ACUTE RETROVIRAL
SYNDROME
Dr. Jennifer Veltman
Acute Retroviral Syndrome (ARS)
• Definitions
• Epidemiology
• Clinical course
• Symptoms
• Diagnosis
• Treatment
What is Acute Retroviral Syndrome???
Definitions:
Acute HIV Infection: Phase of HIV disease
immediately after infection during which the initial
burst of viremia in newly infected patients occurs: antiHIV antibodies are undetectable at this time, while HIV
RNA or p24 antigen are present.
Recent Infection: considered the phase up to 6
months after infected during which anti-HIV antibodies
are detectable.
Early HIV: either acute or recent HIV infection
Acute retroviral syndrome: patient w/ acute HIV
infection w/ symptoms.
Epidemiology
• 40-90% of people infected with HIV develop ARS
• Reported more in those infected via sexual exposure or
health care related (needle stick) compared to IVDU
• Onset 1-6 weeks after exposure. Peak onset is 3 weeks
after exposure.
• Day 0
• exposed to HIV, and infection begins.
• Day 8
• virus is detectable in blood using (PCR)
• antibody test are negative.
• amount of virus in the blood more than doubles every day.
• The CD4 cell count (and total white blood cell count) begins
to drop
• Weeks 2-9
• viral load peaks and begins to decline as the immune system begins
to battle the virus
• highly infectious!!!
• Weeks 10-24
• HIV viral load drops to its lowest point, also known as the set
point, which is different in each person.
• antibody tests become positive for HIV. Seroconversion is
now complete, and chronic HIV infection begins.
Window period
What are the symptoms of Acute
Retroviral Syndrome?
Symptoms
Symptom
# w/ finding (n=209)
Frequency %
Fever
200
96
Enlarged lymph nodes
154
74
Sore throat
146
70
Rash
146
70
Sore muscles or joints
112
54
Low platelets
94
45
Low WBC
80
38
Diarrhea
67
32
Headache
66
32
Nausea/vomiting
56
27
Elevated liver enzymes
38
21
Enlarged liver/spleen
30
14
Thrush
24
12
Neuropathy
13
6
Encephalopathy
12
6
What are some other diseases that
can cause similar signs/symptoms?
• “MONO” (EBV or CMV infection)
• Sore throat, fatigue, enlarged glands, fever, muscle or joint aches,
rash, enlarged liver/spleen, elevated liver enzymes, low platelets
• Influenza
• Muscle aches, fevers, nausea, vomiting, diarrhea, fatigue
• Acute HSV (Primary Herpes Infection)
• Fever, fatigue, sore throat, headache, rash, sore muscles, enlarged
glands near ulcer
• Secondary Syphilis
• Fatigue, headache, poor appetite, nausea, joint aches, fever,
(rarely) meningitis and liver inflammation
• Acute Hepatitis
• Fever, fatigue, elevated liver enzymes, enlarged liver
Symptoms
• Symptoms resolve 10-15 days
• Acute opportunistic infections have been reported
• Examples: P. jirovecii pneumonia, Cryptococci meningitis, and
Candida esophagitis.
• Likely caused by the depression of the CD4+cell count generally
seen in acute HIV infection.
Diagnosis:
• high-level HIV RNA viral load in the absence of anti-HIV
antibodies.
• (+)viral load. (–)ELISA
• ELISA remains negative for an average of 2 to 6 weeks
after the onset of symptoms, despite the appearance of
specific antibodies on a Western blot of the patient’s
serum.
• If VL <10,000, may be false positive b/c usually VL
>100,000 copies/mL
• Pt should have elisa repeated over next 3-6 months to
document seroconversion
Should your patient get on treatment?
Pros of starting treatment during Acute
Retroviral Syndrome
• Pros:
• Symptom relief
• Decreases viral reservoir and viral set point
• Decrease rate of viral mutation by suppressing viral replication
• Prevent immune destruction
• Public health, reduces transmission to serodiscordant sexual
partners
Cons of starting treatment during Acute
Retroviral Syndrome
• Cons:
• Toxicity of medications
• Risk of developing drug resistance if adherence is poor
• Quality of life w/ daily medication in which strict adherence is
necessary
• Cost
The Setpoint Study (ACTG A5217): Effect of Immediate Versus Deferred Antiretroviral Therapy
on Virologic Set Point in Recently HIV-1–Infected Individuals
In 1 year, about
half of patients
needed to start
ART in Delayed
Treatment group
Time to meeting eligibility criteria for initiation or reinitiation of antiretroviral therapy (ART) for the immediate
treatment (IT) and deferred treatment (DT) groups over the 96 weeks of the study; times were significantly
longer in the IT group (P < .001; log–rank test).
