Joseph
December 15th, 2008, 11:17
http://www.circumcisionandhiv.com/2008/12/more-confounding-evidence-weakens-conclusions-of-african-circumcision-rcts.html
Sunday, December 14, 2008
More confounding evidence weakens conclusions of African circumcision RCTs
The Lancet has published an article (11/3/2008) that looked at "cell-mediated immunity" to HIV-1. They summarized their objective thusly:
Background Observational data and non-human primate challenge studies suggest that cell-mediated immune responses might provide control of HIV replication. The Step Study directly assessed the efficacy of a cell-mediated immunity vaccine to protect against HIV-1 infection or change in early plasma HIV-1 levels.
Statistics were collected on circumcision status in men because "cell-mediated" refers to immunity responses at the cellular level where HIV first challenges or enters the body. Foreskins or lack of them clearly are implicated.
It has been pointed out that whatever the objective of this study, certain characteristics of the subjects point to a couple of important points. Table 4 appears to show uncircumcised men in the placebo arm were significantly LESS likely to contract incident HIV infections (1.4% to 4.2% per year). Whereas, in vaccine recipients, uncircumcised men had modestly (non-significantly) higher HIV incidence.
Also, people who were uncircumcised were significantly more likely to have higher immune response to Ad5 (see table 1). Does this suggest that circumcision has an impact on immune response to Ad5 and maybe to other pathogens? If so, this might point to some immune benefits with an intact foreskin -- for responding to HIV as well as other pathogens.
EDIT: The reason cell-mediated immunity has gotten attention recently is due to the fact that the Merck vaccine in question here failed miserably and intact men were widely reported to have been made more vulnerable by the vaccine. While that appeared to be true, the de Witte study [pdf], published shortly after the African circumcision RCTs, appeared to show a very strong and efficacious response against HIV infection from Langerin, a substance that comes from the Langerhans cells. These were the very cells vilified without evidence by the pro-circumcision forces that have promoted circumcision before and after HIV came along and who conducted the African studies, as the evil that circumcision excises and therefore reduces rates of infection. Clearly, it is more complicated than that and the evidence is far from settled or even fully collected or analyzed.
Download Buchbinder-Lancet-Mediated-Cell-Immunity
Reference
Lancet 2008; 372: 1881–93
Published Online
November 13, 2008
DOI:10.1016/S0140-
6736(08)61591-3
Sunday, December 14, 2008
More confounding evidence weakens conclusions of African circumcision RCTs
The Lancet has published an article (11/3/2008) that looked at "cell-mediated immunity" to HIV-1. They summarized their objective thusly:
Background Observational data and non-human primate challenge studies suggest that cell-mediated immune responses might provide control of HIV replication. The Step Study directly assessed the efficacy of a cell-mediated immunity vaccine to protect against HIV-1 infection or change in early plasma HIV-1 levels.
Statistics were collected on circumcision status in men because "cell-mediated" refers to immunity responses at the cellular level where HIV first challenges or enters the body. Foreskins or lack of them clearly are implicated.
It has been pointed out that whatever the objective of this study, certain characteristics of the subjects point to a couple of important points. Table 4 appears to show uncircumcised men in the placebo arm were significantly LESS likely to contract incident HIV infections (1.4% to 4.2% per year). Whereas, in vaccine recipients, uncircumcised men had modestly (non-significantly) higher HIV incidence.
Also, people who were uncircumcised were significantly more likely to have higher immune response to Ad5 (see table 1). Does this suggest that circumcision has an impact on immune response to Ad5 and maybe to other pathogens? If so, this might point to some immune benefits with an intact foreskin -- for responding to HIV as well as other pathogens.
EDIT: The reason cell-mediated immunity has gotten attention recently is due to the fact that the Merck vaccine in question here failed miserably and intact men were widely reported to have been made more vulnerable by the vaccine. While that appeared to be true, the de Witte study [pdf], published shortly after the African circumcision RCTs, appeared to show a very strong and efficacious response against HIV infection from Langerin, a substance that comes from the Langerhans cells. These were the very cells vilified without evidence by the pro-circumcision forces that have promoted circumcision before and after HIV came along and who conducted the African studies, as the evil that circumcision excises and therefore reduces rates of infection. Clearly, it is more complicated than that and the evidence is far from settled or even fully collected or analyzed.
Download Buchbinder-Lancet-Mediated-Cell-Immunity
Reference
Lancet 2008; 372: 1881–93
Published Online
November 13, 2008
DOI:10.1016/S0140-
6736(08)61591-3