1. N ORTHWEST A IDS E DUCATION AND T RAINING C ENTER Major Changes to the HHS Adult and Adolescent HIV Treatment Guidelines: April 2015 Brian R. Wood, MD Assistant Professor of Medicine, University of Washington Medical Director, NW AETC ECHO Last Updated: April 16, 2015

2. Source: HHS Antiretroviral Therapy Guidelines. AIDS Info (www.aidsinfo.nih.gov) US Health and Human Services (HHS) Adult and Adolescent Antiretroviral Therapy Guidelines

3. Restructuring of “What to Start” List of Initial Regimens May 2014 Guidelines: Recommended Regardless of CD4/VL Recommended Only if VL <100K April 2015 Guidelines: Recommended Regimens Alternative Regimens Other Regimens

4. HHS Antiretroviral Therapy Guidelines: April 8, 2015 Recommended Regimens Source: 2015 HHS Antiretroviral Therapy Guidelines. AIDS Info (www.aidsinfo.nih.gov) ^Only for patients with pre-treatment estimated CrCl ≥ 70 ml/min *Only for patients who are HLA-B*5701 negative

5. HHS Antiretroviral Therapy Guidelines: April 8, 2015 Alternative Regimens “Regimens that are effective and tolerable, but have potential disadvantages when compared with the recommended regimens, have limited use in certain patient populations, or have less supporting data from clinical trials.” Source: 2015 HHS Antiretroviral Therapy Guidelines. AIDS Info (www.aidsinfo.nih.gov)

6. HHS Antiretroviral Therapy Guidelines: April 8, 2015 Alternative Regimens Source: 2015 HHS Antiretroviral Therapy Guidelines. AIDS Info (www.aidsinfo.nih.gov) + Only for patients with HIV RNA 200 cells/mL ^Only for patients with pre-treatment estimated CrCl >70 mL/min *Only for patients who are HLA-B*5701 negative

7. HHS Antiretroviral Therapy Guidelines: April 8, 2015 Other Regimens “Regimens that, in comparison with Recommended and Alternative regimens, may have reduced virologic activity, limited supporting data from large clinical trials, or other factors such as greater toxicities, higher pill burden, drug interaction potential, or limitations for use in certain populations.” Source: 2015 HHS Antiretroviral Therapy Guidelines. AIDS Info (www.aidsinfo.nih.gov)

8. HHS Antiretroviral Therapy Guidelines: April 8, 2015 Other Regimens *Only for patients who are HLA-B*5701 negative + Only for patients with HIV RNA <100K copies/mL ^Only for patients with pre-treatment estimated CrCl >70 mL/min ∞ Only for patients with HIV RNA 200 cells/mL

9. NRTI-Sparing Options For Initial Therapy Two Regimens Now Listed in Guidelines Sources: NEAT/ANRS143: Raffi F et al. Lancet. 2014;384:1942-51. GARDEL: Cahn P et al. Lancet Infect Dis. 2014 Jul;14(7):572-80.

10. Considerations When Selecting an Initial ART Regimen Source: 2015 HHS Antiretroviral Therapy Guidelines. AIDS Info (www.aidsinfo.nih.gov)

11. Specific Scenarios and ART Regimen Considerations See Table 7 in Guidelines Source: 2015 HHS Antiretroviral Therapy Guidelines. AIDS Info (www.aidsinfo.nih.gov)

12. Specific Scenarios and ART Regimen Considerations See Table 7 in Guidelines Source: 2015 HHS Antiretroviral Therapy Guidelines. AIDS Info (www.aidsinfo.nih.gov)

13. Isolated CNS Virological Failure Or “Neurosymptomatic Viral Escape” New-onset CNS signs and symptoms (usually subacute) Breakthrough of HIV in CNS despite suppressed plasma VL Often abnormal brain MRI and CSF lymphocytic pleocytosis CSF HIV RNA > plasma HIV RNA In most patients, find evidence of drug-resistant CSF virus Must distinguish from: CNS infections, CSF RNA “blip,” HAND without CNS viral breakthrough Source: 2015 HHS Antiretroviral Therapy Guidelines. AIDS Info (www.aidsinfo.nih.gov)

14. Other Updates to the Guidelines Updated sections -Diagnosis of acute HIV -Treatment of HIV type 2 (HIV-2) -Interactions between ARV’s and anti-HCV DAA’s (table 12) -Side effects of ARV’s (table 15) -General drug-drug interactions of ARV’s (table 17) -Cost considerations -New section on poor CD4 recovery & immune activation Sections largely unchanged -Baseline evaluation -Switching ART -Therapeutic drug monitoring -CD4 and VL monitoring -HIV-TB coinfection -Adherence counseling; transmission prevention Source: 2015 HHS Antiretroviral Therapy Guidelines. AIDS Info (www.aidsinfo.nih.gov)