Clinical Aspects of HIV Disease
Dec 17, 2015
Clinical Aspects of HIV Disease
ObjectivesPart I: Overview of clinical aspects of HIV
infection and associated clinical disease– Acute infection– HIV Basics– Whirlwind tour of opportunistic infections in
HIV/AIDS– Prevention of opportunistic infection
Part II: Overview of occupational exposure risks and management for health care workers
Take Home Points1) Every organ system is impacted by HIV
infection
2) Best strategy is for PREVENTION of morbidity with timely diagnosis of HIV infection and antiretroviral therapy
The beginning: Acute Retroviral Syndrome (“acute HIV”)
• Up to 80% of new HIV infections present with symptoms of viral illness, many misdiagnosed (influenza, infectious mononucleosis)
• Fever, fatigue, rash, and headache• Lymphadenopathy, pharyngitis, myalgia,
arthralgia, oral candidiasis• Nausea, vomiting, diarrhea; night sweats; oral
ulcers• Duration of illness ranges from a few days to
more than 10 weeks
Acute retroviral syndrome rash
Natural history of untreated HIV infection
Pantaleo G, Graziosi C, Fauci AS. New concepts in the immunopathogenesis ofhuman immunodeficiency virus infection. N Engl J Med. 1993;328:327-35.
Volberding J and Deeks S, Lancet 2010;376:49-62
HIV Lifecycle and Drug Targets
HIV Lifecycle and Drug Targets
Volberding J and Deeks S, Lancet 2010;376:49-62
Co-receptor inhibitors
Fusion inhibitors
Reverse transcriptase inhibitors
Integrase inhibitors
Protease inhibitors
Currently available antiretroviral therapy
Treatment regimens are much simpler today
• Fixed-drug, multi-class combination pills (one pill once daily)– Tenofovir/emtricitabine/efavirenz– Elvitegravir/cobicistat/emtricitabine/tenofovir
disoproxil fumarate– Emtricitabine/rilpivirine/tenofovir disoproxil
fumarate
• Once daily or twice daily regimens (3 pills once daily, 3 pills twice daily)
Goals of Treatment
• Reduce HIV-associated morbidity and prolong the duration and quality of survival
• Restore and preserve immunologic function
• Maximally and durably suppress plasma HIV viral load
• Prevent HIV transmission
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at http://aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Section accessed 2/14/13, page D-1.
Who should be treated?
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at http://aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Section accessed 2/14/13, page E-2.
Risk for opportunistic infectionCD4 Count Level of
CompromiseInfections Neoplasms
>500 cells/mm3 Minimal Solid organ, skin cancers
200-499 cells/mm3 Minimal-Moderate Tuberculosis, bacterial pneumonia, sinusitis, seborrhea, oral candidiasis, acute diarrhea
Solid organ, skin cancers
100-200 cells/mm3 Moderate PCP, chronic diarrhea, toxoplasmosis, esophageal candidiasis
Kaposi’s sarcoma, lymphoma
<50 cells/mm3 Severe CMV, MAC
A Whirlwind Tour of Infections in HIV/AIDS
#1: Dermatologic Infectious Manifestations of HIV/AIDS
Local Bacterial
Disseminated Bacterial
Superficial Fungal
Disseminated Fungal
Viral and Parasitic
Staph aureus folliculitis or abscessImpetigoCellulitisPseudomonas
Bartonella (bacillary angiomatosis)Atypical mycobacteria(MAC)
CandidaDermatophytes
CryptococcusCoccidiodesHistoplasmosisPenicilliosis
HSVVZVHPV
Scabies
Disseminated bacterial: Bacillary angiomatosis
Disseminated Fungal: Cryptococcus
Local Bacterial: staph aureus (MRSA) skin abscess
Viral: Herpes simplex
Viral: Dermatomal herpes zoster (varicella)
Norwegian Scabies
Important Non-infectious Dermatologic Manifestations
• Seborrheic dermatitis
• Eosinophilic folliculitis
• Drug hypersensitivity
• Kaposi’s sarcoma (sort of infectious…HHV-8)
Seborrheic dermatitis
Eosinophilic folliculitis
Drug hypersensitivity
Kaposi’s sarcoma
Kaposi Sarcoma
Kaposi Sarcoma
#2: Oral manifestations of HIV/AIDS
Infectious Non-Infectious
Oral candidiasis (thrush)Necrotizing gingivitis Herpes simplex virusCMVOral hairy leukoplakia (Epstein-Barr Virus)
