Immune response in genital tract may explain why some exposed women not infected with HIV

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Women who are repeatedly exposed to HIV but do not become infected may be protected by HIV antibody and virus-specific cellular responses produced in their genital tract, say the authors of a study in Kenyan sex workers published in the March 30th edition of AIDS. The study’s authors are hopeful that their finding may help in the search for an HIV vaccine.

The researchers studied women who had taken part in a trial from 1998 to 2002 in which high-risk Kenyan female sex workers were given monthly antibiotics (Kaul, 2004). In that trial, the antibiotic reduced the risk of a sexually transmitted infection, but not of infection with HIV.

After the trial finished, 24 women who had become infected with HIV were matched with 89 women who had remained HIV-negative despite repeated exposure to the virus. The researchers studied cervicovaginal secretions (CVS) in both groups of women.

Glossary

clades

The term for the different sub-types of HIV.

proliferation

Multiplication (e.g. of immune system cells) to control an infection.

CD8

A molecule on the surface of some white blood cells. Some of these cells can kill other cells that are infected with foreign organisms.

antibiotics

Antibiotics, also known as antibacterials, are medications that destroy or slow down the growth of bacteria. They are used to treat diseases caused by bacteria.

immunoglobulin

Another name for antibodies. An antibody is a protein substance produced by the immune system in response to a foreign organism (such as bacteria, virus or parasite).

Crucially, the samples were taken at the beginning of the original trial, allowing the researchers to see if there were any protective factors present at the start.

They found that highly exposed, persistently negative (HEPS) women were far more likely to have vaginal secretions containing a type of antibody called immunoglobulin A (IgA) that was active against HIV.

These women were also more likely to have evidence of HIV-specific T-cell proliferation in their cervicovaginal tract than those who had become infected with HIV.

Several potential immune defences have been described in HEPS individuals, including HIV-specific CD8+ and CD4+ T cells, CD8+ antiviral factors and HIV neutralising IgA.

But this is study is the first to show an association between reduced HIV transmission and prior detection of both genital HIV-neutralising IgA and HIV-specific cellular proliferation.

In fact, HIV acquisition was lowest in those women with both these immune responses present at the start of the study- suggesting the responses have an additive effect.

The HIV-neutralising activity was more common against certain HIV-1 types – termed clades – than others in this study. Activity was more common against clade C than clade A – even though clade A is the most common in Kenya.

But the authors say different HIV isolates vary hugely in how sensitive they are to neutralisation. Therefore a much broader panel of clade A and C isolates would need to be tested before firm conclusions could be drawn.

They add that they cannot prove that these immune responses were the reason women did not become infected but that these data suggest the induction of these responses could be an important target for HIV vaccine development.

References

Hirbod TY et al. HIV-neutralizing immunoglobulin A and HIV-specific proliferation are independently associated with reduced HIV acquisition in Kenyan sex workers. AIDS 22: 727-735, 2008.

Kaul R et al. Monthly antibiotics chemoprophylaxis and incidence of sexually transmitted infections and HIV-1 infection in Kenyan sex workers: a randomized controlled trial. JAMA 291: 2555-2562, 2004.