challenges faced implementing an rct and a cohort study evaluating new pmtct interventions in south...
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Challenges faced implementing an RCT and a cohort study evaluating new PMTCT interventions in South Africa
Peter Bock1, Eula Mothibi1, Anita Jason1, Saba Shembe1, Bongiwe Ndondo1, Geoffrey Fatti1, Sarah Wampold1, Nandi Siegfried4 & Ashraf Grimwood1
4th South African AIDS Conference Durban 2009
ConclusionsThere is the need for significant improvement in the public sector PMTCT services in South Africa. The superior efficacy of triple ARV therapy should see it adopted as the standard of care for developing
countries by the WHO in the future. These studies will contribute valuable information on the effectiveness and cost benefits of triple therapy and patient advocates in the provision of PMTCT care in
South Africa which can be reviewed by future policy makers.
INSTITUTIONS
1.Absolute Return for Kids 2. KwaZulu Natal Department of Health 3. Western Cape Department of Health 4. Trials Unit Medical Research Council
Acknowledgements: The following people have assisted with the design and implementation of the studies: (Alphonso Malgas, Anita Jason, Anne Magege, Dean Solomon, Esca Scheepers, Lindsay Wilson, Mary
Sihlangu, Michael Brown, Michael Phiilips, Mokgadi Malahlela, Nickesh Maharaj, Nontuthuzela Manjezi, Nozipho Galo & Shiraaz Josuub), colleagues at ARK central UK (Colin Almeleh, Marion Hassan & Paul
Bernstein), the Clinical Trials Unit at the Medical Research Council in Cape Town (Salla Atkins), the Western Cape Department of Health (Brenda Smuts, Karen Jennings & Virginia Zweigenthal), Emile van Donk
from the Netherlands Cancer Institute and Mike Clarke the Director of the Cochrane Centre in the UK
Kraaifontein PMTCT RCTStudy Design : Randomised control trial.
Randomisation: Simple randomisation using Tenalea software
Enrolment start date: 23 March 2009
Period of enrolment : 18 months
Expected sample size: 450
Intervention arm: Triple ART (AZT, 3TC & Kaletra) covering breast feeding + Patient Advocate+ Usual
care
Control arm: Triple therapy+ Usual care
Primary Objective : Investigate the effect of a PA on the rate of infant PCR testing at 6 weeks
Secondary objectives: Effect of PA on ART adherence, infant feeding practices & Post weaning PCR
uptake
Comparisons : Between arms and to historical data
Duration of follow up: Till 18 months post partum
Figure 1: National averages of key indicators the PMTCT programme in South Africa (Health Systems Trust)
Sundumbili A
NC
PMTCT clinic
Start ARV
Delivery
PCR 6 w
eeks
PCR post
weaning
18 mth Elisa
HIV
+
Decline study
ConsentCD4 result
PA
ARV workup: Fast track (5 to 10 days) including 3 counselling sessions and home visit.
PA: Minimum monthly visits PA: Minimum 6 weekly visits
NB: ARV adherence& good obstetric practice
NB: Loss to follow up, infant feeding , PCR uptake , ARV adherence & IMCI
HIV negative or decline test twice
DAY 1 DAY 5 DAY 9 to 14 18 MONTHS
Timeline
ARK Sundumbili PMTCT study
DOH care
What happens in the study
Day 1: First visit to the antenatal clinic•All pregnant women receive HIV test•HIV positive women receive a CD4 cell count and referral to the study coordinator (SC) in the PMTCT clinic.
Day 5: HIV positive women return for CD4 cell result.•The SC will offer the women a place in the study if she is eligible
•The PA will see the mother regularly both during pregnancy and after delivery up until the infant is 18 months old.
Triple therapy
ARV workup : Starts on Day 5. and is 1 week long, including 3 counselling sessions , a home visit by a PA, and integrated antenatal care.
ARV regimen: will include AZT, 3TC and NVP or Kaletra and will be continued to cover the breast feeding period.
NB. Once patients have entered the study it is very important they are not lost to follow up!
NB. Adherence to medication is very important !
The study question?
Should the standard care for HIV positive women include triple ARV therapy and a patient advocate?
What is included in the study?
HIV positive pregnant women enrolling in the study receive :•three ARVs•services of a patient advocate (PA)* or community health worker
Patients declining to be in the study receive:•DOH standard of care •shorter course of two ARVs•no services of a PA.
What happens after birth ?
It is very important the baby is tested for HIV at 6 weeks and again 6 weeks after the mother has stopped breast feeding.
Babies who test HIV positive will immediately be referred to an ARV clinic.
Mothers may choose to breast feed or formula feed their infant.
NB. Mothers must not practice ‘mixed feeding’ as the mixing of solids and liquids or breast and formula milk increases the chance of the baby getting HIV.
Ant enatal clinic
ARV
clinic
Star t ARV
Deli very
PCR
6 wee ks
PCR
post weanin g
18 month Elisa
HIV
+
Decline study
Off
er ed informe d C
onsen tC
D4 r esult
Triple therapy
HIV negative or decline test twice
DAY 1 DAY 5 DAY 9 to 14
ARK PMTCT randomised control trial, Kraaifontein PA vs. No PA
DOH care
Enrol for study
Rand om
ise
PAN
o PA
Inclusion criteria
•CD4>250cells/mL•Booking at KFTN or DBVN •Permanent resident •Booking < 36 weeks•No PA
Trial arms
•Intervention arm: Triple therapy & PA •Control arm: Triple therapy & no PA
Primary outcome
•Infant PCR uptake at 6 weeks
Key Facts :
Rand om
ised control trial
Sundumbili PMTCT studyStudy Design : Prospective cohort study
Expected enrolment start date: 10 April 2009
Period of enrolment : 1 year
Expected sample size: 1000
Intervention arm: Triple (ART AZT, 3TC & Kaletra) covering breast feeding + Patient Advocate+ Usual
care
Control arm: No control
Primary Objective : Investigate the effect of the intervention on vertical transmission rates at 6weeks
Secondary objectives: Effect of a PA on ART adherence, infant feeding practices & transmission of
HIV through breast feeding
Comparison: To historical data
Duration of follow up: Till 18 months post partum
BackgroundThere are serious deficiencies in PMTCT programmes across South Africa (Figure 1) with low uptake of HIV testing, low uptake of PMTCT, infant PCR testing rates of less than 30% at 6 weeks and almost no
routine data recording PCR testing after the cessation of breast feeding. In addition 6 week Infant HIV positivity rates with dual therapy regimens remain between 6 and 10%. Effective provision of triple therapy
has been shown to reduce vertical transmission to below 1% in the developed world. Absolute Return for Kids (ARK) will conduct two studies to evaluate a new model of care for PMTCT starting in February 2009.
The Patient Advocate (PA)
PAs to provide community based support for patients on ART. and may have contact with participants at both the clinic and in the community. The PAs conditions of service are closely aligned with those of DOH home based carers. PAs for the study will receive 3 training modules on relevant aspects of HIV/AIDS and PMTCT care. There are no formal criteria for background level of education.
A PA coordinator will be appointed at Kraaifontein who will manage the link between the PAs and the clinic based staff. A ratio of 1 PA to 30 mother infant pairs will be used. The role of the patient advocate includes health promotion around HIV AIDS and its treatment, adherence to ART, breast feeding, accessing the health service as well as broader holistic support.
PAs at Sundumbili CHC