Host Response in Acute Infection, Setting the Stage for Disease Outcome MOAX01
Type:
Oral abstract session Back
Venue: Session Room 12
Interpretation: None
Time: 10:45 - 12:15
Code: MOAX01
Co-Chairs: Michael Betts, United States
Pradeep Seth, India

    Presentations in this session:
10:45
MOAX0101
Powerpoint (1 MB)		Polyfunctional Immune Responses to HIV in acute Infection
Michael Betts, United States

11:00
MOAX0102
Abstract
Powerpoint (1.3 MB)		Clinical correlations of inflammatory cytokines in the female genital tract during acute HIV-1 infection
Presented by Lisa Bebell, South Africa
L. Bebell1, J.-A. Passmore2, C. Williamson3, K. Mlisana4, I. Iriogbe4, Q. Abdool Karim4, S.A. Karim4, and the CAPRISA Acute Infection Study Team
1Columbia University College of Physicians and Surgeons, Centre for the AIDS Programme of Research in South Africa, Durban, South Africa, 2University of Cape Town, Division of Medical Virology, Department of Laboratory Sciences, Cape Town, South Africa, 3University of Cape Town, Division of Medical Virology, Institute of Infectious Diseases and Molecular Medicine, Cape Town, South Africa, 4University of KwaZulu Natal, Centre for the AIDS Programme of Research in South Africa, Durban, South Africa

11:15
MOAX0103
Abstract		Interferon regulatory factor 1: a novel determinant of resistance to infection by HIV-1 in highly exposed uninfected sex-workers
Presented by Hezhao Ji, Canada
H. Ji1, T. Ball1, J. Kimani2, P. McLaren1, C. Marlin1, A. Hill3, F. Plummer4
1University of Manitoba, Department of Medical Microbiology & Infectious Diseases, Winnipeg, Canada, 2University of Nairobi, Department of Medical Microbiology, Nairobi, Kenya, 3Oxford University, The Wellcome Trust Centre for Huamn Genetics, Oxford, United Kingdom, 4Public Health Agency of Canada, National Microbiology Laboratory, Winnipeg, Canada

11:30
MOAX0104
Abstract
Powerpoint (1.6 MB)		Clinical and immunological impact of HAART during acute HIV-1 infection
Presented by Hendrik Streeck, United States
H. Streeck1, H. Jessen2, G. Alter1, N. Teigen1, M. Waring1, A. Jessen2, I. Stahmer3, J. v.Lunzen3, X. Gao4, M. Lichterfeld1, T. Allen1, M. Carrington4, B. Walker1, M. Altfeld1, J. Rockstroh5
1Massachusetts General Hospital, Partners AIDS Research Center, Boston, United States, 2Private Practice Jessen/Jessen, Berlin, Germany, 3University of Eppendorf, Infectious Disease, Hamburg, Germany, 4National Cancer Institute, Laboratory of Genomic Diversity, Frederick, United States, 5University of Bonn, Internal Medicine, Bonn, Germany

11:45
MOAX0105
Abstract
Powerpoint (2.42 MB)		Comprehensive analysis of HIV-specific IL-2 and IFN- immune responses in treatment-naïve individuals in acute infection early disease (AIED) versus long term non progressors (LTNP) and individuals with progressive disease
Presented by Ndongala Lubaki, Canada
N. Lubaki1, Y. Peretz1, M.P. Boisvert2, R. Boulassel1, C. Tremblay3, R. LeBlanc4, D. Rouleau5, C. Tsoukas1, J.P. Routy1, N. Bernard1
1McGill University, Montreal, Canada, 2Montreal General Hospital Research Institute, Montreal, Canada, 3Centre Hospitalier de l'Universite de Montreal, Montreal, Canada, 4Clinique Medicale G.L.R, Montreal, Canada, 5Hopital Notre Dame, Universite de Montreal, Montreal, Canada





Audio files:
  1. English audio file (mp3 format, 41.6 MB)

Rapporteur reports

Science Track A: Biology and Pathogenesis of HIV report by Dr. Nicole Bernard

The data presented at this session addressed issues relating to understanding correlates of immune protection. The focus was to examine responses in primary infection or in long term non rogression that may be associated with better disease outcome.

M Betts

Long term non progressors are more likely to have HIV specific CD4 and CD8 immune responses with greater funtionality (4 or 5 functions) compared with progressors.

