885. Pregnancy Outcomes and Pharmacokinetics in Pregnant Women Living with HIV Exposed to Long-Acting Cabotegravir and Rilpivirine in Clinical Trials

Abstract Background Limited data exist among women living with HIV who become pregnant while exposed to long-acting (LA) cabotegravir (CAB) and rilpivirine (RPV). We report outcomes in pregnant participants and LA pharmacokinetic (PK) tail data in pregnant women exposed to CAB+RPV with live births. Methods Women of reproductive potential exposed to ≥ 1 dose of CAB+RPV (oral/LA) from ViiV-sponsored Phase 2/3/3b clinical treatment studies and the compassionate use program were included in this analysis and pregnancies identified. Per protocol, upon identification of pregnancy, CAB+RPV was discontinued and an alternative regimen initiated, with continued quarterly PK sampling for 52 weeks post last injection during long-term safety follow-up (LTFU). Descriptive characteristics of pregnant women and birth outcomes and available CAB and RPV PK during pregnancy for those with live births are summarized. Results As of March 31, 2021, 26/325 women of reproductive potential (age 18–49 years) became pregnant while exposed to CAB+RPV (5 oral, 21 LA [including 3 following LA discontinuation]). There were 11 live births (1 oral, 10 LA), of which 10 had no reported congenital abnormalities and 1 had reported congenital ptosis, in a pre-term infant with intrauterine growth restriction. There were 9 elective terminations and 6 miscarriages (5 in first 9 weeks of gestation). Ten women exposed to intramuscular CAB+RPV LA became pregnant with subsequent live birth outcomes, including 3 infants conceived during the PK tail in LTFU. All women were virologically suppressed at time of pregnancy identification. In women becoming pregnant on LA dosing, plasma CAB and RPV concentrations during pregnancy were within the range of expected concentrations in non-pregnant women. Two of 10 women with live births exposed to CAB+RPV LA continued LA therapy during pregnancy (compassionate use program participants). Conclusion Pregnancy outcomes in women exposed to CAB+RPV at conception are consistent with earlier findings. There was 1 reported congenital anomaly among 11 live births. CAB and RPV PK tail in pregnancy was within the expected range for non-pregnant women. Ongoing monitoring of birth defects within the antiretroviral pregnancy registry and pregnancy surveillance within the treatment program continues. Disclosures Parul Patel, PharmD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Susan L. Ford, PharmD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Mark Baker, PhD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Claudia Meyer, MBChB, MRCP, MSc, FRCPath, DTM&H, GlaxoSmithKline (Employee, Shareholder) Louise Garside, PhD, GlaxoSmithKline (Employee) Ronald D’Amico, DO, MSc, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Rodica Van Solingen-Ristea, MD, Janssen Research and Development (Employee)ViiV Healthcare (Employee) Herta Crauwels, PhD, Janssen (Employee) Joseph Polli, PhD, FAAPS, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Ciara Seal, BS, GlaxoSmithKline (Employee, Shareholder) Shanker Thiagarajah, MB ChB, GlaxoSmithKline (Employee, Shareholder) Eileen Birmingham, MD, MPH, Janssen Research and Development (Employee, Shareholder) William Spreen, PharmD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Bryan Baugh, MD, Janssen, Johnson & Johnson (Employee, Shareholder) Matthew Bosse, DO, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Vani Vannappagari, MBBS, MPH, PhD, ViiV Healthcare Limited (Employee)


Background.
Limited data exist among women living with HIV who become pregnant while exposed to long-acting (LA) cabotegravir (CAB) and rilpivirine (RPV). We report outcomes in pregnant participants and LA pharmacokinetic (PK) tail data in pregnant women exposed to CAB+RPV with live births.
Methods. Women of reproductive potential exposed to ≥ 1 dose of CAB+RPV (oral/LA) from ViiV-sponsored Phase 2/3/3b clinical treatment studies and the compassionate use program were included in this analysis and pregnancies identified. Per protocol, upon identification of pregnancy, CAB+RPV was discontinued and an alternative regimen initiated, with continued quarterly PK sampling for 52 weeks post last injection during long-term safety follow-up (LTFU). Descriptive characteristics of pregnant women and birth outcomes and available CAB and RPV PK during pregnancy for those with live births are summarized.
Results. As of March 31, 2021, 26/325 women of reproductive potential (age 18-49 years) became pregnant while exposed to CAB+RPV (5 oral, 21 LA [including 3 following LA discontinuation]). There were 11 live births (1 oral, 10 LA), of which 10 had no reported congenital abnormalities and 1 had reported congenital ptosis, in a pre-term infant with intrauterine growth restriction. There were 9 elective terminations and 6 miscarriages (5 in first 9 weeks of gestation). Ten women exposed to intramuscular CAB+RPV LA became pregnant with subsequent live birth outcomes, including 3 infants conceived during the PK tail in LTFU. All women were virologically suppressed at time of pregnancy identification. In women becoming pregnant on LA dosing, plasma CAB and RPV concentrations during pregnancy were within the range of expected concentrations in non-pregnant women. Two of 10 women with live births exposed to CAB+RPV LA continued LA therapy during pregnancy (compassionate use program participants).
Conclusion. Pregnancy outcomes in women exposed to CAB+RPV at conception are consistent with earlier findings. There was 1 reported congenital anomaly among 11 live births. CAB and RPV PK tail in pregnancy was within the expected range for non-pregnant women. Ongoing monitoring of birth defects within the antiretroviral pregnancy registry and pregnancy surveillance within the treatment program continues.
Disclosures Background. The COVID-19 pandemic has disrupted health care services for people living with HIV (PLWH). This study aimed to compare rates of clinical visits, viral load monitoring and antiretroviral therapy (ART) regimen discontinuation among virally suppressed PLWH in the US before and during the COVID pandemic.
Methods. The study population consisted of ART-experienced PLWH ≥18 years of age and active in care in the OPERA cohort within 2 years prior to 31OCT2020. Virally suppressed PLWH (i.e., viral load < 200 copies/mL) were included if they switched to either dolutegravir/lamivudine or a dolutegravir-or bictegravir-based 3-drug regimen between 01MAY2019 and 30APR2020. The study periods spanned from 01MAY2019 to 28FEB2020 (pre-COVID) and 01MAR2020 to 31OCT2020 (during COVID). Incidence rates of clinical visits, viral load measurements and regimen discontinuation were estimated using univariate Poisson regression for both study periods. In-person visits comprised any scheduled or walk-in outpatient, inpatient, emergency or laboratory visit. Telehealth visits comprised any phone or video encounters.

Conclusion.
The COVID pandemic has led to an important reduction in the frequency and type of clinical follow-up visits and viral load monitoring among virally suppressed PLWH in the US. A reduction in regimen discontinuation rates was also observed, presumably associated to less frequent follow-up. The long-term impact of the pandemic on HIV care remains uncertain.