GRIPP– Herpes Simplex Virus Type-2 Treatment and HIV Infection:

International Guidelines Formulation and the Case of Ghana

Burris H1, Adu-Sarkodie Y2, Parkhurst J1, Baafuor KO2, Mayaud P1

 1 London School of Hygiene & Tropical Medicine, London, UK

2 Kwame Nkrumah University of Sciences & Technology, Kumasi, Ghana

Study Aim & Design

• To evaluate the process of incorporating evidence from international or national research into international or national policies/guidelines

• Case study: – incorporating management of Herpes simplex virus (HSV)

into genital ulcer disease (GUD) guidelines;– International level: WHO– National level: Ghana

International level

National level

Policy

Policy

Practice

Research(multicentre trials, modelling,

CE, reviews, meta-analysis)

GRIPP: from an RPC perspective…

C

C

C C

Communication

International level

National level

Policy

Policy

Practice

GRIPP: from an RPC perspective…

C

Research(trials, observational, CE)

Research (operational, health systems)

C

C

C

Communication

Background: GUD & HSV

• GUD proven cofactor of HIV acquisition or transmission (Cameron 1989; Hayes 1995; Gray 2001)

• GUD aetiologies include syphilis, chancroid and herpes simplex virus (HSV)– Relative prevalence has changed over time, with HSV now

dominant aetiology (>40%) (Mayaud 2004)

• Syndromic approach to GUD management promoted by WHO: 1994 vs. 2003

1994 WHO GUD algorithmPatients complaining

of ulcers

Treat for syphilis and chancroid.

No treatment.Sore or ulcer present?

YES

NO

• Only treats for TP and HD

Courtesy: D. Mabey

2003 WHO GUD algorithm• Treats for HSV-2 if ulcer has sign or symptom for

HSV-2 (first arm)• Otherwise treat for TP or HD (second arm)• Includes prevalence threshold for treating

everyone for HSV-2 in second arm

Patients complaining of ulcers

Treat for HSV-2.Treat for syphilis and chancroid. Treat for

HSV-2 if above prevalence threshold?

No treatment.Sign or symptom

for HSV-2 ?Sore or ulcer

present?

YES YES

NONO

First arm of algorithm Second arm of algorithm

Herpes treatment often not provided because:• Self-limited disease (in HIV negatives)

• Perceived to be ineffective (1-2 days gain in healing rates)

• Does not prevent recurrences (unless provided daily)

• Expensive (US$0.5 per day, but generics could be as cheap as US$0.07)

• Access/availability (private sector, HIV clinics)

• Lack of awareness (among planners, clinicians, patients, community…)

• Lack of epidemiological data (GUD aetiology, seroprevalence)

• Complicated algorithm?

HSV-HIV and International Policy Context

• HSV-HIV synergies++ • WHO Consultation on HSV Research (London, 2001)

• HSV-HIV trials (2002-09) (ANRS, CDC, Gates, NIH, WT)– Strategies: episodic (5d) vs. suppressive (daily) therapy– Populations: HIV+ and HIV-, men/women, Asia/SSA/LAC/US– Outcomes: HIV acquisition (in HIV-), HIV infectivity (genital shedding in HIV+), HIV

transmission (serodiscordant couples), HIV disease progression

• Global Strategy for the Prevention and Control of STI (2006-15) adopted at WHA (Geneva, June 2006)

• Formation of International HSV-HIV Collaborative group (London, October 2007)

• Acyclovir Access study planned with WHO (2007-08)• Revision of WHO GUD management guidelines + international HIV-HSV

meeting (Montreux, April 2008)

Ghana• GUD management policy in Ghana

– Based on WHO; last revision guidelines 2000

• ANRS1212 HSV-HIV trial (2002-2006): Ghana+CAR– Multicentre RCT of acyclovir (400mg x3 for 5d) in addition to synd. mx. for

GUD episodes among women– Results:

• 50% of GUD caused by HSV-2; 50% of patients HIV+• small impact of acyclovir on ulcer healing, no impact on HIV genital shedding or

plasma viral load• Impact on healing in subgroups: HIV+ with low CD4, primary herpes

– Dissemination/Communication: • national w’shops in 2002 and 2006 (preceded by w’shop on interpretation of results

with WHO STI and WHO Afro staff… but little “national” representation!)

