Important note: Information in this article was accurate in September 2001. The state of the art may have changed since the publication date.

Studies on Exposed Seronegative Cohorts

IAVI Report - July / September 2001

Location	Investigators	Type of cohort	Source of Information (journal or conference)	Data published or presented
The Nairobi ESN women are not the only group of exposed seronegative individuals being followed prospectively. Similar examples of possible HIV resistance have been reported from other cohorts, which typically fall into one of three categories: commercial sex workers (CSW) (who are usually exposed to many different HIV strainst), "serodiscordant couples (wherein one partner is HIV-positive, the other, negative), and perinatally exposed infants (see article, "Closing in on Immune Protection in the Women of Pumwani"). Recently published or presented finding from CSW and serodiscordant couple cohorts are listed in the tables below and to the right.
Northern Thailand (Chiang Mai and Lamphun)	Chiang Mai HEPS Working Group	Female sex workers	J Infect Dis 1999 Jan;179(1):59-67	Criteria: >2yrs sex work, >2 STDs, HIV-1 seronegative Resistance associated with HLA B18. Env-specific IgA detected in the cervix of 6/13 ESN women.
Addis Ababa, Ethiopia	Ethio-Netherlands AIDS Research Project	Female sex workers	AIDS Res Hum Retroviruses 2001 Mar 20;17(5):433-41	Criteria: >5yrs sex work, HIV-1 seronegative. No evidence for role of certain non-immune factors in HIV resistance (co-receptor polymorphism, co-receptor expression levels, beta-chemokine production and cellular resistance to HIV infection in vitro).
Abidjan, Côte d'Ivoire	Institute of Tropical Medicine, Belgium	Female sex workers	International Conference on AIDS 2000:Durban, SA, Abstract No. WePeA3995	Some evidence of decreased CXCR4 expression and increased beta-chemokine production in both ESN and HIV+ FSW.
Chiang Rai, Thailand	Thai Ministry of Public Health and US CDC	Female sex workers	AIDS Res Hum Retroviruses 2001 May 20;17(8):719-34 International Conference on AIDS 1998: Geneva, Switzerland, Abstracts No. 599/31120 & 603/31127 6th Conference on Retroviruses and Opportunistic Infections 1999: Chicago, Abstract No. 83	Criteria: >3yrs sex work, HSV-2 & syphillis+, HIV-1 seronegative. Resistance associated with HLA-A11 CTL responses to HLA-A-matched subtype E peptides (most commonly to Nef, also to Pol, Gag, Env) detected in 4/7 ESN. ESNs tended to have higher frequencies of polymorphisms in both the CCR5 promoter region and the gene for the chemokine SDF-1 (both aassociated with slower progression in HIV+ individuals) and higher spontaneous RANTES production by PBMC. Novel CD4/CD14-associated HIV suppressive activity detected in the blood.
Location	Investigators	Type of cohort	Source of Information (journal or conference)	Data published or presented
Chiang Mai, Thailand	Thai Couples HEPS Group	Serodiscordant couples	6th Conference on Retroviruses and Opportunistic Infections 1999: Chicago, Abstract No. 51	ESNs from a cohort of women married to HIV-infected men were compared to wives who became infected. Factors that did not differ between the two groups: HLA class I alleles, CCR5 D32 genotype and prsence of SLP1 (an HIV-inhibiting protein) in the cervicovaginal lavage. Husbands' samples showed no differences in seminal viral load, HIV co-receptor use or defects in viral accessory genes. More than half the ESNs showed HIV-specific T-cell responses. ESNs showed CD14-associated HIV suppressive activity
London, UK	Imperial College School of Medicine (St. Mary's, London) and MRC Human Immunology Unit, John Radcliffe Hospital (Oxford, UK)	Serodiscordant couples	Conference on Retroviruses and Opportunistic Infections 2000: Chicago, Abstract Nos. 52 & 53	No mutations in CCR5 co-receptor gene or its promoter region. HIV-specific CD8 T-cells detected in 8/8 ESN partners. Responses to whole HIV proteins but not known peptides, suggesting that responses are directed at unmapped CTL epitopes. Gag-specific CD4 T-cell responses detected in 3/5 ESN tested.
New Jersey, USA	Gladstone Instittute/ Heterosexual AIDS Transmission Study (HATS)	Serodiscordant couples	8th Conference on Retroviruses and Opportunistic Infections 2001: San Francisco, Abstract No. 595	13/16 ESN women showed ELISPOT responses to at least one antigen tested (gag, pol, nef, and env); 9/16 responded to multiple antigens. 5/16 showed responses at multiple time points.
Lusaka, Zambia	University of North Carlolina	Serodiscordant couples	International Conference on AIDS 2000:Durban, SA, Abstract No. WeOrA596	Responded to whole HIV proteins (Gag, Env, Pol). HIV-specific CTL detected in 7/37 ESN.
Seattle, Washington USA	University of Washington School of Medicine and Fred Hutchinson Cancer Research Center	Serodiscordant couples	J Infect Dis 1999 Mar;179(3):548-57	13/36 ESN showed HIV-specific CTL 4/26 had lymphoproliferative responses (top24, gp160 or gp120) detected in 4/36 ESN. 1/36 homozygous for the CCR5 D32 mutation, 10/36 heterozygous. HIV-specific CTL more commonly detected in individuals with wild-type CCR5 genotype.

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