A scanning electron micrograph of a budding HIV-1 virus
Image: CDC / C. Goldsmith, P. Feorino, E. L. Palmer, W. R. McManus
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The male foreskin—an unassuming flap of skin eagerly discarded in some cultures—has taken center stage in recent debates over HIV prevention. Although researchers now agree that its removal is a proved method to reduce HIV spread in heterosexual men, the picture for homosexual men remains a bit foggy.
In the late 1980s observations of heterosexual men in Africa indicated that those who had been circumcised might be at less risk of contracting HIV than men who left their foreskins intact. To definitely test the hypothesis, researchers initiated clinical trials in at-risk populations with low rates of circumcision.
Two studies focused on young urban men (ages 18 to 24) in Kenya and South Africa, whereas a third concentrated on a larger cross-section of rural men (ages 15 to 49) in Uganda. Over 11,000 men volunteered for the trials with one group receiving circumcision on enrollment and a control group delaying surgery until the end of the study.
By tracking newly acquired infections in both groups, investigators discovered that circumcision cut HIV transmission rates by 55 to 65 percent. In fact, all three trials were stopped early due to the overwhelming evidence of circumcision's protective effect.
"It was striking that the trials were in very different settings, but yielded consistent results," says Ronald Gray, study leader for the Uganda trial and epidemiologist at Johns Hopkins Bloomberg School of Public Health in Baltimore. "This was the largest protective effect ever seen next to condom use," adds Sten Vermund, director of the Institute for Global Health at Vanderbilt University School of Medicine in Nashville, Tenn. But the question remained: Why?
Microscopic examination of the foreskin yielded important clues for unraveling the benefits of circumcision. Normally, the skin provides a thick protective barrier stemming from keratin—a tough structural protein also found in hair and fingernails. But on the inner surface of the foreskin, the keratin layer is much thinner, resembling the inner lining of the mouth or eyelid more than the palm of the hand.
In uncircumcised men Langerhans cells—immune cells that are primary targets for HIV transmission—"are more richly concentrated near the surface of the foreskin," says Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases in Bethesda, Md. Without the keratin barrier, HIV can easily access these cells in the foreskin. Following infection, Langerhans cells not only serve as reservoirs for replicating virus, but also transport the virus to nearby lymph nodes where HIV spreads to other immune cells.
In fact, the foreskin's anatomical function actually amplifies the risks. In uncircumcised men the foreskin covers and protects the tip of the penis, paradoxically making the skin there more delicate and prone to microscopic abrasions. These tiny injuries promote inflammation, Fauci says, allowing the virus to come into closer contact with target immune cells. The moist environment that forms under the foreskin also enhances the growth of microbes on the penis's tip, Fauci adds, further stimulating immune responses near the skin's surface.
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38 Comments
Add CommentThe author of this article casts doubt upon her neutrality right in the first sentence when she calls the foreskin "an unassuming flap of skin ". She either has no knowledge of what the foreskin does or she is playing dumb about it. The article says that Anthony Fauci doesn't recommend routine infant circumsion in the US, but if he did, I get the impression the author of this article would be OK with that and totally ignore the human rights issues currently associated with infant circumcision. Another note: Why does uncircumcised Europe have lower HIV and STD rates than generally circumcised USA? Isn't that reason enough to prove that the real world application of mass circumcison doesn't work?
Reply | Report Abuse | Link to thisThese "studies" are so methodologically flawed, it is a crime to even cite them - different populations, different ethnicity, different customs and sexual habits, just to begin.
Reply | Report Abuse | Link to thisIt would be akin to claiming that circumcision CAUSES AIDS, because the largely circumcised US has higher infection rates than Europe.
Apart from the idiotic religious reasons for circumcision, circumcision is also the most common surgical procedure in the US - there is certainly a strong economic incentive for the industry which has sprouted around it, to ensure its continuing acceptance. Africa would not only ensure wider acceptance, but it is a whole new market.
If circumcision is so effective, then why are there six African countries where the circumcised men in those countries are more likely to be HIV+ than the intact men in those countries? Doesn't sound very effective to me.
Reply | Report Abuse | Link to thisIt's not like HIV strikes people at random. Circumcision can only possibly help men who have unsafe sex with HIV+ partners, so why this bizarre obsession with genital surgery when we know that ABC works better than circumcision ever could? (ABC=Abstinence, Being Faithful, Condoms).