Communication with national stakeholdersworkshops, participation of national (+international) stakeholders, researchers, police & army, NGOs, etc, media, press release, RPC newsletter, editorials, ….publications)

C

Daily Graphics, February 2002

“Black Stars To Receive Heroes’ Return”

Study Methods(1) In-depths interviews in Montreux (n=11)

• Researchers, programme managers, WHO staff

(2) In-depths interviews in Ghana (n=8)• High-level sexual health government officials, policy-

makers, leaders in HIV and reproductive health non-profit community, prominent researchers, practitioners

MSc student with supervision of two LSHTM staff; accompanied by senior researcher in Ghana for stakeholders interviews

Theoretical frameworks I(1) Evidence into Policy• Linear/rationalist model: change as problem-solving• Enlightenment model: change requires an accumulation of

information (Weiss C, 1977)

• The “two-worlds” model: need “bridging the gap”• RAPID Study: context, evidence, links, external influences

(ODI)

(2) International to National Policy Transfer• “Looped” and “incremental” policy transfer (Cliff et al. 2004)

• HIV/AIDS as a policy window (Lush L, et al. 2003)

Theoretical frameworks II

(3) Research to National Policy Development• Champions of the cause• Policy change follows practice (Meheus and syndromic

management)

(4) Accounting for context• Health policy triangle: accounting for a complexity of factors

(Walt G & Gilson L, 1994)

• Agenda setting: drivers of change (ODI)

• “Three streams” model: creating a window of opportunity

Findings: international level

Conscious attempt to incorporate evidence into guidelines: high-level quality research from multitude of formats (RCT, meta-analysis, biological experiments, health economics, modelling, policy); consensus building; grading of the evidence; commissioning of further research

Despite inconclusive evidence, changes in guidelines were recommended: HSV treatment incorporated, and highlighted further research required

Importance of “Intellectual Clubs” to get research onto agenda, then into guidelines

Some disconnect between researchers and programmatic staff (“two worlds”)

Findings: national levelMechanisms of GRIPP in Ghana:• Response to donor pressure (influenced by international research and

WHO/International guidelines)

• Need a local “Champion” (at MOH/Govt level)

• Importance of “intellectual clubs” (communities of researchers, practitioners and Govt. officials)

• “Policy will follow practice”

Commissioning ResearchHSV trial perceived as too international, no real local scientific

ownership/champion Turnover of programme staff: discontinuity, lack of ownershipMore locally-relevant research would be operational in nature

Summary

Changes in international GUD guidelines best explained by the ‘Enlightenment framework’

HIV-HSV synergies provided the policy window

Epistemic communities (Haas E, 1990) appear to be a primary internal driver of change in Ghana

Donors are a considerable force shaping national research agenda and set national priorities in Ghana

Importance of WHO Guidelines, particularly as they may tie in into funding/aid

International level

National level

Policy

Policy

Practice

GRIPP: from an RPC perspective…

C

Research(trials, observational, CE)

Research (operational, health systems)

C

C

C

DONORS

Communication

C C

Research(multicentre trials, modelling,

CE, reviews, meta-analysis)

Lessons learnt for RPCInternational level: • importance of high quality and multiple forms of evidence• thematic coalitions with international researchers,

WHO/UNAIDS, DFID and others (eg HSV, HPV, POC, microb.) • being responsive to needs or emerging agendas (eg MC) • exploit windows of opportunityNational level: • successful engagement for GRIPP in other contexts for HSV-

HIV (South Africa, Malawi)• development of the maternal/congenital syphilis research

agenda (Ghana)Communication: • investment in multiple formats and channels of communication,

reinforcing the same/incremental messages to different audiences