hiv drug resistance issues in resource limited settings michael r. jordan md mph who hivdr team...
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HIV Drug Resistance Issues in Resource Limited Settings
Michael R. Jordan MD MPH
WHO HIVDR Team
Geneva, Switzerland
Introduction
End 2009, 5.2 million people on ART of the 15 million in need
The rapid scale-up of ART successful – Standardized, population based approaches– Inexpensive, generic, fixed dose combinations
Emergence of HIV drug resistance (HIVDR) is inevitable– High replication and mutation rate– Necessity for lifelong treatment
Introduction
Universal access to ART accompanied by comprehensive global strategy to assess prevent HIVDR
WHO in collaboration with WHO/HIVResNet is leading global efforts for HIVDR surveillance and monitoring
Global strategy provides data for country programme planning to support evidence-based recommendations at national and regional levels
Implementation of WHO HIVDR strategy end 2009
Countries shaded purple have implemented one or more element of the strategy with support from the Bill and Melinda Gates Foundation; countries shaded turquoise have implemented one of more of the elements of the strategy using alternate funding sources. Coloured pins denote national, regional and specialized HIVDR testing laboratories
TREAT Asia Adult Network
Thailand: HIV-NAT/ Thai Red Cross, Bangkok Ramathibodi Hosp, Bangkok Chiang Mai University, Chiang Mai Chiang Rai Regional Hospital, Chiang
Rai Siriraj Hospital, Bangkok
Malaysia: Sungai Buloh Hosp, Kuala
Lumpur University of Malaya, Kuala
Lumpur Singapore: Tan Tock Seng Hospital,
Singapore
Indonesia: Udayana University, Bali Hospital Cipto Mangunkusumo,
Jakarta
Papua New Guinea: Port Moresby General
Hospital
Philippines: Research Institute for Tropical Medicine,
Manila
Cambodia: NCHADS, Phnom
Penh
Taiwan: National Yang-Ming University,
Taipei
People's Republic of China: Beijing Ditan Hosp, Beijing Queen Elizabeth Hosp, Hong Kong
Japan: Int’l Medical Center of Japan,
Tokyo
India: YRG Care, Chennai Institute of Infectious Diseases,
Pune
South Korea: Yonsei University,
Seoul
PASER network
South Africa• Wits-MMH (Joburg)
South Africa• Muelmed Hospital (Pretoria)• RTC Themba Lethu (Joburg)• RTC Acts Clinic (White River)
Uganda• JCRC (Kampala)• UVRI (Entebbe)
Uganda• JCRC-TREAT sites (Mbale,
Kampala, Fort Portal)
Kenya• CPGH (Mombasa)• Mater (Nairobi)
Zimbabwe• Newlands Clinic (Harare)
Reference laboratories
Clinical sites
Nigeria• LUTH (Lagos)
Zambia• Lusaka Trust (Lusaka)• KARA Clinic (Lusaka)• Coptic Hospital (Lusaka)
South Africa• Wits-MMH (Joburg)• Wits-CHRU (Joburg)
The Netherlands• UMCU (Utrecht)• AMC-CPCD (Amsterdam)
Research centers
Uganda• JCRC (Kampala)• UVRI/MRC (Entebbe)
Kenya• ICRH (Mombasa)
"Widespread, unregulated access to antiretroviral drugs in sub-Saharan Africa could lead to the rapid emergence of resistant viral strains, spelling doom for the individual, curtailing future treatment options, and leading to transmission of resistant virus."
Preventing antiretroviral anarchy in sub-Saharan Africa AD Harries, DS Nyangulu, NJ Hargreaves, O Kaluwa and FM SalaniponiThe Lancet 2001 358: 410-4
HIVDR Transmission Threshold Surveys
Country Year Setting Subtypes ResistanceEthiopia 2005 ANC C, AG <5%
India 2007 VCT C <5%
Malawi 2006 ANC C <5%
South Africa 2002 ANC C <5%
South Africa 2004 ANC C <5%
Swaziland 2006 ANC C, B <5%
Tanzania 2005 ANC A, C, D <5%
Thailand 2005 BD, VCT AE, B <5%
Uganda 2006 ANC A, D, C <5%
VietnamIndonesiaCameronMexico
2006
20072005
VCTVCTANCANC
AE, CRF15
Multiple CRF
<5%<5%
5-15%5-15%
Reasons for Low Prevalence of Transmitted DR HIV
Treatment coverage still relatively low– Especially >3 years ago– Models suggest need widespread treatment for 10 years
HAART from the START– Little history of mono- or dual therapy– Potent NNRTI-based regimens– When PIs used, boosted with RTV
Adherence– Social factors pressure high adherence rates– Greater social capital– Regimens more tolerant to missed doses than unboosted PI-
based HAART
Monitoring emergence of HIVDR during treatment
Meta-analysis 89 studies in sub-Saharan Africa. 78%, 76%, 67% of 13,288 patients showed virological suppression after 6 , 12, 24months; comparable to those from developed countries1
12 studies on acquired HIVDR in Botswana, Cameroon, Côte d’Ivoire, Rwanda, Senegal, Tanzania, Uganda, and Zimbabwe. Patients receiving first-line ART showed large variations in the rate of reported resistance, 3.7%-49% after 24-163 weeks of ART2
1Barth et al, Lancet Inf Dis. 2010; 2Hamers et al. Antivir Ther 2008
Monitoring emergence of HIVDR during treatment
Adoption of global standard for assessing HIVDR in populations on treatment needed
Lack of standardized methodologies make comparison of data difficult and make public health recommendations challenging
HIVDR testing realities in RLS
HIVDR testing is not routinely available in most resource limited settings for individual patient management
HIVDR testing is expensive and complex
Little room change in regimen based on genotyping results
HIVDR Issues
Lack of availability of second and salvage regimens
Second line therapy associated with greater morbidity and mortality1
Technology gaps– Low cost HIVDR testing– Point of care assays– Point mutations assays for population
screening– New specimen technologies
1Hosseinipour M et al. HIV Med 2010
What can we do?
What we must do!
Use available resources wiselyHealth systems strengthening and integrationMonitor patient management and ART programme performance
– Follow standardized prescribing practices
– Minimize lost to follow-up
– Prevent drug stock-outs– Support patient
adherence– Use quality assured drugs
Acknowledgments
WHO HIV DR Team– Silvia Bertagnolio– Karen Kelley
WHO HIVResNet
Data First Consulting– Neil Parkin
Tufts University School of Medicine
– John Coffin– Christine Wanke– Steven Y Hong
United States CDC– Diane Bennett
PharmAccess
TreatAsia
Bill & Melinda Gates Foundation
Spanish Government
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