It's not like we've already tried the things that do work. In Malawi for instance, only 57% know that condoms protect against HIV/AIDS, and only 68% know that limiting sexual partners protects against HIV/AIDS. There are people who haven't even heard of condoms. Btw, Malawi is one of the countries where circumcised men are more likely to be HIV+ than intact men (13.2% v 9.5%).
It just seems really misguided to be hailing genital surgery as the way forward. It would help if some of the major aid donors didn't refuse to fund condom education, or programmes that involve talking to sex workers.
Female circumcision seems to protect against HIV too btw, but we wouldn't investigate cutting off women's labia, and then start promoting that.
I see no reason to suspect the data presented here, nor that circumcision might make me less susceptible to HIV.
Reply | Report Abuse | Link to thisI expect that cutting my lips off would reduce my instance of tooth decay for similar reasons.
I regard neither as compelling reason to carry out these procedures.
And along comes the fly in the ointment . . .
Reply | Report Abuse | Link to thisIf circumcision is effective in preventing HIV, we should see an effect similar to other interventions in similar diseases. For instance, the polio vaccine is only 70% effective yet wiped out the disease in a single generation. In contrast to HIV, polio is an easily transmittable disease and is transmitted by casual contact. HIV requires intimate contact and the transfer of bodily fluids. If circumcision was even nearly as effective as claimed, the vectors of transmission would be sufficiently broken that the disease couldn't survive in The US without constant and massive re-introduction from Africa. That has simply not happened.
Indeed, the ethnic group in The US with the highest circumcision rate, African Americans, also has the highest HIV infection rate with a reported 80% of all infected females in The US being African Americans. This is simply not possible if circumcision has any prophylactic value at all.
Circumcision throughout it's history in The US has been claimed to be the preventave to the most dread disease of the day. These studies are just a continuation of the same myths. After more than 130 years of trying to find a justification for male circumcision, if none has been found yet, it is highly unlikely that one will be found now. However, they will keep trying as exhibited by these studies and others.
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And along comes the fly in the ointment . . .
Reply | Report Abuse | Link to thisIf circumcision is effective in preventing HIV, we should see an effect similar to other interventions in similar diseases. For instance, the polio vaccine is only 70% effective yet wiped out the disease in a single generation. In contrast to HIV, polio is an easily transmittable disease and is transmitted by casual contact. HIV requires intimate contact and the transfer of bodily fluids. If circumcision was even nearly as effective as claimed, the vectors of transmission would be sufficiently broken that the disease couldn't survive in The US without constant and massive re-introduction from Africa. That has simply not happened.
Indeed, the ethnic group in The US with the highest circumcision rate, African Americans, also has the highest HIV infection rate with a reported 80% of all infected females in The US being African Americans. This is simply not possible if circumcision has any prophylactic value at all.
Circumcision throughout it's history in The US has been claimed to be the preventave to the most dread disease of the day. These studies are just a continuation of the same myths. After more than 130 years of trying to find a justification for male circumcision, if none has been found yet, it is highly unlikely that one will be found now. However, they will keep trying as exhibited by these studies and others.
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And along comes the fly in the ointment . . .
Reply | Report Abuse | Link to thisIf circumcision is effective in preventing HIV, we should see an effect similar to other interventions in similar diseases. For instance, the polio vaccine is only 70% effective yet wiped out the disease in a single generation. In contrast to HIV, polio is an easily transmittable disease and is transmitted by casual contact. HIV requires intimate contact and the transfer of bodily fluids. If circumcision was even nearly as effective as claimed, the vectors of transmission would be sufficiently broken that the disease couldn't survive in The US without constant and massive re-introduction from Africa. That has simply not happened.
Indeed, the ethnic group in The US with the highest circumcision rate, African Americans, also has the highest HIV infection rate with a reported 80% of all infected females in The US being African Americans. This is simply not possible if circumcision has any prophylactic value at all.
Circumcision throughout it's history in The US has been claimed to be the preventave to the most dread disease of the day. These studies are just a continuation of the same myths. After more than 130 years of trying to find a justification for male circumcision, if none has been found yet, it is highly unlikely that one will be found now. However, they will keep trying as exhibited by these studies and others.
.
