HIV Diagnosis and Management 2015 Update. Faria Farhat, MD MedStar Washington Hospital Center
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1 HIV Diagnosis and Management 2015 Update Faria Farhat, MD MedStar Washington Hospital Center
2 Objectives Describe the epidemiology and pathogenesis of HIV infection Highlight HIV diagnosis algorithm and key clinical features Identify opportunistic infections and prevention strategies Evaluate treatment options for antiretroviral naïve patients
3 Diagnoses of HIV Infection among Adults and Adolescents, by Sex and Transmission Category, 2012 United States and 6 Dependent Areas Note. Data include persons with a diagnosis of HIV infection regardless of stage of disease at diagnosis. All displayed data have been statistically adjusted to account for reporting delays and missing transmission category, but not for incomplete reporting. a Heterosexual contact with a person known to have, or to be at high risk for, HIV infection. b Includes hemophilia, blood transfusion, perinatal exposure, and risk factor not reported or not identified.
4 Diagnoses of HIV Infection among Adults and Adolescents, by Sex and Race/Ethnicity, 2012 United States and 6 Dependent Areas Note. Data include persons with a diagnosis of HIV infection regardless of stage of disease at diagnosis. All displayed data have been statistically adjusted to account for reporting delays, but not for incomplete reporting. a Hispanics/Latinos can be of any race.
5 Types and Clades HIV-1 causes majority of cases except a minority in West Africa. 3 major classes- M( A-K), N, O. M group has 9 subtypes also called clades. 98% of HIV-1 in US is by subtype B.
6 HIV-2 Found primarily in W.Africa Less transmissible Rarely causes vertical transmission Lower viral load Slower decline of CD4 cells No treatment guidelines Not susceptible to NNRTIs and may have multiple PI muatations.
7 Transmission Sexual exposure - Heterosexual, MSM, Bisexual IV Drug use Transfusion Mother to Child - Vertical Occupational exposure, needle sticks
8 Pathogenesis
9
10 35 yrs old male has a Rapid HIV test at a clinic. HIV ELISA is non reactive. He has multiple sexual partners and has generalized rash. What is the likely etiology and which test should be ordered?
11 Diagnosis of Acute Retroviral Syndrome Nonspecific, febrile illness resembling mononucleosis like illness (comprises of fever, sore throat, enlarged lymph nodes, skin rash, joint aches and general malaise) Aseptic meningitis, Guillain-Barre syndrome, facial nerve palsies, & mononeuritis multiplex Dx of ARS is based on the combination of a negative/indeterminate HIV serology together with a high HIV RNA (viral load). Important to dx HIV at this stage - pts are highly infectious
12 HIV Rapid Tests
13 HIV Rapid Tests
14
15 AIDS Defining Conditions Candidiasis of bronchi, trachea, or lungs Cervical cancer, invasive Coccidioidomycosis, disseminated or extrapulmonary Cryptococcosis, extrapulmonary Cryptosporidiosis, chronic intestinal (longer than one month's duration) Cytomegalovirus disease (other than liver, spleen, or nodes) Cytomegalovirus retinitis (with loss of vision)
