Transcript Slide 1 - Kaiser Permanente

HIVI
HIV Initiative of Kaiser Permanente and Care Management Institute
Laboratory Monitoring for HIV+ Patients:
What You Need to Know
Michael Horberg, MD MAS FACP FIDSA
Executive Director Research, Mid-Atlantic Permanente Research Institute
Director HIV/AIDS, Kaiser Permanente
Vice-Chair, HIV Medicine Association
AMA/HIVMA/HRSA/NCQA Measures (1)
No measures of HIV testing rates or linkages to care
Other Screening Measures
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TB Screening*
STI—gonorrhea/chlamydia*
STI—syphilis (that year)
Hepatitis B screening*
Hepatitis C screening*
High risk injection drug use behavior (that year)
High risk sexual behavior (that year)
Horberg, Aberg, et. al., CID, 2009
*--ever screened
AMA/HIVMA/HRSA/NCQA Measures (2)
Process Measures
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Medical Visit
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Measures retention in care
CD4 cell count twice yearly
PCP prophylaxis if CD4<200
ART prescription if CD4<350 †
Influenza immunization yearly
Pneumococcus immunization ever
Hepatitis B vaccination
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Ever one time and then all three vaccinations (2 measures)
Outcome Measures
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HIV RNA control for all patients on ART
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HIV RNA control after six months on ART
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†
Below limits of quantification for lab used
needs revision
Accountability measure as needs documentation of plan if patient’s HIV RNA
above limit of quantification
Caveats about the HIV Quality Measures
Measures need to change with time
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Entering an era of test/treat; not C
D 4 cutoff for starting ART?
Metrics are parsimonious—not intended to cover the
“universe” of care
DHHS guidelines: q6-12 month checking of CD4 for
patients with BLQ VL and high CD4
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However, this doesn’t apply to Viral Loads—still at least
q6months even if patient has been stable and controlled for
some time
What Should HIV Primary Care Do
Getting everyone tested (HIV and STI)
Get HIV+ patients into care and consider ART
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HPTN 052—treating all radically↓transmission
Routine primary care is key
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Vaccinations—hepatitis, pneumovax, flu
Cancer screening as age/gender appropriate; don’t forget!
STI screening—STIs love HIV+ hosts!
Depression and substance use screening—at least annually
Attention to potential toxicities, metabolic and cardiovascular issues—essential!
Work hard to retain patients in care
Do not forget social services!
All doctors treating HIV should know how to do all of this!
HIVMA/IDSA HIV Primary Care Guidelines—revised version out soon!
Initial Laboratory Studies for ALL HIV+ Patients:
But You Likely Know This
Non-HIV Disease Specific:
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CBC withD ifferential
LiverE nzymes
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Urinalysis
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HAV IgG
 HBcAb, HBsAg, HBsAb
 HCV Ab
ALT, AST, Bilirubin, Alk Phos
Electrolytes, BUN, Creatinine
RBCs, WBCs, Protein
Fasting Lipids and Glucose
Syphilis Screening
GC/Chlamydia
NAAT if available
 Consider all sources
(genital, anus, oropharynx)
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Hepatitis A, B, C Screening
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Blood Chemistries
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G-6-P
D Level
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Especially Black, Mediterranean,
and Asian
Serum Testosterone—where indicated
Note adjustment for age
 Especially for males with fatigue,↓weight or
libido, erectile dysfunction,↓BMD
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Toxoplasma Antibody
Why Worry About Syphilis Here
Rate (per 1,000 person-year)
Rates if Syphilis Incidence in Kaiser Permanente Northern California, by HIV Status
25
20
HIV-infected
15
10
5
HIV-uninfected
0
1995
1996
1997
1998
1999
2000
Year
Horberg, et. al., Sex Transmitted Dis. 2010; 37(1): 53-58
2001
2002
2003
2004
2005
Syphilis Serology - The Old Way
Nontreponemal Test: RPR or VDRL
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Treponemal Test
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Syphilis
No syphilis
No syphilis
(false + RPR)
Syphilis Serology - The New Way
Syphilis Antibody (EIA)
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RPR or VDRL
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Syphilis
Discrepant result - Do TP-PA*
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Syphilis
(false - RPR)
*--or MHA-TP or FTA-ABS
No syphilis
No syphilis
(false + EIA)
The New Strategy
Be Aware—
Primary syphilis
Late latent syphilis
False-positiveE IA
Successfully treated syphilis
Accidentally treated syphilis
Advantages
EIA can be automated
No more false-positive RPRs
Can pick up RPR-negative cases
False negative RPR
False negative RPR
True negative RPR
True negative RPR
True negative RPR
Disadvantages
New class of patients:
PositiveE IA, negative RPR
Discrepant treponemal tests
are confusing
What to do if you forget the logic
Ask: Why was the test done? Is there a history of syphilis?
EIA
RPR
TP-PA
Interpretation
Do
No syphilis
or very early
Be happy or treat
Syphilis
Treat for stage
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No syphilis?
