TB preventative therapy safe in pregnant women

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Pregnant women who are infected with HIV and are at risk of tuberculosis co-infection can undergo isoniazid prevention therapy without causing harm to themselves or their babies, researchers suggested at the 26th annual Conference on Retroviruses and Opportunistic Infections.

In a study that examined outcomes in the “real world” Tshepiso Cohort from Soweto, South Africa, the outcomes generally favoured women who were on isoniazid prevention therapy compared with pregnant women who were not on the treatment, reported Dr Nicole Salazar-Austin, of Johns Hopkins Medicine in Baltimore, and colleagues. “We know that pregnancy and HIV both increase the risk of tuberculosis, which can lead to poor birth outcomes,” Salazar-Austin said.

“Last year a study showed that isoniazid preventive therapy during pregnancy led to a higher risk of poorer birth outcomes,” she said. “Today we looked at other data we had collected in an observational study from 2011 to 2014 in Soweto, South Africa, to look at the safety of isoniazid in these pregnant women and their birth outcomes.

“We found that isoniazid prevention therapy given during pregnancy in our study was not associated with poor maternal or infant outcomes even after we accounted for other factors for worse outcomes such as advanced HIV, advanced maternal age, and low weight gain during pregnancy,” Salazar-Austin said.

In her study, adverse pregnancy outcomes were seen in 11 of 69 women on isoniazid preventive therapy – about 16% of the HIV-infected women in the cohort. That compared with adverse outcomes in 28 of 82 women who were not on isoniazid prevention therapy – or 28% of that group (P=0.09), a non-significant difference.

Maternal or foetal or infant death or tuberculosis occurred in two women in the isoniazid prevention therapy patients compared with three women in those who were not on the therapy (P=1.00) – essentially no difference.

No infant developed tuberculosis; one woman who was not on preventive therapy was diagnosed with tuberculosis; one woman in the preventive therapy arm died during the trial. Foetal demise or stillbirth occurred once in each arm of the study. There was a trend towards more premature births in the women not on preventive therapy – 18 cases of children considered preemies compared with 10 in the prevention therapy group (P=0.06). Maternal and infant hospitalizations were not different statistically, Salazar-Austin reported.

Dr Constance Benson, professor of medicine and global public health at the University of California-San Diego, who was not involved with the research, is quoted as saying: “In this study of a group of women who were not in a clinical trial, sort of a ‘real world’ setting of pregnant women, administration of isoniazid prevention therapy in the clinical context did not result in an increase in adverse birth outcomes. Those are going to be key data that the World Health Organisation (WHO) will take into consideration together with a study last year that suggested there was an impact on children. This study has the potential to impact the WHO guidelines.”

Said Salazar-Austin: “We believe these results will provide some reassurance that isoniazid preventive therapy may be used in the second or third trimester of pregnancy among women with HIV in high prevalence settings. More research is needed to evaluate isoniazid prevention therapy but also to evaluate some of the new tuberculosis preventive therapies.”

She noted that the report is an observational study in a small group of women. “For tuberculosis treatment, I think it is undeniable that you should use isoniazid because it is beneficial, and that benefit outweighs the risk,” she said. “I think for prevention, individual stories need to be weighed as you are preventing but not treating a disease and that story may look different for a woman who is pregnant, for example, and living in a household with an active tuberculosis patient. That person’s risk may be higher, especially if the woman is also living with HIV.”

In addition, she said, the decisions to use isoniazid prevention therapy need to be considered in light of the TB Apprise study, which saw an increased risk of adverse pregnancy outcomes – 23% in the isoniazid arm versus 17% in the group not using the preventive therapy (P=0.009). “So, moving forward the risks should be weighed on an individual basis,” Salazar-Austin said.

Abstract
Background: Pregnancy and HIV both increase the risk of tuberculosis (TB) disease which results in poor maternal and infant outcomes. IMPAACT study P1078 found that isoniazid preventive therapy (IPT) during pregnancy resulted in a higher risk of adverse maternal and neonatal outcomes compared to IPT post-delivery, questioning the safety of IPT in pregnant women living with HIV (PWLHIV).
Methods: Tshepiso was a prospective cohort study evaluating maternal and infant outcomes among PWLHIV with and without active TB disease from January 2011 through January 2014 in Soweto, South Africa. Mother-infant pairs were followed through one year of life. Here we report the outcomes among PWLHIV without TB disease who reported initiating vs not initiating IPT during pregnancy. This was an observational study; IPT was initiated by public antenatal and HIV clinics and not by the study.
Results: The Tshepiso study enrolled 155 PWLHIV without TB disease. This analysis includes 151 women with known pregnancy outcomes; 69 (46%) reported initiating IPT during pregnancy. The median age and CD4 T-cell count at enrollment was 30 years (IQR 27,31) and 364 cells/mm3 (IQR 252,464) for women on IPT vs 29 years (IQR 26,32) and 372 cells/mm3 (IQR 275,477) for women not on IPT. 63 (78%) and 43 (65%) women were on cART, 52 (83%) and 37 (86%) with EFV, respectively. Viral load during pregnancy was <400copies/mL in 60 (75%) women on IPT and 35 (52%) women not on IPT (p=0.004). The proportion of neonates born prematurely was lower in those exposed to IPT during pregnancy compared to unexposed (10% vs 22%; p=0.06). There was no difference in fetal demise (1% vs 1%; p=1.0), low birth weight (9% vs 12%; p=0.51), or congenital anomalies (1% vs 2%; p=1.0). A composite of the four outcomes (16% vs 28%; p=0.08) showed fewer events among infants exposed to IPT. Stratified analyses by viral load suppression did not demonstrate differences in pregnancy outcomes.
Conclusion: In this study, IPT use during pregnancy was not associated with a higher rate of poor maternal or infant outcomes. Though this study had well characterized exposures and outcomes, it was not designed to study the effect of IPT on pregnancy outcomes. IPT exposed and non-exposed PWLHIV may differ in factors associated with adverse outcomes in PWLHIV. More research is needed to evaluate the safety of IPT for PWLHIV given their high risk of TB disease and the poor maternal and infant outcomes associated with maternal TB/HIV co-infection, despite appropriate therapy.

Authors
Nicole Salazar-Austin, Sanjay Lala, Ziyaad Waja, Silvia Cohn, Jennifer Hoffmann, Fildah Mashabela, Christopher Hoffmann, Kelly E Dooley, Richard E Chaisson, Neil A Martinson

Eatg.org material
CROI 2019 abstract


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