What on earth is up with all the anti-circumcision activists on here?? I didn't know there were people out there that had such a strong opinion -- it's crazy. I'm totally indifferent to the concept, and if it happens to help reduce the spread of HIV, then I'd encourage its practice assuming there aren't many disadvantages to it...
Reply | Report Abuse | Link to thisNo one suggested that circumcision was the ONLY protective method against HIV infections. If the tests were controlled for and reproducible, then it seems circumcision does help protect against HIV infection in those exposed to it. As for those claims of circumcised so-and-so country has higher HIV rates than uncircumcised so-and-so country, therefore circumcision is not protective etc., well you've got to be kidding! You can't possibly use that to prove or disprove the fact, because there are other risk factors involved, so yeah, following the Abstinence, Being Faithful, Condoms (plus not using IV drugs etc.) would probably reduce the chances of HIV exposure and thus its rates more than circumcision alone would, but circumcision would still add protection even to those who followed F and C if the test results are correct, as well as to those who don't. I don't know where all the anti-circumcision hatred's coming from, but no one's being forced to get circumcised if they don't want to.
Reply | Report Abuse | Link to thisWhile a huge number (10,900) began the trials, only 201 (64 of them circumcised) are known to have contracted HIV, while 673 (327 circumcised) dropped out, their HIV status unknown. It was deemed unethical to tell them their test results, so they were encouraged to get tested elsewhere. Learning you had HIV, after a painful operation you'd hoped would prevent it, would be a powerful inducement not to go back. So it's entirely possible that circumcision conferred no protection at all.
Reply | Report Abuse | Link to this"I'd encourage its practice assuming there aren't many disadvantages to it"
Reply | Report Abuse | Link to thisThis precise attitude is what..."is up with all the anti-circumcision activists on here"
"no one's being forced to get circumcised if they don't want to."
Reply | Report Abuse | Link to thisPlease engage your brain before writing.
It is more than a little disturbing that the people who comment seem to have analyzed more deeply than the author, or Scientific American, or for that matter, the Bill and Melinda Gates Foundation. It is interesting that the AMA have been so slow to embrace these data, having been burned by Wiswell and his studies, with data that could not be replicated elsewhere.
Reply | Report Abuse | Link to thisForeskins are not evil, nor are they vectors for disease. Circumcision does not prevent HIV, like a condom does. Circumcision in Africa is an attempt at an easy answer, which is never going to work. How does it work that circumcision prevents HIV infection in Africa, but not in the US?
How is it that Denmark and Finland have much lower rates of infection than the US, but do not circumcise, and are not big condom users, either?
Aside from the methodological pitfalls involved in using a pool of
Reply | Report Abuse | Link to thismen who desire to be circumcised (selecting for pre-existing sexual
dysfunction), what's missing from this half-truth is the question
of circumcision's impact on male->female HIV transmission. There
are numerous studies bearing on this issue, quite aside from the
obvious epidemiological comparison to be made between the USA and
Europe, which in itself raises serious doubts about circumcision's
utility in controlling HIV. One need only recognize that circumcision
increases friction during coitus due to the loss of the frictionless
sleeve of the foreskin and the drying out of residual male erotogenic
mucosal tissue. In the absence of such friction the female's intact
mucosa would be expected to provide a strong barrier to HIV receptivity
http://jvi.asm.org/cgi/content/full/74/12/5577?view=long&pmid=10823865
as borne out by empirical findings
http://www.cirp.org/library/disease/HIV/chao/
http://www.circumstitions.com/HIV.html#hetero
Furthermore, unanticipated consequences of circumcision, such as
changes in sexual practices and promiscuity of sexually amputated
men may outweigh any benefits in per-intercourse female->male HIV
transmission rates.
Finally, I note the deafening silence regarding Rebecca Stallings's
findings as reported to the Rio conference on HIV in 2005, which found
a similar prophylactic effect for FGM on female HIV receptivity.
http://www.tzonline.org/pdf/femalecircumcisionandHIVinfectionintanzania.pdf
It's tempting to speculate on the origins this unscientific propaganda
onslaught given the current medico-legal situation in the United States.
One can only hope that whatever the ultimate outcome of this debate, it
will not be used as a post-hoc justification for the wholesale atrocity
which has been committed against non-consenting American infants.
