TB-HIV in pregnant women: Does drug metabolism change?

Dr Diana Wangari, CNS Special Correspondent, Kenya
Photo credit: CNS: citizen-news.org
In a global conference where lung health is addressed in different tracks through parallel and equally stimulating sessions, with emphasis on TB, one often finds oneself struggling about what session to attend and which one to forego on behalf of the other. I was often faced with a similar dilemma while attending the 46th Union World Conference on Lung Health. Therefore, when I came across the session 'Maternal and Infant TB: Advancing our understanding of pathogenesis, treatment and prevention', I had to pause.

How often when discussing TB, does one think of the vulnerable mother and new born infants? More importantly, how many of us, even as doctors, are familiar with the pathogenesis, treatment and prevention of TB in these populations?

This is despite the fact that TB is a leading cause of maternal and infant mortality. The WHO reports that maternal mortality (per 100,000) amongst HIV positive women is 323.3, while in those co-infected with TB it is 12,170. Similarly, maternal mortality in general population (HIV negative women without TB) was 148.6 (per 100,000) while in those with TB it is 3,850.

Therefore, it is essential to learn of the emerging research and novel approaches – in both science and clinical studies– that are moving the maternal and infant TB agenda forward.

A study done in Kenya seemed to suggest that TB drug metabolism changes in TB/HIV treatment during pregnancy. The concentration of efavirenz (EFV), one of the anti-retrovirals utilized, increased above the therapeutic range and this raised the red flag on possible efavirenz induced central nervous toxicity which could impact adherence to anti retroviral treatment (ART).

Dr Rose Kosgei, an obstetrician-gynaecologist at the University of Nairobi's School of Medicine, who took part in the study, sat down with CNS (Citizen News Service) to discuss what the results meant and why there was a need for greater understanding about the pharmacokinetic/ pharmacodynamics differences in pregnant women with TB as we roll out full treatment for this population.

Conceding that there is under reporting of maternal and infant TB even though it is a crucial element in TB control, Kosgei gave CNS an insight on the complications of TB in this vulnerable population.

“TB in pregnancy is actually very common but not many people know this as there is not a lot of data available for this population. More often than not, we do not have a thorough screening process in the antenatal care (ANC) clinics, as compared to other adult populations where TB is well looked out for before initiation of ART therapy. In addition, TB is often missed out during antenatal visits mainly because the presentation mimics that of the physiology of pregnancy. There is thus no sensitive diagnostic tool for TB in pregnant women”.

This, however, does not change the fact that TB can have drastic effects in not only the woman but in her unborn child as well. It is associated with increased maternal and infant mortality, as well as risk of transmission of TB or HIV, depending on the case, to the infant and delivery of low birth weight babies. These complications come with a myriad of other complications as well. Infants born to HIV infected mothers have higher rates of TB --HIV exposed infants have a 10 times higher risk of getting TB and HIV infected infants have a 30 times higher risk.

“TB in maternal and infants group is thus of great concern and hence infection control efforts need to be intensified. In a drive towards zero TB deaths, we often utilize the three ‘I’s Approach of TB control’ that include intensified case finding, INH prevention therapy (IPT) and infection control. A fourth-I has been added and that is the integrated management.

The approach has to be holistic as it is not a matter of treatment alone. Prevention, as in most diseases, is fundamental here too”, felt Kosgei.

Treatment of TB co-infected HIV positive pregnant women

Kosgei’s concern is the drug interaction between the anti-TB medication and the antiretrovirals, which are metabolized in the liver, with EFV, an NNRTI (non-nucleoside reverse transcriptase inhibitor) being an example. Therefore, the interaction, added to the physiology of pregnancy, could lead to a change in levels of the drugs.

“In our study we found that the blood concentration of EFV was increased, and this, in turn, increased the risk of toxicity to the central nervous system. The patient was, therefore, likely to fail to take her medication, probably because of the side effects and as such increased the chances of mother to child transmission of infection”.

Recommendations to address this issue

“Most drug and clinical studies often exclude pregnant women, and yet they do get these infections, including TB. It therefore, presents a challenge on how effective the drugs will be on pregnant women, and we are not too sure about the side effects, as there is no data. There is thus need for further research to include this population, because pregnancy in itself changes the dynamics on various levels”.

Kosgei stressed that there is need for gynaecologists to be involved in TB work as it is often left to clinicians, specializing in internal medicine, even though gynaecologists are facing this issue during in their day- to- day practice. There is certainly need to highlight maternal and infant TB because we cannot work without having the basic understanding and data.

Dr Diana Wangari, CNS Special Correspondent, Kenya
6 December 2015
(Dr Diana Wangari MD, is providing thematic coverage from the 46th Union World Conference on Lung Health in Cape Town, South Africa, with kind support from Lilly MDR TB Partnership. Follow her on Twitter: @diana1wangari)

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