POST-EXPOSURE PROPHYLAXIS, PRE-EXPOSURE PROPHYLAXIS, & TREATMENT OF HIV

POST-EXPOSURE PROPHYLAXIS, PRE-EXPOSURE PROPHYLAXIS, & TREATMENT OF HIV

DISCLOSURE Relevant relationships with commercial entities none Potential for conflicts of interest within this presentation none Steps taken to review and mitigate potential bias N/A

LEARNING OBJECTIVE This lecture is designed to meet the following end-of-week learning objective: 1. Describe the role of antiretrovirals for the treatment, post-exposure prophylaxis, and pre-exposure prophylaxis of HIV infection.

MODULE OBJECTIVES By the end of this module, you should be able to: 1. Describe the role of antiretroviral agents as treatment of HIV infection 2. Describe the role of antiretroviral agents as postexposure prophylaxis (PEP) for HIV infection 3. Describe the role of antiretroviral agents as preexposure prophylaxis (PrEP) for HIV infection

GOALS OF HIV TREATMENT 1. Reduce HIV-associated morbidity 2. Prolong duration and quality of survival 3. Restore and preserve immunologic function 4. Maximally and durably suppress plasma HIV replication 5. Prevent HIV transmission DHHS 2014

PRINCIPLES OF HIV TREATMENT At least 3 active drugs Working on at least 2 distinct areas in HIV life cycle Maximize potency Minimize toxicity

https://aidsinfo.nih.gov/education-materials/factsheets/19/73/the-hiv-life-cycle#

https://aidsinfo.nih.gov/educationmaterials/fact-sheets/19/73/the-hiv-lifecycle#

ANTIRETROVIRAL THERAPIES Drug Class Examples Side-Effects/Notes NRTI (Nucleoside Reverse Transcriptase Inhibitors) NNRTI (Non- Nucleoside Reverse Transcriptase Inhibitors) PI (Protease Inhibitors) FI (Fusion Inhibitors) CCRA (Chemokine Coreceptor Antagonist) INSTI (Integrase Inhibitor) zidovudine, lamivudine, emtricitabine, didanosine, stavuidine, abacavir, tenofovir, nevirapine, etravirine, efavirenz, rilpivirine saquinavir, indinavir, nelfinavir, amprenavir, lopinavir, atazanavir. darunavir enfuvirtide maraviroc raltegravir, elvitegravir, dolutegravir General: nausea, H/A, hepatitis, pancreatitis, rash, myopathy, neuropathy, lactic acidosis, lipoatrophy Zidovudine: anemia Tenofovir: osteoporosis, renal dysfunction/tubulopathy Abacavir: hypersensitivity General: Rash, nausea, vomiting Nevirapine: hepatitis Efavirenz: neuropsychiatric, lipids GI upset, lipodystrophy, high TG/chol, DM, hepatitis and hot flashes, hepatitis Indinavir: kidney stones Increased risk of bact pneumonia, local & systemic reactions Nausea, vomiting, hepatitis, allergy Nausea, GI upset, transaminitis, rash, neuropsychiatric, myopathy, headache

CONSIDERATIONS WHEN CHOOSING A REGIMEN Drug resistance testing Regimen s genetic barrier to resistance Toxicities/risk of allergy Drug interactions Comorbidities and co-infections Pregnancy or pregnancy potential Patient preferences, convenience and adherence potential Cost

What to start Nucleoside reverse transcriptase inhibitor #1 Nucleoside reverse transcriptase inhibitor #2 Integrase Inhibitor or Protease Inhibitor Final regimen DHHS 2016

RECALL: TRANSMISSION OF HIV Shared needles/syringes Maternal-tochild: Sexual contact without barrier contraception Blood transfusion IVDU Health-care related Pregnancy, delivery, breastfeeding

EXPOSURE CATEGORIES Occupational Non-occupational

OCCUPATIONAL PEP ALGORITHM 1 2 3 Treat exposure site and report for evaluation Assess exposure risk Body fluid, type of injury, inoculum size, source patient Assess source and exposed patient and perform baseline testing 4 PEP Management: HBV, HCV, HIV

OCCUPATIONAL HIV EXPOSURE 1 st step is avoiding exposure through workplace safety measures and precautions If exposure occurs, there is a role for HIV post-exposure prophylaxis (PEP) The risk for HIV transmission after percutaneous exposure to the blood of someone living with HIV is ~ 0.3% The risk for HIV transmission after mucous membrane exposure to the blood of someone living with HIV is ~ 0.09% PEP involves starting a 4 week course of antiretroviral therapy shortly (<72h) after exposure to HIV to prevent HIV infection

CHOOSING A PEP REGIMEN 2 Nucleoside reverse transcriptase inhibitors (NRTI) tenofovir + emtricitabine 3 rd agent (integrase inhibitor or boosted protease inhibitor) raltegravir darunavir/ritonavir **These are examples but not the only options for PEP

SUMMARY OF OCCUPATIONAL PEP RECOMMENDATIONS PEP is recommended in occupational exposures to HIV. The HIV status of the source patient should ideally guide the need for PEP. PEP should be started within 72 hours of exposure and continued for 4 weeks. PEP regimens should contain 3 (or more) antiretroviral drugs Expert referral should be made for further evaluation and follow-up Follow-up should include counseling, monitoring for drug toxicity, and HIV testing at baseline, 6 weeks, and at 4 or 6 months.

NON-OCCUPATIONAL PEP (npep) Examples: bites, needlestick/injection drug use, sexual activity Management very similar to occupational PEP: a 4 week course of antiretroviral therapy shortly (<72h) after exposure to HIV to prevent HIV infection 28 days of Rx recommended No recommendations for PEP <72 hours after nonoccupational exposure Blood, genital secretions, or other potentially infectious body fluids of known HIV+ person <72 hours after nonoccupational exposure with blood, genital secretions, or other potentially infectious body fluids of a person of unknown HIV status >72 hours after exposure

SPECIAL CONSIDERATIONS IN npep Prevention, treatment, or supportive care for other exposure-associated health risks and conditions (e.g., bacterial STIs, trauma, HBV/HCV, pregnancy) Counseling and consideration of preexposure prophylaxis (PrEP) if frequently recurring HIV exposures (e.g., injection drug use, or sex without condoms) or 1 course of npep in the past year should be provided

PrEP The use of antiretroviral medications by HIV-negative persons to prevent HIV acquisition in high-risk settings before exposure occurs

A GROWING BODY OF EVIDENCE iprex PROUD IPERGAY Thai IDU Partners-PrEP TDF2 FEM-PrEP VOICE CAPRISA 004

PrEP REGIMEN 2 NRTIs Tenofovir disoproxil fumarate (TDF) Emtricitabine (FTC) Available as a single tablet Other regimens or delivery methods currently under investigation Vaginal ring Injectable

MODULE OBJECTIVES You should now be able to: 1. Describe the role of antiretroviral agents as treatment of HIV infection 2. Describe the role of antiretroviral agents as post-exposure prophylaxis (PEP) for HIV infection 3. Describe the role of antiretroviral agents as pre-exposure prophylaxis (PrEP) for HIV infection