 

L Bebell

The presence of IL-12, IL-10, TNF-alpha, IL-6, IL-8 and IL-1-beta in the cervico-vaginal lavage and plasma of low risk controls, HIV exposed seronegative subjects, sercoconverters and HIV seropositive subjects in acute and early infection was quantified. A positive correlation was detected between fold over background total cytokine levels as a marker for overall cervico-vaginal inflammation and viral load. 

 

H. Ji

Three polymorphisms for Interferon Regulatory Factor 1 (IRF-1) were found to be associated with resistance to infection in a cohort of high risk commercial sex workers but did not influence rate of progression in those already infection. The "good" IRF-1 genotypes may encode variants that influence susceptibility through expression at lower levels. Cells expressing these variant support lower levels of  HIV replication. 

 

H Streek

HIV infected subjects were recruited in acute HIV infection to investigate whether successful treatment with HAART for 6 months changes HIV disease outcomes at the 6 months time point after HAART is withdrawn. Although viral load and CD4 count measures were similar in 2 groups receiving or not 6 months of therapy, HIV-specific immune responses measures were superior in those treated with HAART for 6 months begnning in acute infection.

 

M. Lubaki Ndongala

HIV-specific cells secreting both IFN-gamma and IL-2 are detected in individuals within the first 6 months of infection, although their appearance is delayed for 30 to 60 days from infection. There responses are rare in HIV infected subjects in progressive chronic HIV infection. The magnitude of total IFN-gamma, single IFN-gamma or IFN-gamma and IL-2 secreting cells do not predict where the viral load set point will occur later in infection. 

 

Final comments

The characteristics of immune responses that protect against HIV disease progression is still unknown. It is important not to overinterpret corelations between quantitative measures of immune responses and viral load as demonstrating a cause and effect relationship.

 



Science Track B: Clinical Research, Treatment and Care report by Dr Schlomo Staszewski

Our understanding of host factors involved in the control of early HIV-infection and in the natural immunity against HIV is currently stimulated by new findings from clinical studies using new technologies.

 

This was reflected in the presentations during the Monday morning session on Host Response in Acute Infection, where four important studies were presented. In his keynote lecture Michael Betts, who chaired the session, explained the new concept of the polyfunctional immune responses to HIV in acute infection. Given that HIV specific CD8 cells have a crucial role in the control of viral load, previous attempts to correlate their frequency with the antiviral effect resulted in inconsistent findings. Similarly, the production of gamma-interferon during exposure of cells to HIV does not provide a sufficient explanation for their ability to control HIV replication.

 

It has been shown that CD8 cells may have many measurable responses to antigen presentation in addition to gamma-interferon. These include TNF alpha, IL2, MIP1-beta, CD107a. The greater the number of functions exerted by CD8 cells, the better the antiviral response. A study presented by Lisa Bebell included 24 African women who had seroconverted. Cytokine concentrations were measured in the cervicovaginal lavage before seroconversion, at seroconversion and in early HIV infection. High levels of IL-12, IL-10, TNF-a, IL-6, IL-8, IL-1b in the cervicovaginal lavage correlated with higher viral loads. In addition there was a significant relationship between cervicovaginal inflammation in acute infection and the 9 month viral load. During acute infection high cytokine levels in the cervicovaginal lavage contrasted with low plasma levels measured simultaneously.

 

In a cross sectional study conducted in female sex workers from Nairobi who are known for their natural resistance to HIV, Ji and colleagues were able to demonstrate that two single nucleotide polymorphisms in the IRF-1 (Interferon regulatory factor) gene were strongly associated with increased resistance to HIV.

 

IRF-1 is associated with primary initiation of HIV replication and the polymorphisms 6194A>C and 6516C>T may result in decreased IRF-1 protein expression and diminished IRF-1 response to gamma-interferon.

 

Hendrik Streek reported on a study in seroconvertors, evaluating  the initiation of HAART in acute HIV infection. In addition to viral load and CD4, HIV-specific immunity was compared between 12 treated and 8 untreated patients. During the treatment period of 6 months viorologic and immunologic outcomes were in favour of the treated group. However the benefits were not detected after cessation of treatment. The data suggest that short term treatment of acute HIV infection does not change the long term prognosis.

 

 


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