Download American Academy of HIV Medicine

HIV Diagnosis of Acute Infection
&
Superinfection
Jose-Luis Burgos, MD, AAHIVS
Prevenmed
International Health & Cross Cultural Medicine
University of California, San Diego
Objectives
 Describe
the approach to the diagnosis
of acute retroviral syndrome
 Debate the advantages and
disadvantages of early treatment of
acute HIV infection
 Discuss the evidence for the possibility
of superinfection / reinfection and the
implications for patient education and
management
1 mil
HIV
RNA
100,000
+
_
10,000
Ab
P24 +
1,000
100
Exposure
Symptoms
10
0
20
30
Days
40
50
HIV-1 Antibodies
HIV RNA
Typical Course of Primary HIV
Acute HIV Infection
Acute HIV Infection
Transient symptomatic illness in 40-90%
 Usually mild but can be severe
 2-6 weeks after infection
 Often not recognized by primary care
clinicians

– Symptoms non-specific
– Often resembles influenza, mononucleosis
– “Cold symptoms” absent
Can be asymptomatic
 Duration: 14 days

DHHS Guidelines July 14, 2003
HIV testing
• CDC statistics – illness is still the most common reason for testing
• ER study (inner-city Baltimore)
– Prevalence 11.3%, with majority being AA males, followed by AA women3
• Think HIV – urgent care sites in high-prevalence regions of MA4
– HIV prevalence was 2.2%, higher than state-funded testing programs
– Testing offered to all, not just those perceived as high-risk
– Intense focus on linkage to care: 88% return rate for those HIV+
• Failure to return for results:
– 508 subjects, 55% failed to return for results2
• Opt-out (actively refusing testing) leads to greater acceptance than opt-in
(actively agreeing to testing): 85-98% vs 25-83%1
1. Mbori-Ngacha D. 10th CROI, Boston 2003; #47; 2. Hightow LB, et al. ibid; #918; 3. Henson C, et al. ibid; #38;
4. Walensky RP, et al. ibid; #39
14
Acute HIV Infection
Fever
LAD
Pharyngitis
Rash
96%
74%
70%
70%
Headache
N/V
HSM
Wt loss
32%
27%
14%
13%
Myalgia/arthralgia
Diarrhea
54%
32%
Thrush
Neuro Sx
12%
12%
Neuro: meningoencepalitis or aseptic meningitis; peripheral neuropathy or radiculopathy;
facial palsy, Guillain-Barre syndrome; brachial neuritis; cognitive impairment or
psychosis
CDC 2003
Rash in Acute HIV Infection
 Trunk,
face, extremities
 Palms and soles rarely involved
 5-10 mm diameter
 Erythematous, nonpruritic, painless
Laboratory Findings
Acute HIV Infection
 Lymphopenia
 lymphocytosis
 Atypical lymphocytes
 Transient CD4 decline
 VL: 100,000 – 1,000,000
Diagnosis of Acute HIV Infection

Recognition of clinical symptoms
– No true constellation of signs/sympoms
– Presence of any symptom(s)
– History of activity associated with HIV risk

Detectable plasma HIV RNA
– Highly sensitive
– False positive possible

Detectable p24 Antigen
– Less sensitive
– False positive rare
Acute HIV Infection
 High
virus levels (105-106 copies/mL)
 2-9% of HIV-negative have false
positive results
– Usually associated with low RNA titers
<10,000
 VL
in new infections
– Correlates with rate of CD4 decline
– Prognostic indicator in early disease
Potential Benefits: Early Intervention
Decrease the severity of acute disease
 Alter initial viral set point  alter disease
progression rate
 Suppress viral replication  reduce rate of
viral mutation
 Preserve HIV-specific immune responses

– May permit future discontinuation of therapy
with sustained viral control
Reduce risk for viral transmission
 May minimize viral evolution and
development of viral diversity

DHHS Guidelines July 14, 2003
Potential Risks: Early Intervention
 Decreased
QOL
– Medication side effects
– Drug toxicities
– Dosing constraints
 Drug
resistance if viral suppression
inadequate
 Need for indefinite continuing
therapy
 Expensive
 Potential for transmission of resistant
virus
DHHS Guidelines July 14, 2003
Potential Risks: Early Intervention
 Long
term clinical outcome benefit
has not been documented
 Additional studies are needed to
delineate the role of ARV therapy
during the primary infection period
DHHS Guidelines July 14, 2003
Treatment: Acute HIV Infection
 Weigh
potential benefits against
potential risks
 “Certain authorities endorse
treatment of acute HIV infection on
the basis of the theoretical rationale
and limited but supportive clinical
trial data”
DHHS Guidelines July 14, 2003
Treatment: Acute HIV Infection


Experienced clinicians recommend
consideration of therapy for patients among
whom seroconversion has occurred within
the previous 6 months
“Although the initial burst of viremia among
infected adults usually resolves in 2 months,
treatment during the 2 to 6-month period
after infection is based on the probability
that virus replication in lymphoid tissue is
still not maximally contained by the immune
system during this time”
DHHS Guidelines July 14, 2003
Detuned Antibody Testing





Less sensitive ELISA test
May help distinguish between recent
seroconverters and those with longstanding HIV infection
Current ELISAs can detect relatively low
levels of Ab
HIV Ab levels increase over first few months
– Recent infection: standard ELISA positive
– Detuned assay: negative
Able to diagnose individuals who have
already seroconverted on a standard ELISA
but are still early in infection
HIV Superinfection
HIV Super-Infection
 Coinfection
with a second strain of
HIV during the course of established
HIV-1 infection (Jost, NEJM 347:10, 2002)
 Known to be theoretically possible
 Little direct evidence to support
concept
HIV Superinfection
 2000:
LTNP (patient A) –
unprotected intercourse with ARVexperienced male with progressive
HIV disease (patient B)
 Patient A experienced rapid disease
progression
 Virus harbored original strain and
drug-resistant strain from patient B
Angel, J. CROI 2000, Abs LB2
HIV Superinfection
 Established
infection with HIV-1,
subtype AE
 Well-controlled viremia on HAART;
unable to remain on ART due to liver
toxicity
 Sexual exposure to type B in Brazil
–Unprecedented rise in viral load
and rapid CD4 depletion
–Mixture of B and AE identified
–Rapid emergence of type AE
Jost, S. NEJM 347:10, 2002
HIV Superinfection
 Evidence
supports clades from
different geographic areas have
combined
 Likely due to superinfection of an
individual harboring a virus of one
clade with a second virus of another
clade
McCutchan et al, 1996:N AIDS 10: supp
Robertson et al, 1995: J Mol Evol: 40
SIV Superinfection
SIV superinfection in monkeys may occur,
probably rare
 Difficult to superinfect a monkey with
established SIV even with

– High infectious dose
– IV administration
Possible when challenged with second SIV
strain during or soon after initial infection
with first strain
 Possible “window of opportunity” for
superinfection

Sharpe et al, 1997: J Gen Virol: 78
SIV Superinfection
 Development
of virus-specific
immunity over time
 Primary infection: immunity absent
or too immature to effectively
prevent infection
 Strengthening of virus-specific
immune responses  superinfection
less likely
Sharpe et al, 1997: J Gen Virol: 78
Superinfection
Implications for HC Providers
 Consider
the possibility of
superinfection
 Counsel patients regarding sexual
practices and safer sex
Summary
 Detection
of acute HIV infection
needs to enhanced
 Early intervention in acute HIV
infection may have clinical benefits
 Superinfection needs to be
considered
 Risk reduction counseling must be
ongoing