RALTEGRAVIR vs LPV/R FOR LATE-PRESENTERS PREGNANT WOMEN. Carlos Brites1,2, Isabella Nóbrega3, Ana Gabriela Travassos2, Estela Luz1,2, Cristiani Stelitani2, Sheyla Fernandes3, Carmeire Figueredo3, Cynthia Lorenzo3, Eduardo M. Netto1,2 1- Universidade Federal da Bahia, Brazil, 2- Fundação Bahiana de Infectologia, Bahia, Brazil 3- Centro de Ensino, Diagnóstico, Assistência e Pesquisa em AIDS, Bahia, Brazil

Disclosures Dr. Brites has received research grants awarded to his institution from Merck, Jansen, BMS and Glaxo Smith-Kline. He also received honorarium for consultations/advisory board, and has served as speaker for BMS, Merck, Jansen, and Gilead. This work was funded by Merck, through a MISP (Merck Investigator Study Program), and by CNPq 448402/2014-9

Background and rationale The magnitude of maternal VL at delivery is a strong predictor of HIV-1 MTCT Late-presenters pregnant women need potent ART regimens, capable of providing a fast decrease in VL levels In Bahia, Brazil, around 25% of pregnant women are diagnosed with HIV only after 28 weeks of gestational age Raltegravir provides a rapid drop in VL, and seems to be safe in pregnancy There is no published trial comparing RAL and other ARV drugs in pregnant women

Study Design Hypothesis Primary Endpoints - RAL-based ARV regimens are able to suppress HIV viremia in late-presenters pregnant women to undetectable levels at the moment of delivery Primary Endpoints - the proportion of patients with HIV-1 RNA viral load < 50 copies/ml at the end of pregnancy - time to reach a VL<50 copies / ml* * Time measured from date of study entry/randomization

Study Design Open-label, randomized, pilot study to compare the safety and efficacy of AZT+3TC+Raltegravir vs. AZT+3TC+LPV/r in late-presenters pregnant women. Open-label, randomized 1:1 (N=44) AZT, 3TC, RAL AZT, 3TC, LPV/r Screening Week 2 Week 4 Week 6 Delivery Primary endpoint: VL <50 cps/mL at delivery (Snapshot) Study terminated by IRB after enrollment of 33 patients, due to a significant difference between groups.

Inclusion Criteria and Assessments Confirmed HIV-1 infection VL >1000 copies/ml Gestational age ≥ 28 weeks Age ≥ 15 years Assessments: Time to reach a VL<50 cps/mL Proportion of patients with VL<50 cps/mL at delivery Clinical/laboratory adverse events MTCT rates (RT-PCR for HIV plasma RNA in babies at 4 weeks)

276 Assessed for eligibility 243 Excluded 197 low gestational age, 27 PVL<1,000 cps/mL, 13 prior ART, 6 younger than 15 years 33 randomized LPV/r 16   RAL 17 All participants completed the study

Baseline Characteristics Treatment group Characteristic   Total (N=33) LPV/r (N=16) RAL (N=17) Age (years) Mean 26.7 Race/Ethnicity (N) White 2 - Black/Mixed 31 14 17 Gestational age (weeks) 32.8 32.7 32.5 HIV-1 RNA (cps/mL) Median (Q1-Q3) 15309 (4087-36740) 21143 (3745 - 42750) 12859 (5644 – 23165) CD4 (cells/mL) 509 532 497 Hb (g/dL) 10.7

HIV-1 RNA Plasma Viral Load at Weeks 2, 4, and 6

Proportion VL ≤50 copies/mL ITT, off-ART=failure (SNAPSHOT) Probability of PVL<50 cps/mL at delivery in late presenters pregnant women treated either with Raltegravir or Lopinavir/r plus NRTIs   W2 W4 W6 At delivery LPV/r 1/15 (6%) 2/11 (15%) 2/10 (20%) 4/12 (25%) RAL 7/10 (41%) 9/12 (43%) 10/10 (100%) 13/17 (76%) RR (95% CI) 6.6 (0.9-47.8) 4.9 (1.3- 18.2) 5.0 (1.4-17.3) 3.1 (1.3-7.4) Mean time to delivery was similar for RAL (43 days) and LPV/r (42.4 days) arms

MTCT All newborns received zidovudine for 4 weeks, according to Brazilian guidelines Two newborns in LPV/r arm also received nevirapine (3 doses) because maternal VL>1000 cps/mL at delivery All babies tested negative for HIV-1 plasma RNA at week 4 (RT-PCR)

Summary of Adverse Events Pregnant women AE LPV/r (%) RAL (%) P value Any 10 (62.5) 4 (23.5) 0.03 Diarrhea 5 (31.5) 0.02 Nausea/vomiting Headache 3 (18.7) 0.1 No discontinuation due to AE No SAE detected

Conclusions RAL was significantly more effective than LPV/r in providing VL< 50 cps/mL, at delivery RAL promoted a faster decay in VL, in comparison to LPV/r, at all timepoints LPV/r was less well tolerated than RAL Largely due to GI AE No cases of MTCT detected

Conclusions RAL is a safe and effective option to treat late- presenters, HIV-positive pregnant women and should be considered as a preferred ARV in such situations.

Acknowledgments Study participants Merck CNPq