Aphthous UlcersKaposi’s sarcomaOther Malignancies
Oral candidiasis (thrush)
Oral hairy leukoplakia (EBV)
Herpes simplex
Aphthous Ulcers
#3: Gastrointestinal Manifestations of HIV/AIDS
Esophagitis: Candida
Diarrhea: Parasites (cyclospora, cryptosporidium, isospora)
Colitis: Cytomegalovirus
Normal Colon
#4: PneumoniaBACTERIAL MYCO-
BACTERIAFUNGAL VIRAL OTHER
Pneumococcus TB PCP (P. jirovecii) Influenza KS
H flu MAC Cryptococcus CMV (pneumonitis)
Lymphoid Interstitial Pneumonia
PseudomonasandOther gram negative bacteria
Others (M. kansasii, fortuitum, gordonae)
HistoplasmosisCoccidiodes
Other (meta-pneumovirus, bocavirus, RSV, parainfluenza, etc)
Staph aureus (MRSA)
Aspergillus
Bacterial: Pneumococcal pneumonia
Fungal: Pneumocystis pneumonia (PCP)
Pneumocystis Pneumonia
Malignancy: Kaposi’s sarcoma in airway
Tuberculosis
The Global TB Problem
UNAIDS 2008
#5: Ophthalmic
Bacterial Viral Fungal Parasitic
Syphilis (chorio-retinitis/keratitis)
Herpes (HSV)& zoster (VZV) keratitis
Candida Toxoplasmosis
Staph and others (endoph-thalmitis)
CMV (retinitis)
Cryptococcus
Microsporidium
HIV (retino-pathy)
Pneumo-cystis
Viral: CMV retinitis
Parasitic: Toxoplasma chorioretinitis
#6: Neurologic
Bacterial Viral Fungal Parasitic Other
Meningitis Aseptic meningitis
Cryptococcal meningitis
Toxoplasmosis CNS Lymphoma
Brain abscess Encephalitis:CMVHSVVZV
Aspergillus Neuropathy
Neurosyphilis PML (JC virus) CoccidioidesHistoplasmosis
Primary brain tumor
TB (meningitis,tuberculoma)
HIV (encephalo-pathy/dementia)
Parasitic: Toxoplasma encephalitis
Viral: Progressive Multifocal Leukoencephalopathy (JC virus)
Malignancy: CNS Lymphoma
#7: Hematologic
• Bone Marrow Issues– Anemia (HIV, antiretrovirals,
infectionsParvovirus B19, MAC, TB)– Thrombocytopenia=low platelets (HIV,
immune mediated)– Leukopenia=low white cell count (HIV,
infections)
#8: Oncologic
• Kaposi’s sarcoma: human herpes virus-8 (HHV-8 = KSHV)
• Lymphoma (some Epstein Barr Virus-related)
• Cervical cancer, anorectal cancer (HPV)
• Basal cell carcinoma, melanoma
• Solid organ: colon and lung
Non-AIDS Defining Cancers Rising in the HAART Era
Crum-Clanflone et al, AIDS 2009;23:41-50
Prophylaxis of Infection in HIV
• Primary prophylaxis: A method of regularly scheduled medications to prevent episodes of infection before they occur
• Secondary prophylaxis: Preventive treatment for a subsequent occurrence (relapse) of a disease/infection
Primary Prophylaxis
Infection CD4 Threshold Medication
PCP <200 cells/uL Bactrim or dapsone or atovaquone
Toxoplasmosis <100 cells/uL and seropositive
Bactrim or dapsone+pyrimethamine+leucovorin
Tuberculosis Any CD4 count if PPD+ Isoniazid or rifampin
MAC <50 cells/uL Azithromycin or clarithromycin
Coccidioidomycosis <250 cells/uL and positive serology
Fluconazole or itraconazole
Histoplasmosis <150 cells/uL and from endemic area
Itraconzole
Secondary prophylaxis
• PCP, toxoplasma, CMV, cryptococcus, MAC, VZV and HSV for recurrent outbreaks or disseminated disease
• For life or until “immune reconstitution”
• Long term toxicities and adherence of prophylactic medications often problematic
http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi_041009.pdf
Additional preventive measures: Immunization
• Influenza, Streptococcus pneumoniae (Pneumovax, Prevnar)
• Hepatitis A, B
• Tetanus/diptheria/pertussis
• In general, no vaccination with live virus vaccines (nasal Flumist, others)
Health Maintenance
• Yearly or twice-yearly pap smears for women/anal pap smears for men
• Skin checks (skin cancer surveillance)• Monitoring of lipids, fasting glucose, weight• Diet/exercise• Colonoscopy• Mammogram• Smoking Cessation• Drug, alcohol counseling• Psych/Mood assessment
Aberg et al, Primary Care Guidelines for the Management of Persons Infected with Human Immunodeficiency Virus: 2009 Update by HIVMA/IDSA, CID 2009; 49 (5): 651-681.
