Last reviewed: September 2018
Last updated: September  2018

US and EU drug regulators warn of possible increased risk of neural tube defects in babies born to women taking dolutegravir

The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have both issued alerts after preliminary results from an ongoing study reported an increased risk of serious neural tube defects in women who became pregnant while taking dolutegravir-based regimens. The risk appears to be highest in women taking the drug at the time of becoming pregnant or early in the first trimester.

It is recommended that women of childbearing age with HIV currently taking dolutegravir are counselled about this new potential risk. Pregnant women currently taking dolutegravir should not stop their treatment but should discuss the possible risks with their healthcare provider.

Women of childbearing age with HIV who are trying to become pregnant should discuss alternative antiretroviral therapy regimens with their healthcare provider. Women of childbearing age with HIV who are not planning to become pregnant may be on dolutegravir-based regimens provided their pregnancy test before starting therapy is negative and they consistently use a reliable method of contraception during treatment.

Both the FDA and the EMA said they would continue to monitor results from the ongoing study and would issue further advice as additional data become available.

See Management: approach See Management: treatment algorithm

Original source of update



History and exam

Key diagnostic factors

  • presence of risk factors
  • fevers and night sweats
  • weight loss
  • skin rashes and post-inflammatory scars
  • oral ulcers, angular cheilitis, oral thrush, or oral hairy leukoplakia
  • diarrhoea
  • wasting syndrome
  • changes in mental status or neuropsychiatric function
  • recent hospital admissions
  • tuberculosis (TB)
  • medical comorbidities
  • sexual activity
  • generalised lymphadenopathy
  • Kaposi's sarcoma
  • genital STDs
  • chronic vaginal candidiasis
  • shingles
  • headaches
  • periodontal disease
  • retinal lesions on fundoscopy
  • shortness of breath (SOB) on exertion, cyanosis on exertion, dry cough, silent chest on auscultation

Other diagnostic factors

  • current and prior use of other substances
  • peripheral neuropathy
  • recurrent herpes simplex
  • hepatomegaly or splenomegaly
  • meningeal signs (bacterial or viral meningitis)

Risk factors

  • needle sharing with intravenous drug use
  • unprotected receptive anal intercourse
  • unprotected receptive penile-vaginal sexual intercourse
  • percutaneous needle stick injury
  • high maternal viral load (mother to child transmission)
  • use of progestin-only injectable contraceptives
  • herpes simplex virus type 2 (HSV-2) infection

Diagnostic investigations

1st investigations to order

  • serum HIV enzyme-linked immunosorbent assay (ELISA)
  • serum HIV rapid test
  • HIV non-invasive tests
  • serum Western blot
  • serum p24 antigen
  • serum HIV DNA polymerase chain reaction (PCR)
  • CD4 cell count
  • serum viral load (HIV RNA)
  • pregnancy test
  • serum hepatitis B serology
  • serum hepatitis C serology
  • serum venereal disease research laboratory test
  • Treponema pallidum haemagglutination test
  • rapid plasma reagin
  • tuberculin skin test
  • FBC with differential
  • serum electrolytes
  • serum creatinine
  • urinalysis
Full details

Investigations to consider

  • CXR
  • liver function tests (LFTs)
  • lipid profile
  • plasma glucose
  • hepatitis A serology (IgG)
  • toxoplasma serology (IgG)
  • gonorrhoea and chlamydia testing
  • human leukocyte antigen-B*5701 testing
Full details

Treatment algorithm


Authors VIEW ALL

Assistant Professor of Medicine

Infectious Diseases

Northwestern Memorial Hospital




CJA has been a member of an advisory board on HIV, aging and telomeres for Viiv, and has done consultant work as a member of DSMBs for ABIVAX, Atea, and Biotron. He has also received a grant for Investigator Sponsored Research from Gilead.

Dr Chad J Achenbach would like to gratefully acknowledge Dr Richard Rothman, Dr Michael Ehmann, Dr Linda-Gail Bekker, Dr Catherine Orrell, and Dr Lisa Capaldini, the previous contributors to this topic. ME, LGB, and CO declare that they have no competing interests. RR attended a symposium/conference hosted by a funding agency, Gilead HIV FOCUS program, from which he receives research funds. RR pays staff for an implementation/research program grant from Gilead HIV FOCUS for development of HIV testing programs in Emergency Departments. LC is on the speakers' bureau for the following pharmaceutical companies: GlaxoSmithKline, BMS, Merck, Gilead, Roche, Pfizer, Solvay, Lilly, Serrano, and Tibotec.

Peer reviewers VIEW ALL

Clinical Assistant Professor

University of British Columbia




MH is a member of an advisory board and/or speakers' bureau for Gilead Sciences Canada Inc, Merck Canada Inc, and ViiV Healthcare.

Assistant Professor of Medicine

Harvard Medical School

Director of Research

Global Health Delivery Project

Harvard School of Public Health




WR declares that he has no competing interests.

Infectious Disease Physician

Oxford University Clinical Research Unit

Hospital for Tropical Diseases

Ho Chi Minh City



JD declares that he has no competing interests.

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