Dolutegravir use in a London cohort – including nine pregnant women

29 November 2016. Related: Pregnancy, BHIVA 22nd Manchester 2016.

Polly Clayden, HIV i-Base

Dolutegravir appeared to be safe and effective in pregnancy in a London cohort. Continued data collection is critical.

Antiretroviral registrational trials are not representative of real life HIV cohorts with fewer women and rare pregnancies. Rebecca Simons and colleagues from Guy’s and St Thomas’ NHS Foundation Trust, London, presented data from an assessment of dolutegravir (DTG) in a clinic cohort – since its approval for use in England in January 2015 – at the 22nd BHIVA conference. [1]

The investigators used electronic pharmacy dispensing records to identify patients receiving DTG (plus backbone) or the fixed dose combination (DTG/abacavir/3TC) between 14 January and 30 November 2015.

They identified 181 cohort participants: 127 (70%) men and 54 (30%) women; 9/54 were pregnant. Median age was 42 (range: 22 to 77); 54% white and 25% black-African. Overall 2% were coinfected with hepatitis B and 6% with hepatitis C.

Eight participants started on DTG and 43 the FDC, 38 were switched to DTG and 92 to the FDC.

The reasons for starting with a DTG-based regimen among treatment naive participants were: preference for an FDC (43%) and concern about CNS side-effects (20%). Reasons for switching included: simplification (31%), CNS or gastrointestinal side effects (26%) and virological failure (12%).

In the treatment-naive group, median baseline CD4 was 392 cells/mm3 (range 16-833) and viral load 61,983 copies/mL (range 271-2,018,536). At 12 weeks, 79% had undetectable viral load and 93% were undetectable by 24 weeks. Median time to suppression was 42 days.

In the switching group, median CD4 at switch was 508 cells/mm3 (range 21-1719) and viral load 61,983 copies/mL (range 271- 2,018,536; 72% had a viral load <20 copies/mL at switch; of those 100% remained undetectable. Thirty-eight participants (28%) had a detectable viral load at switch (median 372 copies/mL [range 51-869,544]); 91% suppressed by 12 weeks.

There were 9/181 (5%) discontinuations due to toxicity in the cohort of which symptoms improved in 7/9 after stopping DTG. The reasons for these were: dizziness (22%), insomnia (33%), malaise/myalgia (33%). One participant developed acute kidney injury (reduced eGFR by 52%), which improved after stopping DTG.

The pregnant cohort included nine women: median age 27 years (range 22-41); 6/9 black African, 3/9 black British and 1/9 white. They started/switched to DTG or FDC median gestation of 21/40 weeks (range: 8 to 32) with baseline viral load 4959 copies/mL (range: 19 to 40,025).

Reasons given for use were: rapid viral suppression needed (n=4), previous poor adherence (n=4), previous GI side effects with PI (n=1), avoiding future drug-drug interactions with contraceptive implant (n=1), food requirements (n=1), and tolerance and pill-burden (n=1).

DTG FDC was well tolerated with no discontinuations. All seven women who delivered achieved undetectable viral load <20 copies/mL at delivery, one woman had not yet delivered at the time of analysis and the outcome for the remaining woman was unknown. Four women delivered by elective caesarean section and three vaginally. There was one preterm delivery at 28 + 2 weeks in a woman with pre-existing hypertension. The investigators observed no birth defects and all infants to date are HIV DNA PCR negative.

The investigators wrote: “In this diverse but representative cohort, including a significant proportion of women, virological efficacy and discontinuation rates were similar to phase 3 studies. DTG appeared to be a safe and effective treatment in pregnancy although continued data collection will be required.”

Comment

Like the small cohort receiving DTG/rifampicin shown at Glasgow and described above, [2] small real life studies will contribute to the body of evidence in populations not typically represented in registrational trials, but badly needed to inform global guidance.

References:

1. Simons R et al. Dolutegravir use in 181 patients, 54 women and 9 pregnancies – a real life experience. HIV Medicine, Volume 17, Supplement 1, April 2016. 
Abstracts of the 22nd Annual Conference of the British HIV Association (BHIVA) Manchester. 
19-22 April 2016. Poster abstract 9.
   http://www.bhiva.org/documents/Conferences/2016Manchester/AbstractBook2016.pdf (PDF)
2. Clayden P. Dolutegravir-based ART in combination with rifampicin-based TB treatment is safe in a small cohort of co-infected patients. HTB, 3 November 2016.
   https://i-base.info/htb/30894