Gemeinschaft Sant‘Egidio
Access to Treatment in Africa
Ergebnisse und Herausforderungen aus dem Programm
DREAM
Dieter Wenderlein
Gemeinschaft Sant‘Egidio
Universitätsklinikum Würzburg
Gemeinschaft Sant‘Egidio
Das Programm DREAM der Gemeinschaft Sant’Egidio
(Drug Resource Enhancement against AIDS and Malnutrition)
Comprehensive approach:
- VCT
- Antiretrovirale Therapie (HAART)
- Prävention der Mutter-Kind-Übertragung von HIV (PMTCT)
- Nahrungsmittelhilfen
- Aufklärung
- Fortbildung von “AktivistInnen” zu Multiplikatoren
- Trainingskurse, Fortbildung von medizinischem Personal
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DREAM in Afrika
10 Länder in Subsahara-Afrika
18 Labore zur HIV/AIDS-Diagnostik
31 Therapiezentren:
6 in staatlichen Gesundheitseinrichtungen
22 in kirchlichen Gesundheitseinrichtungen
Bisher wurden
100.000 Patienten mit HIV aufgenommen
65.000 Patienten in ART genommen, darunter 6.000 Kinder
14.000 Kinder in PMTCT geboren
Derzeit 1.300 Schwangerschaften in PMTCT
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Einige Charakteristika von DREAM:
- Komplette Einbindung aller Aktivitäten in die nationalen Gesundheitssysteme
- Kostenlose Versorgung der HIV-Patienten
- Ausschließlich afrikanische Mitarbeiter in den Therapiezentren
- Intensive Mitarbeit von AktivistInnen / Community Health Workers
- Klinische Studien u.a. zu PMTCT (Stillzeit), Adhärenz, Risikofaktoren für
Sterblichkeit, Diagnostik (realtime PCR)
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PMTCT
Schwangere CD4<350
Schwangere CD4>350
Therapieindikation HAART
HAART (AZT/3TC/NVP) ab der 25. SSW bis zum Ende der Stillzeit
(je nach nationaler Leitlinie 6-12 Monate)
Exclusive Breastfeeding bis 6 Monate, nach 6 Monaten complementary feeding
Lebensmittelhilfen , Moskitonetze
Neugeborenes
- ARVs je nach nationaler Leitlinie
(NVP SD, NVP für 4-6 Wochen, ev. mit AZT/3TC)
- Realtime PCR nach 1-2 Monaten, 12 Monaten, 18 Monate AB-Test
- HAART im Falle der Seropositivität
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Methods:
Prospective observational cohort study
Live-born infants of HIV-1-infected women receiving medical care
HIV-1 testing at 1, 6 and 12 months of age
Women with CD4<350: HAART indefinitely
Women with CD4>350: HAART ante- and postnatally for the first 6 months
Exclusiv breastfeeding for 6 months
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Results:
341 infants enrolled at birth
313 mother-infant pairs (92%) completed 6 months of follow-up
283 (83%) completed 12 months of follow-up
HIV-1 diagnosis was ascertained in 287 infants (84%) including 4 who died.
 All 8 transmission occured at women with baseline CD4 > 350
 6 of 8 transmissions in women with baseline VL > 4log
 6 of 8 transmissions in women with less than 3 months antepartum HAART
 The 2 transmissions after 6 months occured in women who did non continue HAART
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Two mothers (0.6%) and 11 infants (3.2%) died; 7 infants (64%) died after
weaning
Country rate
(Mozambique)
Maternal mortality 587/100.000
1000/100.000
Infant mortality
101/1.000
33/1.000
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Favorable pregnancy outcomes with reduction of abortion, stillbirth, and
prematurity rates in a large cohort of HIV+ women in Southern Africa receiving
highly active antiretroviral therapy (HAART) for prevention of mother-childtransmission (PMTCT)
M.C. Marazzi et al. 5th IAS Conference on HIV Pathogenesis, Treatment and
Prevention, Capetown, 19.-22.07.2009
Cohort: 3.273 HIV+ pregnant women from centers in Malawi and Mozambique
from 7/2005 to 12/2008
Regimen: NVP-based HAART at 14 wks (if eligible for own health) or 25 wks
gestation until 6 months postpartum.
Abortion and stillbirths: Defined as fetal death at < or ≥ 32 wks gestation.
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Results:
Median baseline CD4 count: 357/mm3
Median baseline viral load: 4Log c/ml
Median pregnancy duration: 39.1 wks
Median time of pre-delivery HAART: 83 days (CL95%53-108).
Maternal mortality: 1.2%
Significantly associated with
HAART: 7.4% if no HAART vs. 0.7 HAART ≥ 90 days before delivery
CD4 threshold (3.2% vs. 0.7% if ≥ 200; p< 0.001).
Abortion and stillbirth:
25.7% (18/70) in women with no HAART
4.3% (125/2,909) in women receiving HAART for >30 days (p< 0.001).
Low birth weight:1.5% not associated with HAART duration or CD4 count.
