HIV Research in International Settings Wafaa El-Sadr, MD, MPH Columbia University

HIV Research in
International Settings
Wafaa El-Sadr, MD, MPH
Columbia University
Overview of Presentation
• Status of HIV epidemic
• HIV-related research
– where done and who is doing it
• Priority questions– implementation science
• Challenges and solutions
• Conclusions
Adults and children estimated to be living with HIV  2009
Western &
Central Europe
Eastern Europe
& Central Asia
820 000
1.4 million
[720 000 – 910 000][1.3 million – 1.6 million]
North America
1.5 million
East Asia
[1.2 million – 2.0 million]
770 000
Middle East & North Africa
Caribbean
240 000
[220 000 – 270 000]
Central &
South America
1.4 million
[1.2 million – 1.6 million]
[560 000 – 1.0 million]
460 000
[400 000 – 530 000]
South & South-East Asia
4.1 million
Sub-Saharan Africa
[3.7 million – 4.6 million]
[20.9 million – 24.2 million]
Oceania
22.5 million
57 000
[50 000 – 64 000]
Total: 33.3 million [31.4 million – 35.3 million]
UNAIDS, 2010
Antiretroviral Therapy by Region--2001
Number of PLWH receiving ART in low- and middle-income
countries, by region, 2002–2009
UNAIDS, 2010
Change in HIV Incidence
UNAIDS, 2010
HIV Treatment Coverage in Low & Middle
Income Countries
WHO Towards Universal Access 2010
Coverage of HIV Prevention–
Low Resource Countries, 2004-2009
Estimates of Coverage
HIV testing
5%
Condom Use
20%
10%
Antiretroviral Drugs for
PMTCT
70%
30%
75%
25%
9%
Contraception for PMTCT
32%
14%
61%
39%
9% 15%
Male Circumcision
Unmet HIV Prevention Need
20%
0%
47%
72%
28%
20%
2004
53%
40%
2006/7
60%
2009
80%
100%
Unmet HIV Prevention Need
Source: UNAIDS/WHO, 2010
Adapted Ward Cates
CROI 2011
Oral Abstracts
Oral Posters
International Scholars
Implementation Science
The study of methods to improve the uptake, implementation
and translation of research findings into routine and common
practices with the goal of improving program effectiveness and
optimize efficiency
Know-Do
Evidence to Program Gap
Examples of Implementation Science Questions
Questions
Which TB/HIV integration model produces the best clinical and public
health outcomes yet remains efficient and scalable?
What are specific strategies to increase adherence/retention in a particular
program?
What is the balance of fixed and mobile clinics that will most effectively
allow for rapid acceleration of task shifting and decentralization of HIV care
and treatment services?
What is the essential package of laboratory monitoring needed for patients
and how does it vary by stage of HIV disease
Adapted Padian et al, JAIDS 2011
Countries with ICAP-Supported Programs
TUNISIA
KAZAKHSTAN
MOROCCO
ALGERIA
WESTERN
SAHARA
LIBYA
EGYPT
UZBEKISTAN
TURKMENISTAN
MAURITANIA
MALI
NIGER
TAJIKISTAN
ERITREA
SENEGAL
CHAD
THE
GAMBIA
SUDAN
DJIBOUTI
BURKINA
GUINEA
BISSAU
GUINEA
SIERRA
LEONE
LIBERIA
BENIN
COTE
DTVOIR
E
TOGO
NIGERIA
ETHIOPIA
CENTRAL
AFRICAN
REPUBLIC
GHANA
CAMEROON
EQUATORIAL
GUINEA
GABON
REP. OF
THE
CONGO
UGANDA
DEMOCRATIC
REPUBLIC
KENYA
SOMALIA
OF THE CONGO
(ZAIRE)
RWANDA
BURUNDI
TANZANIA
ANGOLA
MALAWI
ANGOLA
ZAMBIA
MADAGASCAR
ZIMBABWE
NAMIBIA
MOZAMBIQUE
BOTSWANA
LESOTHO
SOUTH
AFRICA
SWAZILAND
KYRGYZSTAN
ICAP International Research Portfolio
• 40 active protocols
• 9 countries
• 4 studies with a
multi-country
component
Country
No. of studies
DRC
1
Ethiopia
1
Ivory Coast
4
Kenya
2
Mozambique
7
Rwanda
10
South Africa
2
Swaziland
6
Tanzania
5
Models for Improving Loss-to-follow-up in the Democratic of Congo (DRC)
Strengthening HIV Test Acceptance and Treatment Uptake Study (STATUS)
Epidemiology of HIV-2 or HIV-1/HIV-2 infected patients in Ivory Coast
