HIV positive pregnant Batswana women who enroll on the Prevention of Mother to Child Transmission (PMTCT) programme face a difficult choice: to skip the programme and risk infecting their babies with the HIV virus; take a dolutegravir based ARV regime and risk having a baby with birth defects involving the brain, spine and spinal cord or take an efavirenz based ARV regime and risk exposing their unborn babies to neurologic condition, such as microcephaly, seizures, or eye abnormalities.
Recent findings from the ongoing observational Tsepamo study in Botswana have revealed that expectant mothers who are on PMTCT are more likely to have babies with defects compared to their HIV negative counterparts who are not on the programme.
The study which compared birth outcomes among women initiating dolutegravir-based antiretroviral therapy (ART) and women initiating efavirenz-based ART during pregnancy found that women in both groups were more likely to have birth defects compared to women who are not on PMTCT.
“This large observational study from Botswana found that there was no significant difference in adverse birth outcomes among women who initiated a dolutegravir-based ART regimen during pregnancy, compared to women who initiated an efavirenz-based ART regimen during pregnancy. However, compared to HIV-negative women, both groups of women who initiated ART during pregnancy had an increased risk of adverse birth outcomes, particularly preterm birth and low birth weight” states the report.
The Prevention of mother-to-child transmission (PMTCT, also known as prevention of vertical transmission), refers to interventions to prevent transmission of HIV from an HIV-positive mother to her infant during pregnancy, labor, delivery, or breastfeeding.
Botswana has been rocked by fears that dolutegravir, which is prescribed as a first line core-agent to treat newly diagnosed HIV patients in Botswana may be causing birth defects involving the brain, spine and spinal cord.
Preliminary data from another ongoing study in Botswana found four cases of neural tube defects (NTDs), such as spina bifida, in babies born to mothers who became pregnant while taking the drug. Spina bifida is a congenital defect of the spine in which part of the spinal cord and its meninges are exposed through a gap in the backbone. It often causes paralysis of the lower limbs, and sometimes learning difficulties. The FDA issued an alert earlier this year about serious cases of neural tube birth defects involving the brain, spine and spinal cord that have been reported in babies born to women treated with dolutegravir used to treat HIV. Europe’s medicines regulator has also issued a statement that it was assessing evidence that GlaxoSmithKline’s successful HIV drug might be linked to birth defects, adding it should not be prescribed to women seeking to become pregnant. GSK notified doctors on the potential risk.
Approved by the FDA in 2013, dolutegravir has been on the market for five years, and is available as a single-ingredient product under the brand name Tivicay (ViiV Healthcare) and as a fixed-dose combination tablet with other HIV medicines under the brand names Juluca and Triumeq.
Botswana two years ago became the first country in Africa to introduce dolutegravir which was hailed as the magic pill. Worried about the risks of taking dolutegravir based ARVs, Batswana pregnant HIV positive women have been considering reverting to efavirenz.
A recent study published last week has however revealed that children were 60% more likely to be diagnosed with a neurologic condition, such as microcephaly, seizures, or eye abnormalities, when the antiretroviral regimen their mothers were taking during pregnancy included efavirenz (Sustiva, Bristol-Myers Squibb), new data show.
This is a single study, and more will be needed to better guide clinicians, investigator Claudia Crowell, MD, from Seattle Children’s Hospital and the University of Washington, cautioned during a news conference last week. The children will continue to be followed so that the long-term effects can be assessed, she reported.
“The pendulum has swung back and forth over the years regarding efavirenz use in pregnancy because of concern about potential teratogenicity,” said Gail Shust, MD, a from Hassenfeld Children’s Hospital at NYU Langone Health in New York City, who was not involved with the study.
Currently, the US Food and Drug Administration advises against the use of efavirenz in women of childbearing potential. However, the US Department of Health and Human Services and the World Health Organization suggest that efavirenz can be used throughout pregnancy.
“It will be interesting to see how this study affects these recommendations,” Shust told Medscape Medical News. In the meantime, providers should recommend antiretroviral regimens with the most safety data, she added.