ncrc-tx-experienced-06-21.pptx

File 1 of 1 from HHS Adult ART Guidelines: Treatment-Experienced Patients

Management of Treatment Experience PWH

Details
Management of Treatment-Experienced Patients Guidelines for the Use of Antiretroviral Agentsin Adults and Adolescents June 2021 About This Presentation These slides were developed using the Guidelines updated in June 2021. The intended audience is clinicians involved in the care of patients with HIV. Because the field of HIV care is rapidly changing, users are cautioned that the information in this presentation may become out of date quickly. It is intended that these slides be used as prepared, without changes in either content or attribution. Users are asked to honor this intent. June 2021 Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents Developed by the Department of Health and Human Services (DHHS) Panel on Antiretroviral Guidelines for Adults and Adolescents A Working Group of the Office of AIDS Research Advisory Council (OARAC) June 2021 Outline Definitions Causes of virologic failure (VF) Management of VF Clinical scenarios Discontinuation or interruption of ART Poor CD4 recovery and persistent inflammation despite viral suppression June 2021 Treatment-Experienced Patients The recommended initial ARV regimens should achieve and maintain HIV suppression to below the lower level of detection (LLOD) of HIV RNA assays Virologic rebound or failure of virologic suppression often results in resistance mutations to one or more of the ARVs in the regimen Assessment and management of patients with extensive ART resistance is complex: expert consultation is recommended June 2021 Virologic Response, Definitions (1) Virologic suppression (VS): Confirmed HIV RNA below LLOD (e.g., <50 copies/mL) Virologic failure (VF): Inability to achieve or maintain HIV RNA <200 copies/mL Viral suppression Graphic: National HIV Curriculum, hiv.uw.edu June 2021 Virologic Response, Definitions (2) Incomplete virologic response: Lack of VS to <200 copies/mL after 24 weeks on ART Virologic rebound: Confirmed HIV RNA 200 copies/mL after VS Virologic blip: An isolated detectable HIV RNA level followed by a return to VS Low-level viremia: Detectable HIV RNA <200 copies/mL Virologic rebound Virologic blip Low-level viremia Graphics: National HIV Curriculum, hiv.uw.edu June 2021 Causes of Virologic Failure (VF) (1) Most common: suboptimal adherence, ARV intolerance; also transmitted drug resistance Patient/adherence-related factors Comorbidities that affect adherence (e.g., substance abuse, psychiatric or neurocognitive issues) Unstable housing Missed clinic appointments Interruptions in access to ART Cost/affordability of ARVs Adverse drug effects High pill burden, dosing frequency June 2021 Causes of Virologic Failure (VF) (2) HIV-related factors Transmitted or acquired resistance mutations Prior treatment failure Higher pretreatment HIV RNA (depending on the ART regimen) ARV regimen-related factors Pharmacokinetic problems Suboptimal ARV potency Low genetic barrier to resistance Prior exposure to nonsuppressive regimens Food requirements Drug-drug interactions with concomitant medications Prescription errors June 2021 Managing Patients with VF (1) Carefully assess causes of VF; management will vary according to cause Review HIV RNA, CD4 count, ART history, prior and current ARV resistance test results Resistance is cumulative; consider all past resistance Resistance test should be done while patient is taking the failing regimen, or within 4 weeks of treatment discontinuation If >4 weeks since ARV discontinuation, resistance test may provide useful information, but it may not detect previously selected mutations June 2021 Managing Patients with VF (2) Goal of treatment: virologic suppression (HIV RNA LLOD - <200: ART change not usually required. Development of resistance unlikely. No consensus re management. Check VL q 3 months. VL 200 - <1,000: Drug resistance likely (esp. if VL >500). Manage as for VL 1000. June 2021 Managing VF: Level of Viremia (2) VL 1000 and no ARV resistance mutations identified: Usually caused by suboptimal adherence: assess and address; consider changes, simplification VL 1000 and ARV resistance mutations identified: Modify regimen ASAP, to avoid more resistance mutations and higher viral loads June 2021 Managing VF, Clinical Scenarios: Failure of 1st ART Regimen - INSTI + 2 NRTIs Resistance considerations ART options If resistance to 3TC/FTC but no INSTI resistance Boosted PI + 2 NRTIs (at least 1 fully active) DTG + 2 NRTIs (include at least 1 fully active) Boosted PI + INSTI If EVG or RAL resistance but susceptibility to DTG+/- 3TC/FTC resistance Boosted PI + 2 NRTIs (at least 1 fully active) DTG BID (if HIV is sensitive to DTG) + 2 NRTIs (at least 1 fully active) DTG BID (or possibly BIC*) + boosted PI June 2021 *BIC: no data in patients with VF and EVG or RAL resistance mutations; "its use cannot be formally recommended" in these settings. Managing VF, Clinical Scenarios: Failure of 1st ART Regimen (2) - NNRTI + 2 NRTIs Resistance considerations ART options Most likely: resistance to NNRTI +/- 3TC/FTC (M184V/I) Add'l NRTI mutations may be present DTG + 2 NRTIs (at least 1 fully active) Boosted PI + 2 NRTIs (at least 1 fully active) Boosted PI + INSTI June 2021 Managing VF, Clinical Scenarios: Failure of 1st ART Regimen (3) - Boosted PI + 2 NRTIs Resistance considerations ART options Most likely: no resistance, or resistance only to 