Aside from the methodological pitfalls involved in using a pool of
Reply | Report Abuse | Link to thismen who desire to be circumcised (selecting for pre-existing sexual
dysfunction), what's missing from this half-truth is the question
of circumcision's impact on male->female HIV transmission. There
are numerous studies bearing on this issue, quite aside from the
obvious epidemiological comparison to be made between the USA and
Europe, which in itself raises serious doubts about circumcision's
utility in controlling HIV. One need only recognize that circumcision
increases friction during coitus due to the loss of the frictionless
sleeve of the foreskin and the drying out of residual male erotogenic
mucosal tissue. In the absence of such friction the female's intact
mucosa would be expected to provide a strong barrier to HIV receptivity
http://jvi.asm.org/cgi/content/full/74/12/5577?view=long&pmid=10823865
as borne out by empirical findings
http://www.cirp.org/library/disease/HIV/chao/
http://www.circumstitions.com/HIV.html#hetero
Furthermore, unanticipated consequences of circumcision, such as
changes in sexual practices and promiscuity of sexually amputated
men may outweigh any benefits in per-intercourse female->male HIV
transmission rates.
Finally, I note the deafening silence regarding Rebecca Stallings's
findings as reported to the Rio conference on HIV in 2005, which found
a similar prophylactic effect for FGM on female HIV receptivity.
http://www.tzonline.org/pdf/femalecircumcisionandHIVinfectionintanzania.pdf
It's tempting to speculate on the origins this unscientific propaganda
onslaught given the current medico-legal situation in the United States.
One can only hope that whatever the ultimate outcome of this debate, it
will not be used as a post-hoc justification for the wholesale atrocity
which has been committed against non-consenting American infants.
Circumcision of the penis is 55-65% effective in preventing HIV in men? Well, complete amputation is 100% effective.
Reply | Report Abuse | Link to thiswhat sickens me as much as the thought of having my most precious parts diminished, is how half baked science is embraced with all the hysteria of a Salem witch trial. for every study which shows that circumcision reduces HIV infection in males by 60% (which is not that great a percentage for sacrificing so much sexual sensation), there is another study which shows the opposite. SciAm does a disservice to science by failing to analyze more deeply, and by promoting one set of incomplete studies while ignoring the others. When people turn to a supposedly scientific site, they want to be able to trust that it comes from hard facts and the scientific method, double blind studies, etc. This is an opinion piece masquerading as real science. Someone is getting a little lazy about doing their job, and trying to pick the low hanging fruit. The problem with this, is that real people get harmed on the other end, both with the amputation of healthy parts, risk of infection, MRSA, excessive bleeding where there are few hospitals, etc, along with a false sense of security. Let's design some fair, impartial studies and carry them out according to established scientific principles, and report them honestly. Until then, let's make condoms available, and educate.
Reply | Report Abuse | Link to thisAs one who studied advanced statistics, I have to say that the conclusions are skewed towards a hidden agenda. This is not unusual in this sort of study, but it most certainly misleading. The true conclusion is that circumcision may delay the acquisition of the HIV virus. For example, using the data: uncircumsized men may have 15 encounters before getting infected, whereas in circumsized men it may take 17 encounters to acquire the virus. The end result of publicizing this study will probably result in circumsized men taking more risks, believing that the loss of the foreskin protects them in some way, which it does not.
Reply | Report Abuse | Link to thisIn a very unrelated situation a very similar thing happened in the automotive industry in the USA. A third tail light was installed on test vehicles and the study "proved' that the accident rate went down. However when the law was changed making the tail light mandatory on new vehicles, the accident rate stayed exactly the same. Not suprising at all!
Those of us who study statistics know how numbers and conclusions can be misrepresented, as they were in the African study. I say shame on the researchers for not presenting all the possible conclusions, and shame on Scientific American for abetting the situation. This is not science. The ethics of scientific research demands that if there is a hidden agenda, it must be identified.
In this case, a true represention of the facts are that men who continually have multiple partners WILL acquire the virus, regardless of the skin condition of their penis.
It should be noted that there is a substantial death rate, more so in Africa, from circumcision. And I hardly think that an infant boy can give informed consent to circumcision. Circumcision is, after all, infant mutilation. Female circumcision is practised and condemned (by civilized nations) in many areas of the world. It never ceases to amaze me how barbaric human customs may be. it is still a religious practice to stone to death women who have been raped.