Occupational Exposures to HIV
HIV and Healthcare Workers: Who is at risk?
• Employees, students, contractors, clinicians, nurses, pharmacists, public-safety workers, or volunteers whose activities involve contact with patients or with blood or other body fluids from patients in a health-care, laboratory, or public-safety setting
Exposures
• Percutaneous injury (e.g., a needlestick or cut with a sharp object)
• Contact of mucous membrane or nonintact skin (e.g., exposed skin that is chapped, abraded, or with dermatitis) with blood, tissue, or other body fluids that are potentially infectious
Risk of Transmission
Risk of Infection• Percutaneous exposure to HIV-infected
blood 0.3% (95% CI = 0.2%--0.5%)• Mucous membrane exposure 0.09% (95%
CI = 0.006%--0.5%) • Risk increased with:
– exposure to a larger quantity of blood:• a device visibly contaminated with the patient's
blood • procedure involving a needle being placed directly
in a vein or artery• deep injury
– exposure to blood from source persons with advanced HIV (likely due to high viral load)
Testing source and exposed patient
• Source patient: – Unknown HIV status and available for testing: rapid
ELISA for HIV antibodies, HBsAg, HCV antibody– If at risk for recent HIV or HCV infection nucleic
acid-based testing to r/o acute infection
• Exposed patient– Baseline HIV, hepatitis B, and hepatitis C testing– Follow-up ELISA for HIV Ab at 4-6 weeks, 3 months,
and 6 months after exposure– Risk reduction counseling
Postexposure prophylaxis (PEP)
• Consider risks vs benefits
• Toxicities: mild intolerances, severe, life-threatening reactions, especially liver failure with nevirapine
• Selection of viral resistance
• Pregnancy: teratogenicity, toxicities (avoid ddI and d4T)
Timing of PEP
• PEP should be initiated as soon as possible after risk assessed, within 24 hours ideally
• Up to 72 hours is reasonable, but efficacy is diminished
• All women of reproductive age should have a pregnancy test prior to PEP
PEP REGIMENS • Source status unknown
– Administer PEP for 28 days, if tolerated. – If a source person is determined to be HIV-
negative, PEP should be discontinued. • Source status confirmed
– Basic regimen for low risk: 2 nucleoside reverse transcriptase inhibitors (NRTIs)
– Expanded 3-drug regimen for high risk: Protease inhibitor (often ritonavir-boosted) or raltegravir plus 2 NRTIs
• Monitor toxicity, counsel and educate, re-test for up to 12 months after exposure
PEP for Percutaneous Exposure
U.S. Public Health Service Guidelines, MMWR 2005, Vol 54, RR-9
PEP Mucous Membrane Exposure
U.S. Public Health Service Guidelines, MMWR 2005, Vol 54, RR-9
Take Home Points
1) Every organ system is impacted by HIV infection
1) Best strategy is for PREVENTION of morbidity with timely diagnosis of HIV infection and antiretroviral therapy– As well as primary and secondary prophylaxis
The impact of prevention…