Core Curriculum Review: HIV
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Transcript of Core Curriculum Review: HIV
Core Curriculum Review:
HIV
Jason M . Leider, M.D., Ph.D.NBHN Associate Medical Director of HIV
ServicesAssociate Professor of Internal Medicine,
AECOM
Occupational Bloodborne Exposuresfocus on HIV
• HIV, HBV, HCV are the primary agents– Risk of infection:
• HBV = 27-47%• HCV = 1.9% (range 0%-22%)• HIV = 0.32%
• HIV PEP: based on in vitro evidence, maternal-fetal transmission studies, retrospective case-control studies of occup HIV infxn & recent clinical experience
• PEP is based on type of exposure (hollow-bore needles), depth of penetration, type of host
HIV pathogenesis
• High replication rate (even during asymptomatic early phase)
• High mutation rate: abilty to generate mutiple quasi-species
Natural history of HIV-1 infection over time
CD4 = 200
7-10 yrs
Acute Retroviral Syndrome
Asymptomatic
Persistent Generalized LNopathy
Fever
PM sweats
Diarrhea
Wt loss
Clinical Latency Pre-AIDS conditions
A global view of HIV infection33 million people [30–36 million] living with HIV, 2007
2.2
USA HIV facts
• PLWHA = 1.1 million
• 25% PLWHA are unaware of their HIV dx
• AIDS (but not HIV infxn) is reportable in all 50 states
• 2004: 73% new cases in M (globally, M=F)
• 56,300 new HIV infxns occurred in 2006
• AA & Hisp = 70% new cases
Sequence of reactivity of diagnostic tests for HIV in early infection
Rapid HIV tests
• Results in < 20 min
• Oral or blood tests
• Sensitivity & specificity > 99% (similar to conventional HIV enzyme immunosorbent tests
Four FDA-approved Rapid HIV Tests
Sensitivity
(95% C.I.)
Specificity
(95% C.I.)
OraQuick Advance
- whole blood
- oral fluid
- plasma
99.6 (98.5 - 99.9)
99.3 (98.4 - 99.7)
99.6 (98.5 - 99.9)
100 (99.7-100)
99.8 (99.6 – 99.9)
99.9 (99.6 – 99.9)
Uni-Gold Recombigen
- whole blood
- serum/plasma
100 (99.5 – 100)
100 (99.5 – 100)
99.7 (99.0 – 100)
99.8 (99.3 – 100)
US Public Health Service algorithm for serologic diagnosis of HIV-1/HIV-2 infection.
Risk Assessment Guidelines for HIV+ Patients
• Screen for risk behaviors: IDU, anal intercourse
• Establish past/present h/o psychiatric dz, substance abuse
• Open-ended questions for sx’s of STDs
• Sx’s prompt STD testing
Clinical Evaluation of Patients with Newly Dx’d HIV
Evaluation Frequency
Complete Hx & PE Baseline, as determined clinically (3-4 months)
HIV ab test Confirm on initial visit
CD4 & VL Baseline & q 3-4 months unless changing ARV’s
CBC Baseline & as clinically indicated
Comp metab panel (lytes, gluc, renal, LFTs)
Baseline & as clinically indicated
Fasting lipid profile Baseline & as clinically indicated
Annual assessment of body fat
For pts on HAART
Hepatitis screening Baseline & as clinically indicated
Clinical Evaluation of Patients with Newly Dx’d HIV
Evaluation Frequency
Tuberculin skin test & tb exposure
Baseline & annually
Pap smear Baseline, 6 months & annually if normal
Syphilis, chlamydia, GC, trich
See next slide
Toxoplasmosis Baseline
CMV* Baseline (optional)
CXR Baseline (optional)
Initial, subsequent Visits for STDs in HIV+ Patients
INITIAL• F: screen for syphilis,
trichomonas, GC, chlamydia