Repeat in 1 month
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Syphilis
Treat for stage;
be aware of history
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Other non-HIV Specific Tests to Consider
CXR
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Patients with evidence of Latent TB
Consider if underlying lung disease present for baseline
Pap Test
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Anal and/or cervical
For cervical: q6months until negative then annual
For anal: Have a plan
CMV and other Herpesvirus
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CMV for patients with low risk of infection
Varicella-zoster for patients who deny h/o chickenpox or shingles
I don’t recommend HSV-2 testing but others do
TB screening/testing
HSV-2 Screening—Not Needed--IMHO
70% HIV+ are HSV-2 positive; 95% HSV+ (1 or 2)
CDC still recommends HSV-2 screening for HIV+
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And for MSM generally
Would be if partner was HSV-2+ and protect HSV-2 negative patient
HOWEVER, this info will likely NOT change your management
or later diagnostics
Patients with new lesions (and no h/o anogenital herpes)
should have the lesion typed (not the serum)
NOTE: Routine screening for Varicella-Zoster is also not
recommended
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Except for patients who don’t if they’ve ever had chicken pox or shingles
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Potentially eligible for vaccine
MMWR, 2009, vol. 58, RR-4; MMWR, 2010, vol. 59, RR-12.
TB Screening (1)
For most patients, TST testing is sufficient
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TST preferred in children <5 years old
Interferon-γ Release assay (IGRA) is an option
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“TST in a tube”
Assay measures production of interferon-g by WBC stimulated with M.
tuberculosis antigens.
Can be used in lieu of TST (CDC)
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Especially for patients who may not return
Advantages to IGRA:
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Only one visit
no problems with placement or interpretation
no false positives from BCG (doesn’t happen often anyway)
no confusion due to boosting effect
TB Screening (2)
Disadvantages:
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Requires fresh blood;
Cost higher than PP
D .
Results may fluctuate over time
Optimal role not fully defined yet
For active TB:
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Both TST and IGRA have poor predictive value
Get a tissue/sputum diagnosis!
For latent TB, studies are very limited
Neither test should be used as a “test of cure”
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Reversion has not been shown to reflect cure
TB Calculator
TST
IGRA
Interpretation
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TB likely not present
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TB may be present
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TB may be present
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TB very likely present
Of course, clinical thinking comes first.
HIV-Specific Tests
Serologic Test for HIV
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If not diagnosis confirmed already
Will need for D
A AP certification and other purposes
CD4 Cell Count and Percentage
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There is variation between assays and time of day
Plasma HIV RNA level (“Viral Load”)
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Be aware of changes in assays and cutoffs
Ideally use same assay always in same patient
HIV Resistance Testing
HLA B*5701
Coreceptor Tropism Assay
HIV Resistance Testing
Order at time of diagnosis before ART prescribed
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Even if treatment is not initially planned (although I believe in test/treat)
Can “back mutate” to wild type over time (although resistance mutations
are still “archived”)
Genotype (with adequate interpretation) is sufficient
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For ARV naïve certainly and usually with 1st or 2nd failure
Also for all pregnant women prior to starting ART
Some labs cannot reliably perform if HIV RNA<1000/mL
If suspect integrase inhibitor resistance, need genotype specific for that.
Phenotype should be considered when multiple mutations
suspected and repeated treatment failure
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Especially if multiple exposures to protease inhibitors
Results can take longer to return
HLA B*5701
Should be ordered prior to abacavir therapy
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If HLA B*5701 positive: higher risk for abacavir
hypersensitivity
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Abacavir should not be prescribed if HLA(+)
Note that a negative test does not rule out risk of hypersensitive
reaction 100%
Even if HLA(-), need to counsel patients about
hypersensitivity reaction
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But advise patients that they shouldn’t worry.
No need to order if not going to prescribe abacavir
Usually pretty quick turnaround for results.
Co-receptor Tropism Assay
Informs you if patient has CCR5 tropic virus, CXCR4 tropic
virus, or mixed.
Test should be performed prior to starting a CCR5 antagonist
(at present, that’s maraviroc)
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Some argue to test at time of diagnosis, due to VL needed for results
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However, newer assay can measure at far lower levels (including BLQ level)
Is still an expensive test.
Consider also if virologic failure with CCR5 antagonist
Phenotypes and Genotypes for this
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In US, phenotypes have been used more frequently
IF X4 virus present—maraviroc far less likely to be effective
(and can lead to incomplete suppression of HIV)
Inflammatory Markers
Markers of inflammation not recommended at this time.
However, CRP, D-dimer, IL-6 and hyaluronic acid levels
associated with increased risk of death
IRIS associated with:
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Elevated pre-ART TNF-α
Significant 1 month increase in CRP,D -dimer, IL-6, IL-8, CXCL10,
Interferon-γ
All of this data is from observational studies
These markers would not change management
Boulware, JID, 2011; 203: p.1637-1646.
