NORTHWEST AIDS EDUCATION AND TRAINING CENTER

2014 IAS-USA Treatment Guidelines Brian R. Wood, MD Medical Director, NW AETC ECHO Assistant Professor of Medicine, University of Washington

Presentation prepared by: Presenter Last Updated: 10/16/14

International Antiviral Society-USA Guidelines Updated July 2014

§ Prevention Guidelines – Dr. Marrazzo will discuss 11/6/14 § Treatment Guidelines

Rating Scale

•  Strength of Recommendations: - A: Strong support - B: Moderate support - C: Limited support

•  Quality of Evidence: -  Ia: >1 RCTs published in peer-reviewed literature -  Ib: >1 RCTs presented at peer-reviewed scientific meetings -  IIa: non-RCT’s, cohort, or case-control studies published -  IIb: non-RCT’s, cohort, or case-control studies presented -  III: panel’s analysis of accumulated available evidence

When to Start

ART is recommended regardless of CD4 count

CD4 count <500: AIa

CD4 count >500: BIII

Pregnancy: AIa Chronic hepatitis B: AIIa

HIV-associated nephropathy: AIIa

What to Start: Recommended Initial Regimens

Anchor Backbone Comments Dolutegravir Tenofovir-emtricitabine May increase serum creatinine

Dolutegravir^ Abacavir-lamivudine Abacavir not inferior to tenofovir at high HIV RNA levels if given with dolutegravir

Elvitegravir/cobicistat^

Tenofovir-emtricitabine May increase serum creatinine; similar drug interactions as ritonavir

Raltegravir Tenofovir-emtricitabine Raltegravir twice daily

Efavirenz^ Tenofovir-emtricitabine CNS/psych SE’s; no longer contraindicated in pregnancy but avoid in woman of child-bearing potential

Efavirenz Abacavir-lamivudine Same as above

Rilpivirine^ Tenofovir-emtricitabine Avoid if HIV RNA >100,000 copies or on PPI; taken with full meal

Atazanavir/ritonavir Tenofovir-emtricitabine May cause cholelithiasis/nephrolithiasis; consider H2 blocker/PPI interactions

Darunavir/ritonavir Tenofovir-emtricitabine Once-daily dosing for initial therapy ^Single tablet regimen (STR) option!

Additional Considerations

•  Tenofovir: - Potential for renal and bone toxicity

•  Abacavir: - Associated with cardiovascular events, though data conflicting - HLA-B*5701 must be negative

•  Abacavir/lamivudine: - Less efficacious than tenofovir/emtricitabine when given with

efavirenz or boosted atazanavir if baseline HIV RNA >100,000

What to Start: Alternatives

Anchor Backbone Comments

Raltegravir Abacavir-lamivudine

Abacavir not inferior to tenofovir at high HIV RNA levels if given with raltegravir

Nevirapine 2 NRTI’s Severe hepatotoxicity may occur if CD4 >250 in women or >400 in men; more severe rash than other NNRTI’s

Rilpivirine Abacavir-lamivudine

Not recommended if HIV RNA >100,000 copies

Atazanavir-cobicistat 2 NRTI’s Atazanavir levels equivalent with cobicistat or ritonavir

Darunavir-cobicistat 2 NRTI’s Darunavir levels equivalent with cobicistat or ritonavir

Lopinavir-ritonavir 2 NRTI’s May be less tolerable and have increased CV toxicity

Darunavir-ritonavir Abacavir-lamivudine

Single randomized study available

Darunavir-ritonavir Raltegravir Inferior if CD4 <200 or HIV RNA >100,000 copies

Lopinavir-ritonavir Raltegravir Single study available with significant limitations

Lopinavir-ritonavir Lamivudine Single study available with significant limitations

Estimated Patent Expiration Dates for Branded Antiretrovirals

Year Antiretrovirals

2012 Zidovudine, lamivudine, stavudine, didanosine, saquinavir, nevirapine

2013 Ritonavir, efavirenz, zidovudine/lamivudine

2016 Abacavir, lopinavir/ritonavir (softgel)

2017 Tenofovir, atazanavir, darunavir

2019 Etravirine, abacavir/lamivudine

2024 Tenofovir/emtricitabine

2025 Raltegravir

2026 Tenofovir/emtricitabine/efavirenz, tenofovir/emtricitabine/rilpivirine, dolutegravir

Initiating ART in Special Circumstances

•  “ART should be offered to all individuals with acute infection and should be started as early as possible to maximize benefit” (BIII)

•  Benefits: reduction of proviral DNA and plasma viral load, lower viral set point, robust immune reconstitution

Acute HIV:

•  “The data for initiating ART in elite controllers is stronger than before but still insufficient to recommend routine therapy”

Elite Controllers:

Initiating in Setting of an Acute OI or Tuberculosis

•  Start within first 2 weeks of diagnosis (AIa) •  Includes other AIDS-defining illnesses likely lymphoma

or HPV-related cancer (AIa-BIII) •  Timing less certain for crypto meningitis…(COAT trial)

Acute OI:

•  Within 2 weeks if CD4 count <50 (AIa) •  By 8-12 weeks if higher CD4 count (AIa) •  TB meningitis: optimal timing less certain, but likely

should be started within 2-8 weeks (BIII)

Tuberculosis:

ART Monitoring

HIV RNA

•  4 weeks after ART initiation or change, then every 3 mo (AIa)

• Evaluate for cause of virological failure if HIV RNA >200 copies (AIIa)

CD4

• Once HIV RNA suppressed for >2 years and CD4 consistently >500, monitoring CD4 count is optional (CIII)

“There are insufficient data to make general recommendations for the management of patients with sustained viremia of 50 to 200 copies/mL.” !