3TC/FTC (M184V/I) Continue same regimen Another boosted PI + 2 NRTIs (at least 1 fully active) DTG* + 2 NRTIs (at least 1 fully active) Another boosted PI + INSTI June 2021 *Could consider BIC in place of DTG. If only 1 NRTI is active, DTG preferred to BIC. No data on use of BIC in this setting of VF. Managing VF, Clinical Scenarios: Failure of 2nd (or subsequent) ART Regimen ARV resistance but active ARV options Resistance considerations ART options Consider past and current resistance test results and ART history to design new ART regimen At least 2 fully active ARVs Can use partially active ARVs if no other options Consider ARVs with different mechanisms of action June 2021 Managing VF, Clinical Scenarios: Failure of 2nd (or subsequent) ART Regimen (2) Multiple or extensive resistance and few ARV options Resistance considerations ART options Consider past and current resistance test results and ART history to design new ART regimen Consider tropism test (if MVC is being considered) Consult experts Identify all active or partially active ARVs Consider ARVs with different mechanisms of action Consider investigational ARVs: clinical trial or expanded access program ART discontinuation is NOT recommended June 2021 Managing VF, Clinical Scenarios: Suspected ARV Resistance but Limited/Incomplete ARV and Resistance History - Unknown Resistance considerations ART options Obtain records, if possible Resistance testing: may identify mutations (if patient off ART, mutations may not be detected) Consider restarting previous regimen and obtain VL and resistance test after 2-4 weeks Consider regimen with ARVs with high genetic barriers to resistance (eg, DTG and/or boosted DRV) with close VL monitoring and resistance testing if inadequate viral suppression June 2021 Discontinuation or Interruption of ART (1) Treatment interruptionshould be avoided, if possible:may cause rapid increase in HIV RNA, immunedecompensation, clinical progression Unplanned ART interruption may occur, and sometimes may be necessary June 2021 Discontinuation or Interruption of ART (2) Short-Term Interruptions (days-weeks) Unanticipated: Severe toxicity or inability to take oral medication: Stop all ARV components simultaneously Planned: All ARVs have similar half-lives: Stop all simultaneously ARVs have different half-lives: Some NNRTIs have long half-lives; may stop NNRTI first and stop other ARVs 2-4 weeks later, or replace NNRTI with boosted PI for 4 weeks, then stop all June 2021 Discontinuation or Interruption of ART (3) Planned Long-Term Interruptions Not recommended outside controlled clinical trials If ART must be discontinued, patients should understand risks (re personal health and re HIV transmission) Follow closely: clinical and laboratory monitoring June 2021 Poor CD4 Recovery and Persistent Inflammation Despite Viral Suppression Morbidity and mortality are higher in HIV-infected individuals than in the general population, even with viral suppression E.g., cardiovascular disease, many non-AIDS cancers and infections, COPD, osteoporosis, diabetes, liver disease, kidney disease, thromboembolic disease, neurocognitive dysfunction, frailty Likely related to poor CD4 recovery, persistent immune activation, and inflammation, as well as health-related behaviors and ARV toxicity June 2021 Poor CD4 Recovery Despite VS Low CD4 (especially <200 cells/L, but also up to at least 500 cells/L) despite viral suppression on ART: associated with risk of illness and mortality Lower pretreatment CD4 counts associated with suboptimal CD4 recovery early ART initiation may enhance CD4 recovery June 2021 Poor CD4 Recovery Despite VS: Management Evaluate for underlying causes Malignancy, coinfections (e.g., HCV), medical conditions Medications that may decrease CD4 cells (e.g., cancer chemotherapy, interferon) No consensus on management of patients without evident causes Changing or intensifying the ARV regimen has not been shown to be beneficial, is not recommended IL-2: no benefit, not recommended Other immune-based therapies are being studied June 2021 Persistent Immune Activation and Inflammation Despite VS (1) Immune activation and inflammation improve with suppression of HIV through ART, but do not return to normal Systemic immune activation and inflammation may be independent mediators of risk of morbidity and mortality in patients with viral suppression on ART Poor CD4 recovery on ART (e.g., CD4 <350 cells/L) associated with greater immune system activation and inflammation June 2021 Persistent Immune Activation and Inflammation Despite VS (2) Causes not completely clear: likely include HIV persistence, coinfections, microbial translocation No proven interventions ART intensification or modification: not consistently effective in studies Anti-inflammatory medications and others are being studied Clinical monitoring with immune activation or inflammatory markers is not currently recommended Focus on maintaining viral suppression with ART, reducing risk factors (e.g., smoking cessation, diet, exercise), managing comorbidities (e.g., hypertension, hyperlipidemia, diabetes) June 2021 Websites to Access the Guidelines AETC National Coordinating Resource Centerhttps://aidsetc.org Clinical Infohttps://clinicalinfo.gov June 2021 About This Slide Set This presentation was prepared by Susa Coffey, MD, for the AETC National Resource Center in March 2020. and updated in June 2021. See the AETC NCRC website for the most current version: https://aidsetc.org