HIV Drug Resistance Issues in Resource Limited Settings

1. HIV Drug Resistance Issues in Resource Limited Settings Michael R. Jordan MD MPH WHO HIVDR Team Geneva, Switzerland

2. 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

3. 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

4. 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

5. TREAT Asia Adult Network • South Korea: • Yonsei University, Seoul • India: • YRG Care, Chennai • Institute of Infectious Diseases, Pune • Japan: • Int’l Medical Center of Japan, Tokyo • People's Republic of China: • Beijing Ditan Hosp, Beijing • Queen Elizabeth Hosp, Hong Kong • Taiwan: • National Yang-Ming University, Taipei • Philippines: • Research Institute for Tropical Medicine, Manila • Thailand: • HIV-NAT/ Thai Red Cross, Bangkok • Ramathibodi Hosp, Bangkok • Chiang Mai University, Chiang Mai • Chiang Rai Regional Hospital, Chiang Rai • Siriraj Hospital, Bangkok • Cambodia: • NCHADS, Phnom Penh • Malaysia: • Sungai Buloh Hosp, Kuala Lumpur • University of Malaya, Kuala Lumpur • Papua New Guinea: • Port Moresby General Hospital • Indonesia: • Udayana University, Bali • Hospital Cipto Mangunkusumo, Jakarta • Singapore: • Tan Tock Seng Hospital, Singapore

6. Research centers Clinical sites • Nigeria • LUTH (Lagos) • The Netherlands • UMCU (Utrecht) • AMC-CPCD (Amsterdam) • Uganda • JCRC-TREAT sites (Mbale, Kampala, Fort Portal) • Kenya • ICRH (Mombasa) • Kenya • CPGH (Mombasa) • Mater (Nairobi) • Uganda • JCRC (Kampala) • UVRI/MRC (Entebbe) • South Africa • Wits-MMH (Joburg) • Wits-CHRU (Joburg) • Zambia • Lusaka Trust (Lusaka) • KARA Clinic (Lusaka) • Coptic Hospital (Lusaka) Reference laboratories • Uganda • JCRC (Kampala) • UVRI (Entebbe) • Zimbabwe • Newlands Clinic (Harare) • South Africa • Muelmed Hospital (Pretoria) • RTC Themba Lethu (Joburg) • RTC Acts Clinic (White River) • South Africa • Wits-MMH (Joburg) PASER network

7. "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 2001 358: 410-4

8. HIVDR Transmission Threshold Surveys

9. 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

10. 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

11. 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

12. 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

13. 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

14. What can we do?

15. 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 What we must do!

16. 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 Acknowledgments