HIV Therapeutics 2024 PDF

W4D3 WIS Human Immunodeficiency Virus Therapeutics Akshith Dass, PharmD, BCIDP, BCPS Assistant Professor of Pharmacy Practice NEOMED December 6th, 2024 Slide Credits: Bhavin Mistry, PharmD, BCIDP, BCPS Learning Ob...

W4D3 WIS Human Immunodeficiency Virus Therapeutics Akshith Dass, PharmD, BCIDP, BCPS Assistant Professor of Pharmacy Practice NEOMED December 6th, 2024 Slide Credits: Bhavin Mistry, PharmD, BCIDP, BCPS Learning Objectives Distinguish first line ART regimens for HIV treatment naïve patients Distinguish ART regimens for HIV pre-exposure prophylaxis Distinguish ART regimens for HIV post-exposure prophylaxis Describe monitoring parameters for patients on ART Distinguish the brand and generic names of anti-retroviral agents  What is Human-Immunodeficiency-Virus? Lentivirus Disease was first described in 1981 Untreated, can lead to Acquired-Immune-Deficiency-Syndrome (AIDS) CD4 < 200 or < 14% AIDS defining illness – opportunistic infection Evolution analysis Several transmissions from primates to humans during early 1900’s DiPiro JT. Pharmacotherapy: A Pathophysiologic Approach, 12ed. McGraw-Hill Education. c2021. Chapter 148, Human Immunodeficiency Virus Infection. Jawetz. Medical Microbiology, 28ed. McGraw-Hill Education. C2019. Chapter 44: AIDS and Lentiviruses.  Transmission Sexual MSM Highest risk is from receptive anorectal intercourse (1.4 per 100 sexual acts) Condom use reduces transmission by 80% Parenteral Transmission rate of 0.67 per 100 episodes Perinatal Mother-to-child rate of 25% if not on ART U=U undetectable untransmissable 420 copies ML DiPiro JT. Pharmacotherapy: A Pathophysiologic Approach, 12ed. McGraw-Hill Education. c2021. Chapter 148, Human Immunodeficiency Virus Infection. Jawetz. Medical Microbiology, 28ed. McGraw-Hill Education. C2019. Chapter 44: AIDS and Lentiviruses.  Signs and Symptoms of Primary Disease Fatigue Unexplained weight loss Fever Myalgia Nausea, vomiting, diarrhea Night sweats Recurrent infections due to immunosuppression Aseptic meningitis Pneumonia DiPiro JT. Pharmacotherapy: A Pathophysiologic Approach, 12ed. McGraw-Hill Education. c2021. Chapter 148, Human Immunodeficiency Virus Infection.  Laboratory CD4 count Absolute count (cells/mm3) Percentage (%) Viral load HIV viremia (copies/mL) DiPiro JT. Pharmacotherapy: A Pathophysiologic Approach, 12ed. McGraw-Hill Education. c2021. Chapter 148, Human Immunodeficiency Virus Infection. Drug – Specific Labs Genotype Genetic testing of the viral RNA Identifies specific mutations Phenotype IC50 with ART agents Patients’ strain compared to wild-type 3TC = Lamivudine, FTC = Emtricitabine, ABC = Abacavir, TDF = Tenofovir, AZT = Zidovudine HIV Drug Resistance Database HLA-B*5701 abacavir Tropism maraviroc  Screening CDC Recommendations All persons between 13 – 64 years of age, at least once Annually Men who have sex with men Anal or vaginal sex with an HIV positive person Sex with more than one partner since last HIV test Shared needles, syringes or other drug injection equipment Exchanged sex for drugs or money Been diagnosed or treated for Hepatitis B or Tuberculosis Had sex with someone who fits the above criteria or has a sexual history you do not know HIV Testing. CDC. Atlanta. Accessed November 2023.  Types of HIV Tests Antibody Only testing methodology approved by the US Food and Drug Administration Can detect HIV sooner from vein blood versus finger stick or oral sampling Antigen / Antibody Recommended to be done at a lab, venous blood draw Rapid finger stick option available Nucleic Acid Test (NAT) Can detect HIV sooner than any other methodology Can detect HIV as well as provide viral load Recommended for individuals with high risk of exposure HIV Testing. CDC. Atlanta. Accessed November 2023.  Turn around Time 20 minutes HIV self- tests 30 minutes Rapid antibody test Rapid antigen/antibody test Several days Nucleic Acid Test Antigen / Antibody test (when taken from venous blood) A couple words from our sponsor (CDC) HIV Testing. CDC. Atlanta. Accessed November 2023.  