Transcript here.

Meg Sullivan, MD
Section of Infectious Disease
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L.M. is a 26-year old man who has sex with
men
Last unprotected sexual contact 3 weeks ago
He presents with a 1 week history of fever,
rash, headache, sore throat, and diarrhea
HIV EIA reactive, HIV Western blot
indeterminate, HIV RNA > 10 million
copies/ml; CD4+ lymphocyte count 880/ml
www.aidsetc.org
February 2013
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C.A. is a 56-year-old Haitian woman
Presented to PCP with dysphagia
EGD demonstrated esophageal candidiasis
HIV EIA and WB reactive
CD4+ lymphocyte count 7/ml
www.aidsetc.org
February 2013
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N.C. is a 35-year-old homeless man
No regular shelter use
Recent IV heroin relapse
HIV test performed by OBOT provider
HIV EIA and WB reactive
CD+ lymphocyte count 418/ml
www.aidsetc.org
February 2013
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For which of these patients is antiretroviral
therapy indicated?
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What benefit would accrue to each?
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For which might ART be postponed? Why?
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Developed by the Department of Health
and Human Services (DHHS) Panel on
Antiretroviral Guidelines for Adults and
Adolescents – A Working Group of the
Office of AIDS Research Advisory Council
(OARAC)
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Reduce HIV-related morbidity; prolong
duration and quality of survival
 Restore and/or preserve immunologic
function
 Maximally and durably suppress HIV
viral load
 Prevent HIV transmission
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www.aidsetc.org
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Effective ART with virologic suppression improves and
preserves immune function, regardless of baseline
CD4 count
◦ Earlier ART may result in better immunologic
responses
and clinical outcomes
 Reduction in AIDS- and non-AIDS-associated morbidity and
mortality
 Reduction in HIV-associated inflammation and associated
complications
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ART can significantly reduce risk of HIV transmission”Treatment as Prevention”
Recommended ARV combinations are effective and
well tolerated
www.aidsetc.org
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Exact CD4 count at which to initiate therapy
not known, but evidence points to starting at
higher counts
Current recommendation: ART for all
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ART is recommended for treatment:
 “ART
is recommended for all HIVinfected individuals to reduce the
risk of disease progression.”
◦ The strength of this recommendation varies on the
basis of pretreatment CD4 count (stronger at lower
CD4 levels)
www.aidsetc.org
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Strength of recommendation:
◦ A: Strong
◦ B: Moderate
◦ C: Optional
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Quality of evidence:
◦ I: ≥1 randomized controlled trials
◦ II: ≥1 well-designed nonrandomized trials or
observational cohort studies with long-term
clinical outcomes
◦ III: Expert opinion
www.aidsetc.org
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Recommended for all CD4 counts:
CD4 count <350 cells/µL (AI)
CD4 count 350-500 cells/µL (AII)
CD4 count >500 cells/µL (BIII)
www.aidsetc.org
February 2013
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CD4 count 350 cells/µL or history of AIDSdefining illness:
◦ Randomized control trial (RCT) data show decreased
morbidity and mortality with ART
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CD4 count 350-500 cells/µL:
◦ RCT data as well as nonrandomized trials and cohort
data support morbidity and perhaps mortality benefit
of ART
www.aidsetc.org
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CD4 count >500 cells/µL
◦ Cohort study data are not consistent; some show
survival benefit if ART initiated
◦ Other considerations (eg, potential benefit of ART on
non-AIDS complications, HIV transmission risk)
support recommendation for ART
www.aidsetc.org
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◦ Untreated HIV may be associated with
development of AIDS and non-AIDSdefining conditions
 Earlier ART may prevent HIV-related endorgan damage; deferred ART may not
reliably repair damage acquired earlier
◦ Increasing evidence of direct HIV effects on
various end organs and indirect effects via HIVassociated inflammation
◦ End-organ damage occurs at all stages of
infection
www.aidsetc.org
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Potential decrease in risk of many
complications, including:
HIV-associated nephropathy
Liver disease progression from hepatitis B or C
Cardiovascular disease
Malignancies (AIDS defining and non-AIDS defining)
Neurocognitive decline
Blunted immunological response owing to ART
initiation at older age
◦ Persistent T-cell activation and inflammation
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www.aidsetc.org
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Pregnancy
AIDS-defining condition
Acute opportunistic infection
Lower CD4 count (eg, <200 cells/µL)
Acute/recent infection
Rapid decline in CD4
Higher viral load (eg, >100,000 copies/mL)
HIVAN
HBV coinfection
HCV coinfection
www.aidsetc.org
February 2013
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ARV-related toxicities
 Nonadherence to ART
 Drug resistance
 Cost
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www.aidsetc.org
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ART is recommended for Prevention:
 “ART
also is recommended for HIVinfected individuals for the
prevention of transmission of HIV.”
