Author: John Manning
Position: Professor
Institution: Department of Psychology, University of Central Lancashire, Preston PR1 2HE, UK
E-mail: jtmanning@uclan.ac.uk
Additional Authors: Peter Bundred, Department of Primary Care, University of Liverpool., UK. Peter Henzi, Department of Psychology, University of Central Lancashire, Preston, UK.
Submitted Date: October 31, 2005
Published Date: October 31, 2005
This comment was originally posted as a “Reader Response” on the publication date indicated above. All Reader Responses are now available as comments.

The demonstration by Auvert et al [1] that male circumcision (MC) has a protective effect against HIV infection is convincing evidence that HIV entry is often through the foreskin. A number of studies have reported a 2-7-fold protective effect of foreskin removal against HIV infection [2]. Auvert et al have provided conformation that the association is probably causal. We should now renew our interest in the foreskin in relation to HIV entry, and in particular to the possible protective effect of melanin [3]. MC removes the inner foreskin and frenulum and these structures are rich in Langerhans cells that have HIV receptors on their surface [4]. The foreskin contains much melanin with concentrations in black individuals averaging three times that of whites [5]. Melanin, of course, provides photo-protection, but it also has an important immune function in that it forms a mechanical barrier to penetration of microorganisms through the skin and soluble melanin can prevent HIV replication [6,7]. Thus melanin in the foreskin may reduce the incidence of HIV infection by protecting against venereally acquired sores that provide ready access for the virus. Within Sub-Saharan Africa indigenous peoples are strongly pigmented, indeed they are blacker than one would expect given the values of annual UV light [3]. However, within this area there is still considerable variation in melanization and this variation correlates with HIV rates at the level of the population. Indigenous populations with high melanin concentrations have lower rates of HIV than populations with lighter skins [3]. Further work is now necessary in order to establish whether melanin in the foreskin acts as a barrier to HIV entry. If it does, this knowledge may inform the use of MC. There can be cultural resistance to MC and there are also risks associated with performance of MC in conditions of poor hygiene. In the Sub-Saharan region indigenous males with low melanization may be particularly at risk to HIV infection. Targeting this group may make programmes of MC more effective.

Reference
1. Auvert B, Taljaard D, Lagarde E, Sobngwi-Tambekou J, Sitta R, Puren A
(2005) Randomized, controlled intervention trial of male circumcision for
reduction of HIV infection risk: The ANRS 1265 trial. PLoS Medicine 2(11).
2. Short R (2004) The HIV/AIDS pandemic: new ways of preventing infection in men. Reprod Fertil Dev 16: 555-559.
3. Manning J, Bundred P, Henzi P (2003) Melanin and HIV in sub-Saharan Africa. J Theor Biol 223: 131-133.
4. Szabo R, Short R (2000) How does male circumcision protect against HIV infection? BMJ 320: 1592-1594.
5. Iwata M, Corn T, Iwata S, Everrett M, Fuller B (1990) The relationship between tyrosinase activity and skin color in human foreskins. J Invest Dermatol 95: 9-15.
6. Mackintosh J (2001) The antimicrobial properties of melanocytes, melanosomes and melanin and the evolution of black skin. J Theor Biol 211: 101-113.
7. Montefiori D, Zhou J (1991) Selective antiviral activity of synthetic soluble L-tyrosine and L-dopa melanins against human immunodeficiency virus in vitro. Antiviral Res 15: 11-25.