• M: screen for syphilis, consider sceening for GC, chlamydia (depending on local STD prevalence)
SUBSEQUENT• Repeat screening at
least annually (or as often as 3-6 months)
• F of childbearing potential: routinely test for pregnancy if indicated, counsel on contraception, family planning
Vaccinations of Patients with Newly Dx’d HIV
Vaccinations Frequency
Polyvalent pneumococcal vaccine (esp if CD4>200)
Baseline and at 5 yrs
Influenza Annually during flu season
HBV (for pts at risk) Three-immuniz primary series
HAV (for pts at risk, chronic HBV, HCV, liver dz)
Two-immuniz primary series
According to the US CDC definition, you have AIDS if you are infected with HIV and present with one of the following:
• A CD4+ < 200 cells/µl or CD4+% < 14%• Or one of the following defining illnesses:• Candidiasis of bronchi, trachea, or lungs • Candidiasis esophageal • Cervical cancer (invasive) • Coccidioidomycosis, disseminated or extrapulmonary • Cryptococcosis, extrapulmonary • Cryptosporidiosis, chronic intestinal for longer than 1 month • Cytomegalovirus disease (other than liver, spleen or lymph nodes • Encephalopathy (HIV-related) • Herpes simplex: chronic ulcer(s) (for more than 1 month); or bronchitis, pneumonitis, or
esophagitis • Histoplasmosis, disseminated or extrapulmonary • Isosporiasis, chronic intestinal (for more than 1 month) • Kaposi's sarcoma • Lymphoma Burkitt's, immunoblastic or primary brain • Mycobacterium avium complex • Mycobacterium, other species, disseminated or extrapulmonary • Pneumocystis jiroveci pneumonia (formerly Pneumocystis carinii) • Pneumonia (recurrent) • Progressive multifocal leukoencephalopathy • Salmonella septicemia (recurrent) • Toxoplasmosis of the brain • Tuberculosis • Wasting syndrome due to HIV
Typical relation of clinical manifestations to the CD4+ T-lymphocyte count in HIV-
infected patients
Complications in HAART Era
• Squamous cell cancer of cervix due to HPV
• Chronic HBV• Chronic HCV• Squamous cell cancer of anus due to HPV
(high grade abnlties need f/u w/ hi resolution anoscopy, bx)-> tx is topical imiquimod, podophylotoxin; laser, surgical cold scalpel excision
Follow-up Recommendations for Abnormal Cervical Cytology
Pap Smear ResultRecommendation
ASCUS (with severe inflammation) Evaluate for infection; if found, treat and recheck Pap smear in 2–3 months
ASCUS Follow-up Pap smear every 4–6 months for 2 years (until three consecutive Pap smears are negative)
If another ASCUS, consider colposcopy
ASCUS (neoplastic process suspected) Follow-up Pap smear every 4–6 months; or colposcopy and biopsy if LSIL persists; or immediate colposcopy
LSIL Follow-up Pap smear every 4–6 months; or colposcopy and biopsy if LSIL persists; or immediate colposcopy
HSIL (cervical intraepithelial neoplasia 2 or 3, carcinoma in situ)
Colposcopy and biopsy of abnormal area
or
Squamous cell carcinoma
From Kaplan JE, Masur H, Holmes KK; USPHS; Infectious Disease Society of America. Guidelines for preventing opportunistic infections among HIV-infected persons – 2002. Recommendations of the U.S. Public Health Service and the Infectious Diseases Society of America. MMWR Recomm Rep 51 (RR-8):1–52, 2002.