How to Optimize PMTCT Effectiveness (HOPE) Project in Ivory Coast
An Evaluation of Enhanced Tuberculosis Case-finding to Reduce Mortality Among Persons With Advanced HIV Presenting For HIV Care in Emergency Plan
Countries (EMRG)
Identifying Optimal Models of HIV Care approaches in sub-Saharan Africa
Development, implementation and evaluation of a comprehensive Prevention intervention in Care and Treatment Settings (PiCTS). Kenya, Tanzania
Establishment of sentinel cohorts of patients enrolled in HIV care and treatment services in Mozambique
Assessing enablers and barriers to the implementation of complex PMTCT regimens and ART in pregnancy in Mozambique
Evaluation of a symptom based flowchart for tuberculosis diagnosis in children in Mozambique
Quality of HIV counseling and testing in maternity in Mozambique
The role of Traditional Birth Attendants (TBA) in active defaulter tracing and adherence programs in Mozambique
Mother-infant pair linkage using paper-tracking systems in Mozambique
Evaluate TB screening of pregnant women at two PMTCT sites in Gaza Province in Mozambique
Qualitative study of ART adherence in Mozambique
Evaluation of a new patient tracking system on patient care and perceptions of care in Mozambique
Sharing HIV/AIDS responsibility Efforts (SHARE) in Nigeria
Evaluating adherence to antiretroviral therapy among HIV care and treatment patients in Rwanda
Smear negative and extra pulmonary tuberculosis diagnosis and outcomes in Rwanda
Operating characteristics of a screening instrument for the detection of active tuberculosis in adult outpatients with HIV infection in Rwanda
Evaluation of TB screening approaches for HIV-infected children in Rwanda
Estimating HIV incidence in two populations in Rwanda: High-risk women and female VCT clients- Project Ubuzima in Rwanda
Peer Educator for Adherence, Referral and Linkages Program Evaluation (PEARL study) in Rwanda
National Pulmonary Tuberculosis Prevalence Survey in Rwanda
Assessing HIV Prevention, Care & Treatment at Sites Supported by Columbia University-International Center for AIDS Care and Treatment Programs (ICAP) in
Rwanda
Evaluation of the quality of the national antiretroviral treatment program in Rwanda, 2004 - 2005
Evaluation of access and utilization of PMTCT services in Rwanda
BED and A1 Assay Validation Work, Kigali Incidence Study -- Project Ubuzima, Kigali, Rwanda
Evaluation of Access to and Acceptance of HIV Counseling and Testing Among Patients with Tuberculosis in Rwanda
Operating characteristics and effectiveness of a screening instrument for the detection of active tuberculosis in adult outpatients with HIV infection in the Eastern
Cape, South Africa
Design, implementation and assessment of a nurse mentor training program in HIV care and treatment in Eastern Cape, South Africa
Swaziland HIV Incidence Measurement Survey (SHIMS)
Swaziland National ART Program Evaluation: Treatment Outcomes and Cost-Effectiveness during 2004-2009
Swaziland in-service HIV training assessment
Assessment of impact of the ART Program on people receiving Anti-Retroviral Therapy in Swaziland following six years of ART implementation in the country
Feasibility Pilot of the Evaluation of Expert Client Program: Swaziland National ART Program
Etiologic Survey for Genital Infections Among HIV-infected Adults Entering HIV Care: A Pilot Study in Tanzania
HIV Combination Prevention in Tanzania
Neonatal Circumcision Situation Assessment in Tanzania
A range of methodologies…
• Qualitative methods
– Key informant interviews
– Focus group discussions
• Quantitative methods
– Group randomized studies
– Cohort studies
