CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

Conclusion: In premature infants, the NVP dosing regimen studied was safe and achieved trough concentrations above the 0.1 μg/mL prophylaxis target. NVP concentration at the initial visit increased with decreasing gestational age and subsequent concentrations decreased with increasing postnatal age. No treatment related adverse events were observed. 759 SAFETY OF 6-WEEK TRIPLE ANTIRETROVIRAL PROPHYLAXIS IN HIGH-RISK HIV-EXPOSED INFANTS Suvaporn Anugulruengkitt 1 , Piyarat Suntarattiwong 2 , Pradthana Ounchanum 3 , Ussanee Srirompotong 4 , Watsamon Jantarabenjakul 1 , Jiratchaya Sophonphan 5 , Tim R. Cressey 6 , Chitsanu Pancharoen 1 , Thanyawee Puthanakit 7 , for the CIPHER_AEPEP StudyTeam 1 Chulalongkorn Univ, Bangkok, Thailand, 2 Queen Sirikit Natl Inst of Child Hlth, Bangkok, Thailand, 3 Chiang Rai Prachanukroh Hosp, Chiang Rai, Thailand, 4 Khon Kaen Hosp, Khon Kaen, Thailand, 5 HIV Netherlands Australia Thailand Rsr Collab, Thai Red Cross AIDS Rsr, Bangkok, Thailand, 6 Prog for HIV Prevention and Treatment, Chiang Mai, Thailand, 7 Chulalongkorn Univ, Bangkok, Thailand Background: Triple-drug antiretroviral prophylaxis of zidovudine (AZT)/lamivudine (3TC)/nevirapine (NVP) for high risk HIV-exposed neonates is recommended within the Thai national program. However, there are limited data about the safety and drug concentration achieved with this regimen initiated at birth. Methods: Prospective cohort of infants born from HIV-infected pregnant women in 4 clinical sites in Thailand. Neonates with high risk of HIV transmission (mother has HIV RNA >50 copies/mL prior to delivery or received ART <12 weeks) received AZT and 3TC twice daily, plus NVP (4 mg/kg/dose) once daily, for 6 weeks. As a control group, neonates with standard risk of HIV transmission who received 4-weeks of AZT were also enrolled. Blood for complete blood count, aspatate transaminase (AST), alanine transaminase (ALT) were drawn at birth, aged 1, 2 and 4 month. Adverse events were graded according to DAIDS toxicity table 2014. Sparse plasma NVP concentrations were collected at week 1, 2 and 4 and assayed by a validated liquid chromatography-triple quadrupole mass spectrometry assay. Target NVP plasma trough concentration for prophylaxis was >100 ng/mL. Results: From October 2015 to August 2016, 94 infants were enrolled. 31 neonates received triple ARV prophylaxis and 63 infants received AZT only. Overall, median (IQR) gestational age and birth weight were 38 (37-39) weeks and 2.8 (2.5-3.2) kg, respectively. Maternal ART during pregnancy were 39 (42%) TDF/3TC/EFV, 13 (14%) AZT/3TC/LPV/r, 11 (12%) TDF/3TC/LPV/r and 28 (30%) others. Median (IQR) infant hemoglobin at week 1 and 4 were 16.3 (15.3-18.1) and 10.4 (9.3-11.7) g/dL with no significant difference between the groups. There was no difference in adverse event rates between triple and AZT prophylaxis; all grade anemia (43.6% vs 39.9%), grade 3-4 anemia (3.2% vs 3.1%), all grade neutropenia (3.2% vs 3.0%), grade 3-4 neutropenia (1.1% vs 0.3%), elevated AST (1.1% vs. 1.5%), and elevated ALT (3.2 vs. 4.0%). No infants were diagnosed HIV-infected at age 4 months. NVP concentrations were available from 18 infants: geometric mean (%CV) plasma NVP concentrations were 3075 (67), 2109 (92) and 1438 (72) ng/mL at weeks 1, 2 and 4, respectively (Figure 1). All infants maintained nevirapine concentrations >100 ng/mL during the first 4 weeks. Conclusion: Triple ART infant prophylaxis with 6-weeks of AZT/3TC/NVP in high risk HIV-exposed infants appears to be safe with high NVP concentrations being rapidly achieved and maintained during the first 4 weeks of life.

Poster and Themed Discussion Abstracts

760 SAFETY & PHARMACOKINETICS OF THE MONOCLONAL ANTIBODY, VRC01, IN HIV-EXPOSED NEWBORNS Coleen K. Cunningham 1 , Elizabeth J. McFarland 2 , Edmund V. Capparelli 3 , Petronella Muresan 4 , Charlotte Perlowski 5 , Megan Valentine 5 , Elizabeth Smith 6 , John R. Mascola 7 , Barney S. Graham 7 , for the IMPAACT P1112Team 1 Duke Univ, Durham, NC, USA, 2 Univ of Colorado, Aurora, CO, USA, 3 Univ of California San Diego, La Jolla, CA, USA, 4 Harvard Univ, Boston, MA, USA, 5 FHI360, Durham, NC, USA, 6 DAIDS, NIAID, Rockville, MD, USA, 7 Vaccine Rsr Cntr, NIAID, Bethesda, MD, USA Background: Despite advances in the use of antiretroviral therapy (ART) to prevent mother to child HIV transmission (MCTC), children still become infected for a variety of reasons. A long acting monoclonal antibody might provide a strategy to further prevent transmission. Methods: This is an ongoing, prospective, open label, dose escalating study of a HIV neutralizing, monoclonal antibody, VRC01, administered as a single 20 or 40 mg/kg subcutaneous (SC) dose within 72 hours of birth to infants at increased risk of HIV transmission. Healthy infants and their mothers receive ART as indicated to prevent MTCT. Infants complete safety assessments over 4 hours immediately after dosing and then have safety and pharmacokinetic (PK) measures at 24 hours, days 3, 7, 14, 28, weeks 8, 16 and 24. A non-compartmental PK analysis is used except for CL./F and Vss/F which are estimated using a 2-compartment model. Target VRC01 level is 50 mcg/mL on day 28. Results: Both dose groups are fully accrued (13 each) from 10 sites in the continental US, Puerto Rico, and South Africa. Approximately half enrollees are male (56%) and black (52%). VRC01 was administered soon after birth, at a mean age of 1.8 (SD 1.0) days. Most infants (12/13) in the lower dose group received a single injection (average volume 0.6 mL) while 12/13 infants in the higher dose group received two injections (average volume 0.7 mL). Safety data are available for 25/26 subjects and PK data through day 28 for the lower dose are available for 12/13 (one child was under-dosed and excluded from PK analysis). Overall, VRC01 was well tolerated with no attributable serious systemic reactions. Local reactions were common, occurring in six (46%) and nine (75%) infants in the low and high dose groups, respectively. None of the local reactions were serious and 100% and 90% in the 20 and 40 mg dose groups, respectively, resolved within four hours of injection. Pain at the injection site was reported in only two infants, both grade 1. The PK measures for 12 infants in the 20 mg/kg group are shown in the table. Conclusion: These preliminary results indicate that VRC01 administered to neonates via the SC route is safe and well tolerated. The PK for the lower dose demonstrate circulating antibody through day 28 of life close to but below the target in 9/12 (75%). The half-life of VRC01 would support monthly injections for infants at ongoing risk of HIV infection through breastfeeding.

CROI 2017 329