HIV 2023 - Student - Tagged.pdf

HIV Learning Objectives Identify risk factors associated with the acquisition of HIV. Explain how to diagnose HIV in the inpatient and outpatient settings. Determine when to start an appropriate regimen for most PLWHA. Understand the causative pathogens and pathophysiology for specific OIs and when...

HIV Learning Objectives Identify risk factors associated with the acquisition of HIV. Explain how to diagnose HIV in the inpatient and outpatient settings. Determine when to start an appropriate regimen for most PLWHA. Understand the causative pathogens and pathophysiology for specific OIs and when to expect them. Explain & Discuss the characteristic presentations and prophylaxis and treatment for specific OIs Apply foundational and clinical knowledge to optimize care of PLWH. Acquiring HIV Ways HIV CANNOT be Transmitted Casual contact Saliva, sweat, tears Urine Air or water Social kissing Feces Vaccines made from blood products (e.g., HBV) Mosquitoes, ticks, other insects Contact with toilet seats or faucet handles HIV Acquisition Primary Routes Sexual Parenteral Perinatal You can only get HIV by coming into direct contact with certain body fluids from a person with HIV who has a detectable viral load Blood Semen (cum) and pre-seminal fluid Rectal fluids Vaginal fluids Breast milk Direct contact = HIV in these fluids must get into the bloodstream of an HIV-negative person through a mucous membrane (rectum, vagina, mouth, or tip of the penis); open cuts or sores; or by direct injection Risk Factors for HIV Acquisition Primary Routes in the US Acquisition of other STIs IVDU Unprotected sex or multiple partners HIV can affect anyone regardless of sexual orientation, race, ethnicity, gender, age, or where they live Risk behaviors = anal or vaginal sex or sharing needles or syringes with an HIV-positive partner Anal sex is the highest-risk behavior Prevention Tools Use condoms correctly every time you have sex Pre-exposure prophylaxis (PrEP) and Post-exposure prophylaxis (PEP) Treatment as Prevention (TasP) Testin g for HIV Who should get tested? All adolescents and adults 13-64 years of age at least once If “high risk”, then minimally every year *“high risk” = PWID and their sex partners, persons who exchange sex for money or drugs, sex partners of persons with HIV infection, and MSM or heterosexual persons who themselves or whose sex partners have had more than one sex partner since their most recent HIV test Benefits of Early HIV Diagnosis Early awareness  achieving and maintaining undetectable VL  extended life expectancy ART initiation Reduces HIV-associated morbidity and mortality Greatly decreases HIV transmission to others May reduce risk of serious non-AIDS‒related diseases Routine Opt-Out Screening Patients informed they will be tested for HIV unless they say otherwise Conducting risk-based screening may fail to identify PLWHA Benefits Removes the stigma associated with HIV testing Fosters earlier diagnosis and treatment Reduces risk of transmission Is cost-effective Nucleic acid tests (NATs) Detects HIV RNA (e.g., viral load test) Requires blood sample from vein Return time: several days Types of Tests Antigen/antibody combination tests Detects HIV p24 antigen, HIV IgM, and IgG antibodies Requires blood sample from vein or finger prick Return time: 30 minutes to several days Antibody tests Detects HIV IgM and/or IgG antibodies Requires blood or oral fluid Return time: 20-30 minutes When to Test Window period Time between potential HIV exposure and before seroconversion during which markers of infection (p24 antigen and antibodies) are still absent or too scarce to be detectable Test once ~45 days and again at 90 days Test Generations Second Generation (e.g., OraQuick) Detects IgG antibodies Window period: 26-90 days Third Generation Lab Tests (not recommended for use) Detects IgG antibodies and IgM antibodies Window period: 23-60 days Third Generation POC Tests Detects IgG antibodies and IgM antibodies