April 27, 2018
3 min read

ART regimens containing tenofovir appear not to increase birth risks

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Newly reviewed data from two United States-based cohort studies showed that an ART regimen containing tenofovir is not associated with a higher risk for adverse birth outcomes when taken by pregnant women with HIV to protect their babies, researchers said.

The finding contradicts results from the recent PROMISE trial, which identified potential risk factors associated with pregnant women taking tenofovir disoproxil fumarate, emtricitabine and ritonavir-boosted lopinavir (TDF-FTC-LPV/r) as ART.

Three-drug ART taken appropriately throughout pregnancy, labor and delivery can help reduce the risk for mother-to-child transmission of HIV during childbirth to less than 1%, according to the CDC, but recommendations concerning which ART regimens to consider are based on limited clinical safety data, according to Kathryn Rough, ScD, then a doctoral student at the Harvard T.H. Chan School of Public Health, and colleagues.

In the PROMISE trial, which was conducted in India and sub-Saharan Africa, infants born to mothers who had taken TDF-FTC-LPV/r during pregnancy were more than twice as likely to be born very premature — before 34 weeks — or at a very low birth weight than those whose mothers had taken zidovudine, lamivudine and lopinavir/ritonavir (ZDV-3TC-LPV/r).

In the current study, Rough and colleagues described the PROMISE findings as “unexpected, given that numerous observational studies had shown the use of TDF-FTC-based regimens during pregnancy to be safe with respect to most infant outcomes.”

“Understanding the safety of in utero exposure to TDF-FTC-based regimens is critical, because the WHO recommends a once-daily TDF-FTC-based regimen as first-line therapy for all HIV-infected adults, including pregnant women,” they wrote in The New England Journal of Medicine.

For their study, Rough and colleagues compared data from two multisite U.S. studies of pregnant women with HIV and their infants to evaluate the risk for preterm birth (before 37 weeks), very preterm birth (before 34 weeks), low birth weight and very low birth weight in infants who were exposed to TDF-FTC-LPV/r, ZDV-3TC-LPV/r and another tenofovir-containing regimen, TDF-FTC with atazanavir/ritonavir (TDF-FTC-ATV/r).

According to the review, among 4,646 birth outcomes involving 3,847 women, infants born to mothers receiving TDF-FTC-LPV/r had a similar risk for preterm birth (RR, 0.90; 95% CI, 0.60 to 1.33) and low birth weight (RR = 1.13; 95% CI, 0.78-1.64) compared with women receiving ZDV-3TC-LPV/r, Rough and colleagues reported. Compared with women receiving TDF-FTC-ATV/r, infants born to women receiving TDF-FTC-LPV/r had a similar or slightly higher risk for preterm birth (RR = 1.14; 95% CI, 0.75-1.72) and low birth weight (RR = 1.45; 95% CI, 0.96-2.17). According to Rough and colleagues, there were no significant differences in the regimens in terms of risk for very preterm birth or very low birth weight.

In a statement, Rohan Hazra, MD, chief of the NIH branch that oversaw funding for the study, said the findings provide “reassurance that regimens containing TDF are appropriate for use during pregnancy.”

Study co-author Judith S. Currier, MD, professor of medicine and division chief of infectious diseases at the University of California, Los Angeles, and associate director of the UCLA Center for Clinical AIDS Research and Education, agreed that the results were reassuring.

“These data provide reassurance about the safety of tenofovir in pregnancy and underscore the importance of examining the safety of new ART regimens in pregnancy as we move away from the use of boosted PIs,” Currier told Infectious Disease News.

But she also noted some limitations of the study, including a much smaller number of women in the TDF-FTC-LPV/r arm — just 2.8% of infants included were exposed to this regimen — than in the PROMISE trial.

Additionally, in subgroup analyses of women who initiated ART before conception, the researchers found that the risks for preterm birth, low birth weight and any adverse outcome were higher in the TDF-FTC-LPV/r group than the other two arms.

“Concerns regarding the use of TDF-FTC-LPV/r during pregnancy remain,” Rough and colleagues wrote.

They said further investigation is warranted to understand the differences in outcomes among women who initiated ART before conception. – by Gerard Gallagher

Editor’s note: In the United States, tenofovir/emtricitabine is marketed as Truvada ( Gilead), lopinavir/ritonavir is marketed as Kaletra (AbbVie), lamivudine/zidovudine is marketed as Combivir (ViiV), atazanavir is marketed as Reyataz (Bristol-Myers Squibb) and lopinavir is marketed as Norvir (AbbVie).


Rough K, et al. N Engl J Med. 2018;doi:10.1056/NEJMoa1701666.

Disclosures: Currier reports grants from Theratechnologies outside the submitted work. Hazra reports no relevant financial disclosures. Rough reports receiving grants from NIAID and Harvard T.H. Chan School of Public Health during the conduct of the study, grants from Pfizer and personal fees from Google outside the submitted work. Please see the study for all other authors’ relevant financial disclosures.