Is Highly Active Antiretroviral Therapy (HAART) in pregnancy protective against maternal mortality? Results from a large

DREAM cohort in Malawi and Mozambique

Presented by Leonardo Palombi (Italy).

G. Liotta1 , S. Mancinelli1 , E. Gennaro 2, P. Scarcella1, K. Saines-Nielsen3,N. Abdul Magid4, P. Germano5, J. Haswell6, G. Guidotti7 , E.Buonomo1,

A. Doro Altan1, L. Palombi1 , MC. Marazzi8

1 University of Tor Vergata, Public Health Dept., Rome. Italy. 2 University “G. D’Annunzio” , Chieti, Italy 3 UCLA. Pediatrics. Los Angeles, USA4 DREAM Program. Community of S. Egidio, Maputo, Mozambique. 5 DREAM Program. Community of S. Egidio, Rome, Italy. 6 DREAM Program. Community of S. Egidio, Blantyre, Malawi. 7 Pisa University, Italy8 LUMSA University, Rome, Italy

TUAB0201TUAB0201

Background

HIV-1 infection is a major cause of maternal mortality (MM) in resource-limited settings.

The DREAM (Drug Resource Enhancement against AIDS and Malnutrition) Program routinely offers triple ART from pregnancy throughout the postpartum period regardless of maternal CD4 cell count for prevention of mother to child HIV transmission (PMTCT) at clinical centers in sub-saharan Africa.

We evaluated the uptake of triple ART and maternal mortality in our PMTCT cohort at our centers in Malawi and Mozambique.

In prior cohort studies, our group reported a significant association between duration of triple ART in pregnancy and maternal mortality

Methods Study design: Retrospective cohort Records for all HIV+ pregnant women accessing 16

DREAM centers in Malawi and Mozambique from 6/2002 to 6/2010 were reviewed. • Group 1: Women starting triple ART during pre-

natal care, n = 8169.• Group 2: Pregnant women on established triple

ART for their own health, n = 1981 Women identified in pregnancy were offered NVP-

based triple ART at 14 weeks (if required for health) or 25 weeks gestation until 6 months for PMTCT.

Specific Aims

1. To determine risk factors associated with maternal mortality during pregnancy until 6 weeks postpartum.

2. To compare mortality, ART uptake, loss to follow-up and laboratory parameters between women receiving triple ART for PMTCT and women on established ART during pregnancy.

3. To evaluate mortality in women beyond the immediate postpartum period according to duration of triple ART exposure with adjustment for time in medical care and duration of antenatal ART.

Baseline parameters: 10,150 womenfrom 6/02 – 6/10 in Malawi + Mozambique

Median IQR: 25 - 75

Age 26 years 23-30

CD4 cells/ mm3 392 258- 563

Log HIV-1 3.9 3.2- 4.4

BMI 23.4 21.5 – 25.7

Hemoglobin 10.0 9.0 – 11.0

Comparison between groups

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Baseline parameters Group 1N=8,169

Mean (SD)

Group 2N =1,982

Mean (SD)

p

HAART in days 832 (586) 1459 (621) <0.001

CD4 cell count 431 (275) 354 (366) <0.001

Viral load cps/ml 3.6 (1.3) 3.8 (1.5) <0.001

Body Mass Index 23.8 (3.6) 22.0 (3.8) <0.001

Hemoglobin 9.9 (3.4) 10.1 (1.9) 0.26

Refusal/Loss to follow up

9.8 3.9 <0.001

Maternal Mortality 1.1 0.7 0.17

Maternal mortality (MM)

Deaths up to 42 days postpartum: 101 (0.99%)• Group 1 (ART during PMTCT): 87/ 8169 (1.1%)• Group 2 (established ART): 14/1981 (0.7%)• Deaths by CD4 cell count strata:

• < 350 cells/ mm3: 1.3%• > 350 cells/ mm3: 0.7%

• Deaths by triple ART exposure:• < 30 days of antenatal ART: 22/ 991 (2.2%) • > 90 days of antenatal ART: 35/ 5260 (0.7%)

