of the human immune system) under the foreskin may be a source of entry for the HIV virus. Excising the foreskin removes what is thought to be a main entry point for the HIV virus. History Valiere Alcena, in a 1986 letter to the New York State Journal of Medicine, noted that low rates of circumcision in parts of Africa had been linked to the high rate of HIV infection. Aaron J. Fink several months later also proposed that circumcision could have a preventive role when the New England Journal of Medicine published his letter, "A possible explanation for heterosexual male infection with AIDS," in October, 1986. By 2000, over 40 epidemiological studies had been conducted to investigate the relationship between circumcision and HIV infection. A meta-analysis conducted by researchers at the London School of Hygiene & Tropical Medicine examined 27 studies of circumcision and HIV in sub-Saharan Africa and concluded that these showed circumcision to be "associated with a significantly reduced risk of HIV infection" that could form part of a useful public health strategy. A 2005 review of 37 observational studies expressed reservations about the conclusion because of possible confounding factors, since all studies to date had been observational as opposed to randomized controlled trials. The authors stated that three randomized controlled trials then underway in Africa would provide "essential evidence" about the effects of circumcision on preventing HIV. Experimental evidence was needed to establish a causal relationship, so three randomized controlled trials (RCT) were commissioned as a means to reduce the effect of any confounding factors. Trials took place in South Africa, Kenya and Uganda. All three trials were stopped early by their monitoring boards because those in the circumcised group had a substantially lower rate of HIV incidence than the control group, and hence it was seen as unethical to withhold the procedure, in light of strong evidence of efficacy. In 2009, a Cochrane review which included the results of the three randomized controlled trials found "strong" evidence that the acquisition of HIV by a man during sex with a woman was decreased by 54% (95% confidence interval, 38% to 66%) over 24 months if the man was circumcised. The review also found a low incidence of adverse effects from circumcision in the trials reviewed. WHO assessed the trials as "gold standard" studies and found "strong and consistent" evidence from later studies that confirmed the results.