P13-19. Dolutegravir in pregnancy – effects on HIV-positive women and their infants

Riikka Bornhede [1,2], Sandra Soeria-Atmadja [2,3], Katarina Westling [4], Karin Pettersson [1,2], Lars Navér [2,4]
Affiliates: [1] Department of Obstetrics and Gynecology, Karolinska University Hospital, Stockholm, Sweden. [2] Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden. [3] Department of Pediatrics, Karolinska University Hospital, Stockholm, Sweden. [4] Department of Medicine, Huddinge, Unit of Infectious Diseases and Dermatology, Karolinska Institutet, and Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.

Background
Antiretroviral therapy (ART) to pregnant women is effective to reduce mother-to-child transmission (MTCT) of hiv. Vertical transmission can be reduced from previous 25 – 40 % to < 0.5 %. An effective and safe ART is vital in maternal care during pregnancy. In Sweden, 60-80 children are born to HIV-positive women each year. About half of them are born in Stockholm at Karolinska University Hospital. The development of new ART for treatment of HIV has increased the efficacy, the quality of life and decreased unwanted side-effect in people living with HIV. The benefits of new treatment options may be helpful when treating pregnant women, although new drugs are seldom tested in a pregnant population. Dolutegravir (DTG), an integrase inhibitor, has quickly become part of the first line treatment in many high-income countries because of the benefits of once daily dosage, rapid decrease in HIV RNA, high tolerability and low risk of resistance development. DTG is not a recommended first line drug in pregnancy. Clinical praxis in Sweden and in many other countries is, however, to continue an effective ART initiated before pregnancy. In our clinical practice, we have noticed an increasing number of pregnant women on DTG before pregnancy and also a tendency to start DTG therapy during pregnancy. As there are only a few publications of DTG use during pregnancy, we found it valuable to analyze the Stockholm pregnancy cohort in this aspect.

Methods
A retrospective cohort study of all pregnant women and children exposed to DTG in any phase of the pregnancy at Karolinska University Hospital, 2014 – August 2017. Information about maternal health, treatment, pregnancy and child outcome were collected from medical records and the quality registry InfCare HIV.
All women received a once daily dose of 50 mg DTG. No measurement of plasma levels of DTG was performed

Results
Thirty-six women met the inclusion criteria. All were singleton pregnancies. Twenty-eight women gave birth while two pregnancies are still ongoing with due dates in late August. Four spontaneous abortions occurred before gestational week (GW) 20, three in the 1st trimester and one in GW 19. One late termination was performed due to anhydramnion.
Thirty (83 %) had a known HIV- infection before entering pregnancy, 14 were on DTG and kept the treatment unchanged. Twenty-two women started DTG during pregnancy, one as late as in GW 38+1.
Eighteen (61 %) gave birth by caesarian section (CS) while 10 delivered vaginally. Only two women had HIV RNA levels > 50 copies/mL at birth (141 and 107) and delivered by CS. No effect on maternal liver function was seen.
The rate of preeclampsia was 8.5 %. One woman was diagnosed with myelitis and the child was delivered prematurely in GW 34+1 due to her myelitis and preeclampsia. The remaining children were born at GW >37+0. Two children remain unborn. No gross malformations were noted. All children received prophylaxis according to the national recommendations. All postnatal HIV-testing of the children have been negative.

Conclusion
No increased maternal or infant morbidity was detected in this retrospective study of DTG in pregnancy. The numbers of spontaneous abortions are comparable to the back-ground population and the preeclampsia rate 8.5 % was slightly higher than the expected 4 % (n.s.). This is probably the largest observational study of DTG during pregnancy so far, but the number is indeed small and further studies are needed to evaluate the safety and efficacy of DTG in pregnancy.