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Prematurity: Strongly associated with short/absent HAART:
 70.8% reduction overall (Mantel-Heanszel OR=0.16; CL95%:0.12-0.21) and within each
CD4 strata.
 Body Mass Index (OR 0.27; CL95% 0.15-0.50) and VL at delivery (OR 1.44;
CL95% 1.22-1.70) strongly associated with prematurity by multivariate analysis.
CD4 count
Pre-delivery
HAART (days)
Premature
delivery (N.)
%
OR
>500
<30
>30
TOTAL
43/77
121/712
164/789
55.8
17.0
20.8
0.16
0.10-0.26
351-500
<30
>30
TOTAL
27/56
94/661
121/717
48.2
14.2
16.9
0.18
0.10-0.31
201-350
<30
>30
TOTAL
45/63
124/779
169/842
71.4
15.9
20.1
0.08
0.04-0.13
≤200
<30
>30
TOTAL
10/32
85/497
95/529
31.3
17.1
18.0
0.45
0.21-0.99
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Palombi L et. al. Limited Risk of Drug Resistance after Discontinuation of
Antiretroviral Prophylaxis for the Prevention of Breastfeeding Transmission of HIV.
J Acquir Immune Defic Syndr. 2011 May 4. [Epub ahead of print]
Evaluated cohort: 70 HIV-infected pregnant women
CD4>350/mm3
2 treatments sites in Malawi (Lilongwe, Blantyre)
PMTCT Regime:
AZT 300mg + 3TC 150mg + NVP 200mg BID
Starting in week 25 of gestational age (or as soon as possible after
that) until 6 months postpartum
3 week tail of AZT 300mg+3TC 150mg
Plasma sample collected
Baseline before drug administration (genotyping)
Delivery
Months 1, 3, 6 postpartum
1-2 months after drug discontinuation (genotyping)
6 months after drug discontinuation (genotyping)
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Median duration of HAART during pregnancy:
Median total duration of HAART:
Median time from interruption of all drugs and testing:
63 days
240 days
60 days
(interquartile range, 58-64)
Results:
 5 women had NNRTI mutations after HAART discontinuation (7.1%, 95% CI 1.11-13.17)
 Risk of developing resistance mutations in compliant women who receive ARV
prophylaxis and interrupt drugs 6 months after delivery is limited, after all with a long
tail of 3 weeks
 The HIV-RNA level at the moment of drug discontinuation was significantly higher
(P = 0.02) in women subsequently developing mutations.
 2 had the same mutation archived in baseline HIV-DNA.
 Only 2 women with undetectable viral load during treatment had presence of
resistance after drug discontinuation. These women had archived resistance at baseline
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 3 women had, at least once, detectable viral load and presence of mutations during
treatment (K103N+G190A, K101E, K103N+Y188C)
 Presence of mutations after drug discontinuation associated with previous emergence of
resistance during treatment (underlying the importance of drug adherence in these
patients)
 Six months after drug discontinuation (month 12) there was persistence of mutations
only when the mutations were previously archived in baseline HIV-DNA.
 None of the infants born to these women was infected with HIV.
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Probleme - Herausforderungen
1.Leichter gesagt als getan: WHO Leitlinien 2009
(z.B. Rapid advice: Use of antiretroviral drugs for treating pregnant women and preventing HIV
infection in infants, WHO November 2009)
- Einsatz von EFV zu Beginn der Schwangerschaft
- Breiter Einsatz von NVP bei HIV-exposed children (“from birth until 6 weeks of age”,
“from birth until one week after all exposure to breast milk has ended”)
- PI/r bleiben weiterhin second line
2. Unzureichender Zugang zu den nötigen diagnostischen Methoden:
- Abdeckung mit CD4-Bestimmung unzureichend
- Referenzlabore für Viruslast-Bestimmung, Realtime PCR (dried blood spot!)
- Referenzlabore mit Möglichkeit der Resistenztestung
3. Systeme zum Monitoring der Adhärenz
Optimierung des Patientenflusses von VCT zu Treatment
- Defaulter tracing von Patienten lost to follow up
- Einsatz von AktivistInnen, Community Health Workers, Support Groups
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4. Schnelle Ausweitung und Optimierung der Qualität von HAART
- zu niedrige Raten auf HIV getesteter Personen
- HAART als Prävention („Test and treat“)
5. Schnelle Ausweitung und Optimierung der Qualität von PMTCT
- zu niedrige Raten auf HIV getesteter schwangerer Frauen
- HAART auch für Schwangere ohne Therapieindikation bis zum Ende der
Stillzeit (Option B des Rapid advice Use of antiretroviral drugs for treating
pregnant women and preventing HIV infection in infants
- Richtiges Abstillen (kein abrupt weaning)
- Richtige Ernährung des Kindes nach Stillzeit (Wasserqualität)
6. Finanzierungssicherheit (donor fatigue)
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Vielen Dank!

Ergebnisse und Herausforderungen aus dem Programm DREAM