and Breast Milk Passage
Intravenous administration of tenofovir to pregnant cynomolgus monkeys resulted in a fetal/maternal concentration of 17%, demonstrating that tenofovir crosses the placenta.1  

Human Studies in Pregnancy

In a retrospective population pharmacokinetic study of 46 pregnant women and 156 non-pregnant women receiving combination regimens including tenofovir, pregnant women had a 39% higher apparent clearance of tenofovir compared with non-pregnant women, which decreased slightly but significantly with increasing age.2 In a P1026s study of 19 pregnant women receiving tenofovir-based combination therapy at 30 to 36 weeks’ gestation and 6 to 12 weeks postpartum, the percentage of women with tenofovir AUC exceeding the target of 2 μg*hour/mL (the 10th percentile in non-pregnant adults) was lower in the third trimester (74%, 14 of 19 women) than postpartum (86%, 12 of 14 women) (P = 0.02); however, trough levels were similar in the two groups.3 In another study of 34 women receiving tenofovir plus emtricitabine in the third trimester and postpartum, tenofovir AUC, peak, and trough were all about 25% lower in pregnant women compared to postpartum women, but these decreased exposures were not associated with virologic failure.4 Standard dosing during pregnancy continues to be recommended.

Placental and Breast Milk Passage
In studies of pregnant women on chronic tenofovir, the cord-to-maternal-blood ratio ranged from 0.60 to 1.03, indicating high placental transfer.3-6 In studies of pregnant women receiving single-dose tenofovir (with and without emtricitabine) in labor, the drugs were well tolerated and the median tenofovir cord-to-maternal-blood ratio at delivery ranged from 0.55 to 0.73.7,8 Intracellular tenofovir concentrations were detected in the peripheral blood mononuclear cells from cord blood in all infants after a single maternal dose of 600 mg tenofovir with 400 mg emtricitabine, but intracellular tenofovir diphosphate was detectable in only 2 (5.5%) of 36 infants.9

Sixteen breast milk samples were obtained from five women who received 600 mg tenofovir at the start of labor followed by 300 mg daily for 7 days. Tenofovir levels in breast milk ranged from 5.8 to 16.3 ng/mL, resulting in nursing infants ingesting an estimated daily amount of tenofovir that corresponds to 0.03% of the proposed oral dose of tenofovir for neonates.10 Because the form of tenofovir in breastmilk is expected to have lower bioavailability than tenofovir, these exposures are likely overestimates. No studies have measured tenofovir blood levels in infants breastfed by women taking tenofovir.

A retrospective analysis of 7,275 women (1,199 receiving tenofovir-based combination antiretroviral therapy) demonstrated a slight reduction in pregnancy rates, but the findings were limited by the observational nature of the data and additional studies are needed for confirmation.11

Teratogenicity/Developmental Toxicity
In a study of 431 pregnancies occurring during an HIV pre-exposure prophylaxis trial in which HIV-uninfected women were randomized to placebo, tenofovir, or tenofovir plus emtricitabine, there was no difference in risk of congenital anomalies between the tenofovir-containing and placebo arms.12 No association was seen between maternal tenofovir and offspring birth defects in three large U.S. cohorts: PACT 219/219C (n = 2,202 with 214 first-trimester tenofovir exposures), P1025 (n = 1,112 with 138 first-trimester tenofovir exposures),13,14 and Pediatric HIV AIDS Cohort Study (n = 2,580 with 431 first-trimester tenofovir exposures).15 In the French Perinatal Cohort, no association was found between birth defects and tenofovir with a power of 70% for an odds ratio of 1.5 (n = 13,124 with 823 first-trimester tenofovir exposures).16 Finally, in the Antiretroviral Pregnancy Registry, sufficient numbers of first-trimester exposures to tenofovir in humans have been monitored to be able to detect at least a 1.5-fold increased risk of overall birth defects. No increase in birth defects has been observed with tenofovir. Among cases of first-trimester tenofovir exposure reported to the Antiretroviral Pregnancy Registry, the prevalence of birth defects was 2.2% (47 of 2,141 births; 95% confidence interval [CI], 1.6% to 2.9%), compared with a 2.7% total prevalence in the U.S. population, based on Centers for Disease Control and Prevention surveillance.17

