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

 "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 Salaniponi The Lancet : 410-4

HIVDR Transmission Threshold Surveys CountryYearSettingSubtypesResistance Ethiopia2005ANCC, AG<5% India2007VCTC<5% Malawi2006ANCC<5% South Africa2002ANCC<5% South Africa2004ANCC<5% Swaziland2006ANCC, B<5% Tanzania2005ANCA, C, D<5% Thailand2005BD, VCTAE, B<5% Uganda2006ANCA, D, C<5% Vietnam Indonesia Cameron Mexico VCT ANC AE, CRF15 Multiple CRF <5% 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 countries 1  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 weeks of ART 2 1 Barth et al, Lancet Inf Dis. 2010; 2 Hamers 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 mortality 1  Technology gaps –Low cost HIVDR testing –Point of care assays –Point mutations assays for population screening –New specimen technologies 1 Hosseinipour M et al. HIV Med 2010

What can we do?

What we must do!  Use available resources wisely  Health systems strengthening and integration  Monitor 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