Postpartum weight gain is higher with dolutegravir- compared with efavirenz-based ART among African women

12 March 2020. Related: Conference reports, Pregnancy, Side effects.

Polly Clayden, HIV i-Base

Two analyses presented at CROI 2020 show higher weight postpartum among African women receiving dolutegravir (DTG) compared with efavirenz (EFV). [1, 2]

Concerns are growing about weight gain with DTG use, but there has been no previous analysis of this phenomenon in pregnancy and the postpartum period.

Data from a randomised controlled study, conducted in South Africa and Uganda and a cohort study in Botswana, found differences also varied by country in the first analysis and weight gain with DTG-based ART was similar to that among negative women in the other.

DolPHIN-2

A secondary analysis of the DolPHIN-2 study showed increased postpartum weight gain in women living with HIV receiving DTG vs EFV. But differences in weight gain also varied by site with higher weight gain in South African compared with Uganda. 

DolPHIN-2 is an open label trial randomising pregnant women from Uganda and South Africa starting ART from 28 weeks’ gestation to DTG vs EFV plus 2 NRTIs.

The study measured maternal weight at: enrolment, less than 14 days of delivery and at 6, 12, 24 and 48 weeks postpartum.

Women were enrolled between January and August 2018 and follow-up data were censored September 2019. A total of 232 women, with mean age of 28 years, were included. Median follow-up was 60 months.

At enrolment (median gestation 31weeks): mean weight was 73 kg and mean BMI 30 kg/m2. There was higher mean third trimester weight in South Africa vs Uganda: 80 vs 67 kg.

Across arms and sites, mean change in weight from enrolment to 6 weeks post-partum was -6.1 kg. Mean weight change between 6 and 72 weeks postpartum was different by site: Uganda decreased by 0.6 kg; South Africa increased by 2.8 kg.

Mean predicted postpartum weight (mixed effects linear regression model) was higher in the DTG vs EFV arm: 4.3 kg (95% CI 0.64 to 8.06) difference.

This was also higher in South Africa vs Uganda: 13 kg (95% CI 9.28 to 16.72).

The investigators observed similar findings for BMI.

Tshilo Dikotla

Women living with HIV receiving DTG had persistently higher weight through 18 months postpartum than those on EFV but similar weight to HIV negative women, in the Tshilo Dikotla cohort study, conducted in Botswana.  

The study enrolled pregnant HIV negative women and positive women receiving either tenofovir (TDF)/emtricitabine or lamivudine (XTC)/DTG or TDF/XTC/ EFV started during or before pregnancy.

This analysis included women with weight measurements 1 to 18 months postpartum.

Of 406 women, 170 received DTG and 114 EFV. Women on DTG or EFV were older than HIV negative women: median age 28.5 vs 33.0 vs 25.0 years respectively, p<0.01. And they had more children: 3 vs 3 vs 1, respectively, p<0.01. 

Weight gain per week between second and third trimester was highest in HIV negative women vs DTG vs EFV: 0.3 vs 0.2 vs 0.1 kg/week respectively, p<0.01. And duration of breastfeeding was longest: 35.7 vs 19.0 vs 22.6 weeks respectively, p<0.01.

There were no differences in income, gestational diabetes, gestational age at delivery, or BMI at 4 weeks postpartum across groups.

Among women with HIV, no differences in CD4 or log viral load at enrolment were seen between the DTG and EFV groups. More women on EFV were receiving ART at conception: 86% vs 35.3%, p<0.01.

After adjusting for age, gestational diabetes, breastfeeding duration, and weight gain between second and third trimester, compared to HIV negative women, women receiving DTG had similar postpartum weight through 18 months but were about 5 kg heavier postpartum than women on EFV, p<0.01.   

This association remained in subgroup analysis of women living with HIV after adjustment for same confounders as above plus CD4, viral load and ART at conception: DTG vs EFV (ref), coefficient 2.4, p=0.04.

comment

Long-term follow up of DolPHIN-2 is ongoing and weight will be assessed through 2 years post-partum.

References (URLs will be added after CROI makes these public.

1. Malaba TR et al. Postpartum weight changes in women initiating DTG vs EFV in pregnancy: DolPHIN-2. CROI 2020. Boston MA. 8–11 March 2020. Poster abstract 771.http://www.croiconference.org/sessions/postpartum-weight-changes-women-initiating-dtg-vs-efv-pregnancy-dolphin-2 (abstract and poster)
2. Jao J et al. Dolutegravir use is associated with higher postpartum weight compared to efavirenz. CROI 2020. Boston MA. 8–11 March 2020.  Poster abstract 772.
   http://www.croiconference.org/sessions/dolutegravir-use-associated-higher-postpartum-weight-compared-efavirenz (abstract and poster)