Lopinavir and atazanavir

in pregnancy: preterm delivery rates,

infant outcomes and virological efficacy.

Dr Melissa PerryGuy’s & St Thomas’ NHS Foundation Trust

LondonUnited Kingdom

Low rates of mother-to-child transmission of HIV in UK & Ireland

Townsend et al CROI 2013 poster 906

What we know?Excellent ART coverage Excellent PMTCT

Preterm delivery concernsDrug or drug class? Timing of ART?

Lorenzi P, Spicher VM, Laubereau B et al. AIDS 1998; 12: F241–F247

Association between ART and PTD

European Collaborative Study. J Acquir Immune Defic Syndr 2003;32: 380–387.

Association between ART and PTD

Townsend CL, Cortina-Borja M et al AIDS 2007; 21: 1019–1026.

1.5-fold increased risk of PTD on ART - No association between PTD and PI-containing ART

Townsend CL, Willey BA et al. AIDS 2009; 23: 519–524.

Association between ART and PTD

European Collaborative Study AIDS 2000; 14: 2913–2930.

Association between ART and PTD- particularly marked in patients on PI’s

European Collaborative Study. AIDS 2004; 18: 2337–2339.

Association between ART and PTD- particularly marked in patients on PI’s

Cotter AM, Garcia AG, Duthely ML et alJ Infect Dis 2006; 193: 1195–1201.

Association between ART and PTD - only if ART included a PI

Schulte J, Dominguez K, Sukalac T et al Pediatrics 2007; 119: e900–e906.

Association between ART and PTD - only if ART included a PI

Tuomala RE, Shapiro DE, Mofenson LM et al. N Engl J Med 2002; 346: 1863–1870.

No Association between ART and PTD

Tuomala RE, Watts DH, Li D et al. J Acquir Immune Defic Syndr 2005;38:449–473.

No Association between ART and PTD

Kourtis AP, Schmid CH, Jamieson DJ, Lau J. AIDS 2007;21: 607–615

No Association between PTD and PI-containing ART

Powis KM, Kitch D, Ogwu A et al. J Infect Dis 2011; 204: 506–514.

Association between PI-based ART and PTD

Kesho Bora Study Group, de Vincenzi I. Lancet Infect Dis 2011; 11: 171–180.

No Association between ART and PTD

www.bhiva.org

As per HIV treatment guidelines for non pregnant individuals - based on VL, CD4 & genotype

Conceive on ART remain on the same ART*

Commencing ART for maternal health start ART ASAP

All women should commence ART by 24W*No recommended dose adjustments.Therapeutic drug monitoring - only consider.

In clinical practice:Two most commonly used PIs in pregnancy

in the UK are ritonavir-boosted lopinavir and ritonavir-boosted atazanavir

Our Question?Atazanavir or lopinavir in pregnancy?

OutcomesPre term deliveryInfant outcomes

transmissionbirth weightphototherapy requirementbirth defects

Tolerability and viral responseclinical and virological aspects

Retrospective case note review9 London HIV specialist care centres

All pregnanciescommenced on atazanavir or lopinavir

orconceived on atazanavir or lopinavirdelivered 1st Sept 2007 - 30th Aug 2012

Resultsn=493 pregnancies Median age 33 years Ethnicity

81% Black African. HIV acquisition

97% through heterosexual exposure0.6% from injecting drug use

Hepatitis co-infectionHep B – 4%Hep C – 1%

Atazanavir LopinavirTotal number of patients: 187 306

Use of Lopinavir vs. Atazanavir in Pregnant women over time

0

2

4

6

8

10

12

14

Sept 07 - August 12

Num

ber o

f pat

ient

s

AtazanavirLopinavir

NRTI Backbone

Atazanavir Lopinavir% on standard dose 88% 92%

Atazanavir

3%

20%

7%

70%

Truvada

Combivir

Kivexa

Other

Lopinavir

24%

8%6%

62%

Numbers of patients

Atazanavir Lopinavir Total

Conceived on95 82 177

Post conception 92 224 316

Total 187 306 493

% of women who delivered <37W

*8 percent (1 in 13) of general population UK live births are born preterm

Atazanavir Lopinavir p-value

Overall: 19 (13%) 40 (14%) ns

Conceived on 11 (15%) 8 (12%) 0.98

Post conception 16 (20%) 24 (12%) 0.12

Atazanavir Lopinavir

Transmissions 1 (0.7%) 1 (0.4%)

Overall MTCT rate: 0.5%

% requiring phototherapy 2 (2%) 2 (1%)

Birth defects 3 (3%) 2 (2%)(Conceived on)

% <2500g birth weight 23 (15%) 40 (15%)

Infant outcomes

Tolerability / toxicity

Atazanavir Lopinavir

Conceived on 2 (2%) 5 (6%)

Post conception 5 (5%) 24 (11%)

55% related to nausea & vomiting

Viral load decay

(despite the majority of women on ATV/r receiving the standard 300/100mg dose and co-prescribed tenofovir.)

Atazanavir Lopinavir

Gestation 20w 22w (at starting ART)

% VL<=50 cps/ml 85% 81% 0.61 at delivery

Median days VL <= 50 cps/ml 56days 43days 0.52

ConclusionsBoth regimens were successful in preventing MTCT

No significant difference between ATV/r and LPV/r in

preterm delivery rates infant outcomes

tolerability and toxicity virological efficacy

The PTD rates were comparable to those reported in previous studies and more favourable than others

Limitations• Retrospective case note review

• Small case numbers• Lacks power

• Limited scope for multivariable logistic regression analysis

SummaryThis is the first study comparing

pregnancy outcomes between these two PIs.

This study suggests both PI regimens at standard dosing are comparable in terms of virological efficacy, preterm delivery rates and infant outcomes.

Disclosure

I have received travel grants from Abbott, Boehringer Ingelheim, ViiV, Gilead.

Authors & Affiliations Melissa Perry1, Katie Conway1, Caroline Sabin2,

Stuart Flanaghan3, Ellen Dwyer4, Stevenson J4, Larissa Mulka5, Anna McKendry6, Elizabeth Williams8, Alison Barbour10, Sherie Roedling6, Rimi Shah7, Jane Anderson3, Mette Rodgers4, Chris Wood8, Liat Sarner9, Phillip Hay10, Graham Taylor5, Annemiek DeRuiter1.

1Guys and St Thomas NHS Foundation Trust.

2Department of Infection and Population Health, Division of Population Health, UCL Medical School.

3Homerton University Hospital NHS Foundation Trust. 4Croydon University Hospital.5Imperial College Healthcare NHS Trust. 6Central and North West London NHS Foundation Trust.7Barnet and Chase Farm hospital NHS trust. 8The North Middlesex University Hospital NHS Trust. 9Barts Health NHS Trust.10St Georges Healthcare NHS Trust

Questions?