CROI 2020 Abstract eBook
130LB SAFETY AND EFFICACY OF DTG VS EFV AND TDF VS TAF IN PREGNANCY: IMPAACT 2010 TRIAL Lameck Chinula 1 , Sean S. Brummel 2 , Lauren Ziemba 2 , Lynda Stranix- Chibanda 3 , Anne Coletti 4 , Chelsea Krotje 5 , Patrick Jean-Philippe 6 , Lee Fairlie 7 , Tichaona Vhembo 3 , Deo Wabwire 8 , Risa M. Hoffman 9 , Paul E. Sax 10 , Jeffrey S. Stringer 11 , Judith S. Currier 9 , Shahin Lockman 10 1 University of North Carolina Project–Malawi, Lilongwe, Malawi, 2 Harvard T.H. Chan School of Public Health, Boston, MA, USA, 3 University of Zimbabwe, Harare, Zimbabwe, 4 FHI 360, Durham, NC, USA, 5 Frontier Science & Technology Research Foundation, Inc, Amherst, NY, USA, 6 DAIDS, NIAID, Rockville, MD, USA, 7 Wits Reproductive Health and HIV Institute, Johannesburg, South Africa, 8 Makerere University–Johns Hopkins University Research Collaboration, Kampala, Uganda, 9 University of California Los Angeles, Los Angeles, CA, USA, 10 Brigham and Women's Hospital, Boston, MA, USA, 11 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Background: We compared the safety and virologic efficacy of dolutegravir (DTG) + emtricitabine (FTC)/tenofovir alafenamide fumarate (TAF) vs. DTG + FTC/tenofovir disoproxil fumarate (TDF) vs. efavirenz (EFV)/FTC/TDF in pregnant women. Methods: Pregnant women with HIV-1 in 9 countries were randomized 1:1:1 to start open-label DTG+FTC/TAF, DTG+FTC/TDF, or EFV/FTC/TDF at 14-28 weeks gestational age (GA). Up to 14 days’ pre-entry antiretroviral treatment (ART) was permitted. In primary efficacy analysis, we compared the combined DTG-containing arms to the EFV arm for non-inferiority (-10%margin), then superiority, with regard to delivery HIV RNA<200 cp/mL. Safety outcomes compared between all arms were a) composite adverse pregnancy outcome (preterm delivery [PTD]<37 weeks, small for GA [SGA]<10th centile, stillbirth [SB] or spontaneous abortion [SAB]); b) maternal grade>3 adverse event (AE) through 14 days postpartum; and c) infant grade>3 AE through 28 days. Neonatal death (NND, <28 days) was also evaluated. Results: We randomized 643 women: 217 to DTG+FTC/TAF, 215 to DTG+FTC/ TDF, and 211 to EFV/FTC/TDF. Baseline medians were: GA 21.9 weeks, HIV RNA 903 cp/mL, CD4 count 466 cells/uL; 83% took ART prior to entry (median 6 days). Median antepartum follow-up was 17.4 weeks. Delivery HIV RNA, available for 605 (94.1%) women, was <200 cp/mL in 395 of 405 (97.5%) in the combined DTG arms vs 182 of 200 (91.0%) in the EFV/FTC/TDF arm (difference 6.5% [95%CI 2.0%, 10.7%]; p=0.005). Pregnancy outcomes were available for 640 (99.5%). Fewer women in the DTG+FTC/TAF arm (24.1%) had an adverse pregnancy outcome than in DTG+FTC/TDF (32.9%, p=0.043) or EFV/FTC/TDF (32.7%, p=0.047) arms. Although SB was more frequent with DTG+FTC/TAF (3.7%) and DTG+FTC/TDF (5.2%) than EFV/FTC/TDF (1.9%) (all by-arm p-values ≥0.05; post-hoc), NND was more frequent with EFV+FTC/TDF (4.8%) than DTG+FTC/ TAF (1.0%, p=0.019) or DTG+FTC/TDF (1.5%, p=0.053). Combined SB or NND rates were similar by arm (post-hoc analysis). At least one grade>3 AE occurred in 148 (23.0%) women and 105 (17.0%) infants (all by-arm p-values ≥0.05). Two babies were diagnosed with HIV at <14 days, one each in DTG+FTC/TAF and DTG+FTC/TDF arms (maternal delivery HIV-1 RNA 58,590 and <40 cp/mL, respectively). Conclusion: DTG-containing ART started at GA 14-28 weeks had superior virologic efficacy at delivery to EFV/FTC/TDF. DTG+FTC/TAF had the lowest composite frequency of adverse pregnancy outcomes. Maternal and infant AE outcomes were similar by arm.
DOLUTEGRAVIR-CONTAINING ART DOES NOT REDUCE ETONOGESTREL IMPLANT CONCENTRATIONS Rena Patel 1 , Randy Stalter 1 , Maricianah Onono 2 , Evelyn Brown 3 , Lilian Adeojo 4 , Catherine K.Adhu 5 , Kimberly K. Scarsi 6 1 University of Washington, Seattle, WA, USA, 2 Kenya Medical Research Institute, Nairobi, Kenya, 3 University of Washington in Kenya, Nairobi, Kenya, 4 NIH, Bethesda, MD, USA, 5 Jaramogi Oginga Odinga Teaching & Referral Hospital, Kisumu, Kenya, 6 University of Nebraska Medical Center, Omaha, NE, USA Background: Concomitant use of efavirenz-containing antiretroviral therapy (ART) is known to reduce etonogestrel (ENG) concentrations, leading to reduced contraceptive effectiveness of subdermal implants. Dolutegravir (DTG)-containing ART is now the preferred first-line regimen for women of reproductive potential. However, DTG’s drug-drug interactions with hormonal contraceptives have been narrowly evaluated thus far, and understanding any potential for interactions between subdermal implants and DTG is important as countries pursue national rollout of DTG-containing ART. Methods: We conducted a prospective, open-label pharmacokinetic study among women of reproductive potential in Kisumu, Kenya. Women were either HIV-positive, virologically suppressed, and receiving DTG-containing ART for at least 30 days prior to enrollment, or HIV-negative and not receiving any antiretrovirals (control group). An ENG 68mg subdermal implant was placed as part of routine clinical care and women were enrolled in this study within 2 weeks of implant placement. Blood samples were drawn at 2, 4, 8, 12, 16, 20, and 24 weeks after study entry. We analyzed plasma ENG concentrations using a validated LC-MS/MS assay (range 25-30,000 pg/mL). We describe per visit ENG concentrations using median (range) and compare the concentrations per visit between DTG-containing ART and the control groups using geometric mean ratio (GMR; 90% confidence interval) and the Wilcoxon rank sum test. Results: All women were black African. The median age was 35 and 25 years, and weight was 62.5 and 59.0 kg in the DTG-containing ART and control groups, respectively. Women in the DTG-containing ART group were on this ART for a median of 6.7 (range 4.3-8.3) months prior to study enrollment. ENG plasma concentrations for the DTG and control groups were 692 (470-989) and 588 (277-1050) pg/mL at week 2, respectively, and decreased to 456 (250-720) and 268 (136-496) pg/mL by week 24, respectively (Table). ENG exposure in the DTG- containing ART group was 19-54% higher compared to controls (all p<=0.05). Conclusion: In the first of its kind study, we observed modestly higher ENG concentrations among women using DTG-containing ART vs. HIV-negative women. Our findings suggest that no detrimental drug-drug interactions exist with concomitant use of ENG implants and DTG. DTG-containing ART represents a preferable alternative to efavirenz-containing ART for women already using or desiring an ENG implant.
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