– Cross-sectional surveys
• Data collection
– Questionnaires/interviews with patients and health workers
– Data abstraction from routinely collected data
– Site characteristics assessment tools
GCP Training
• Barriers
– Non- Anglophone
investigators have
difficulty completing
GCP training
– Module content and
examples are US
focused and not relevant
to international research
– Field internet
connections hinder
completion of web
courses
• Suggestions
– Consider translated
modules e.g. French and
Portuguese
– Design modules with
international focus
appropriate for
international
investigators
– Adequate local training
given at the time of study
launch rather than
required early in the
process
The Protocol Approval Process
• Multiple levels
• Local and international
1
2
3
4
5
IN COUNTRY &
NY REVIEW
OGAC PHE
Committee
LOCAL IRB
CU IRB
CDC Atlanta
GAP ADS
 In-country
investigators
 ICAP-NY
investigators
 Local CDC Office
Feedback
&
Revision
 Submitted via the
local CDC office
ADS
Feedback
&
Revision
 Local IRB approval
 Other in-country
approvals e.g.
administrative
approval from
MOH
Feedback
&
 Submitted via
RASCAL
Revision
Feedback
&
Revision
CDC IRB
 If CDC
investigators are
involved
 Submitted via
ICAP NY
 Administrative
approval for
release of funds
Multiple IRBs Review Processes
• Synchronizing reviews, comments and
versions
– If submissions are simultaneous, different IRBs will
provide feedback at different times
– If submissions are done consecutively, the process
takes more time
– Deciding which IRB to submit to first:
• For example, CU IRB usually gives more comments
requiring protocol changes yet requires local IRB
approval before they provide final approval
Field implementation of IRB requirements
• Getting timely approvals when there is
national/MoH agenda and imperatives
• Adhering to required formats e.g. having the
international PI name on the consent form,
which may conflict with local requirements
• Using IRB stamped versions of tools
– Running out of these forms
Local issues
• Local IRBs will usually approve first time
protocols within reasonable time but
– Renewals/modifications may take longer in some
countries
– Some countries have several levels of approvals
which take more time
• Getting certified translators to fulfill IRB
requirements can be difficult with some local
dialects
– Example: Changana and Macua in Mozambique
Example: PiCTS study
• Multi-country multi-site PHE: Kenya and Tanzania under
ICAP, + Namibia
• Initial IRB submission done simultaneously in Oct 08
• IRB approval dates:
–
–
–
–
Kenya local IRB
CDC IRB
CU IRB
Tanzania
Jan-09
Feb-09
Feb-09
• Mainland IRB
• Zanzibar IRB
Apr-09
Jun-09
• Several rounds of revisions
Interpretation of IRB Non Human Subject
Research (NHSR) determination
• Program evaluations can be considered
NHSR even if they include interaction with
human subjects (with no identifiable
information) but
• the determination will say ‘no interaction with
human subjects’
• Publication of program evaluations may
require additional approval but
• This is not the case where there is no interaction with human
subjects?
• How to deal with publications to share local lessons learned?
Conclusions
• Substantial advances in tackling the HIV epidemic, but
many unanswered questions remain
• Priority of pragmatic questions—implementation
science
• Need to respond to the local circumstances and needs
• Importance of considering the flow of approvals
• Clearer definitions and interpretation of NHSR
• Challenge of non-traditional research
• Establishing responsive systems for support of
international research is a key priority