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When Less is More: Transmission of Drug-Resistant HIV in Canada

When Less is More: Transmission of Drug-Resistant HIV in Canada. STIRRHS Conference Montreal, Quebec June 3, 2006. Why do this project?. HIV challenge 5000 new cases annually Living long with HIV through HAART. 333 HIV Positive Patients. 155/191 Partners HIV Negative.

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When Less is More: Transmission of Drug-Resistant HIV in Canada

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  1. When Less is More: Transmission of Drug-Resistant HIV in Canada STIRRHS Conference Montreal, Quebec June 3, 2006

  2. Why do this project? • HIV challenge • 5000 new cases annually • Living long with HIV through HAART

  3. 333 HIV Positive Patients 155/191 Partners HIV Negative Who is Spreading HIV ? 75/333 (23%) UnprotectedIntercourse 18/75 (24%) Drug Resistant HIV

  4. So what’s the problem? • HAART regimen is demanding • Adherence must be >95% • 57-77% of patients cannot adhere optimally • At 80% adherence drug resistance develops

  5. Barriers to Reducing Spread • Drugs are not “user-friendly” • Adherence is not optimal • Not all sex is safe

  6. Hypothesis • The spread of drug-resistant HIV virus can be reduced by redesigning the strategy of treatment targeted towards one of these three pillars: • Improving adherence • Reducing the development of drug-resistance • Reducing risk sexual and drugs-associated behaviour

  7. Objectives This collaborative group will use a transdisciplinary approach to improve patient adherence to HAART and prevent the spread of drug-resistant HIV by: • Optimizing drug combinations/delivery • Alleviating side effects to treatment • Identifying factors associated with decreased adherence specific to the Canadian population • Furthering “safe-sex” techniques

  8. Objectives Objective 3 Modify risk behaviour ADHERENCE TO HAART RISK BEHAVIOUR Objective 2 Influence development of resistance Objective 1 Influence adherence DEVELOPMENT OF RESISTANCE SPREAD OF RESISTANT HIV

  9. Objective 1: Adherence • Understand the problems of adherence to HAART • Design, implement and evaluate a computer-based tool designed to improve management of drug side effects • To modify the influence of side-effects of therapy on drug adherence by designing alternative drug delivery methods

  10. Design (1) • Understand the problem of adherence and barriers related to HAART • 1st year: Qualitative study: understand point of view, motivation, psychological concerns of patient and health professionals, study of barriers to therapy adherence (implementation, analysis)

  11. Design (2) • Development of an intervention • Information-motivation-behavioural skills model • Specific intervention…

  12. Design (3) • Stratify in three groups: <80%, 80-95% and >95% adherence to HAART • Evaluation of intervention • RCT

  13. Primary Health Outcome Measures Level of Adherence Level of Drug-resistant HIV Number of New Cases of Drug-Resistant HIV

  14. The Problem of Side Effects • Cluster randomized, controlled trial • HIV positive patients • Clinic waiting rooms

  15. The Problem of Side Effects • Half of treatment centers will complete a computer based survey • Length of illness • Adherence to treatment • Side effect profile • Risky sexual behavior

  16. The Problem of Side Effects • The computer will provide a print out of the side effect profile • Pharmacists will review the profile and determine the likely causal agents • Physicians will use the information to give patients coping strategies and/or prescriptions to abate side effects

  17. The Problem of Side Effects • Additionally, the computer will provide the patient with information regarding adherence and risk of drug resistant HIV as well as decreasing transmission as the survey is being completed • Issues can then be further discussed with the clinician

  18. The Problem of Side Effects At the completion of the study, we will compare the control and intervention groups to determine if there is a difference in adherence between the groups

  19. HIV INFECTION HAART NON-ADHERENCE RESISTANCE SPREAD Complex regimen Toxicity Mechanisms of resistance

  20. The aims of this project are • to simplify drug regimen by developing new drug delivery methods • reduce toxicity by using newer agents

  21. Complex Regimen Three classes of drugs A, B & C : A1,B1 and C1 Some in empty stomach / others in full stomach Multiple pills, large size Toxicity New drug delivery methods such as Transdermal patch New combination of drugs – for example A1, B2 and C3

  22. Methods to Improve Adherence • New Drug Delivery Methods • Transdermal patch • Reduce toxicity • Combination of drugs A1, B2 and C3

  23. New Drug Delivery Methods Study Design Randomized control trial Participants : non-adherent patients The usual oral regimen (n=50) Transdermal patch (n=50) Adherent patients (>95%) (n=50) For three months Outcomes: Drug concentrations Viral load CD4 counts Patient compliance – side effects

  24. New Drugs Patients will be randomized to receive either • A1, B1, C1 • A1, B2, C3 As transdermal patches Outcomes: Side effect profile Viral load CD4 counts

  25. Objective 2Mechanisms of Resistance • Non- adherence (50%) patients • Mutations in viral enzymes & proteins • The aim of this study will be to elucidate the mechanisms of drug resistance to HAART

  26. Study DesignHIV will be cultured from non-adherent (50%) patients • Mutations in the viral enzyme and proteins to be determined using DNA • 3-D structure of the proteins determined

  27. In vitro cell culture studies • to compare the efficacy of the usual and the new combinations of drugs • To compare the development of drug resistance Outcome: Drug resistance – viral counts

  28. Experimental Design • Cultured HIV will be incubated with increasing concentrations (1uM to 1mM) of either the usual or new combinations of drugs for 24 hours to 72h • Different regimens of failing drug adherence • At the end of treatment period perform – viral counts and examine for mutations in HIV

  29. Bench to Bedside • RCT to compare drug resistance in the usual and the new combination of drugs • Newly identified HIV patients will be randomized to receive either • Usual drug combination or the new drug combinations for 1 year • Examine viral load, CD4 counts, mutations in HIV

  30. Objective 3: Reduce risk behaviour • Assessment of risk behaviour • Survey • Correlate risk-behaviour with adherence, viral load and resistance • Intervention • Educate – show movie, talk to clinic nurse, doctor, educate doctor • Provide needles and condoms • Test intervention with questionnaire • Evaluate intervention efficiency

  31. Objective 3: Reduce risk behaviour • Objective: to reduce spread of HIV by risk behaviour • Research design: case-control, prospective • Primary measure of health outcome: risk behaviour after intervention

  32. Members HIV-positive patients and partners Doctors Psychologists Anthropologist/ Sociologist Basic scientist/ pharmacologist, virologist Epidemiologist Computerperson Contribution To adhere or not to adhere and behave Clinical perception Theoretical concepts Understand determinant factors Resistance development studies bghjewlfbyw Obvious Software design Team members and their contributions

  33. Nils Chaillet Li Chen Barbra de Vrijer Pia Elustondo Laura Gaudet Sownd Sankaralingam Dr William Fisher Dr Robert Platt Dr Lise Goulet The real team members

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