HIV+/HBV+ Co-infected Patients
• 10% of HIV+ pts also have HBV
• HIV/HBV pts have incr’d ESLD & death due to HBV than HBV only pts
• HBSAg+ pts: check HBeAg, HBeAb
• Check ast, alt, bili, alb, PT, HBV DNA
• HBV DNA helps monitor response to tx, not prognosis
• Liver bx is best to determine prognosis
Tx of HIV+/HBV+ Patients• Candidates: active liver inflamm, incr’d alt/ast, HBeAg+, HBV DNA >
105 c/mL
• PEG IFN
• Lamivudine (3TC) leads to HBeAg seroconv in 22% of tx’d pts, but
easy to develop resistance
• Tenofovir + 3TC or Adefovir + 3TC are better than 3TC monotx
• Baraclude (Entecavir) Not Recommended for HIV/HBV Co-Infected
Patients Who Are Not Also Receiving HAART Due to Potential for
Development of HIV Resistance
HIV+/HCV+ Co-infected Patients
• 30-40% of HIV+ pts also have HCV• HIV/HBV pts have incr’d ESLD & death
due to HCV than HCV only pts• 70% HCV+ pts are geno 1• Response rate to tx best for geno 2,3;
worse for geno 1, 4• HCV RNA helps for response to tx, not
prognosis• Liver bx is best to determine prognosis
Tx of HIV+/HCV+ Patients
• PEG IFN/RBV
• HCV only, geno 1: Cure rates = 30-40%
• HCV only, geno 2,3: Cure rates = 70-80%
• APRICOT study: SVR = 40% (62% for geno 2,3; 29%
geno 1)
• For geno 1, HCV VL > 800,000 c/mL: SVR = 19%
Progression of HIV disease to AIDS or death by initial CD4 count
HAART strategy in 1996
• Hit early, hit hard: CD4<500, VL > 10,000 c/mL
• Changed due to:– toxicities assoc w/ HAART, – failure to demonstrate clinical benefit,– concerns about resistance
• Cost of HAART = $10k to $15k/yr in USA
Likelihood of progression to AIDS or death in the pretreatment (A) and treatment (B)
era.
Indications for Initiation of Therapy: Chronic Infection
Clinical Category
CD4+ T Cell Count
Plasma HIV RNA
Recommendation
Symptomatic (AIDS, severe symptoms)
Any value Any value Treat
Asymptomatic, AIDS
<200 cells/µL
Any value Treat
Asymptomatic >200 cells/µL but
<350 cells/µL
Any value Treatment should be offered, with consideration of pros and cons
Indications for Initiation of Therapy: Chronic Infection
Clinical Category
CD4+ T Cell Count
Plasma HIV RNA
Recommendation
Asymptomatic >350 cells/µL
≥100,000 copies/mL
Most clinicians recommend deferring therapy; some will treat
Asymptomatic >350 cells/µL
<100,000 copies/mL
Defer therapy
Current Antiretroviral Medications
NRTI• Abacavir ABC• Didanosine DDI• Emtricitabine FTC• Lamivudine 3TC• Stavudine D4T• Zidovudine ZDV
• Tenofovir TDF
NNRTI• Delavirdine DLV• Efavirenz EFV• Nevirapine NVP• Etravirine ETV
Integrase Inhibitor• Raltegravir RAL
PI• Amprenavir APV• Atazanavir ATV• Darunavir DRV • Fosamprenavir FPV• Indinavir IDV• Lopinavir LPV• Nelfinavir NFV• Ritonavir RTV• Saquinavir SQV
– hard gel HGC– tablet INV
• Tipranavir TPV
Fusion Inhibitor/Entry Inhibitor• Enfuvirtide T-20• Maraviroc MVC
Initial Treatment: Preferred Components
*Avoid in pregnant women and women with significant pregnancy potential.**Emtricitabine can be used in place of lamivudine and vice versa.
•Efavirenz*
OR
•Atazanavir + ritonavir
•Fosamprenavir + ritonavir (BID)
•Lopinavir/ritonavir (BID)
NNRTI Option
PI Options
Tenofovir + emtricitabine**
Zidovudine + lamivudine**
+
NRTI Options
Use of HIV RNA & CD4+ T Cell Levels to Guide Therapy
Decisions• Syndrome consistent with acute HIV infection• Initial evaluation of new HIV diagnosis• Every 3-4 months in the untreated patient• Immediately prior to initiating therapy• 2-8 weeks after initiating therapy• Every 3-4 months in patients on therapy• As clinically indicated
Testing for Drug Resistance• Adjunct to guide antiretroviral therapy
• Combine with obtaining a drug history and maximizing drug adherence
• Research supports use in certain settings
• Genotyping vs. phenotyping
• Limitations of resistance testing and specific indications
The Use of Drug Resistance Testing
RECOMMENDED COMMENT
Acute HIV infection, if treatment is to be started
•To determine if resistant virus was transmitted; guide treatment decisions.
