Title

ART for women of reproductive age

Code

TUSY01

Session Type

Symposia Session

Venue

Palacio de Iturbide 1 y 2

Date Time

Tuesday 23 July, 11:00 - 12:30

Co-Chairs:

Carlos del Rio, Emory School of Public Health, United States
Ambassador Deborah Birx, US President's Emergency Plan for AIDS Relief (PEPFAR), United States

The session will start with an update of the evidence, followed by a discussion on the use of dolutegravir (DTG) in women of reproductive age. What are the global and national policy implications? Should Sexually Transmitted Infections (ISTIs) no longer be considered for women of reproductive age? The objective is to examine the new data on neural tube defects among infants of pregnant women on DTG and the policy implications, as well as the implications for women living with HIV.

11:00 TUSY0101	Introduction

11:02 TUSY0102	Update from the TSEPANO Study Rebecca Zash, Harvard T.H. Chan School of Public Health, United States	Slides

11:22 TUSY0103	PEPFAR update Heather Watts, Office of the Global AIDS Coordinator, US Department of State, United States	Slides

11:42 TUSY0104	Woman living with HIV from Africa Jacque Wambui, NEPHAK, Kenya	Slides

12:02 TUSY0106	Questions and answers

12:07 TUSY0107	Closing remarks

AUTHOR

Laura Waters

SUMMARY

The association between DTG and neural tube defects (NTDs) has been a dominant theme in the field since the initial Tsepamo results were released in May 2018. This session summarises the research since, the community response and the eagerly anticipated update to the Tsepamo cohort data.

HIGHLIGHTS

The initial 0.94% NTD signal has been attenuated to 0.3% with 1257 more pre-conception DTG pregnancies. Most other cohorts are grossly underpowered. Studies exploring mechanisms have been undertaken: inconsistent results for folate-receptor antagonism (at supra-clinical DTG doses) and animal studies (though folate reverses zebrafish DTG toxicity). NTD must be contextualized with other pregnancy outcomes (e.g. PIs & pre-term delivery, unknown long-terms impact of in utero ART exposure). How to monitor future pregnancy outcomes? Without Tsepamo running at dolutegravir rollout, the signal may have been missed. Pregnancies are under-reported to antiretroviral pregnancy registry; pharma could be asked to include pregnancy pharmacovigilance in licensing submissions. The fragmented & varied initial responses to the signal included little or no community engagement and the statement at the IAS 2018 conference on Amsterdam from The African Treatment Access Partnership provided a clear voice that this should not have happened and overall dolutegravir benefits outweigh risks.

CRITICAL ASSESSMENT

Tsepamo may never refute the DTG NTD signal if it is not real. Guidelines must engage the community; discussions with women must include reproductive/contraceptive plans & ART pros/cons with informed choice central to decisions. Let’s engage with regulators to discuss whether earlier engagement of clinicians/researchers/the community should be employed before safety signals are reported; with benefit of hindsight, the NTD response could have been more coordinated & less confusing. Folate-antagonism may be a mechanism of ART toxicity but regardless, health benefits of folate supplementation are irrefutable & global implementation is a priority. And please report to APR at http://www.apregistry.com/