16 AIDS Defining Conditions Encephalopathy, HIV-related Herpes simplex: chronic ulcer(s) (longer than one month's duration); or bronchitis, pneumonitis, or esophagitis Histoplasmosis, disseminated or extrapulmonary Isosporiasis, chronic intestinal (longer than one month's duration) Kaposi's sarcoma Lymphoma, Burkitt's (or equivalent term) Lymphoma, immunoblastic (or equivalent term) Lymphoma, primary, of brain
17 AIDS Defining Conditions Mycobacterium avium complex or M. kansasii, disseminated or extrapulmonary Mycobacterium tuberculosis, any site (pulmonary or extrapulmonary) Mycobacterium, other species or unidentified species, disseminated or extrapulmonary Pneumocystis carinii pneumonia Pneumonia, bacterial and recurrent Progressive multifocal leukoencephalopathy (PML) Salmonella septicemia, recurrent Toxoplasmosis of brain Wasting syndrome due to HIV
18 Case # 1 25 years old female with HIV, CD4 150, presents with c/o severe left sided chest pain. The pain was sudden in onset. Pt also c/o dry cough for the past one week along with worsening shortness of breath. On exam patient has temperature 102 F. She is tachycardic and tachypneac. PO2 on room air is 60. CXR shows pneumothorax
19 Case # 2 24 yrs old female with HIV, CD4 20, presents with a new onset seizure Patient is confused and febrile CT head shows ring enhancing lesions
20
21 Case # 3 24 yrs old male with HIV, CD4 count 375 Develops headache followed by generalized weakness Patient is not on HAART
22 CT head
23 CT head Ddx: - Lymphoma - Toxoplasma - TB - Bacterial infection - Fungal infection - Glioblastoma
24 29 yrs old male with CD4 count 46, c/o headache and fever for 2 weeks
25 42 yrs old female with blurred vision, CD4 count 75
26 Prevention of opportunistic infections Type of infection CD4 count Regimen PCP <200 Bactrim Dapsone Atovaquone Toxoplasmosis <100+IgG to toxo Bactrim Dapsone+Pyrime thamine Atovaquone MAC <50 Zithromax Clarithromycin Rifabutin
27 Managing a Patient Newly Diagnosed with HIV
28 Baseline Labs CD4 cell count: measure of HIV-associated immunodeficiency, most important criterion for initiation of ART & opportunistic infection (OI) prophylaxis Viral load: measures viral activity and replication, correlates with transmission, dz progression, and is the most important indicator of the success of HAART Genotypic resistance test: determines drug susceptibility; HLA B5701 abacavir hypersensitivity
29 Baseline Labs Hepatitis A/B/C serology Other STDs: syphilis, GC Screening for Latent Tuberculosis - skin test/quantiferon gold Toxoplasma, cytomegalovirus serology Glucose-6-phosphate dehydrogenase (G6PD) level
30 Baseline Labs CBC w/ diff CMP: hepatitis, Cr Fasting lipid panel Urinalysis: proteinuria HIVAN Pap smears (vaginal/anal): screen for Human papilloma virus assoc dysplasia. Vaccinations: pneumovax, influenza vaccine, tetanus toxoid, hepatitis A/B vaccine
31 Recommendations for Initiating ART All HIV-infected individuals to reduce the risk of disease progression CD4 count <350 cells/mm 3 (AI) CD4 count 350 to 500 cells/mm 3 (AII) CD4 count >500 cells/mm 3 (BIII). ART also is recommended for HIV-infected individuals for the prevention of transmission of HIV Perinatal transmission (AI) Heterosexual transmission (AI) Other transmission risk groups (AIII).
