Cut, cut, cut

A QUANTUM OF SCIENCE

Are HIV rates in the US substantial enough to merit a policy of circumcision?

Following evidence of the protective effect against HIV infection, recent news articles report that the CDC is mulling the idea of endorsing circumcision for all male infants born in the United States. But will it have that much impact?

First, the science: how does circumcision prevent HIV infection? HIV infections occur when the virus gains entry to cells by binding to a protein called CD4, found on the surface of cells. Cell types rich in CD4 are thus easier targets for a successful HIV infection. One such cell type is the Langerhans cell, a part of the primate epidermal tissue related to defending the body against invading microbes. As it happens, primate foreskin is rich in Langerhans cells, meaning plenty of CD4 protein for the AIDS virus to bind to and invade the body. By removing the foreskin through circumcision, an easy point of entry for the virus is blocked.

(Interestingly, CD4-rich Langerhans cells are found in human foreskin and vaginal tissues, but not in oral or rectal tissues. This suggests that HIV infections use a different biochemical route when introduced into the body through those tissues.)

The idea of reducing the risk of contracting HIV through circumcision is far from new. In 1987 a letter was published in the New England Journal of Medicine suggesting exactly that, and studies done in the last fifteen years bear out that theory. While the methods used and areas studied (largely in Africa) varied, the conclusions were so striking that in at least one case a circumcision/HIV infection study was halted years early so the findings could be considered for public policy discussions. Depending on the area studied and the risk factors of those involved in the study, HIV infection rates were found to be as much as 50% lower among circumcised African men than their intact counterparts. Various attempts have been made to expand the conclusions of individual studies through meta-analysis papers and their conclusions found an even greater protective effect of circumcision when those studied were from high-risk populations.

So why not support a policy of encouraging circumcision in the United States? The same studies being reviewed by the CDC have some counterindications that are well worth considering in any kind of policy discussion.

First, the benefits of circumcision are greatly enhanced among high-risk populations. This means that for the average American man (whose risk is far, far lower than the average African man) the benefits are considerably lessened. This could well have something to do with the fact that an estimated 79% of American men are already circumcised – though as rates of circumcision have fallen to around 65% in the most recent surveys, that number is now trending downward. Secondly, use of barrier protection is far more prevalent in America among all demographics, another factor that reduces the positive impact of circumcision protection. Another risk factor related to the need for additional preventative measures against HIV infection – the rate of STDs causing lesions or ulcers, such as herpes or syphilis, which help HIV enter the body during sexual contact – is lower in America than in most African nations, and treatment for those afflictions is considerably more available. Finally, almost all the research done in this area has been performed in Africa. This means there is a possibility that things could be different among Caucasian populations, simply because they are biochemically distinct from non-Caucasians.

The need for additional research is clear. Until scientists can repeat the highly successful African studies in America, Europe, or ideally both – since circumcision is much less common in European nations than in America – the benefits of circumcision for Western populations will remain a question too open for a substantive policy debate to take place.


For more information:

CDC mulls routine circumcision of infants to reduce spread of HIV (NY Daily News, 25-Aug-09)

Circumcision and heterosexual transmission of HIV infection to men. (Fink, 1987)

Comparative investigation of Langerhans' cells and potential receptors for HIV in oral, genitourinary and rectal epithelia. (Hussain, 1995)

Male circumcision and risk of HIV infection in sub-Saharan Africa: a systematic review and meta-analysis. (Weiss, 2000)

Male circumcision for HIV prevention in young men in Kisumu, Kenya. (Bailey, 2007)

Langerhans cells.


© AQOS / P. Smalley (2009)
Reproduction with attribution is appreciation

Newest AIDS drug: Sugar?

A QUANTUM OF SCIENCE
Common polysaccharide prevents HIV infection in mice

Researchers at Meharry Medical College School of Medicine in Nashville recently reported that HIV-1 infections were blocked in mice by a surprising compound: cyclodextrin, a common cyclic sugar used extensively in food, pharmaceuticals and commercial products such as dryer sheets and Febreze.

