Spach/HIV/Acute HIV/PP
HIV: Acute (Primary) Infection
David H. Spach, MD
Medical Director, Northwest AIDS Education and Training CenterAssociate Professor of Medicine,Division of Infectious Diseases
University of Washington, Seattle
Case History
A 27-year-old man presents with a 48 hour history of fever, lymphadenopathy, severe fatigue, and rash. He had high risk sexual activity with 2 other men 7 days ago. He has no known prior medical problems.
Spach/HIV/Acute HIV/PP
Acute (Primary) HIV
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8Time
HIV RNA
“Set Point”
6 months3 months
HIV Antibodies
Acute HIV
Spach/HIV/Acute HIV/PP
Acute HIVEarly Events in
Transmucosal Infection
From: Kahn J, Walker BD.N Engl J Med 1998;339:33-9.
Spach/HIV/Acute HIV/PP
Case History: Question
A diagnosis of acute (primary) HIV is suspected. Which of the following best supports this diagnosis?
1) A negative HIV antibody test and HIV RNA 1,0002) A negative HIV antibody test and HIV RNA 200,000 3) A positive HIV antibody test and HIV RNA of 2,0004) A positive HIV antibody test and HIV RNA of 50,000
Spach/HIV/Acute HIV/PP
HIV: Manifestations of Primary Infection
44%
52%
55%
57%
59%
74%
86%
0 20 40 60 80 100Patients %
Adenopathy
Pharyngitis
Headache
Rash
Myalgias
Lethargy
Fever
Most Common Symptoms: N = 160
ii
From: Vanhems P. AIDS 2000;14:375.Spach/HIV/Acute HIV/PP
Acute (Primary) HIV
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8Time
HIV RNA
“Set Point”
6 months3 months
HIV Antibodies
Spach/HIV/Acute HIV/PP
Plasma HIV RNA Levels
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8Time
HIV RNA
Acute HIV
“Set Point”
6 months
Spach/HIV/Acute HIV/PP
HIV Infection: Natural History
0
200
400
600
800
1000
0 2 4 6 8 10 12 14
Years
CD4 Cell Count
Acute HIV Infection
Year 1
Spach/HIV/Acute HIV/PP
Risk of Progression to AIDS: HIV RNA & CD4
19
42
73
93
22
40
57
78
5 15
26
48
67
0
20
40
60
80
100
Percentage with AIDS
CD4 <350 CD4 351-500 CD4 > 500
Progression to AIDS at 6 Years < 500
501 - 3,000 3,001 - 10,000
10,001 - 30,000 > 30,000
From: Mellors J et al. Science 1996;272:1167-70.
HIV RNA Level (bDNA)
Spach/HIV/Acute HIV/PP
Immune Response to Acute HIV Infection
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8Time
HIV RNA
Acute HIV
Weak CTL
Moderate CTL
Strong CTL
Rapid Progression
Moderate Progression
Slow Progression
From: Walker BD. Nature 2000;407:313-4.
6 months
Spach/HIV/Acute HIV/PP
HIV Primary Infection Isolates
2
1
7
2
6
0
2
4
6
8
10
Resistant Isolates %
NRTI NNRTI PI
1996-1998
1999-2000
3
From: Little SJ. JAMA 1999;282:1142-9. Little SJ. 8th Conf Retrovirus. Abstract 756
N = 108 PatientsNewly HIV-Infected Phenotypic Data: 10-fold Resistance
Spach/HIV/Acute HIV/PP
HIV Primary Infection Isolates
NRTI NNRTI PI
2 1 1
10
16
1
0
5
10
15
20
Resistant Isolates %
> 2.5-10 Fold Resistance
> 10 Fold Resistance
From: Little SJ. JAMA 1999;282:1142-9.
N = 141 Patients Phenotypic Data
Spach/HIV/Acute HIV/PP
HIV Primary Infection Isolates
16.3%
12.5%
7.5%
2.5%3.8%
0
5
10
15
20
25
30
Resistant Isolates %
Any Antiretroviral Drug
Any Nucleoside Analog
Any Non-nucleoside Analog
Any Protease Inhibitor
Multi-Drug Resistant
From: Boden D. JAMA 1999;282:1135-1141.
N = 80 Patients Genotypic Data
Spach/HIV/Acute HIV/PP