 Other Safety Data
Among 382 pregnancies occurring in 302 women in Uganda and Zimbabwe participating in the DART trial—approximately two-thirds of whom received tenofovir through more than 90% of their pregnancies—there were no differences noted in mortality, birth defects, or growth.18 In the Pediatric HIV/AIDS Cohort Study from the United States, 449 (21%) of the 2,029 HIV-exposed but uninfected infants had in utero exposure to tenofovir, and there was no difference at birth between those exposed to combination drug regimens with or without tenofovir in low birthweight, small-for-gestational-age, and newborn length-for-age and head circumference-for-age z-scores (LAZ and HCAZ, respectively). However, at age 1 year, infants exposed to combination regimens with tenofovir had a slight but significantly lower adjusted mean LAZ and HCAZ than those without tenofovir exposure (LAZ: -0.17 vs. -0.03, P = 0.04; HCAZ: 0.17 vs. 0.42, P = 0.02), but no difference in weight-for-age z-score (WAZ). There were no significant differences between those with and without tenofovir exposure at age 1 year when defining low LAZ or HCAZ as ≤1.5 z-score. Thus, these slightly lower mean LAZ and HCAZ scores are of uncertain significance.19 In a different U.S. study (P1025), maternal tenofovir use was similarly not associated with differences in body size parameters at birth; however, among the 1,496 infants followed for 6 months, tenofovir exposure after the first trimester, relative to no exposure, was associated with being underweight (WAZ <5%) at age 6 months (OR [95% CI]: 2.06 [1.01, 3.95], P = 0.04).20 

In a cross-sectional study of 68 HIV-exposed uninfected children enrolled at ages 1 to 6 years who had in utero exposure to combination regimens with (N = 33) or without (N = 35) tenofovir, evaluation of quantitative bone ultrasound and parameters of bone metabolism gave similar measures between groups.21 In contrast, a study evaluating whole body dual-energy X-ray absorptiometry scans within 4 weeks of birth among 74 infants exposed to more than 8 weeks of tenofovir in utero and 69 infants with no tenofovir exposures, the adjusted mean whole body bone mineral content (BMC) was significantly lower in the tenofovir group by 6.3 g (P = 0.004) as was the whole-body-less-head BMC (-2.6 g, P = 0.056). The duration and clinical significance of these findings require further longitudinal evaluation.22


Excerpt from Table 7a
Generic Name
Trade Name
Formulation  Dosing Recommendations Use in Pregnancy
Tenofovir Disoproxil Fumarate




TDF (Viread)
  • 300 mg
  • 40 mg/1 g oral powder
  • TDF 300 mg plus FTC 200 mg tablet
  • TDF 300 mg plus FTC 200 mg plus EFVc 600 mg tablet
  • TDF 300 mg plus FTC 200 mg plus RPV 25 mg tablet
  • TDF 300 mg plus FTC 200 mg plus EVG 150 mg plus COBI 150 mg tablet
Standard Adult Dose
TDF (Viread) 
  • 300 mg once daily without regard to food
  • 8 mg/kg (up to maximum 300 mg), take with food
  • 1 tablet once daily without regard to food
  • 1 tablet once daily at or before bedtime. Take on an empty stomach to reduce side effects.
  • 1 tablet once daily with food
  • 1 tablet once daily with food
PK in Pregnancy:
  • AUC lower in third trimester than postpartum but trough levels adequate
Dosing in Pregnancy:
  • No change in dose indicated.
High placental transfer to fetus.b

No evidence of human teratogenicity (can rule out 1.5-fold increase in overall birth defects). 

Studies in monkeys (at doses approximately 2-fold higher than that for human therapeutic use) show decreased fetal growth and reduction in fetal bone porosity within 2 months of starting maternal therapy. Human studies demonstrate no effect on intrauterine growth, but data are conflicting about potential effects on growth outcomes later in infancy.

If HBV-coinfected, it is possible that an HBV flare may occur if TDF is stopped; see HIV/Hepatitis B Virus Coinfection.

Renal function should be monitored because of potential for renal toxicity.
a Individual antiretroviral drug dosages may need to be adjusted in renal or hepatic insufficiency (for details, see Adult Guidelines, Appendix B, Table 7).
b Placental transfer categories—Mean or median cord blood/maternal delivery plasma drug ratio:
   High: >0.6
   Moderate: 0.3–0.6
   Low: <0.3
c See Teratogenicity for discussion of EFV and risks in pregnancy.

Key to Abbreviations: AUC = area under the curve; COBI = cobicistat; EFV = efavirenz; FTC = emtricitabine; HBV = hepatitis B virus; PK = pharmacokinetic; RPV = rilpivirine; TDF = tenofovir disoproxil fumarate


