World Health Organization Department of Reproductive Health and Research TFa_Ethics_GVA_Jun03/1

MTCT-Prevention: MTCT-Prevention: The Kesho Bora studyThe Kesho Bora study

Tim FarleyTim Farley

Department of Reproductive Health and Department of Reproductive Health and ResearchResearch

World Health OrganizationWorld Health Organization

World Health Organization Department of Reproductive Health and Research TFa_Ethics_GVA_Jun03/2

BackgroundBackground• Majority of MTCT-prevention research focused on saving infant from Majority of MTCT-prevention research focused on saving infant from

HIV infectionHIV infection• Care needs of mother (and family) have received relatively little Care needs of mother (and family) have received relatively little

attentionattention• Rapidly increasing access to care in resource-limited settings allows Rapidly increasing access to care in resource-limited settings allows

more comprehensive approach to MTCT preventionmore comprehensive approach to MTCT prevention• Programmes linking MTCT prevention and care are beginning to be Programmes linking MTCT prevention and care are beginning to be

implementedimplemented

World Health Organization Department of Reproductive Health and Research TFa_Ethics_GVA_Jun03/3

RationaleRationale• Efficacy of interventions to prevent mother-to-child Efficacy of interventions to prevent mother-to-child

transmission (MTCT) of HIV in resource-constrained transmission (MTCT) of HIV in resource-constrained settings must be improvedsettings must be improved

• Health of HIV-infected mothers identified in MTCT-Health of HIV-infected mothers identified in MTCT-prevention programmes needs more attentionprevention programmes needs more attention

• Alternatives to replacement feeding for children born to Alternatives to replacement feeding for children born to HIV-infected mothers need to be identifiedHIV-infected mothers need to be identified

World Health Organization Department of Reproductive Health and Research TFa_Ethics_GVA_Jun03/4

Overall ObjectiveOverall Objective• To optimize use of antiretrovirals to reduce risk of To optimize use of antiretrovirals to reduce risk of

MTCT and provide for mother’s healthMTCT and provide for mother’s health

– Explicit link between MTCT-prevention and careExplicit link between MTCT-prevention and care

– Address key policy questions in providing ARV therapy Address key policy questions in providing ARV therapy based on MTCT-prevention interventionbased on MTCT-prevention intervention

World Health Organization Department of Reproductive Health and Research TFa_Ethics_GVA_Jun03/5

Design DetailsDesign Details• Women stratified on disease stage in late pregnancyWomen stratified on disease stage in late pregnancy

– CD4+ count < 200 cells/mmCD4+ count < 200 cells/mm33 or HIV Stage III or IV or HIV Stage III or IV• Initiate triple ARV-therapy (ZDV+3TC+NVP)Initiate triple ARV-therapy (ZDV+3TC+NVP)

– CD4+ count > 500 cells/mmCD4+ count > 500 cells/mm33

• Offered short-course MTCT prophylaxis Offered short-course MTCT prophylaxis (1 month ZDV + single dose NVP) (1 month ZDV + single dose NVP)

– CD4+ count in range 200-500 cells/mmCD4+ count in range 200-500 cells/mm33

• Randomised to receive short-course or extended triple-ARV MTCT prophylaxis Randomised to receive short-course or extended triple-ARV MTCT prophylaxis (ZDV+3TC+NVP) for max 6 months(ZDV+3TC+NVP) for max 6 months

– Regular follow up of mothers and infants for 2 yearsRegular follow up of mothers and infants for 2 years

World Health Organization Department of Reproductive Health and Research TFa_Ethics_GVA_Jun03/6

Key Justice ConsiderationsKey Justice Considerations• Women who require treatment for their own HIV disease Women who require treatment for their own HIV disease

initiate life-long triple ARV therapyinitiate life-long triple ARV therapy• Women not (yet) requiring care receive MTCT-prevention Women not (yet) requiring care receive MTCT-prevention

prophylaxis (short-course or extended regimen)prophylaxis (short-course or extended regimen)• All women whose health deteriorates during study initiate All women whose health deteriorates during study initiate

life-long triple-ARV therapylife-long triple-ARV therapy

World Health Organization Department of Reproductive Health and Research TFa_Ethics_GVA_Jun03/7

Ethical Challenges (1)Ethical Challenges (1)• SustainabilitySustainability

– Study period up to 2 years following deliveryStudy period up to 2 years following delivery

– Care needs during study provided from study resourcesCare needs during study provided from study resources

– Study being conducted in sites where Study being conducted in sites where • Care programme currently exists, orCare programme currently exists, or

• Care programme under development and expected to be operational before end of studyCare programme under development and expected to be operational before end of study

– Close partnerships being developed with governments and NGOs to provide long-Close partnerships being developed with governments and NGOs to provide long-term careterm care

• Study team not able to provide cast-iron guarantee of long-term careStudy team not able to provide cast-iron guarantee of long-term care

World Health Organization Department of Reproductive Health and Research TFa_Ethics_GVA_Jun03/8

Ethical Challenges (2)Ethical Challenges (2)• Justice considerationsJustice considerations

– Priority for initiating triple ARV therapyPriority for initiating triple ARV therapy• Mothers in study who require therapyMothers in study who require therapy• Mothers in study whose health deteriorates during studyMothers in study whose health deteriorates during study• Mothers in study whose health deteriorates after the studyMothers in study whose health deteriorates after the study

– Under discussion (balance justice vs. resources)Under discussion (balance justice vs. resources)• Partners of study volunteers who require therapyPartners of study volunteers who require therapy• Children of study volunteers who require therapyChildren of study volunteers who require therapy• Health-care workers involved with studyHealth-care workers involved with study

– Community advisory panel to advise (decide?) on who qualifies for long-term careCommunity advisory panel to advise (decide?) on who qualifies for long-term care

World Health Organization Department of Reproductive Health and Research TFa_Ethics_GVA_Jun03/9

Ethical Challenges (3)Ethical Challenges (3)• CoercionCoercion

– Life-long ARV therapy only offered to women volunteering for study cohortLife-long ARV therapy only offered to women volunteering for study cohort

• ComplianceCompliance– Therapy programmes usually require demonstrated ability to comply with burdensome Therapy programmes usually require demonstrated ability to comply with burdensome

tablet scheduletablet schedule

• ViolenceViolence– Will priority access to ARV therapy for partners expose women to unwanted Will priority access to ARV therapy for partners expose women to unwanted

pregnancy?pregnancy?

• Does volunteering for study confer right to free life-long care?Does volunteering for study confer right to free life-long care?

World Health Organization Department of Reproductive Health and Research TFa_Ethics_GVA_Jun03/10

Current Status (June 2003)Current Status (June 2003)• SitesSites

– Bobo Dioulasso, Mombasa, Moshi, NairobiBobo Dioulasso, Mombasa, Moshi, Nairobi

• ApprovalsApprovals– WHO Ethics CommitteesWHO Ethics Committees– Local (and national) ethical approval underwayLocal (and national) ethical approval underway

• Study instruments and procedures (including ARV therapy) Study instruments and procedures (including ARV therapy) – Under development, advanced draft availableUnder development, advanced draft available

• Study start date …last quarter 2003Study start date …last quarter 2003