World Health Organization Department of Reproductive Health and Research TFa_Ethics_GVA_Jun03/1 MTCT-Prevention: The Kesho Bora study Tim Farley Department of Reproductive Health and Research World Health Organization

World Health Organization Department of Reproductive Health and Research TFa_Ethics_GVA_Jun03/2 Background Majority of MTCT-prevention research focused on saving infant from HIV infectionMajority of MTCT-prevention research focused on saving infant from HIV infection Care needs of mother (and family) have received relatively little attentionCare needs of mother (and family) have received relatively little attention Rapidly increasing access to care in resource- limited settings allows more comprehensive approach to MTCT preventionRapidly increasing access to care in resource- limited settings allows more comprehensive approach to MTCT prevention Programmes linking MTCT prevention and care are beginning to be implementedProgrammes linking MTCT prevention and care are beginning to be implemented

World Health Organization Department of Reproductive Health and Research TFa_Ethics_GVA_Jun03/3 Rationale Efficacy of interventions to prevent mother-to- child transmission (MTCT) of HIV in resource- constrained settings must be improvedEfficacy of interventions to prevent mother-to- child transmission (MTCT) of HIV in resource- constrained settings must be improved Health of HIV-infected mothers identified in MTCT-prevention programmes needs more attentionHealth of HIV-infected mothers identified in MTCT-prevention programmes needs more attention Alternatives to replacement feeding for children born to HIV-infected mothers need to be identifiedAlternatives to replacement feeding for children born to HIV-infected mothers need to be identified

World Health Organization Department of Reproductive Health and Research TFa_Ethics_GVA_Jun03/4 Overall Objective To optimize use of antiretrovirals to reduce risk of MTCT and provide for mother’s healthTo optimize use of antiretrovirals to reduce risk of MTCT and provide for mother’s health –Explicit link between MTCT-prevention and care –Address key policy questions in providing ARV therapy based on MTCT-prevention intervention

World Health Organization Department of Reproductive Health and Research TFa_Ethics_GVA_Jun03/5 Design Details Women stratified on disease stage in late pregnancyWomen stratified on disease stage in late pregnancy –CD4+ count < 200 cells/mm 3 or HIV Stage III or IV Initiate triple ARV-therapy (ZDV+3TC+NVP)Initiate triple ARV-therapy (ZDV+3TC+NVP) –CD4+ count > 500 cells/mm 3 Offered short-course MTCT prophylaxis (1 month ZDV + single dose NVP)Offered short-course MTCT prophylaxis (1 month ZDV + single dose NVP) –CD4+ count in range cells/mm 3 Randomised to receive short-course or extended triple-ARV MTCT prophylaxis (ZDV+3TC+NVP) for max 6 monthsRandomised to receive short-course or extended triple-ARV MTCT prophylaxis (ZDV+3TC+NVP) for max 6 months –Regular 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 Considerations Women who require treatment for their own HIV disease initiate life-long triple ARV therapyWomen who require treatment for their own HIV disease initiate life-long triple ARV therapy Women not (yet) requiring care receive MTCT- prevention prophylaxis (short-course or extended regimen)Women not (yet) requiring care receive MTCT- prevention prophylaxis (short-course or extended regimen) All women whose health deteriorates during study initiate life-long triple-ARV therapyAll women whose health deteriorates during study initiate life-long triple-ARV therapy

World Health Organization Department of Reproductive Health and Research TFa_Ethics_GVA_Jun03/7 Ethical Challenges (1) SustainabilitySustainability –Study period up to 2 years following delivery –Care needs during study provided from study resources –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-term 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) Justice considerationsJustice considerations –Priority 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) 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 care

World Health Organization Department of Reproductive Health and Research TFa_Ethics_GVA_Jun03/9 Ethical Challenges (3) CoercionCoercion –Life-long ARV therapy only offered to women volunteering for study cohort ComplianceCompliance –Therapy programmes usually require demonstrated ability to comply with burdensome tablet schedule ViolenceViolence –Will priority access to ARV therapy for partners expose women to unwanted 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) SitesSites –Bobo Dioulasso, Mombasa, Moshi, Nairobi ApprovalsApprovals –WHO Ethics Committees –Local (and national) ethical approval underway Study instruments and procedures (including ARV therapy)Study instruments and procedures (including ARV therapy) –Under development, advanced draft available Study start date …last quarter 2003Study start date …last quarter 2003