Summary of Recommended Regimens The most extensively studied combination antiretroviral regimens for treatment-naïve patients generally consist of two NRTIs plus either one NNRTI or a PI (with or without ritonavir boosting). A list of Panel-recommended components for initial therapy in treatment-naïve patients can be found in Table 6 . Potential advantages and disadvantages of the components recommended as initial therapy for treatment-naïve patients are listed in Table 7 to guide prescribers in choosing the regimen best suited for an individual patient. A list of agents or components not recommended for initial treatment can be found in Table 8 . Some agents or components that are not recommended for use because of lack of potency or potential serious safety concerns are listed in Table 9
Transcript of "SYNCing Guidelines- Catanzaro"
Guideline Summary:When to Start ART Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Andy Catanzaro, MD Infectious Diseases email@example.com March 2012
Outline Overview of HIV therapy Initiation of Therapy Special Issues2 October 2011 www.aidsetc.org
HIV Terms/Acronyms TermsART: Antiretroviral TherapyHIV Viral Load: amount of virus in the bloodUndetectable Viral Load: Goal of TherapyCD4 Count: Immune MarkerGenotype: Sensitivity of the Virus to Medications3 October 2011 www.aidsetc.org
What are ‘The Guidelines’ for HIV TherapyIndependent panel of expertsReview Current Literature on HIVMake RecommendationsStrength of Evidence given for each guidance (www.aidsinfo.nih.gov) October 2011 www.aidsetc.org
What the Guidelines Address Baseline evaluation Laboratory testing When to initiate & change therapy Therapeutic options ART-associated adverse effects6
What the Guidelines Address Treatment of acute HIV infection Special considerations (pregnant, injection drug users, coinfected with HBV, HCV, or TB) Preventing secondary transmission7
Websites to Access the Guidelines http://aidsinfo.nih.gov http://www.aidsetc.org8
Goals of Treatment Improve quality of life Reduce HIV-related morbidity and mortality Restore and/or preserve immunologic function Suppress HIV viral load Prevent HIV transmission9
Use of CD4 Cell Levels to Guide Therapy Decisions CD4 count The major indicator of immune function Most recent CD4 count is best predictor of disease progression A key factor in decision to start prophylaxis Important in determining response to ART Adequate response: CD4 increase 50-150 cells/µL per year *10
Studies in patients CD4>500 Favor Treatment Neutral on Treatment NA-ACCORD ART-CC CASCADE11
ART in Treatment Recommended forAll PatientsCD4 count Strength of the Evidence for the Recommendation Recommendation<350 Strong Data from randomized clinical trials350-500 Strong Data from non-randomized clinical trials>500 Moderate Expert Opinion12
Use of HIV RNA Levels to Guide Therapy Decisions HIV RNA May influence choice of ART Critical in monitoring response to ART Goal of ART: HIV RNA below limit of detection (ie, <20-75 copies/mL, depending on assay)13
Use of HIV RNA Levels to Guide Therapy Decisions (2) RNA monitoring Check at baseline Before initiating ART 2-4 weeks (not more than 8 weeks) after start or change of ART, then every 4-8 weeks until suppressed to <200 copies/mL Every 3-4 months with stable patients; may consider every 6 months for stable adherent patients with VL suppression >2-3 years Isolated “blips” may occur (transient low-level RNA, typically <400 copies/mL), are not thought to predict virologic failure ACTG defines virologic failure as confirmed HIV RNA >200 copies/ mL14
When to Start ART Potent ART may improve and preserve immune function in most patients with virologic suppression, regardless of baseline CD4 count ART indicated for all with low CD4 count or symptoms Earlier ART may result in better immunologic responses and better clinical outcomes Reduction in AIDS- and non-AIDS-associated morbidity and mortality Reduction in HIV-associated inflammation and associated complications Reduction in HIV transmission Recommended ARV combinations are considered to be durable and tolerable15