  1. Tarantal AF, Marthas ML, Shaw JP, Cundy K, Bischofberger N. Administration of 9-[2-(R)-(phosphonomethoxy)propyl]adenine (PMPA) to gravid and infant rhesus macaques (Macaca mulatta): safety and efficacy studies. J Acquir Immune Defic Syndr Hum Retrovirol. 1999;20(4):323-333. Available at
  2. Benaboud S, Hirt D, Launay O, et al. Pregnancy-related effects on tenofovir pharmacokinetics: a population study with 186 women. Antimicrob Agents Chemother. 2012;56(2):857-862. Available at
  3. Burchett S, Best B, Mirochnick M, al e. Tenofovir pharmacokinetics during pregnancy, at delivery, and postpartum. 14th Conference on Retroviruses and Opportunistic Infections; 2007; Los Angeles, CA.
  4. Colbers AP, Hawkins DA, Gingelmaier A, et al. The pharmacokinetics, safety and efficacy of tenofovir and emtricitabine in HIV-1-infected pregnant women. AIDS. 2013;27(5):739-748. Available at
  5. Bonora S, de Requena DG, Chiesa E, al e. Transplacental passage of tenofovir and other ARVs at delivery. 14th Conference on Retoviruses and Opportunistic Infections; February 25-28, 2007, 2007; Los Angeles, CA.
  6. Hirt D, Urien S, Ekouevi DK, et al. Population pharmacokinetics of tenofovir in HIV-1-infected pregnant women and their neonates (ANRS 12109). Clin Pharmacol Ther. 2009;85(2):182-189. Available at
  7. Flynn PM, Mirochnick M, Shapiro DE, et al. Pharmacokinetics and safety of single-dose tenofovir disoproxil fumarate and emtricitabine in HIV-1-infected pregnant women and their infants. Antimicrob Agents Chemother. 2011;55(12):5914-5922. Available at
  8. Mirochnick M, Taha T, Kreitchmann R, et al. Pharmacokinetics and safety of tenofovir in HIV-infected women during labor and their infants during the first week of life. J Acquir Immune Defic Syndr. 2014;65(1):33-41. Available at
  9. Hirt D, Ekouevi DK, Pruvost A, et al. Plasma and intracellular tenofovir pharmacokinetics in the neonate (ANRS 12109 trial, step 2). Antimicrob Agents Chemother. 2011;55(6):2961-2967. Available at
  10. Benaboud S, Pruvost A, Coffie PA, et al. Concentrations of tenofovir and emtricitabine in breast milk of HIV-1-infected women in Abidjan, Cote d'Ivoire, in the ANRS 12109 TEmAA Study, Step 2. Antimicrob Agents Chemother. 2011;55(3):1315-1317. Available at
  11. Maskew M, Westreich D, Firnhaber C, Sanne I. Tenofovir use and pregnancy among women initiating HAART. AIDS. 2012;26(18):2393-2397. Available at
  12. Mugo NR, Hong T, Celum C, et al. Pregnancy incidence and outcomes among women receiving preexposure prophylaxis for HIV prevention: a randomized clinical trial. JAMA. 2014;312(4):362-371. Available at
  13. Brogly SB, Abzug MJ, Watts DH, et al. Birth defects among children born to human immunodeficiency virus-infected women: pediatric AIDS clinical trials protocols 219 and 219C. Pediatr Infect Dis J. 2010;29(8):721-727. Available at
  14. Knapp KM, Brogly SB, Muenz DG, et al. Prevalence of congenital anomalies in infants with in utero exposure to antiretrovirals. Pediatr Infect Dis J. 2012;31(2):164-170. Available at
  15. Williams PL, Crain M, Yildirim C, et al. Congenital anomalies and in utero antiretroviral exposure in human immunodeficiency virus-exposed uninfected infants. JAMA Pediatr. 2015;169(1):45-55. Available at
  16. Sibiude J, Mandelbrot L, Blanche S, et al. Association between prenatal exposure to antiretroviral therapy and birth defects: an analysis of the French perinatal cohort study (ANRS CO1/CO11). PLoS Med. 2014;11(4):e1001635. Available at
  17. Antiretroviral Pregnancy Registry Steering Committee. Antiretroviral Pregnancy Registry international interim report for 1 Jan 1989 - 31 July 2014. Wilmington, NC: Registry Coordinating Center. 2014. Available at
  18. Gibb DM, Kizito H, Russell EC, et al. Pregnancy and infant outcomes among HIV-infected women taking long-term ART with and without tenofovir in the DART trial. PLoS Med. 2012;9(5):e1001217. Available at
  19. Siberry GK, Williams PL, Mendez H, et al. Safety of tenofovir use during pregnancy: early growth outcomes in HIV-exposed uninfected infants. AIDS. 2012;26(9):1151-1159. Available at
  20. Ransom CE, Huo Y, Patel K, et al. Infant growth outcomes after maternal tenofovir disoproxil fumarate use during pregnancy. J Acquir Immune Defic Syndr. 2013;64(4):374-381. Available at
  21. Vigano A, Mora S, Giacomet V, et al. In utero exposure to tenofovir disoproxil fumarate does not impair growth and bone health in HIV-uninfected children born to HIV-infected mothers. Antivir Ther. 2011;16(8):1259-1266. Available at
  22. Siberry GK, Jacobson DL, Kalkwarf HJ, et al. Lower Newborn Bone Mineral Content Associated with Maternal Use of Tenofovir Disoproxil Fumarate During Pregnancy. Clin Infect Dis. 2015. Available at

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