Window period: 23-90 days Fourth Generation Lab Test (e.g., Abbott Architect HIV Ag/Ab) Detects IgG antibodies, IgM antibodies, p24 viral antigen Window period: 18-45 days (finger prick = up to 90 days) HIV At-Home Self-Test Not confirmatory Sensitivity = 93% Specificity = 99% Positive Predictive Value = 90% Negative Predictive Value = 99% Outpatient HIV Testing 4th generation test HIV-1/2 Ag/Ab combination immunoassay Automated, laboratory-based, p24/IgM/IgG sensitive (-) (+) HIV-1/2 Ab differentiation immunoassay Negative for HIV-1 p24 Ag, HIV-1 Ab, and HIV-2 Ab (-) (+) Antibodies detected HIV-1 (-) or indeterminate HIV-2 (-) Infected with HIV-1, HIV-2, or both Biological false positive test or acute HIV-1 infection HIV-1 nucleic acid test (+) HIV-1 nucleic acid test (+) Acute HIV-1 infection NAT (-) HIV-1 nucleic acid test (-) Negative for HIV-1 Inpatient HIV Testing HIV-1/2 Ag/Ab combination immunoassay Automated, laboratory-based, p24/IgM/IgG sensitive (-) (+) HIV RNA Viral Load 4th generation test NAT Negative for HIV-1 p24 Ag, HIV-1 Ab, and HIV-2 Ab Quantity of virus present can help elucidate time since infection DW is a 30 yo AAF requests an HIV test from her PCP at her annual wellness check-up. Which test(s) did she most likely receive? A. B. C. D. 3rd generation NAT Oraquick® HIV viral load 4th generation p24 antigen/IgG/IgM Starting Antiretrovir al Therapy Initiating Antiretroviral Therapy All individuals regardless of CD4 count if they are mentally and clinically able to ART should be initiated in those with early infection Recommendations apply to adolescents and adults, including older patients Does Everyone Start Immediately? Hospitalized Patients Typically not started until genotype results are available May hold off until patient readiness and adherence with OI medication is assessed by clinic follow-up Community Patients Patient readiness to start ART needs to be assessed prior to prescribing medication Can be started prior to genotype results, but may be deferred until results are available Selecting a Regimen Treatment Goals Maximally and durably suppress plasma HIV RNA Restore and preserve immunologic function Reduce HIV-associated morbidity Prolong the duration and quality of survival Prevent HIV transmission Virologic Success Should occur within 12-24 weeks of ART initiation Predictors: Low baseline viremia High potency of the ARV regimen Tolerability of the regimen Convenience of the regimen Excellent adherence to the regimen Initial Characteris tics to Consider Pretreatment HIV RNA level Pretreatment CD4 count HIV genotype HLA-B*5701 status Individual preferences Anticipated adherence to the regimen Drug-drug interactions Comorbid conditions Side effect profile DW is a 30 yo AAF who was recently diagnosed with acute HIV. She has a viral genotype performed at her baseline visit, and she is scheduled to return next month to repeat the genotype. Why? A. B. C. D. Need to confirm resistance patterns Determine OI prophylaxis Influence other baseline labs to draw Pharmacogenomic dosing considerations Regimen-Specific Considerations Regimen’s barrier to resistance Potential adverse effects and drug toxicities Known or potential drug interactions with other medications Convenience Pill/injection burden Dosing frequency Food requirements Cost and access Barrier to Resistan ce Number of mutations in an antiretroviral's therapeutic target that are required to confer a clinically meaningful loss of susceptibility to the drug Impacted by drug structure, inhibitory quotient, therapeutic index, and pharmacokinetic characteristics HIV drug resistance database ( https://hivdb.stanford.edu/ ) Assessment of regimen efficacy and safety are primarily based on Determining an Appropriate Regimen Surrogate marker endpoints Incidence and severity of ADRs Additional considerations Post-marketing safety data Observational cohort data published in peer-reviewed publications Experience of clinicians and community members who are actively