BACKGROUND AND PURPOSE:

• Lockman et al. (The Lancet, 2021) compared the safety and efficacy of three antiretroviral regimens started in pregnancy

METHODS:

• Multicenter, open-label, randomized controlled, phase 3 trial
  • This International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) 2010/Virologic Efficacy and Safety of ART Combinations with TAF/TDF, EFV, and DTG (VESTED) study
• Participants
  • Pregnant women ≥18 years
  • Confirmed HIV-1 infection
  • 14 to 28 weeks gestation
  • Excluded:  History of previous antiretroviral use | Up to 14 days of antiretroviral therapy during the current pregnancy was permitted
• Interventions
  • Treatment A: Once-daily oral dolutegravir 50 mg | Once-daily oral fixed-dose combination emtricitabine 200 mg and tenofovir alafenamide fumarate 25 mg
  • Treatment B: Once-daily oral dolutegravir 50 mg | Once-daily oral fixed-dose combination emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg
  • Treatment C: Once-daily oral fixed-dose combination of efavirenz 600 mg, emtricitabine 200 mg, and tenofovir disoproxil fumarate 300 mg
• Study design
  • Randomized 1:1:1
  • Stratified by gestational age (14 to 18, 19 to 23, and 24 to 28 weeks gestation) and country
• Primary efficacy outcome
  • The proportion of participants with viral suppression
    • HIV-1 RNA concentration <200 copies per mL, at or within 14 days of delivery
• Primary safety outcomes
  • Composite adverse pregnancy outcome: Preterm delivery | SGA | Stillbirth | Spontaneous abortion
  • Occurrence of serious maternal and infant adverse events

RESULTS:

• Treatment A: 217 women | Treatment B: 215 | Treatment C: 211
  • Median gestational age at enrollment: 21.9 weeks (IQR 18.3 to 25.3)
  • Median HIV-1 RNA concentration: 902.5 copies per mL (152.0 to 5182.5)
    • HIV-1 RNA concentrations of <200 copies per mL: 28% of participants
  • Median CD4 count: 466 cells per μL (308 to 624)
• More patients in treatment groups A and B had viral suppression at delivery vs group C
  • Treatments A and B: 98% had suppression
  • Treatment C: 91% had suppression
  • Estimated difference 6.5% (95% CI, 2.0 to 10.7); P = 0.0052
• Significantly fewer participants in the treatment group A had a composite adverse pregnancy outcome vs treatment groups B or C
  • Treatment B
    • Treatment A: 24%
    • Treatment B: 33%
    • Estimated difference −8.8% (95% CI, −17.3 to −0.3); P = 0.043
  • Treatment C
    • Treatment C: 33%
    • Estimated difference −8.6% (95% CI, –17.1 to −0.1); P = 0.047
• The proportion of participants or infants with grade 3 or higher adverse events did not differ among the three groups
• The proportion of participants who had a preterm delivery was significantly lower in the treatment A group than the treatment C group
  • Treatment A: 6%
  • Treatment C: 12%
  • Estimated difference −6.3% (95% CI, –11.8 to −0.9); P = 0.023
• Neonatal mortality was significantly higher in the treatment C group than in either
  • Treatment A
    • Treatment C: 5%
    • Treatment A: 1%
    • P = 0.019
  • Treatment B
    • Treatment B: 2%
    • P = 0.050

CONCLUSION:

• When antiretroviral therapy was started in pregnancy, treatments containing dolutegravir (A and B) resulted in better viral suppression than a combination of efavirenz, emtricitabine, and tenofovir disoproxil fumarate (C)
• The dolutegravir, emtricitabine, and tenofovir alafenamide fumarate regimen (A) had the lowest frequency of adverse pregnancy outcomes and neonatal deaths
• The authors conclude

When started at 14–28 weeks of pregnancy, all three ART regimens studied in this trial led to high rates of virological suppression

…the results of this trial showed that the efficacy and safety of dolutegravir-containing ART regimens observed in non-pregnant adults are also evident when started in pregnancy

These findings affirm the WHO recommendation to use dolutegravir in all populations, including in pregnant women, and suggest that dolutegravir, emtricitabine, and tenofovir alafenamide fumarate might be preferred

Learn More – Primary Sources:

Efficacy and safety of dolutegravir with emtricitabine and tenofovir alafenamide fumarate or tenofovir disoproxil fumarate, and efavirenz, emtricitabine, and tenofovir disoproxil fumarate HIV antiretroviral therapy regimens started in pregnancy (IMPAACT 2010/VESTED): a multicentre, open-label, randomised, controlled, phase 3 trial

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