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Clinical Aspects of HIV
Disease
Objectives
Part 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 Points
1) 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 of
human immunodeficiency virus infection. N Engl J Med. 1993;328:327-35.
HIV Lifecycle and Drug Targets
Volberding J and Deeks S, Lancet 2010;376:49-62
HIV Lifecycle and Drug Targets
Protease inhibitors
Co-receptor inhibitors
Fusion inhibitors
Reverse transcriptase inhibitors
Integrase inhibitors
Volberding J and Deeks S, Lancet 2010;376:49-62
Currently available antiretroviral
therapy
REVERSE TRANSCRIPTASE INHIBITORS
NUCLEOSIDES (NRTIs)
NONNUCLEOSIDES (NNRTIs)
PROTEASE
INHIBITORS (Pis)
Lamivudine (3TC)
Nevirapine
Lopinavir
Zidovudine (AZT)
Efavirenz
Atazanavir
Tenofovir (TDF)
Etravirine
Darunavir
Abacavir (ABC)
Rilpivirine
Saquinavir
Stavudine (d4T)
Fosamprenavir
Didanosine (ddI)
Nelfinavir
Emtricitabine (FTC)
Ritonavir
FUSION INHIBITOR
Enfuvirtide
INTEGRASE INHIBITORS
Raltegravir
Elvitegravir
Dolutegravir
ENTRY INHIBITOR
Maraviroc (CCR5
antagonist)
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 infection
CD4 Count
Level of
Compromise
Infections
Neoplasms
>500 cells/mm3
Minimal
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
Solid organ, skin
cancers
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
abscess
Impetigo
Cellulitis
Pseudomonas
Bartonella
(bacillary
angiomatosis)
Atypical
mycobacteria(
MAC)
Candida
Dermatophytes
Cryptococcus
HSV
Coccidiodes
VZV
Histoplasmosis HPV
Penicilliosis
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 virus
CMV
Oral hairy leukoplakia (Epstein-Barr
Virus)
Aphthous Ulcers
Kaposi’s sarcoma
Other Malignancies
Oral candidiasis (thrush)
Oral hairy leukoplakia (EBV)
Herpes simplex
Aphthous Ulcers
#3: Gastrointestinal
Manifestations of HIV/AIDS
Diarrhea
Acute bacterial (Salmonella, Shigella, Campylobacter, Yersinia,
E.coli, C.difficile)
Chronic parasitic (cryptosporidiosis, giardiasis, microsporidiosis,
isospora)
Viral (CMV colitis)
Medications
Malabsorption
HIV enteropathy
Esophagitis
Candida
CMV
HSV
Medications
Pancreatitis
HIV
Antiretroviral therapy
Hepatitis
Hepatitis A, B, C
Medications
Malignancy
KS, lymphoma
Esophagitis: Candida
Diarrhea: Parasites (cyclospora,
cryptosporidium, isospora)
Colitis: Cytomegalovirus
Normal Colon
#4: Pneumonia
BACTERIAL
MYCOBACTERIA
FUNGAL
VIRAL
OTHER
Pneumococcus
TB
PCP (P. jirovecii) Influenza
KS
H flu
MAC
Cryptococcus
CMV
(pneumonitis)
Lymphoid
Interstitial
Pneumonia
Pseudomonas
and
Other gram
negative
bacteria
Others
(M. kansasii,
fortuitum,
gordonae)
Histoplasmosis
Coccidiodes
Other
(metapneumovirus,
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
Syphilis
(chorioretinitis/k
eratitis)
Fungal
Parasitic
Herpes Candida Toxoplas
(HSV)
mosis
& zoster
(VZV)
keratitis
Staph
CMV
Cryptoco Microspo
and
(retinitis) ccus
ridium
others
(endophthalmitis)
HIV
(retinopathy)
Pneumocystis
Viral: CMV retinitis
Parasitic: Toxoplasma
chorioretinitis
#6: Neurologic
Bacterial
Viral
Fungal
Parasitic
Other
Meningitis
Aseptic
meningitis
Cryptococcal
meningitis
Toxoplasmosis
CNS
Lymphoma
Brain abscess
Encephalitis:
CMV
HSV
VZV
Aspergillus
Neuropathy
Neurosyphilis
PML (JC virus)
Coccidioides
Histoplasmosis
Primary brain
tumor
TB (meningitis, HIV
tuberculoma)
(encephalopathy/dementi
a)
Parasitic: Toxoplasma
encephalitis
Viral: Progressive Multifocal
Leukoencephalopathy (JC virus)
Malignancy: CNS Lymphoma
#7: Hematologic
• Bone Marrow Issues
– Anemia (HIV, antiretrovirals,
infectionsParvovirus 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 Virusrelated)
• 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, publicsafety 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, lifethreatening 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 HIVnegative, 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
U.S. Public Health Service Guidelines, MMWR 2005, Vol 54, RR-9
PEP for Percutaneous
Exposure
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…