74. Maternal Dolutegravir (DTG) Use During Pregnancy and Birth Outcomes: The Antiretroviral Pregnancy Registry (APR)

Abstract Background The APR is prospective exposure-registration cohort study, monitoring for early warning signals of major teratogenic effects of antiretrovirals (ARV) used during pregnancy. This analysis aimed to assess maternal demographics, pregnancy and neonatal outcomes including birth defects among infants with periconception and prenatal exposure to DTG using APR data. Methods Descriptive analysis with frequency tabulation of pregnancy and neonatal outcomes is reported. Periconception is defined as any exposure within two weeks prior to or through 28 days after conception. Results There were 1010 prospectively reported pregnancies with exposure to DTG through 31January2021, with 526 periconception exposures, 105 exposed later during 1st trimester, 260 during 2nd trimester and 119 during 3rd trimester. Maternal median age at conception was 30 years and 77.0% of pregnancies were reported from the United States. At the time of reporting, 46.6% had CD4 count ≥500 cells/µL, 31.8% had 200-499 cells/µL, 12.5% had < 200 cells/µL and 9.1% unknown. The 1010 DTG exposed pregnancies resulted in 1036 outcomes: 956 (92.3%) live births (26 twin pairs), 12 (1.2%) stillbirths, 28 (2.7%) induced abortions, and 38 (3.7%) spontaneous abortions. Among live births, 39 (4.1%) reported birth defects. For 1st trimester exposures, overall defect prevalence was 3.3% (19/576, 95% CI:2.0-5.1) and for 2nd/3rd trimester exposures defect prevalence was 5.3% (20/380, 95% CI:3.2-8.0). One neural tube defect (NTD) case of anencephaly with periconception DTG exposure was reported. Among the 873 singleton, live births without birth defects, 92 (10.5%) were preterm (< 37 weeks of gestation); 103 (11.8%) had low birth weight (lbw) < 2500 grams including 22 (2.5%) < 1500 (very lbw) grams. Conclusion APR data do not demonstrate an increased risk of overall birth defects with DTG use above the population expected rate of defects (2.72 to 4.17 per 100 live births from Metropolitan Atlanta Congenital Defects Program [MACDP] and Texas Birth Defects Registry [TBDR] respectively). The number of periconception exposure outcomes is not yet sufficient to evaluate potential association of DTG with NTD. The Registry continues to closely monitor birth defects, including NTDs in pregnancies exposed to DTG and other integrase inhibitors. Disclosures Vani Vannappagari, MBBS, MPH, PhD, ViiV Healthcare Limited (Employee) Jessica Albano, PhD, MPH, Syneos Health (Employee, Shareholder) Leigh Ragone, MS, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Taylor Cook, BS, Syneos Health (Employee) Angela Scheuerle, MD, ViiV (Independent Contractor) William R. Short, MD, Gilead Sciences (Individual(s) Involved: Self): Consultant; ViiV (Individual(s) Involved: Self): Consultant Claire Thorne, MSc, PhD, MSD (Grant/Research Support)ViiV Healthcare (Grant/Research Support, Other Financial or Material Support, Contributor to Think Tank)

Methods. Descriptive analysis with frequency tabulation of pregnancy and neonatal outcomes is reported. Periconception is defined as any exposure within two weeks prior to or through 28 days after conception.
Conclusion. APR data do not demonstrate an increased risk of overall birth defects with DTG use above the population expected rate of defects (2.72 to 4.17 per 100 live births from Metropolitan Atlanta Congenital Defects Program [MACDP] and Texas Birth Defects Registry [TBDR] respectively). The number of periconception exposure outcomes is not yet sufficient to evaluate potential association of DTG with NTD. The Registry continues to closely monitor birth defects, including NTDs in pregnancies exposed to DTG and other integrase inhibitors.
Disclosures Background. The primary analysis of the STAT study demonstrated the feasibility, efficacy, and safety of using DTG/3TC as a first-line regimen in a test-and-treat setting through 24 weeks, with therapy adjustments for baseline resistance or hepatitis B virus (HBV) co-infection. Here we present secondary analyses through Week 48 of virologic outcomes in participants by baseline viral load (VL).
Methods. STAT is a single-arm study of treatment-naive adults with HIV-1 infection who initiated DTG/3TC ≤ 14 days after HIV-1 diagnosis without availability of screening/baseline laboratory results. If baseline testing indicated DTG or 3TC resistance, HBV co-infection, or creatinine clearance < 30 mL/min/1.73 m 2 , then antiretroviral therapy (ART) was potentially adjusted and participants remained on study. Efficacy analyses included proportion of participants with HIV-1 RNA < 50 c/mL regardless of ART regimen at Week 48, among all participants (ITT-E missing = failure analysis) and among participants with available HIV-1 RNA data at Week 48 (observed analysis).
Results. Of 131 enrolled, DTG/3TC treatment was adjusted in 10 participants, and of those with available data (n=7), all (100%) achieved HIV-1 RNA < 50 c/mL at Week 48. At Week 48, 82% (107/131) of all participants ( Figure 1) and 97% (107/110) of those with available data (Figure 2) achieved HIV-1 RNA < 50 c/ mL. Of participants with baseline VL ≥ 500,000 c/mL, 89% (17/19) achieved HIV-1 RNA < 50 c/mL at Week 48; the remaining 2 withdrew from study. Of participants with baseline VL ≥ 1,000,000 c/mL, 90% (9/10) achieved HIV-1 RNA < 50 c/mL at Week 48 (Table); the remaining participant withdrew consent. Of the 17 participants with baseline VL ≥ 500,000 c/mL with available data through Week 48, 76% (13/17) achieved virologic suppression by Week 24. One participant with baseline VL ≥ 500,000 c/mL switched from DTG/3TC before the Week 48 assessment. Of the 9 participants with baseline VL ≥ 1,000,000 c/mL with available data through Week 48, most participants (8/9; 89%) were suppressed by Week 24. Figure 1. Virologic outcomes at Week 48, overall and by baseline VL and CD4+ cell count: ITT-E missing = failure analysis.  Conclusion. These data provide evidence for the efficacy and feasibility of using DTG/3TC as a first-line regimen in a test-and-treat setting, including among participants with very high baseline VL.