1. 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

2. 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 /2014-9

3. 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

4. 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

5. 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.

6. 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)

7. 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

8. 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
( )
21143
( )
12859
(5644 – 23165)
CD4 (cells/mL)
509
532
497
Hb (g/dL)
10.7

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

10. 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
( )
4.9
( )
5.0
( )
3.1
( )
Mean time to delivery was similar for RAL
(43 days) and LPV/r (42.4 days) arms

11. 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)

12. Summary of Adverse Events Pregnant womenAE
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

13. 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

14. 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.

15. Acknowledgments
Study participants
Merck
CNPq