The Body PRO Covers: The 8th Conference on Retroviruses and Opportunistic Infections

Immunology: Miscellaneous

February 5, 2001

  • "Resistance Factors" in Highly Exposed Persistently Seronegative (HEPS) Women Married to HIV-Infected Men in Chiang Mai, Thailand (Poster 51)
    Authored by A. Duerr, C. Costello, V. Suriyanon, V. Robison, and the Thai Couples HEPS Group
    View the original abstract

  • Genetic, Virological, and Immunological Characterization of a Cohort of Long-Term Monogamous HIV-Discordant Couples (Poster 52)
    Authored by R. Braganza, S. Beddows, S. Frazeo, T. Dong, T. Rostron, S. Rowland-Jones, J. Weber, and S. Fidler
    View the original abstract

Epidemiologic studies from around the world have identified a number of individuals who are repeatedly exposed to HIV, but remain uninfected. Through the genetic analysis of one such group, commercial sex workers in central Africa, host factors that might protect from HIV were first identified. In these people, a deletion in the gene encoding the co-receptor for HIV, CCR5, called CCR5D32, was found to protect against infection with some strains of HIV. Several other factors have been associated with reduced risk of sexual transmission of HIV. It is hoped that by understanding how a few individuals remain "immune" to infection by HIV that therapies can be developed to protect the many others who remain at risk or to treat those already infected.

Factors Possibly Associated with Decreased Risk of HIV Transmission
  • Viral subtype

  • Low seminal fluid HIV viral load

  • Defects in HIV regulatory genes

  • Co-receptor utilization (CCR5 vs. CXCR4)

  • Mutations in CCR5

These two studies provide an extension to the knowledge base of possible differences between the exposed but seronegative and those who become infected. The first study (#51) is an analysis of repeatedly-exposed Thai women married to HIV-infected men (serodiscordant relationships). This study compared 23 such exposed and seronegative women to 12 HIV-unexposed and 15 recently infected women. The exposed and uninfected women had been married for greater than two years, had intercourse greater than two times per week and rarely or never used condoms. The study failed to find a genetic basis for protection, noting no differences in HIV co-receptor use or co-receptor mutations, alterations in HIV regulatory genes or seminal viral loads. Indeed, the HIV isolated from the women's husband (when tested) was fully capable of infected cells isolated from the blood of the woman.

A separate study form the United Kingdom examined eight serodiscordant British couples (six homosexual, two heterosexual) (#52). Again, investigators failed to find a genetic basis for non-transmission, showing that in vitro, the virus present in the infected partner was capable of infecting cells from the non-infected partner.

Both studies did find evidence of immunologic exposure among the exposed but uninfected partners. Using a specialized assay called the ELISPOT, cellular immune responses could be measured against several HIV proteins.

These studies offer little to today's patients or health care providers; indeed, the seemingly never-ending consultations for the newly diagnosed provides a frequent reminder to me of the distances that HIV research must traverse before these data can bear clinical fruit. Nevertheless, the mere existence of these serodiscordant couples tells us that protection from productive HIV infection can and does happen. I trust that someday, we will be able to understand why.

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