32 Recommendations for Initiating ART Clinical Category History of AIDS-defining illness Pregnant women HIV-associated nephropathy (HIVAN) Hepatitis B (HBV) coinfection, when HBV treatment is indicated* Recommendation Initiate ART
33 Recommendations for Initiating ART Patients initiating ART should be willing and able to commit to lifelong treatment and should understand the benefits and risks of therapy and the importance of adherence. Patients may choose to postpone ART Providers may elect to defer ART, based on patients clinical or psychosocial factors
34 Current ARV Medications NRTI Abacavir (ABC) Didanosine (ddi) Emtricitabine (FTC) Lamivudine (3TC) Stavudine (d4t) Tenofovir (TDF) Zidovudine (AZT, ZDV NNRTI Delavirdine (DLV) Efavirenz (EFV) Etravirine (ETR) Nevirapine (NVP) Rilpivirine (RPV) PI Atazanavir (ATV) Darunavir (DRV) Fosamprenavir (FPV) Indinavir (IDV) Lopinavir (LPV) Nelfinavir (NFV) Ritonavir (RTV) Saquinavir (SQV) Tipranavir (TPV) Integrase Inhibitor (II) Raltegravir (RAL) Elvitegravir Dolutegravir Fusion Inhibitor Enfuvirtide (ENF, T-20) CCR5 Antagonist Maraviroc (MVC) June
35 Initial Treatment: Choosing Regimens 3 main categories: 1 NNRTI + 2 NRTIs 1 PI + 2 NRTIs 1 II + 2 NRTIs Combination of NNRTI, PI, or II + 2 NRTIs preferred for most patients Fusion inhibitor, CCR5 antagonist not recommended in initial ART Advantages and disadvantages to each type of regimen Individualize regimen choice
36 Initial Regimen For Treatment Naïve Patients NNRTI-Based Regimen: EFV/TDF/FTC(AI) PI-Based Regimens: ATV/r plus TDF/FTC (AI) DRV/r plus TDF/FTC(AI)
37 Initial Regimen For Treatment Naïve Patients INSTI-Based Regimens: DTG plus ABC/3TC (AI) DTG plus TDF/FTC (AI) EVG/cobi/TDF/FTC (AI) RAL plus TDF/FTC (AI)
38 Initial Regimen For Treatment Naïve Patients For patients with pre-art HIV RNA <100,000 copies/ml: NNRTI-Based Regimens: EFV plus ABC/3TC (AI) RPV/TDF/FTC (AI) PI-Based Regimen: ATV/r plus ABC/3TC (AI)
39 Alternative Regimens PI-Based Regimens: DRV/r plus ABC/3TC (BII) LPV/r plus ABC/3TC (BI) LPV/r plus TDF/FTC (BI) INSTI-Based Regimen: RAL plus ABC/3TC (BII)
40 Caution EFV is teratogenic, avoid in women who are planning to become pregnant or who are sexually active and not using effective contraception TDF should be used with caution in patients with renal insufficiency ATV/r should not be used in patients who require >20 mg omeprazole equivalent per day
41 Caution RPV is not recommended in patients with pretreatment HIV RNA >100,000 copies/ml Higher rate of virologic failure if pre- ART CD4 count <200 cells/mm 3 Use of PPIs with RPV is contraindicated
42 Caution EVG/COBI/TDF/FTC should not be started in patients with an estimated CrCl <70 ml/min, and should be changed to an alternative regimen if the patient s CrCl falls below 50 ml/min
43 Adverse Reactions Abacavir: HSR,? Cardiovascular events Tenofovir: renal impairment, including proximal tubulopathy and acute or chronic renal insufficiency, decrease in BMD Zidovudine: Bone marrow suppression, especially anemia and neutropenia
44 PI Class Disadvantages Metabolic complications such as dyslipidemia, insulin resistance, and hepatotoxicity GI adverse effects CYP3A4 inhibitors and substrates: potential for drug interactions more pronounced with RTV-based regimens
45 Protease Inhibitors Atazanavir Indirect hyperbilirubinemia PR interval prolongation Nephrolithiasis, cholelithiasis Skin rash Absorption depends on food and low gastric ph
46 Integrase Inhibitor Raltegravir Twice-daily dosing Lower genetic barrier to resistance than with boosted PI-based regimens Increase in creatine kinase, myopathy, and rhabdomyolysis Severe hypersensitivity reactions including SJS and TEN
47 Dolutegravir: - Once-daily dosing Oral absorption can be reduced by simultaneous administration with products containing polyvalent cations (e.g., Al+++, Ca++, or Mg++ containing antacids or supplements, multivitamin tablets with minerals Effective at double dose (50 mg twice daily) against some RAL- and EVGresistant viruses
48 Drug Interactions
49 Drugs that should not be used with antiretroviral agents
50 Interruption and Modification of Antiretroviral Therapy Interruption should be avoided Increases risk of transmission Selection of drug-resistant mutants especially with NNRTIs Particularly dangerous in hep B co infections which can result in acute flares of hepatitis B, including fulminant hepatitis.
51 Web Sites to Access the Guidelines aidsinfo.nih.gov
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