•Consider resistance testing if treatment is deferred.
Chronic HIV infection before starting ART
•Transmitted drug-resistant virus is common in some areas; is more likely to be detected earlier in the course of HIV infection; consider resistance testing earlier in the course of infection
Pregnancy •Recommended before initiation of ART or prophylaxis, or if incomplete viral suppression on ART
Virologic failure during ART •To assist in selecting active drugs for a new regimen.
Suboptimal suppression of VL after starting ART
•To guide treatment decisions.
The Use of Drug Resistance Testing
NOT USUALLY RECOMMENDED
COMMENT
After discontinuation of drugs • Resistance mutations may become minor species in the absence of selective drug pressure.
Plasma VL <1000 HIV RNA copies/mL
• Resistance assays unreliable if HIV RNA is low.
Complications of HAART
• Metabolic– Insulin resistance
• Protease inhibitors
– Hyperlipidemia (high chol/LDL/trig)• Assoc w/ most PI’s except unboosted ATV
– Body fat redistribution (lipodystrophy)• Lipoatrophy: loss of facial fat/limbs
– Esp assoc with stavudine
• Low long-term risk for CV dz?
Prognosis with HAART tx
• HAART can:– Suppress viral replication– Permit adquate immune system recovery
• Lasting concerns: – long-term adherence– SE mgmt (esp CV events)
• HAART is not a cure (cannot eliminate long-lived T-cell population)
Four FDA-approved Rapid HIV Tests
Sensitivity
(95% C.I.)
Specificity
(95% C.I.)
Reveal G2
- serum
- plasma
99.8 (99.2 – 100)
99.8 (99.0 – 100)
99.1 (98.8 – 99.4)
98.6 (98.4 – 98.8)
Multispot
- serum/plasma
- HIV-2
100 (99.9 – 100)
100 (99.7 – 100)
99.9 (99.8 – 100)
OraQuick Advance HIV-1/2
• CLIA-waived for finger stick, whole blood, oral fluid; moderate complexity with plasma
• Store at room temperature
• Screens for HIV-1 and 2
• Results in 20 minutes
Obtain finger stick specimen…
Insert loop into vial and stir
Collect oral fluid specimens by swabbing gums with test device.
Gloves optional; waste not biohazardous
Insert device; test develops in 20 minutes
PositiveNegative
Reactive Control
Positive HIV-1/2
Read results in 20 – 40 minutes
Uni-Gold Recombigen
• CLIA-waived for finger stick, whole blood; moderate complexity with serum, plasma
• Store at room temperature
• Screens for HIV-1
• Results in 10 minutes
Add 1 drop specimen to well
Add 4 drops of wash solution
Read results in 10 -12
minutes
Positive Negative
Reveal G2
• CLIA moderate complexity with serum, plasma
• Reconstitute and refrigerate reagents
• Screens for HIV-1
• Perform test in 5 minutes
Centrifuge to obtain serum or plasma
Add buffer to reconstitute conjugate. (Sufficient for 15 tests;
Refrigerate to store)
Add 3 drops buffer to moisten membrane
Add one drop of serum or plasma, followed by 3 drops of
buffer.
Add 4 drops of Colorimetric Detection Agent
Add 3 drops of buffer to wash
Read results immediately
Reactive
Negative
Multispot HIV-1/HIV-2
• CLIA moderate complexity with serum, plasma
• Refrigerate reagents
• Distinguishes HIV-1 from HIV-2
• Perform test in 15 minutes
Dilution of plasma or serum
Remove and discard pre-filter
Several timed reagent & wash steps
Negative HIV-1 & HIV-2 Positive
Peptide HIV-2
Recombinant HIV-1
Peptide HIV-1
Reactive Control