ArticlesDolutegravir versus efavirenz in women starting HIV therapy in late pregnancy (DolPHIN-2): an open-label, randomised controlled trial
Introduction
Delayed initiation of antiretroviral therapy (ART) until the third trimester of pregnancy is common in many settings where HIV is prevalent and is associated with increased mother-to-child transmission of HIV and infant mortality.1, 2, 3 In the Uganda Demographic Health Survey,1 the first antenatal clinic appointment occurred at an average of 27·9 weeks; and in South Africa, 11–19% of pregnant women presented at 28 weeks gestation or later.2
Although the causes of infant HIV transmissions are multifactorial, one important factor might be the inability of existing first-line efavirenz-based therapy to suppress HIV viral load at or before labour and birth, a time when transmission risk is highest. The integrase inhibitor dolutegravir reduces HIV viral load to less than 50 copies per mL after a median of 28 days in non-pregnant adults, compared with 84 days for efavirenz.4 Dolutegravir might consequently be particularly useful for women presenting late in pregnancy; however, safety and efficacy data are insufficient.
We aimed to assess whether the rapid virological decline, tolerability, and high HIV resistance barrier of dolutegravir-containing regimens4 conferred additional benefits to HIV-positive women initiating treatment in late pregnancy.
Section snippets
Study design and participants
DolPHIN-2 was a randomised, open-label trial done in South Africa and Uganda. In Cape Town, South Africa, participants were enrolled at Gugulethu Community Health Centre, following recruitment from eight primary antenatal facilities in the surrounding area. In Kampala, Uganda, participants were enrolled at the Infectious Diseases Institute, following recruitment at Kawempe Hospital (a tertiary obstetric referral unit) or eight primary antenatal facilities throughout Kampala and Wakiso District.
Results
Between Jan 23, and Aug 15, 2018, we screened 280 pregnant mothers and randomly assigned 268 to treatment (figure 1; table 1). Median time on treatment until birth was 55 days (IQR 33–77) days: 52 days (31–75) in the dolutegravir group and 59 days (37-80) in the efavirenz group.
The primary endpoint of viral load less than 50 copies per mL at birth by intention-to-treat analysis was met in 89 (74·2%) of 120 mothers receiving dolutegravir, compared with 50 (42·7%) of 117 in the efavirenz group (
Discussion
Women on dolutegravir-based therapy were more likely to achieve viral loads less than 50 copies per mL (or less likely to have a viral load of ≥50 copies per mL) at the time of giving birth compared with those taking efavirenz-based regimens, when initiated in the third trimester. These data address an important knowledge gap around antepartum transmission of HIV in women initiating treatment late in pregnancy,13, 14 whereas other studies have assessed the use of dolutegravir earlier in
Data sharing
We adhere to the principles of the UK Concordat on Open Research Data, which recognises that research data should wherever possible be made openly available for use by others in a manner consistent with relevant legal, ethical, disciplinary, and regulatory frameworks and norms, and with due regard to the cost involved. Our data will be assigned a DOI through deposition in the University of Liverpool Research Data Catalogue ([email protected]) and shared under a Data Transfer agreement (or
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