Clinical trial development programmes frequently exclude children, pregnant women (PW) and people with HIV-associated tuberculosis (TB). Until now, this lack of data has prevented WHO from being able to recommend these ARV drugs across all populations. Ongoing studies will provide data that can allow for a revision of this recommendation in the coming 1–2 years. Further, strengthened ARV post-marketing, ARV drug toxicity monitoring and pregnancy registry or congenital anomaly surveillance programmes are important sources of data to address these gaps.
Findings from HIV services in Botswana, which has provided DTG to pregnant women with HIV for more than 1 year, demonstrate that birth outcomes (stillbirth, neonatal death, preterm birth and smallness for gestational age) do not differ between women receiving EFV-based therapy and those receiving DTG-based therapy. This observation is based on retrospectively collected data from more than 5000 women, 16% of whom were receiving DTG regimens. There was also no excess of congenital anomalies among infants born to women taking DTG, although relatively few of these women started DTG in the first trimester. Two different clinical trial networks have assessed DTG safety and pharmacokinetics in pregnant women, and reported that DTG was well tolerated and reached levels expected to achieve HIV suppression.4, 5
Several clinical trials assessing the effectiveness, safety, tolerability and/or pharmacokinetics of DTG during pregnancy are either underway or about to start, with findings expected between 2018 and 2021.
4: Mulligan N, Best B, Capparelli E, Stek A, Barr E, Smith E et al. Dolutegravir pharmacokinetics in HIV-infected pregnant and postpartum women. Conference on Retroviruses and Opportunistic Infections, 22–26 February 2016, Boston, MA, USA (Abstract 438; http://www.croiconference.org/sessions/dolutegravirpharmacokinetics-hiv-infected-pregnant-andpostpartum-women-0, accessed 1 July 2017). 5: Bollen P, Colbers A, Schalkwijk S, Konopnicki D, Weizsäcker K, Hidalgo Tenorio C et al. A comparison of the pharmacokinetics of dolutegravir during pregnancy and postpartum. 18th International Workshop on Clinical Pharmacology of Antiviral Therapy. Chicago, IL, USA. 14–16 June 2017.