Meeting NewsPerspective

Tshepiso study: Preventive TB therapy not associated with poor pregnancy outcomes

SEATTLE — Initiating isoniazid preventive therapy for tuberculosis during pregnancy is not associated with a higher rate of poor maternal or infant outcomes, according to observational results from the Tshepiso study presented at CROI.

Nicole M. Salazar-Austin, MD, assistant professor of pediatrics at the Johns Hopkins University School of Medicine, and colleagues noted that research has shown pregnancy and HIV raise the risk for TB, and that the disease can result in poor maternal and infant outcomes. A previous randomized trial, IMPAACT P1078, found that isoniazid preventive therapy (IPT) during pregnancy resulted in a higher risk for adverse maternal and neonatal outcomes compared with IPT after delivery, raising questions about its use.

Tshepiso was a prospective cohort study evaluating maternal and infant outcomes among pregnant women with HIV, with and without active TB, Salazar-Austin and colleagues noted. From January 2011 through January 2014 in Soweto, South Africa, they followed mother and infant pairs through 1 year of life.

As part of the observational study, Salazar-Austin and colleagues analyzed the impact of initiating or not initiating IPT during pregnancy on maternal and infant outcomes among pregnant women with HIV without active TB.

The analysis included 151 women, of whom 46% reported initiating IPT during pregnancy. At enrollment, the median age of the participants was 29 years and their median CD4 count was 373 cells/mm3 among women on IPT compared with 29 years and 364 cells/mm3 among women not on IPT. According to Salazar-Austin and colleagues, 66% of women on IPT also were on ART compared with 78% of women not receiving IPT. Of the women on IPT, 85% were being treated with efavirenz compared with 83% of women not on IPT.

During pregnancy, 40% of women receiving IPT had a viral load less than 20 copies/mL compared with 56% of women not on IPT (P = .004).

Among women exposed to IPT during pregnancy, the researchers observed a lower proportion of poor birth outcomes compared with unexposed women, 16% vs. 28%.

“This was true even after we accounted for other reasons for poor birth outcomes such as advanced HIV disease, advanced maternal age and low weight gain during pregnancy,” Salazar-Austin said during a news conference.

However, they noted that the study was not designed to analyze the effect of IPT on pregnancy outcomes, and that more research into the safety of IPT for pregnant women with HIV is warranted.

“We’re hoping that these results will provide some reassurance that isoniazid preventive therapy can be used in the second or third trimester of pregnancy among women living with HIV in high-burden settings,” Salazar-Austin said. “Certainly, more research is needed to evaluate IPT but also to evaluate some of the new TB preventive therapy regimens including 12 weekly doses of rifapentine and isoniazid (3HP) and one-month daily rifapentine and isoniazid (1HP) for pregnant women living with HIV.”  – by Marley Ghizzone

Reference:

Salazar-Austin N, et al. Abstract 77. Presented at: Conference on Retroviruses and Opportunistic Infections; March 4-7, 2019; Seattle.

Disclosure: Salazar-Austin reports no relevant financial disclosures.

SEATTLE — Initiating isoniazid preventive therapy for tuberculosis during pregnancy is not associated with a higher rate of poor maternal or infant outcomes, according to observational results from the Tshepiso study presented at CROI.

Nicole M. Salazar-Austin, MD, assistant professor of pediatrics at the Johns Hopkins University School of Medicine, and colleagues noted that research has shown pregnancy and HIV raise the risk for TB, and that the disease can result in poor maternal and infant outcomes. A previous randomized trial, IMPAACT P1078, found that isoniazid preventive therapy (IPT) during pregnancy resulted in a higher risk for adverse maternal and neonatal outcomes compared with IPT after delivery, raising questions about its use.

Tshepiso was a prospective cohort study evaluating maternal and infant outcomes among pregnant women with HIV, with and without active TB, Salazar-Austin and colleagues noted. From January 2011 through January 2014 in Soweto, South Africa, they followed mother and infant pairs through 1 year of life.

As part of the observational study, Salazar-Austin and colleagues analyzed the impact of initiating or not initiating IPT during pregnancy on maternal and infant outcomes among pregnant women with HIV without active TB.

The analysis included 151 women, of whom 46% reported initiating IPT during pregnancy. At enrollment, the median age of the participants was 29 years and their median CD4 count was 373 cells/mm3 among women on IPT compared with 29 years and 364 cells/mm3 among women not on IPT. According to Salazar-Austin and colleagues, 66% of women on IPT also were on ART compared with 78% of women not receiving IPT. Of the women on IPT, 85% were being treated with efavirenz compared with 83% of women not on IPT.

During pregnancy, 40% of women receiving IPT had a viral load less than 20 copies/mL compared with 56% of women not on IPT (P = .004).

Among women exposed to IPT during pregnancy, the researchers observed a lower proportion of poor birth outcomes compared with unexposed women, 16% vs. 28%.

“This was true even after we accounted for other reasons for poor birth outcomes such as advanced HIV disease, advanced maternal age and low weight gain during pregnancy,” Salazar-Austin said during a news conference.

However, they noted that the study was not designed to analyze the effect of IPT on pregnancy outcomes, and that more research into the safety of IPT for pregnant women with HIV is warranted.

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“We’re hoping that these results will provide some reassurance that isoniazid preventive therapy can be used in the second or third trimester of pregnancy among women living with HIV in high-burden settings,” Salazar-Austin said. “Certainly, more research is needed to evaluate IPT but also to evaluate some of the new TB preventive therapy regimens including 12 weekly doses of rifapentine and isoniazid (3HP) and one-month daily rifapentine and isoniazid (1HP) for pregnant women living with HIV.”  – by Marley Ghizzone

Reference:

Salazar-Austin N, et al. Abstract 77. Presented at: Conference on Retroviruses and Opportunistic Infections; March 4-7, 2019; Seattle.

Disclosure: Salazar-Austin reports no relevant financial disclosures.

    Perspective
    Constance A. Benson

    Constance A. Benson

    I think IPT in pregnancy is going to be a topic of ongoing discussion. This … was not a randomized clinical trial, it was not done in the context of a research protocol and it does not include idealized patients that we sometimes have to recruit in the studies to have a more homogenous group. This was a more real-world application of IPT, meaning that the women were pregnant and got IPT because they were felt to have a clinical indication to get it, not because they were being randomly assigned in a clinical trial. Although it is not as a big as the randomized trial was, the researchers actually showed the opposite effect to what the randomized clinical trial demonstrated last year. What that gives us is a body of data from one study that we can apply in discussing and trying to interpret the body of data in the other study, and those are very key things to be done when we are trying to parse out what is the real meaning of these data. I think there will be more discussion on this topic, but the focus should be on a risk-benefit analysis. In the real world, pregnant women need to get IPT to reduce their risk of active TB. How best to do that when you also have this concern about whether there is going to be an adverse birth outcome? You need to weigh the risks and benefits. This study gives us the tools to be able to do that.

    The take-home message is: In a real-world setting where pregnant women are given IPT in the context of what their clinical providers think they need, there is no markedly increased risk to them of an adverse birth outcome, at least in the context of what they were coming into that study with. The take-away message is there needs to be more evaluation of the other risk factors associated with adverse birth outcomes in the IMPAACT study presented at CROI 2018, and how those risk factors might apply to a more real-world setting so that we as clinicians can balance that risk-benefit ratio.

    • Constance A. Benson, MD
    • Professor of medicine and global public health
      University of California, San Diego

    Disclosures: Benson reports receiving a research grant and has a grant pending from Gilead Sciences, and receiving consulting or advisor fees from GlaxoSmithKline and ViiV Healthcare.

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