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…