RALTEGRAVIR vs LPV/R FOR LATE-PRESENTERS PREGNANT WOMEN.

Slides:



Advertisements
Similar presentations
Switch to RAL-containing regimen - Canadian Study - CHEER - Montreal Study - EASIER - SWITCHMRK - SPIRAL.
Advertisements

PROMISE Introduction to PROMISE Protocol May 6, 2009.
Comparison of INSTI vs PI  FLAMINGO  GS  ACTG A5257.
Presenter : Dr T. G. Nematadzira on behalf of The IMPAACT PROMISE 1077BF/1077FF Team Efficacy and Safety of Two Strategies to Prevent Perinatal HIV Transmission.
Switch to TDF/FTC/RPV  SPIRIT Study. SPIRIT study: Switch PI/r + 2 NRTI to TDF/FTC/RPV TDF/FTC/RPV STR 24 weeks 48 weeks Primary Endpoint Secondary Endpoint.
Single-Dose Perinatal Nevirapine plus Standard Zidovudine to Prevent Mother to Child Transmission of HIV-1 in Thailand NEJM July 15, 2004 Lallemant et.
TO EVALUATE EARLY ANTIVIRAL RESPONSE AND SAFETY OF A DUAL BOOSTED PROTEASE INHIBITORS REGIMEN INCLUDING LOPINAVIR/r (LPV) PLUS AMPRENAVIR (AMP) OR FORTOVASE.
1 Atazanavir (ATV) With Ritonavir (RTV) or Saquinavir (SQV) vs Lopinavir/Ritonavir (LPV/RTV) in Patients With Multiple Virologic Failures 24-Week Results.
Switch to LPV/r monotherapy  Pilot LPV/r  M  LPV/r Mono  KalMo  OK  OK04  KALESOLO  MOST  HIV-NAT 077.
Comparison of NNRTI vs PI/r  EFV vs LPV/r vs EFV + LPV/r –A5142 –Mexican Study  NVP vs ATV/r –ARTEN  EFV vs ATV/r –A5202.
Switch to LPV/r monotherapy  Pilot LPV/r  M  LPV/r Mono  KalMo  OK  OK04  KALESOLO  MOST  HIV-NAT 077.
02-15 INFC Substitution of raltegravir for ritonavir-boosted protease inhibitors in HIV-infected patients: The SPIRAL study* 1 Date of preparation:
Effect of High-Dose HSV-2 Suppressive Therapy on Plasma HIV-1 RNA levels: a randomized, cross over trial 6 th IAS conference, Rome, Italy th July,
Switch to RAL-containing regimen  Canadian Study  CHEER  Montreal Study  EASIER  SWITCHMRK  SPIRAL  Switch ER.
POWER 3 Study Confirms Safety and Efficacy of Darunavir/Ritonavir in Treatment-Experienced Patients Slideset on: Molina JM, Cohen C, Katlama C, et al.
Tipranavir/Ritonavir Superior to Comparator PI/Ritonavir at Week 48 in Multiclass-Experienced Patients Slideset on: Hicks CB, Cahn P, Cooper DA, et al.
Adefovir Suppresses HBV DNA Levels in Lamivudine-Resistant HIV/HBV Patients Slideset on: Benhamou Y, Thibault V, Vig P, et al. Safety and efficacy of adefovir.
EPZICOM ® Virologic Response in ART-Naïve Patients with Baseline Viral Loads Above and Below 100,000c/mL Using the A5202 Endpoint K. Pappa, J. Hernandez,
Switch to PI/r monotherapy
Rilpivirine-TDF-FTC versus Efavirenz-TDF-FTC STaR Trial
Treatment-Naïve Adults
Comparison of PI vs PI ATV vs ATV/r BMS 089
ARV-trial.com Switch to TDF/FTC/EFV AI Study 1.
Comparison of INSTI vs INSTI
Dolutegravir plus Rilpivirine as Maintenance Dual Therapy SWORD-1 and SWORD- 2: Design
Comparison of INSTI vs PI
Switch to PI/r + 3TC vs PI/r monotherapy
VESTED Quiz Game
Etravirine in Treatment Experienced DUET-2 (TMC125-C216)
VESTED Quiz Game
ARV-trial.com Switch to LPV/r + RAL KITE Study 1.
Etravirine versus Protease Inhibitor in ARV-Experienced TMC 125-C227
Switch RPV-TDF-FTC from NVP-Based Regimen NEAR-Rwanda Trial
Etravirine in Treatment Experienced DUET-1 (TMC125-C206)
Darunavir/r versus Other PIs in Treatment Experienced POWER 1 and 2
Intensification with INSTI
LPV-RTV versus LPV-RTV + ZDV-3TC in Treatment-Naïve MONARK Trial
Switch to DTG + 3TC ASPIRE Study.
NRTI-sparing SPARTAN PROGRESS RADAR NEAT001/ANRS 143 A VEMAN
Phase 3 Treatment Naïve HIV Coinfection
Switch to DRV/r + 3TC DUAL Study.
Comparison of NNRTI vs NNRTI
Why Dolutegravir? Daniel R. Kuritzkes, M.D.
Comparison of PI vs PI ATV vs ATV/r BMS 089
Switch to BIC/FTC/TAF GS-US GS-US GS-US
Switch to DRV/r monotherapy
Switch to LPV/r monotherapy
Comparison of NNRTI vs PI/r
Comparison of PI vs PI ATV vs ATV/r BMS 089
Comparison of INSTI vs EFV
Comparison of EFV vs MVC
Comparison of PI vs PI ATV vs ATV/r BMS 089
Switch to LPV/r monotherapy
Switch to RAL-containing regimen
Comparison of INSTI vs INSTI
Comparison of NNRTI vs PI/r
Comparison of NRTI combinations
Switch to RAL-containing regimen
Intensification with INSTI
Comparison of PI vs PI ATV vs ATV/r BMS 089
NRTI-sparing SPARTAN PROGRESS RADAR NEAT001/ANRS 143 A VEMAN
Switch to ATV/r monotherapy
Switch to LPV/r monotherapy
ARV-trial.com Switch to ATV/r + RAL HARNESS Study 1.
ARV-trial.com Switch to DTG/ABC/3TC STRIIVING NEAT
Comparison of PI vs PI ATV vs ATV/r BMS 089
NRTI-sparing SPARTAN PROGRESS RADAR NEAT001/ANRS 143 A VEMAN
DTG + 3TC vs DTG + TDF/FTC GEMINI.
Comparison of PI vs PI ATV vs ATV/r BMS 089
Comparison of INSTI vs INSTI
Presentation transcript:

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