1 / 37

Changing Therapy

Changing Therapy. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents published October 2006 AETC NRC Slide Set. About this Presentation.

dora
Télécharger la présentation

Changing Therapy

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Changing Therapy Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents published October 2006 AETC NRC Slide Set

  2. About this Presentation These slides were developed using the October 2006 guidelines. The intended audience is clinicians involved in the care of patients with HIV. The user is cautioned that, due to the rapidly changing field of HIV care, this information could become out of date quickly. Finally, it is intended that these slides be used as prepared, without changes in either content or attribution. Users are asked to honor this intent. -AETC National Resource Center http://www.aidsetc.org

  3. Changing Therapy:Contents • Considerations • Treatment regimen failure • Treatment options • Testing for resistance • Treatment interruption

  4. Changing Therapy:Considerations • Clinical status • HIV RNA level on 2 tests • CD4+ T cell count • Remaining treatment options • Potential viral resistance • Medication adherence • Patient education

  5. Changing Therapy: Treatment Regimen Failure • Virologic failure: • Incomplete virologic response: HIV RNA >400 copies/mL after 24 wks, >50 after 48 wks • Virologic rebound: repeated detection of HIV RNA after viral suppression • Immunologic failure: • CD4 increase of <25-50 cells/µL in first year of therapy • CD4 decrease below baseline, on therapy • Clinical failure: • occurrence of HIV-related events (after >3 months on therapy; excludes immune reconstitution syndromes)

  6. Treatment Regimen Failure: Assessment • Review antiretroviral history • Physical exam for signs of clinical progression • Assess adherence, tolerability, pharmacokinetic issues • Resistance testing (while patient is on therapy) • Identify treatment options

  7. Treatment Regimen Failure: Assessment • Possible causes: • Suboptimal adherence • Medication intolerance • Pharmacokinetic issues • Suboptimal drug potency • Viral resistance • Approach depends on cause of regimen failure and remaining antiretroviral options

  8. Treatment Regimen Failure: Assessment Therapeutic options: • Clarify goals: If extensive resistance, viral suppression may not be possible, but aim to reestablish maximal virologic suppression • Remaining ARV options • Base treatment choices on expected efficacy, tolerability, adherence, future treatment options, past medication history, and resistance testing

  9. Virologic Failure: Changing an ARV Regimen (1) General principles: • Prefer at least 2 fully active agents to design a new regimen • Determined by ARV history and resistance testing • If 2 active agents are not available, consider ritonavir-boosted PI plus optimized ARV background, and/or reusing prior ARVs to provide partial activity • Consider potent ritonavir-boosted PI and a drug with a new mechanism of action (e.g., entry inhibitor) plus an optimized ARV background: may have significant activity

  10. Virologic Failure: Changing an ARV Regimen (2) General principles (2): • In general, 1 active drug should not be added to a failing regimen because drug resistance is likely to develop quickly. In some patients with advanced HIV and few treatment options, this may be considered to reduce the risk of immediate clinical progression. • Consult with experts

  11. Treatment-Experienced Patients: Goals of Therapy Limited prior treatment: • Maximum viral suppression • Consider early change to prevent further resistance mutations Extensive prior treatment: • Preservation of immune function • Prevention of clinical progression • Balance benefits of partial viral suppression with risk of additional resistance mutations

  12. Changing Therapy: Treatment Options Limited prior treatment with low HIV RNA: • Intensification (e.g., tenofovir) • Pharmacokinetic (PK) enhancement • Change to new regimen

  13. Changing Therapy: Treatment Options Limited prior treatment with single drug resistance: • Change 1 drug • PK enhancement • Change to new regimen

  14. Changing Therapy: Treatment Options Limited prior treatment with >1 drug resistance: • Change drug classes and/or add new active drugs

  15. Changing Therapy: Treatment Options Prior treatment with no resistance identified: • Consider nonadherence or possibility that patient was off medications at time of resistance test • Consider resuming same regimen or starting new regimen and repeat resistance testing early (2-4 wks)

  16. Changing Therapy: Treatment Options Extensive prior treatment with resistance: • Avoid adding single active drug • Seek expert advice • If few or no treatment options, consider continuing same regimen. Other possible strategies: • PK enhancement • Therapeutic drug monitoring • Retreatment with prior medications • Multidrug regimens (limited by complexity, tolerability) • New ARV drugs, e.g., enfuvirtide, investigational drugs • Treatment interruptions not recommended