Ongoing Monitoring of HIV+ Patients
HIV Specific:
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Viral Load/CD4 Count
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q3-4 months vs. q6months
Same caveats as before
Resistance testing if virologic
failure
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Cautions about “blips”
Failure if VL>200/mL (DHHS,
2011)
If integrase inhibitor resistance
suspected, need to specify also
genotype for this
Non-HIV Specific but related to
Treatment:
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Toxicity monitoring specific to
medication
Routine health maintenance
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Check blood pressure
Digital prostate exam for men
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PSA? If >50 consider
Dilated optho exam at least
annually if CD4<50
Fasting lipid and glucose at
least annually
STI screening
Bone disease screening
Cancer screening
Some Comments about Medication Monitoring
In general, therapeutic drug monitoring not needed
Toxicity monitoring is specific to medications
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As Z
D V and “d” drugs less used, fewer indications for CBC,
lactic acid level
Most PI medications affect lipids and glucose.
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Even though atazanavir does not affect lipids, aging and HIV itself
can lead to cardiovascular disease.
Many toxicities are not diagnosed through blood or
urine tests
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Example, facial lipoatrophy
Monitoring Patients on Tenofovir
Major toxicity concern for tenofovir is renal effects
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Proximal renal tubular dysfunction or Fanconi Syndrome:
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proteinuria, glucosuria, phosphaturia leading to hypophosphatemia,
elevated creatinine
Most would recommend for tenofovir:
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Urinalysis (proteinuria may come first)
Creatinine clearance (can be calculated from SCr)
Many recommend serum phosphorous
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Serum phosphate should be sufficient
However, some nephrologists consider this insensitive
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Can consider fractional excretion of phosphorous
Need to also consider issues of bone loss
DHHS Adult/Adolescent ART Guidelines, 2011; Rho and Perazella,
Current Drug Safety, 2007
Bone Disease Monitoring in HIV+ Patients (1)
Low BMD is very common among HIV+
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Increased fracture rates among HIV+
Likely multi-factorial causation
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Poorer nutrition, weight loss, smoking and alcohol
Lower Vitamin-D levels (60-75% among HIV+)
Hypogonadism
Studies have described small but significant BMD loss after
initation of ART
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2-6%; Not usually progressive
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Same seen immediately among women at menopause
Possibly PIs (?more with ATV than EFV)
Tenofovir has been associated with more loss than other regimens
McComsey, et. al., CID, 2010 51: p. 937-946; Calmy, et. al., JID, 2009, 200: p. 1746-1754
Bone Disease Monitoring in HIV+ Patients (2)
What to do?
All HIV+ with fragility fracture should get bone densitometry
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Also for women >65, younger women if ≥1 risk factor for osteoporosis,
men >50 (if risk—otherwise 70+*)
All patients with abnormal exams should be evaluated for
secondary causes of low BMD
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Including diet, vitamin D levels, substance use (SMOKING too!),
hypogonadism (male and female), steroids use
Vitamin D levels (25-OH level)
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Optimal level: 30-60ng/mL
More sensitive levels (1,25-OH) likely not needed
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In most cases, PTH level not needed if good faith effort at repleting low
vitamin D level hasn’t happened
Consider also for: men>50, post-menopause women, African-American,
prior h/o fragility fracture, lower BMD
Don’t usually need calcium level; recheck 6-12 months after repletion
*Recent recommendations say all HIV+ men>50
Screening for Cancer
Colon cancer—recent data suggests no increased risk in HIV+
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However, colonoscopy at age 50 and then q10 years if negative
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American College Gastroenterology—start AA at age 45 (not ACS or USPSTF)
Consider fecal immunohemoglobin testing annually (could be when given flu
shots)
Breast Cancer—doesn’t appear to have increased risk among
HIV+ women
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Annually at age 50 (younger if consider higher risk?)
Cervical pap smear—discussed earlier
Anal paps issue is what to do for follow-up
GET YOUR PATIENTS TO STOP SMOKING!!!!
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Also, alcohol and substance use counseling and screening
Also, sexual risk behavior counseling, diet and exercise, seat belt use
Anal Paps—Where We are Today
Higher risk of anal cancer among HIV+ with prior h/o anogenital warts
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102-fold greater rate of anal cancer among HIV+ compared to HIV
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Vast majority of HIV+ MSM have prior HPV exposure
Lower frequency if heterosexual male
Issue with anal paps is follow-up
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If abnormal anal pap—high resolution anoscopy by experienced anoscopist
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Aggressively treat active warts—anal and genital
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Many now recommend HRA +/- pap as approach
Cryotherapy, topical 5-FU, laser,
Anal cancer is aggressive—refer for treatment to experienced surgeon and oncologist
Importance of good viral control to help treatment
However, it’s unclear what follow-up surveillance should be
Silverberg, Leyden, Horberg et al. AIDS 2009, 23:2337-45; MMWR, 2009,
vol. 58: RR-4; HIVMA HIV Primary Care Guidelines
“Working together, I am confident that we can
stop the spread of HIV and ensure that those
affected get the care and support they need.”
--President Barack Obama
Strive only for the best. Be proud.
The great work continues.
Thank you