The structure of cyclodextrin is a hollow ring, perfect for complexing hydrophobic molecules (such as fragrances, in the case of Febreze) and binding them tightly. This also makes cyclodextrin a good carrier molecule for pharmaceuticals, encapsulating drugs and aiding their delivery to different parts of the body. Surprisingly, the use of cyclodextrin in the food industry held the key to its role in preventing HIV infection. In the food industry cyclodextrins are employed for the preparation of cholesterol free products, allowing cholesterol to be sequestered inside the hollow ring of cyclodextrin and more easily removed from the food matrix.

Researchers have known for some time that there was a link between cholesterol and HIV infection. Cholesterol is an essential part of cell membranes, helping them stay fluid and permeable for normal trans-membrane traffic. Lipid rafts, a specialized structure rich in cholesterol, is required for HIV-1 to infect new cells. Though the research is still preliminary, cyclodextrin’s ability to bind and sequester cholesterol appears to play a role in preventing successful HIV infections. Trials in mice demonstrated a transient, reversible protective effect when female mice were challenged with HIV-laden semen. Similar experiments in primates have not fared as well, but issues with those studies have sparked several more extensive trials and the scientific community is abuzz with the possibilities.

Among the most exciting properties of cyclodextrin from a pharmaceutical standpoint is its safety. Discovered in 1891, cyclodextrins have been used for decades in foods and medicines. Its toxicity is extremely low, even when used in high dosages, and since it is composed entirely of sugar molecules there is little chance of complications or immune reactions. Only time will tell whether this humble molecule will find a new role in the prevention of HIV infections, but pharmaceutical giant Johnson & Johnson is already pursuing it as a therapeutic and prophylactic.

For more information:

http://www.the-scientist.com/templates/trackable/display/blog.jsp?type=blog&o_url=blog/display/55807&id=55807

© A Quantum of Science / P. Smalley (2009)
Reproduction with attribution is appreciation!

Smoking AIDS

A QUANTUM OF SCIENCE

Anti-retrovirals are now drugs of abuse in South Africa; will this lead to resistant HIV?

The newest chapter in the AIDS saga in Africa is unfolding in the townships of South Africa, where the demographic of 15-21 year olds are engaging in a new practice: grinding up anti-retroviral drugs designed to suppress HIV and prevent it from becoming AIDS, mixing the powder with tobacco or marijuana, and smoking it to achieve hallucinogenic and anxiolytic effects.

A recent BBC article goes into further detail, but mainly focuses on the social aspect of the new form of drug abuse. Doctors and health care policy activists in South Africa are gravely concerned about not only the interruption of the intended use of the drugs - which has led to shortages and long lines in many areas - but also the possibility that this abuse of the drugs will cause resistant strains of HIV to arise.

This seems unlikely for several reasons. First, smoking a pharmaceutical innately changes the molecular structure of the drug. The heat involved might well be expected to break down the structure into inactive forms, or combine key parts of the molecule with oxygen and likewise eliminate its antiviral activity. Without activity, the drug cannot cause resistance to arise. The second reason this fear is ungrounded is that in order to cause resistance, those abusing this drug must also be HIV-positive. While there is likely to be some overlap in a country whose HIV-positive population is 3.2% among that age/sex demographic [LINK], it is unlikely to be enough to cause undue concern from a health policy standpoint.

Clearly there is a health policy crisis in South Africa regarding the proper administration of anti-retroviral drugs. Concerns about drug abuse aside, the phenomenon is preventing those who really need such drugs from obtaining them, and this alone is sufficient reason to take action. But fears of a super-HIV, resistant to the anti-retroviral cocktails of drugs currently capable of controlling (though not eradicating) HIV, are overblown in this case.

© AQOS / Peter Smalley (2009)
Reproduction with attribution is appreciation