When to Start ART Exact CD4 count at which to initiate therapy not known, but evidence points to starting at higher counts Current recommendation: ART for all patients with CD4 Randomized control trial (RTC) data support benefit of ART if CD4 count ≤350 cells/µL No RTC data on benefit of ART at CD4 counts of >350 cells/µL, but observational cohort data exist Currently available ARVs are effective and well tolerated16
Potential Benefits of Early Therapy (CD4 count >500 cells/µL) Cohort study data show survival benefit if ART initiated at CD4 count >500 cells/µL Earlier ART may prevent HIV-related end organ damage; deferred ART may not reliably repair damage acquired earlier Increasing evidence of direct HIV effects on various end organs and indirect effects via HIV-associated inflammation End organ damage occurs at all stages of infection17
Potential Benefits of Early Therapy (CD4 count >500 cells/µL) (2) Potential decrease in risk of many complications, including: HIV-associated nephropathy Liver disease progression from hepatitis B or hepatitis C Cardiovascular disease Malignancies (AIDS defining and non-AIDS defining) Neurocognitive decline Blunted immunological response owing to ART initiation at older age Persistent T-cell activation and inflammation18
Potential Benefits of Early Therapy (CD4 count >500 cells/µL) (3) Prevention of sexual and blood borne transmission of HIV Prevention of mother-to-child transmission of HIV Prevention of transmission to a sexual partner19
Potential Limitations of Early Therapy (CD4 count >500 cells/µL) ARV-related toxicities Drug resistance Non-adherence to ART Cost20
Recommendations for Initiating ART (3) Patients may choose to postpone ART Providers may elect to defer ART, based on patients’ clinical or psychosocial factors caveat: do we really know who is ready?21
Consider More Rapid Initiation of ART(e.g. before the genotype is available) Pregnancy Acute opportunistic infection Lower CD4 count (eg, <200 cells/µL) Rapid decline in CD4 Higher viral load HIV Associated Nephropathy HBV coinfection when HBV treatment is indicated22
Consider Deferral of ART Clinical or personal factors may support deferral of ART If CD4 count is low, deferral should be considered only in unusual situations, and with close follow-up When there are significant barriers to adherence If comorbidities complicate or prohibit ART “Elite controllers” and long-term nonprogressors23
Initial ART Regimens: DHHS Categories Preferred Randomized controlled trials show optimal efficacy and durability Favorable tolerability and toxicity profiles24
Initial Treatment: Choosing Regimens 3 main categories: 1 Non-nucleoside Reductase Inhibitor + 2 Nucleside Reductase Inhibitor (NRTI) 1 Protease Inhibitor + 2 NRTIs 1 Integrase Inhibitor + 2 NRTIs Combinations preferred for most patients (Bias: Once Daily Preferred by patients)25
Initial Therapy: Fixed Dose CombinationsPreferred: Once-daily dosing High virologic efficacyTDF/FTC Active against HBV(Truvada) Potential for renal toxicityAlternative: Once-daily dosing Risk of hypersensitivity reaction if positive forABC/3TC HLA-B*5701(Epzicom) Possible inferior efficacy if baseline HIV RNA >100,000 copies/mL Active against HBVAcceptable: Twice-daily dosing Preferred for pregnant womenZDV/3TC More toxicities than TDF/FTC or ABC/3TC(Combivir)26
Initial Regimens: PreferredNNRTI based EFV/TDF/FTC (Atripla) 1,Protease ATV/r (Reyataz/Norvir) + TDF/Inhibitor FTC (Truvada) based DRV/r (Prezista/Norvir) + TDF/ FTC (Truvada)²Integrase RAL (Isentress BID) +Inhibitor based TDF/FTC (Truvada)Pregnant women LPV/r (Kaletra BID) + ZDV/3TC (Combivir)² 1. EFV should not be used during the first trimester of pregnancy or in women trying to conceive or not using effective and consistent27 contraception.
Drug-Drug InteractionsToo CommonAlways check new medicationsResources: Guidelines, Uptodate, Epocrates October 2011 www.aidsetc.org
Websites to Access the Guidelines http://www.aidsetc.org http://aidsinfo.nih.gov29
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