Reply | Report Abuse | Link to thisDear loosely_coupled: your name is more ironic and poignant than you know. Research this subject and you will find out why.
Reply | Report Abuse | Link to thisSomebody FORCED circumcision on me and others force it upon countless other children. Some of these African HIV articles mention talk of campaigns to circumcise children.
Reply | Report Abuse | Link to thisThere is ALWAYS a disadvantage to amputating healthy body parts.
Reply | Report Abuse | Link to thisThe bottom line is that the efficacy of amputating male body parts is dubious at best. Barbara Juncosa, the author, failed to include analyses such as these:
Reply | Report Abuse | Link to thishttp://www.futuremedicine.com/doi/full/10.2217/17469600.2.3.193
http://www.cbc.ca/news/viewpoint/vp_strauss/20051121.html
http://www.samj.org.za/index.php/samj/article/view/1811/2152
http://www.samj.org.za/index.php/samj/article/viewFile/2734/2140
There is no science without peer review.
There is no science without reproducible results.
In fact, the foreskin's anatomical structure actually DECREASES the risks:
Reply | Report Abuse | Link to thishttp://www.nature.com/nm/journal/v13/n3/abs/nm1541.html
http://www.nature.com/nm/journal/v13/n3/abs/nm0307-245.html
It is possible that Langerin, produced by the foreskin, could actually be used to develop microbicides.
Lysosyme, which is present beneath the foreskin, (also in tears and breast milk) is known to be a potent HIV killer.
Reply | Report Abuse | Link to thisThe author is clearly incorrect when he states that circumcision has been proven to reduce the spread of HIV. The claim being made is that it reduces male receptivity to HIV. The question of its impact on male to female transmission is hardly ever discussed, but increased vaginal abrasion due to circ suggests it may be counterproductive in that regard, and empirical data implies that the male->female direction more than offsets the reduction in female->male transmission.
Reply | Report Abuse | Link to thisThere are many natural ways to rid your body of HIV. In contrast with the traditional antiviral cocktails of medicine today, which cost thousands, have severe side effects, and comes with the double edged sword delema,meaning if the virus doesn’t kill you the cocktails will, this medicine is all natural.Please visit this site for the full information about this subject……http://pushgood-nomorehiv.blogspot.com/
Reply | Report Abuse | Link to thisPeople of all walks of life are not exempted of having STD infections. The surest way to keep you from any STD infection is to avoid getting involved in sexual activity with different partners. Have a regular STD Testing at Local STD Testing Centers to be sure that you are really safe.
Reply | Report Abuse | Link to thissource: http://simplestdtesting.com/resources/
The title is not congruent with the conclusion.
Reply | Report Abuse | Link to thisQuesting wrote: "I don't know where all the anti-circumcision hatred's coming from, but no one's being forced to get circumcised if they don't want to".
Reply | Report Abuse | Link to thisUm, so you think that most of the circumcised US guys actually gave CONSENT to their circumcision?! Most circumcisions are FORCED on babies or minors!
Questing wrote: "I don't know where all the anti-circumcision hatred's coming from, but no one's being forced to get circumcised if they don't want to".
Reply | Report Abuse | Link to thisUm, so you think that most of the circumcised US guys actually gave CONSENT to their circumcision?! Most circumcisions are FORCED on babies or minors!
In these "conclusions" there is no mention of hygiene during these studies. For example did the test subjects clean their genitals before and/or after intercourse? Did they bathe? How clean were their clothes? Their environment?
Reply | Report Abuse | Link to thisThe way it's written it seems like these things were not even considered. I don't think it's an accident that hygiene isn't mentioned.
J. Wilson, that is only one of the factors not controlled for. See David Gisselquist's demolition of the studies' methodological and ethical flaws here http://tinyurl.com/7deqtap and weep.
Reply | Report Abuse | Link to thisUnscientific article - scientists should focus on science, not biased views. You show your bias very quickly when you make the false claim 'Although researchers now agree that its removal is a proved method to reduce HIV spread in heterosexual men' - there are many many studies that show that is simply not true, and that those who claimed it was were biased.
Reply | Report Abuse | Link to thisWow, Questing, way to ignore the studies showing that HIV is more prevalent in the circumcised in many African countries! Just like the author of this incredibly biased article.