  17. Testing for Drug Resistance • Recommended in case of virologic failure, to determine role of resistance and maximize the number of active drugs in a new regimen • Combine with obtaining a drug history and maximizing drug adherence • Research supports use in certain settings • Perform while patient is taking ART (or within 4 weeks of regimen discontinuation)

  18. Genotyping • Detects drug resistance mutations in specific genes, e.g., reverse transcriptase and protease • Sequencing or probing • Results within 1-2 weeks • Interpretation of mutations and cross-resistance is complex • Consultation with specialists is recommended

  19. Phenotyping • Measures the ability of viruses to grow in various concentrations of antiretroviral drugs • Results within 2-3 weeks • More expensive than genotyping • The ratio of the IC50s of the test and reference viruses is reported as the fold increase in IC50, or fold resistance • Interpretation may be complex • Consultation with specialists is recommended

  20. Drug Resistance Testing: Limitations • Lack of uniform quality assurance • Relatively high cost • Insensitivity for minor viral species (<10-20%)

  21. Drug Resistance Testing • Resistance assays should be performed while the patient is taking antiretroviral regimen • Data suggesting the absence of resistance should be interpreted carefully in relation to the prior treatment history

  22. Drug Resistance Testing

  23. Drug Resistance Testing

  24. Drug Resistance Testing

  25. Interruption of Antiretroviral Therapy • Many possible reasons for short- or long-term treatment interruption • Potential risks and benefits vary according to the patient’s clinical and immunologic status, duration of interruption, and other factors

  26. Interruption of ART: Short-term Possible scenarios include: • Drug toxicity • Illness that precludes oral medication • Surgery • Nonavailability of drugs

  27. Interruption of ART: Short-term Considerations for stopping ARVs: • In case of severe or life-threatening toxicity: • Stop all drugs simultaneously • When all ARVs have similar half-lives: • Stop all drugs simultaneously • When ARVs have different half-lives: • Stopping all ARVs simultaneously may result in functional monotherapy • Consider staggered discontinuation, or substitution of shorter half-life ARVs (see below)

  28. Interruption of ART: After Pregnancy • Women who started ART during pregnancy to decrease risk of mother-to-child transmission • If pretreatment CD4 is above currently recommended ART starting levels and patient wishes to stop therapy after delivery

  29. Interruption of ART: Long-term Potential risks, including • Viral rebound, • CD4 decline • Disease progression, • Development of drug resistance • Increase in risk of HIV transmission Planned therapy interruptions cannot be recommended outside of clinical trials.

  30. Interruption of ART: Long-term Several scenarios: • Patients who started ART during acute HIV infection • Optimal duration of treatment and consequences of discontinuation are unknown; studies ongoing • Patients with treatment failure, extensive ARV resistance, and few available treatment options • Partial virologic suppression from ART has clinical benefit • Not recommended outside clinical trial setting

  31. Interruption of ART: Long-term • Patients on ART with CD4 above levels recommended for starting therapy; baseline CD4 either above or below recommended threshold: • Conflicting and incomplete data; several studies of structured treatment interruptions show increased risk of disease progression and death • CD4 decline after treatment interruption is related to pretreatment CD4 nadir

  32. Interruption of ART: ARV-Specific Issues Discontinuation of efavirenz or nevirapine: • These ARVs have long half-lives; stopping drugs in an ART regimen simultaneously may result in functional mono- or dual therapy • The optimal interval between stopping these and other ARVs is not known • Consider substitution of a PI for the NNRTI for a period of time before stopping all ARVs

  33. Interruption of ART: ARV-Specific Issues Discontinuation and reintroduction of nevirapine: • If nevirapine has been interrupted for more than 2 weeks, it should be restarted with the usual dose escalation period

  34. Interruption of ART: ARV-Specific Issues Discontinuation of emtricitabine, lamivudine, or tenofovir in patients with hepatitis B: • Flare of hepatitis may occur on discontinuation of any of these ARVs • Monitor closely • Consider initiating adefovir for HBV treatment • Entecavir should not be used in patients not on suppressive ART

  35. Interruption of ART: Long-term If therapy must be discontinued, counsel patients on: • Need for close clinical and laboratory monitoring • Risks of treatment interruption • Behavioral guidelines to reduce risk of HIV transmission

  36. Web Sites to Access the Guidelines • http://www.aidsetc.org • http://aidsinfo.nih.gov

  37. About This Slide Set • This presentation was updated by Susa Coffey, MD for the AETC National Resource Center in October 2006 and revised in April 2007. • See the AETC NRC Web Site for the most current version of this presentation. http://www.aidsetc.org

More Related