HIV infection causes a rapid depletion of immune cells in semen, investigators report in an article published in the online edition of the Journal of Acquired Immune Deficiency Syndromes. This immune depletion could render HIV-positive men more vulnerable to sexually transmitted infections, suggest the researchers, and such infections can increase the risk of onward HIV transmission.
However, the team of US investigators also found that HIV treatment leads to the restoration of immune system cells in semen.
Most cases of HIV have been sexually transmitted. The risk of sexual HIV transmission is affected by a number of factors including the stage of HIV infection, and the presence of an untreated sexually transmitted infection. Both these factors can increase viral load in semen, increasing the likelihood of HIV transmission.
Previous research has found that soon after infection with HIV there is massive loss of immune system cells in a number of sites in the body, most notably the gut.
However, the effects of HIV, disease stage and HIV treatment on the profile of immune system cells in the male genital tract have not been well described.
US researchers hypothesised that infection with HIV would cause a reduction in CD4 cell count in semen. To test this, they compared both the CD4 cell counts and other white blood cell counts in the semen of HIV-positive men with such counts in HIV-negative men. The investigators also measured the effect of HIV treatment (dual NRTI therapy, and triple therapy including indinavir, a drug that can effectively penetrate the genital tract) to assess the effect of HIV treatment on the restoration of the immune system in the male genital tract.
Their research was based on semen samples obtained from 102 HIV-negative men and 98 HIV-positive men who were not taking HIV treatment. The samples were obtained between 1988 and 1993 from Boston-based men who have sex with men. Samples from patients taking antiretroviral therapy were obtained between 1996 and 1997, and also originated from men, from Boston, who have sex with men.
Results showed that HIV-positive men had significantly lower levels of all immune system cells measured in semen. This included lower total white blood cell count (p = 0.0008), lower macrophage count (p = 0.0026), lower T-lymphocyte count (p = 0.0001), lower CD4 cell count (p = 0.0001), lower CD4 T-lymphocyte count (p = 0.001) and lower CD8 T-lymphocyte count (p = 0.0063).
No significant correlation was found between CD4 cell count in blood and CD4 cell count or any other white blood count in semen. Further analysis showed that irrespective of whether the men had a blood CD4 cell count above or below 500 cells/mm3, the majority had an undetectable CD4 cell count in their semen.
Although the investigators did not study the effect of primary (or acute) HIV infection, they found that six of the seven men with the highest blood CD4 cell count (above 1000 cells/mm3) had an undetectable CD4 cell count in their semen. The investigators suggest that this provides evidence that “genital CD4 cell depletion occurs early in HIV disease, before profound reduction in peripheral CD4 cell counts.”
Next the investigators looked at the effect of HIV treatment on the immune profile of cells in semen.
First they looked the impact of dual NRTI therapy. Men taking such treatment had higher concentrations of total white cell count (p = 0.003), CD8 cells (p = 0.0001), activated T-lymphocytes (p = 0.0001) and macrophages (p = 0.03) than did HIV-positive men not taking any anti-HIV drugs.
Six months after the addition of the protease inhibitor indinavir (Crixivan) to this dual treatment, the investigators noted a significant increase in CD4 cell count in both semen and blood.
“Results from this study indicate that CD4 T cells are depleted in the male genital tract during HIV infection”, write the investigators, who add “antiretroviral-naive HIV-positive men in this study also had reduced seminal CD8 T-lymphocyte concentrations, suggesting that HIV infection impairs antiviral cellular defence mechanisms in the genital tract.”
Depleted immune function in the genital tract could, the investigators believe, render men “more susceptible to concomitant sexually transmitted disease infections that can increase the risk of HIV transmission.”
The investigators suggest that macrophages “are likely primary HIV host cells in the male genital tract and vectors of HIV transmission.”
Two men with late-stage HIV infection had evidence of immune activation in their semen. This was accompanied by a very high viral load, and the researchers conclude: “it is possible that men such as these with apparent genital immune activation and elevated HIV titres in their semen are highly infectious and may contribute disproportionately to HIV transmission.”
Politch JA et al. Depletion of CD4+ T cells in semen during HIV infection and their restoration following antiretroviral therapy. J Acquir Immune Defic Syndr (online edition), 2009.