Reply | Report Abuse | Link to thisWhy, if circumcision is so good at preventing HIV, did researchers in other African countries not find the same thing?
Why are both the HIV and circumcision rates so incredibly high in the U.S., while in Finland, where circumcision is almost unheard of, the HIV rate is so low?
In answer to your questioning where the "circumcision hatred" is coming from, the answer relates to your comment "no one's being forced to get circumcised..."- consider infant circumcision. Are these baby boys asking to have the most sensitive part of their penis taken off?
Are they asking to be put at risk for an inordinate number of issues later in life, not to mention the many risks that are immediate (amputation, buried penis, excessive bleeding, death)?
Are they given any choice in the matter at all?
No, they are subjected to a horrifyingly painful procedure (usually with no anesthetic- the use of which has been shown to be almost completely ineffective anyway) that permanently alters what will later most likely be their favorite body part, with no thought of what their wishes may be.
If a man chooses to be circumcised- after being given REAL information, rather than biased pseudo-scientific garbage- he has every right to do so. Until that time, his penis should remain whole and uncut!
I am incredibly disappointed that S.A. chose to publish this ridiculously UN-scientifically-based article.
No one is getting forced to get circumcised?? What about the millions of infants that are forcibly circumcised every year, without anesthesia?
Reply | Report Abuse | Link to thisThe circumcised groups in the RCTs had 2 months extra HIV protection because they were not allowed to have sex while they healed from surgery. The studies did not control for this lead-time bias.
Reply | Report Abuse | Link to this"In fact, all three trials were stopped early due to the overwhelming evidence of circumcision's protective effect."
Actually, they terminated the trials early so the HIV rate among the circumcised group, which got 2 months' bonus protection, would not have a chance to catch up to the HIV rate in the control group. At this point, they also circumcised the control group so no follow-up studies could be done.
It is worth noting that these RCTs were not conducted by infectious disease experts, but by known circumcision proponents. Dr. Auvert had been a proponent of circumcision since at least 2003; Pr. Moses since at least 1994; Pr. Bailey since at least 1998.
By the WHO's own figures, only 1 out of 18 countries surveyed in Africa has a lower HIV rate among circumcised men, with the remaining 17 countries showing either a significantly higher HIV rate among circumcised men or no difference at all. A handful of African prime ministers have rejected circumcision campaigns on the basis that circumcision has greatly increased the prevalence of AIDS in their countries. Circumcision campaigns, particularly among uneducated Third World populations, mislead men and their partners to believe they do not need to implement safe sex practices because they are already protected by circumcision. Nothing could be further from the truth; in fact we are seeing HIV spread more rapidly among circumcised groups in Africa. Condoms, not circumcision, prevent the spread of HIV.
In addition to the other sexual and immunological functions of the foreskin (see http://www.norm.org/lost.html), circumcision removes the lubricating function of the foreskin, making for more friction during intercourse which can cause vaginal tears and microfissures through which HIV can enter the partner's bloodstream. It is plausible that mass male circumcision puts women at greater risk for contracting HIV, unless these women habitually use artificial lubrication with circumcised partners.
The natural sexual lubrication created by the foreskin contains the enzyme lysozyme, which is a known agent for killing HIV in vitro. Circumcision strips men of this protection.
In 2005, Stallings & Karugendo found that circumcised women in Tanzania had significantly lower HIV rates. No American would think to implement those findings and promote female circumcision; why the double-standard?
Most recent non-biased studies show that circumcised men are actually more prone to HIV and other STD infections, this correlates with the US having higher HIV infections than Europe where genital cutting of boys is rare. The old studies that claimed there is a HIV prevention were likely biased and only show that in Southern Africa where water is scarce, likely being dirty may increase risk of disease. Which is totally irrelevant to most of the world.
Reply | Report Abuse | Link to thisHaving a scientific mind means you have the ability of critical thinking, you simply should not accept a study's findings if the people involved have monetary reasons for a specific outcome, that is a conflict of interest. The people who tout these pro-circumcision studies often profit of it, there is over $1,000,000,000 that has come from the US and much of it is spent promoting circumcision in Africa... Why not promote Condoms? That is the logical, scientifically supported method to prevent HIV... not amputation of a perfectly healthy body part that likely has no if not a negative impact on the HIV epidemic.