Goals of Treatment Decrease morbidity and mortality Slow disease progression Decrease viral replication Undetectable viral load (< 20 copies/mL) Prevent complications Improve immune system CD4 count as high as possible DiPiro JT. Pharmacotherapy: A Pathophysiologic Approach, 12ed. McGraw-Hill Education. c2021. Chapter 148, Human Immunodeficiency Virus Infection. Panel on Antiretroviral Guidelines for Adults and Adolescents. Department of Health and Human Services. Accessed November 2023. Role of the Pharmacist Monitor side effects Reduce drug-drug interactions Promote adherence First line agents for treatment naïve patients r im Apretude People who do NOT have a history of using CAB-LA as PrEP, one of the following: Bictarvy (bictegravir-emtricitabine-tenofovir alafenamide) Tivicay (dolutegravir) with Descovy (emtricitabine-tenofovir alafenamide) Tivicay (dolutegravir) with Truvada (emtricitabine-tenofovir disoproxil fumarate) Tivicay (dolutegravir) with CimDuo (lamivudine-tenofovir disoproxil fumarate) Dovato (dolutegravir-lamivudine) Do not use Dovato if: NRTI backbone HIV RNA > 500,000 copies/mL Hepatitis B viral co-infection or before results of Hepatitis B virus testing Before results of HIV genotypic resistance testing for reverse transcriptase NSTI First line agents for treatment naïve patients People who have a history of using CAB-LA as PrEP INSTI genotype resistance testing should be performed before starting ART If ART is to be initiated before results of genotypic testing results, then choose: Symtuza (darunavir-cobicistat-emtricitabine-tenofovir alafenamide) Prezcobix (darunavir-cobicistat) OR Prezista (darunavir) w/ ritonavir along with Descovy (emtricitabine-tenofovir alafenamide), OR Truvada (emtricitabine-tenofovir disoproxil fumarate), OR CimDuo (lamivudine-tenofovir disoproxil fumarate)  Response to Treatment First check up 2 – 8 weeks after starting treatment Assess tolerance Assess response 0.5 log10 copies/mL reduction in viral load at week 4 Viral load ≤ 400 copies/mL after 24 weeks Viral load ≤ 50 copies/mL after 48 weeks DiPiro JT. Pharmacotherapy: A Pathophysiologic Approach, 12ed. McGraw-Hill Education. c2021. Chapter 148, Human Immunodeficiency Virus Infection. Panel on Antiretroviral Guidelines for Adults and Adolescents. Department of Health and Human Services. Accessed November 2023. Chronicity of HIV Labs and doctor visits every 3 months... Forever! Each visit CD4 count Viral load 1 – 4 times a year CBC, BMP, LFTs, Lipid Panel, HbA1c  Pre-Exposure Prophylaxis (PrEP) All sexually active persons should be informed on PrEP All persons should be screened for other sexually transmitted infections (STIs) Educations should be provided for pregnancy deterrents Negative HIV must be done within 30 days prior to initiation of PrEP And every 3 months thereafter PreExposure Prophylaxis for the Prevention of HIV Infection in the United States – 2021 Update. Department of Health and Human Services. Accessed November 2023.  Assessing Sexual Risk Factors PreExposure Prophylaxis for the Prevention of HIV Infection in the United States – 2021 Update. Department of Health and Human Services. Accessed November 2023.  Assessing Persons Who Injects Drugs (PWID) PreExposure Prophylaxis for the Prevention of HIV Infection in the United States – 2021 Update. Department of Health and Human Services. Accessed November 2023.  Agents Approved for PrEP Truvada (emtricitabine + tenofovir disoproxil fumarate) taken Descovy (emtricitabine + tenofovir alafenamide) daily Apretude (cabotegravir) INSTI Bimonthly intramuscular injections with or without oral cabotegravir lead in PreExposure Prophylaxis for the Prevention of HIV Infection in the United States – 2021 Update. Department of Health and Human Services. Accessed November 2023.  Post Exposure Prophylaxis (PEP) Occupational PEP (oPEP) Most commonly occurs as needlestick Non-occupational PEP (nPEP) Unprotected sexual contact Injection drug use Need to assess exposure risk and initiate treatment as soon as possible; within 72 hours of exposure DiPiro JT. Pharmacotherapy: A Pathophysiologic Approach, 12ed. McGraw-Hill Education. c2021. Chapter 148, Human Immunodeficiency Virus Infection.  Agents Approved for PEP Normal renal function – Duration of 28 days Preferred Tivicay (dolutegravir) with Truvada (emtricitabine-tenofovir disoproxil fumarate) Isentress (raltegravir) with Truvada (emtricitabine-tenofovir disoproxil fumarate) Alternative Prezista (darunavir) with Norvir (ritonavir) with Truvada (emtricitabine-tenofovir disoproxil fumarate) DiPiro JT. Pharmacotherapy: A Pathophysiologic Approach, 12ed. McGraw-Hill Education. c2021. Chapter 148, Human Immunodeficiency Virus Infection.  Agents Approved for PEP Renal dysfunction, CrCl < 60 ml/min – Duration of 28 days Preferred Tivicay (dolutegravir) with Combivir (zidovudine-lamivudine) Isentress (raltegravir) with Combivir (zidovudine-lamivudine) Alternative Prezista (darunavir) with Norvir (ritonavir) with Combivir (zidovudine-lamivudine) DiPiro JT. Pharmacotherapy: A Pathophysiologic Approach, 12ed. McGraw-Hill Education. c2021. Chapter 148, Human Immunodeficiency Virus Infection. OHIV.org – HIV Hotline 1-800-332-2437