engaged in patient care Appropriate Regimens ≥2 Drugs 2 Classes Appropriate HIV Regimen Preferred Initial Regimens for MOST PEOPLE WITH HIV *For people with HIV who do not have a history of using long-acting cabotegravir as pre-exposure prophylaxis Triumeq® INSTI Dolutegravir + TAF/TDF + FTC/3TC + Biktarvy® 2 NRTIs Dovato®*** All regimens must be balanced with HIV resistance, DDIs, and ADRs ***INSTI + 1 NRTI: except for individuals with HIV RNA >500,000 copies/mL, HBV coinfection, or in whom ART is to be started before the results of HIV genotypic resistance testing for reverse transcriptase or HBV testing are available Initial Regimens in CERTAIN CLINICAL SITUATIONS INSTI + 2 NRTIs Genvoya® Stribild® RAL + TAF/TDF + FTC/3TC Disadvantages ↑ toxicity ↑ pill burden ↓ supporting data Limitations in more patients Boosted PI + 2 NRTIs Darunavir + cobicistat/ritona vir + TAF/TDF + FTC/3TC Atazanavir + cobicistat/ritona vir + TAF/TDF + FTC/3TC Darunavir + cobicistat/ritona vir + Epzicom® NNRTI + 2 NRTIs Delstrigo® Doravirine + Descovy® Efavirenz + TAF/TDF + FTC/3TC Symfi® Rilpivirine + Truvada® / Descovy® DW is a 30 yo AAF who is taking Kaletra® + Epzicom®. She is complaining of frequent diarrhea and doesn’t want to take so many pills per day. Which of the following regimens would be the best option for DW? PMH: HTN, GERD, hyperlipidemia, HBV Current medications: amlodipine 5 mg PO daily, omeprazole 20 mg daily A. B. C. D. Odefsey® Triumeq® Raltegravir + Epzicom® Prezcobix® + Epzicom® What drug class has a BBW for hepatitis exacerbation, and when would you be concerned about this happening? A. B. C. D. INSTI – upon initiation of an interacting drug NNRTI – within 2 weeks of initiation PI – after the first dose NRTI – upon abrupt discontinuation 1st clinical manifestations that alerted clinicians to the occurrence of HIV Opportunist ic Infections (OIs) Occur ~7-10 years after infection with HIV Prior to ART, patients survived ~1-2 years after the initial manifestation of AIDS Most patients, to this day, continue to present with an OI as the sentinel event leading to a diagnosis of HIV infection Candidiasis Yeast! Epidemiolo gy Causative organism: Candida albicans (majority) Location of infection: mouth, throat, esophagus When: CD4 cell counts 200 cells/mm3 x >3 months + ART TMP-SMX 15-20 mg/kg/day divided q6-8h Dosed on TMP component + actual body weight Pharmacolog ical Treatment PO steroids? X Only if room air PO2 3 months + ART Pharmacological Treatment Pyrimethamine 50-75 mg PO daily (actual body weight-based) + sulfadiazine 1,000-1,500 mg PO q6h + leucovorin 10-25 mg PO daily MIN. Alternatives: pyrimethamine + clindamycin, TMP-SMX, atovaquone + pyrimethamine, atovaquone, pyrimethamine + azithromycin MAC Epidemiology Causative organism: Mycobacterium avium complex (MAC) Location of infection: lymph nodes, liver, spleen, bone marrow, lungs, GI tract, and rarely, skin When: CD4 cell counts < 50 cells/mm3 Also, HIV RNA < 1,000 copies/mL, viral replication despite ART, previous or concurrent OIs, reduced lymphoproliferative immune response ~20-40% incidence without effective ART or chemoprophylaxis With care, < 2 cases per 1,000 person-years Clinical Manifestations Fever, night sweats, weight loss, fatigue, diarrhea, and abdominal pain Laboratory abnormalities Anemia, elevated alk phos Hepatomegaly, splenomegaly, or lymphadenopathy Chest X-ray Focal consolidation, cavitation PPD and Quantiferon Gold could not discriminate between active TB, MAC, or latent TB Risk and Prevention At Risk CD4 count < 50 cells/mm3 Prophylaxis Azithromycin 1,200 mg PO once weekly until CD4 count is > 100 cells/mm3 x 3 months; not needed if ART initiated immediately Clarithromycin 500 mg PO BID + ethambutol 15 mg/kg actual body weight PO daily +/rifabutin 300 mg PO daily MIN. Pharmacological Treatment Alternatives: substitute azithromycin for clarithromycin, substitute moxifloxacin, levofloxacin or amikacin for rifabutin Summary of Prophylax is Breakpoi nts CD4 count