Presentazione di PowerPoint

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Mother-to Child Transmission in Limited-Resource
Settings The role of the DREAM Programme
Liotta G, Palombi L, Guidotti G, Scarcella P,
Mancinelli S Bartolo M, Narciso P, Perno CF,
Valls Balsquez M, Loureiro S, Abdul Magid N, Da
Cruz Gomez A, Marazzi MC
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Background - Limits of PMTCT programs in
Resource-Limited Settings

• High rate of refusal/lost-to-follow up
• Low rate of deliveries attended by skilled
  personnel, that limited the impact of the
  delivered-centered approach
• Lack of solution for the Transmission through the
  breast milk
• Resistance to First-Line drugs after
  mono/bi-therapy
• Lack of connection between PMTCT programs and
  treatment programs

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Background - The DREAM approach

• Dream provides HAART to prevent MTCT according to
  this general framework
• Free-of charge approach in a public health
  setting
• Medical follow up
• Lab Monitoring including CD4 cell count and viral
  load
• Nutritional evaluation and supplementation
• Intensive program to reinforce the adherence
  including Health Education and Peer Education
  managed by People Living with HIV
• Informatics management
• Cooperation with National and Local Authorities
  within the National AIDS Networks

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• Objective
• To protect the health of both the mother and the
  newborn
• Setting
• Three health centers located in Maputo and Beira
  Mozambique
• The DREAM program have been providing HAART to
  prevent MTCT since May 2002
• Eligibility
• HIV positive pregnant women at any stage of
  pregnancy, after the 14th week, irrespective of
  CD4 cells count

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HAART Criteria
Nutritional supplementation and multivitamin were
given to the women. After six months the baby
should be weaned
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Population (August 2005)
Refusal rate 14.3 Overall lost to follow up
rate 8,3 22,6 Women who ended the protocol
77,4
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Population - Baseline
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Results

• Pregnancy Outcome -1,287 pregnancies brought to
  term
• PMTCT Outcome - 663 children born before August
  2004
• Children Health Outcome - 663 children born
  before August 2004
• Toxicity - 651 women who delivered before august
  2003 53 pregnant women on treatment for more
  than 14 days (8/2005)
• Resistances - 42 women stopped treatment after
  delivery
• HIV Mothers Health Outcome - 321 pregnant women
  stopped treatment after delivery

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Results - Pregnancy outcome
29 pairs total number of children 1,252
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Results - Abortion and Stillbirth cumulative
number per 100 observation months according to
the length of pre-delivery HAART
p lt 0.001
Length of HAART (days)
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Results Childrens health outcome
(663 children born before August 2004 censor
date August 2005)
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Results - HIV vertical transmission outcome
On treatment more than 60 days of HAART
pre-delivery nutritional supplementation
multivitamin Formula feeding
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• A) of patient ending the protocol 77.4
• B) Reduction of the expected HIV transmission
  rate
• (0.35 0.051/0.35) 0.854 (85.4)
• Risk reduction A B 66.1

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Results - Factors affecting HIV transmission at
delivery (19 cases out 560, 3.4)
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Toxicity - Grade 3-4 Toxicity in the DREAM
Cohort (703 patients)HIV medicine, in press
74 patients started treatment with Stavudine
due to pre-HAART anemia
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Grade 2-4 Hepatotoxicity Onset Time by CD4 Cell
Count before Starting HAART. Linear Regression
Model 86 cases
p lt 0.001
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Resistances
42 unselected women that completed the protocol
were assessed for genotypic resistance, in a time
period between 2-6 months after therapy
interruption All carried a subtype C strain 37
(88.1) showed no mutations associated with
resistance 5 (11.9) carried mutations associated
with resistance to nevirapine 3 K103N 2
G190S Resistances to 3TC and AZT-D4T were not
detectable
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CD4 cells count after stopping HAART according to
initial CD4 cells count percentiles(Median time
of HAART 109 days IQ76-158)
Baseline CD4 cells count percentiles
Stop HAART
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CD4 cells count trend until 18 months after
stopping HAART (red-orange lines, 321 pregnant
women taking HAART for PMTCT, for about four
months) or never taking HAART (bleu-ligth blue
lines, 630 patients do not qualified to start
treatment)
Stop HAART
First CD4 count
First CD4 count
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HIV-RNA levels (median of Log) in plasma and in
various milk fractions of two groups of pregnant
women group A receiving HAART group B do not
receiving any ARV drugs
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Conclusion

• The program achieved the following results
• Reduction of about 85 of the HIV vertical
  transmission rate
• Reduction of Maternal Mortality Rate and Infant
  Mortality Rate
• Reduction of about 85 of pregnancy negative
  outcome
• Overall population coverage of about 80
• An estimated population impact of about 66
• No increase of ARVs resistance
• Availability of a reliable strategy to prevent
  vertical transmission during breatsfeeding
• Improving health of the women
• These results are independent from the place of
  delivery

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HAART in pregnancy...

• Is effective and the results are independent from
  the setting of delivery
• Makes potentially possible the breastfeading
  (formula feeding seems not to be a reliable
  approach to expand the program)
• Present a very limited life-threatening risk and
  the hepatic toxicity seems, in a large cohort, to
  be limited

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HAART in pregnancy...

• Is well accepted by the patients close to 80 of
  the invited women completed the protocol
• Is associated with a decreased rate of viral
  resistance compared with single dose nevirapine

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Triple therapy in pregnancy could be the right
answer for mothers and children in Africa