 “Treatment as Prevention”
www.aidsetc.org
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HPTN 052 Study Design
Stable, healthy, serodiscordant couples, sexually active
CD4+ count: 350 to 550 cells/mm3
Randomization
Immediate ART
CD4 350-550
Delayed ART
CD4 <250
Primary Transmission Endpoint
Virologically-linked transmission events
Primary Clinical Endpoint
WHO stage 4 clinical events, pulmonary tuberculosis, severe
bacterial infection and/or death
HPTN 052:
HIV-1 Transmission Breakdown
Total HIV-1 Transmission
Events: 39
Unlinked or
TBD
Transmissions:
11
Linked
Transmissions:
28
Immediat
e Arm: 1
Delayed
Arm: 27
• 23/28 (82%) transmissions in sub-Saharan
Africa
• 18/28 (64%) transmissions from female to
male partners
(p < 0.001)
96% efficacy
 Perinatal transmission
 Recommended for all HIV-infected
pregnant women (AI)
 Sexual transmission
 Recommended for all who are at risk of
transmitting HIV to sexual partners (AI for
heterosexuals, AIII for other transmission risk
groups)
www.aidsetc.org
February 2013
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Young MSM
Acute HIV infection
CD4 count preserved
Very high viral load
Should we treat him?
Why?
www.aidsetc.org
February 2013
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Preservation of CD4 count in normal range
? Prevention of CV risk, HAND, malignancy
? Prevention of transmission
◦ High viral load associated with increased
infectiousness
◦ Prevention by ART not as well established for MSM
as for heterosexual couples
www.aidsetc.org
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 “Patients starting ART should be willing
and able to commit to treatment and
should understand the benefits and risks
of therapy and the importance of
adherence.”
 Patients may choose to postpone ART
 Providers may elect to defer ART, based
on an individual patient’s clinical or
psychosocial factors
www.aidsetc.org
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www.aidsetc.org
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Clinical or personal factors may support
deferral of ART
◦ If CD4 count is low, deferral should be
considered only in unusual situations, and with
close follow-up
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When there are significant barriers to
adherence
If comorbidities complicate or prohibit ART
“Elite controllers” and long-term
nonprogressors
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A major determinant of degree and
duration of viral suppression
Poor adherence associated with virologic
failure
Optimal suppression requires 90-95%
adherence
Suboptimal adherence is common
10/06
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Regimen complexity and pill burden
Poor clinician-patient relationship
Active drug use or alcoholism
Unstable housing
Mental illness (especially depression)
Lack of patient education
Medication adverse effects
Fear of medication adverse effects
10/06
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Age, race, sex, educational level,
socioeconomic status, and a past history
of alcoholism or drug use do NOT reliably
predict suboptimal adherence.
Higher SES and education levels and lack
of history of drug use do NOT reliably
predict optimal adherence.
10/06
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Emotional and practical supports
Convenience of regimen
Understanding of the importance of
adherence
Belief in efficacy of medications
Feeling comfortable taking medications
in front of others
Keeping clinic appointments
Severity of symptoms or illness
10/06
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Establish readiness to start therapy
Provide education on medication dosing
Review potential side effects
Anticipate and treat side effects
Utilize educational aids including pictures,
pillboxes, and calendars
10/06
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Simplify regimens, dosing, and food
requirements
Engage family, friends
Utilize team approach with nurses,
pharmacists, and peer counselors
Provide accessible, trusting health care
team
10/06
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Older Haitian woman with OI
CD4 very low
Should we treat her?
Why?
www.aidsetc.org
February 2013
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Immunologic recovery
◦ Likely somewhat blunted secondary to AIDS and
low nadir count
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Decreased risk for further OI
Decreased AIDS-related mortality
Except for tuberculous and cryptococcal
meningitis, early ART reduces M/M especially
if CD4 <50
www.aidsetc.org
February 2013
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Young middle-aged homeless man
Irregular housing
Recent IDU relapse
CD4 low, but > 350
Should we treat him?
Why?
www.aidsetc.org
February 2013
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Benefits
◦ Decreased HIV morbidity
◦ ? Decreased mortality
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But NC is at high risk for nonadherence
How can we help him with that?
www.aidsetc.org
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www.aidsetc.org
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Allows effective, durable viral
suppression
3 standard combinations
◦ 2 NRTI + 1 NNRTI
◦ 2 NRTI + 1 PI
◦ 2 NRTI + 1 II
www.aidsetc.org
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Preferred
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Alternative
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Other
◦ Randomized controlled trials show optimal efficacy
and durability
◦ Favorable tolerability and toxicity profiles
◦ Effective but have potential disadvantages
◦ May be the preferred regimen for individual patients
◦ May be selected for some patients but are less
satisfactory than preferred or alternative regimens
www.aidsetc.org
February 2013
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TDF/FTC preferred
◦ What coinfection is also treated by this
combination?
◦ What cormorbidities might make this combination a
suboptimal choice?
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ABC/3TC alternative
◦ What test should be performed prior to using
abacavir? Why?
www.aidsetc.org
February 2013
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EFV preferred
◦ In what population should EFV NOT be used?
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RPV alternative
◦ Is RPV an optimal choice if VL > 100K?
◦ What class of drugs is contraindicated in
combination with RPV?
www.aidsetc.org
February 2013
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ATV/r and DRV/r preferred
◦ What drug class must be used with caution in
combination with ATV?
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FPV/r and LPV/r alternative
Which comorbidities might make PI a
suboptimal choice?
What drug classes interact with PIs?
www.aidsetc.org
February 2013
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RAL preferred
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EVG alternative
◦ What comorbidity contraindicates EVG?
www.aidsetc.org
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http://www.aidsetc.org
http://aidsinfo.nih.gov
www.aidsetc.org
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