Hogan C M et al. J Infect Dis. 2011;infdis.jir699
Guidelines say…
• Treatment optional , unless pregnant, then recommended
What to say to patients…
from www.aids.gov/hiv-aids-basics
• Within 2-4 weeks after HIV infection, many, but not all, people
develop flu-like symptoms, often described as “the worst flu ever.”
Symptoms can include fever, swollen glands, sore throat, rash,
muscle and joint aches and pains, fatigue, and headache. This is
called “acute retroviral syndrome” (ARS) or “primary HIV infection,”
and it’s the body’s natural response to the HIV infection.
• During this early period of infection, large amounts of virus are
being produced in your body. The virus uses CD4 cells to replicate
and destroys them in the process. Because of this, your CD4 count
can fall rapidly. Eventually your immune response will begin to
bring the level of virus in your body back down to a level called a
viral set point, which is a relatively stable level of virus in your
body. At this point, your CD4 count begins to increase, but it may
not return to pre-infection levels. It may be particularly beneficial to
your health to begin ART during this stage.
• It is important to be aware that you are at particularly high risk of
transmitting HIV to your sexual or drug using partners during this
stage because the levels of HIV in your blood stream are very
high. For this reason, it is very important to take steps to reduce
your risk of transmission.
References
• DHHS guidelines for the use of antiretroviral agents in
HIV-1 infected adults and adolescents; considerations for
antiretroviral use in special patient populations. Acute
and recent HIV infection. Last updated 2/12/13.
http://aidsinfo.nih.gov/guidelines/html/1/adult-andadolescent-arv-guidelines/20/acute-and-recent--early--hiv-infection
• Mendel's
• http://www.thebody.com/content/art16805.html
• Emedicine accessed 8/10/13
Now, how much do you remember?
• Definitions
• Epidemiology
• Clinical course of ARS
• Symptoms
• Diagnosis
• Treatment
What are the most common
signs/ symptoms in Acute
Retroviral Syndrome?
Symptoms
Symptom
# w/ finding (n=209)
Frequency %
Fever
200
96
Enlarged lymph nodes
154
74
Sore throat
146
70
Rash
146
70
Sore muscles or joints
112
54
Low platelets
94
45
Low WBC
80
38
Diarrhea
67
32
Headache
66
32
Nausea/vomiting
56
27
Elevated liver enzymes
38
21
Enlarged liver/spleen
30
14
Thrush
24
12
Neuropathy
13
6
Encephalopathy
12
6
What are the Pros of treating
patients during Acute
Antiretroviral Syndrome?
Pros of starting treatment during Acute
Retroviral Syndrome
• Pros:
• Symptom relief
• Decreases viral reservoir and viral set point
• Decrease rate of viral mutation by suppressing viral replication
• Prevent immune destruction
• Public health, reduces transmission to serodiscordant sexual
partners
What are the Cons of treating
patients during Acute
Antiretroviral Syndrome?
Cons of starting treatment during Acute
Retroviral Syndrome
• Cons:
• Toxicity of medications
• Risk of developing drug resistance if adherence is poor
• Quality of life w/ daily medication in which strict adherence is
necessary
• Cost
How do you diagnosis Acute
Retroviral Syndrome?
Diagnosis:
• high-level HIV RNA viral load in the absence of anti-HIV
antibodies.
• (+)viral load. (–)ELISA
• ELISA remains negative for an average of 2 to 6 weeks
after the onset of symptoms, despite the appearance of
specific antibodies on a Western blot of the patient’s
serum.
• If VL <10,000, may be false positive b/c usually VL
>100,000 copies/mL
• Pt should have elisa repeated over next 3-6 months to
document seroconversion
When are HIV patients the most
infectious?
• Day 0
• exposed to HIV, and infection begins.
• Day 8
• virus is detectable in blood using (PCR)
• antibody test are negative.
• amount of virus in the blood more than doubles every day.
• The CD4 cell count (and total white blood cell count) begins to
drop
• Weeks 2-9
• viral load peaks and begins to decline as the immune system begins to
battle the virus
• highly infectious!!!
• Weeks 10-24
• HIV viral load drops to its lowest point, also known as the set
point, which is different in each person.
• antibody tests become positive for HIV. Seroconversion is now
complete, and chronic HIV infection begins.
What is the window period?
Window period
Thank you!