Mozambique MMR 520 (0.52%) Unicef 2009

Malawi MMR 1100 (1.1%) Unicef 2009

Multivariate analysis of Maternal Mortality: logistic regression forward stepwise model

Outcome variable Maternal Death

OR 95% CL p

Shorter ART exposure 1.72 1.36 – 2.17 0.001

Baseline Viral Load 0.84 0.61 – 1.17 0.3

Baseline CD4 count 1.57 1.19 – 2.06 < 0.001

Baseline Hemoglobin 1.42 1.06– 1.91 0.02

Baseline BMI 1.98 1.47 – 2.64 < 0.001

Maternal Mortality according to pre-delivery duration of triple ART

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Days of antenatal triple ART

Antenatal observation daysMean (CL95%)

No. of deaths % N

0 - 30 154 (124-185) 22 2.2 991

30 - 90 175 (166-185) 44 1.1 3899

91 - 270 262 (251-274) 21 0.6 3282

> 270 1059 (733-1386)* 14 0.7 1978

Total 373 (309-438) 101 1.0 10150

* p<0.001

Mortality in women over 4 years adjusted for observation time under triple ART

Days of antenatal triple ART

Total Observation time - days

mean (CL95%)

No. of deaths % N

0-30 779 (738-821) 45 4.5 991

31-90 817 (799-835) 92 2.4 3899

91-270 865 (846-885) 58 1.8 3282

> 270 1459 (1431-1486) 39 2.0 1978

Total 954 (942-967) 234 2.3 10150

Risk factors for mortality up to 4 years following delivery- Cox regression analysis

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Sig. HR 95.0% CI for HR

Lower Upper

HAART >270 (reference) 0.000 1.0

0-30 days 0.000 5.5 3.5 8.7

31-90 0.000 2.8 1.9 4.3

91-270 0.003 1.9 1.2 2.8

Viral Load > 5Log (reference) 0.008 1.0

<4 CLog/ml 0.025 0.6 0.3 0.9

4.0-5.0 0.857 0.9 0.6 1.4

CD4 >350 0.000 1.0

< 200 Cell/microL 0.000 1.9 1.3 2.7

200-350 0.001 1.7 1.2 2.3

Sig. HR 95.0% CI for HR

Lower Upper

BMI >20.0 (reference) 0.000 1.0

<18.5 0.000 2.7 1.8 4.0

18.5-20.0 0.012 1.7 1.1 2.5

Hb >10.0 (reference) 0.019 1.0

8.0-10.0 gr/100cc 0.017 1.6 1.1 2.4

<8.0 0.016 1.4 1.1 1.9

Risk factors for mortality up to 4 years following delivery- Cox regression analysis

(2)

CD4

Viral Load

Hemoglobin

BMI

Summary Maternal mortality is significantly associated with

duration of triple ART, baseline CD4 cell count, BMI and degree of anemia.

Women on established ART while pregnant, women with CD4 counts > 350 and women with > 90 days of antenatal ART have a lower mortality risk during pregnancy and immediate postpartum period.

Women with extended antenatal ART (beyond 270 days prior to delivery) have the highest four year survival benefit.

Summary Provision of triple ART in pregnancy carries a significant

survival benefit and renders maternal mortality in HIV+ women (1%) equivalent or lower to population country-wide statistics and significantly lower than the mortality of untreated HIV+ mothers in Malawi (6%). Lettow 2011

Women who present to medical care late in pregnancy and receive shorter courses of triple ART (lowest triple ART exposure in absolute terms) have a higher mortality risk over 4 years.

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Conclusions Triple ART for PMTCT purposes have a

significant impact on maternal mortality in resource-limited settings.

Extended triple ART carries a survival benefit extensive to all women regardless of CD4 cell strata.

Provision of triple ART to all HIV-infected women significantly decreases the risk of maternal death in the short and medium term. 19

Grazie!

• To our patients• To our sponsors• To the members of

the DREAM Program