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