Sabin Russell

Circumcision may cut AIDS risk

Researchers have routinely dismissed the idea that the procedure can stem the spread of HIV. That may be about to change.

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Circumcision may cut AIDS risk

Young Nelson Mandela sat in a row of 27 teenage boys, anxiously awaiting the arrival of the ingcibi, who was about to change them from boys to men. The old man soon knelt before the future president of South Africa, pulled the 16-year-old’s foreskin forward, and brought down the ceremonial blade in a single, swift motion.

“I looked down and saw a perfect cut, clean and round, like a ring,” Mandela wrote in his remarkable autobiography, “Long Walk to Freedom.” “I count my years as a man from the date of my circumcision.”

At the dawn of the 21st century, circumcision may confer more than manhood to a new generation of African boys. It could help to determine whether or not they, their future wives and girlfriends, or their children will die of AIDS.

As the latest United Nations report laid out in stark detail this week, the epidemic is now threatening an entire generation of Africans. In nations where the adult infection rate exceeds 15 percent, UNAIDS projects that one-third of today’s 15-year-olds will eventually die of AIDS. In South Africa, where HIV infection rates jumped to 20 percent from 12 percent two years ago, half the 15-year-olds are similarly doomed. And in neighboring Botswana, where 36 percent of adults are infected, only one in three 15-year-olds can expect to be spared.

For more than a decade, AIDS researchers studying the catastrophic spread of HIV throughout Africa have been amassing a body of evidence suggesting that the epidemic is not consuming populations at a uniform rate, but seems cruelly selective in the people and places it does the most harm. In 1988, American anthropologist Priscilla Reining drew up a map of the African cities enduring the highest HIV infection rates and superimposed upon it a map of those places where the predominant cultural practices were to circumcise or not to circumcise. The correlation was striking: HIV was spreading fastest in places where male circumcision was not routinely performed. Despite this, in the decade since the correlation’s discovery, the issue has been routinely ignored, ducked and dismissed.

“It’s fascinating that the one intervention that is simple, apparently effective, cheap and lifelong is the one most violently opposed by men in this field,” said Brian Williams, a South African AIDS researcher who is studying the disease in the mining communities west of Johannesburg. Even members of his own government health department do not take the issue seriously, he said. “There is a strange reluctance even to discuss it.”

There will be no way to avoid the topic, however, at the 13th International AIDS Conference to be held in South Africa next month. Armed with years of epidemiological data, researchers are determined to bring the debate out of the shadows. No one expects the developing world to embark on a sudden, mass circumcision program, but supporters are hopeful for an open and frank debate. With hope for a vaccine a distant dream and the cost of medications out of reach, circumcision could be a low-cost, one-time intervention that could slow the spread of this global plague.

“The more you look at AIDS, the more you can see that the circumcision hypothesis has a lot of explanatory power,” said Edward Green, an anthropological consultant with the U.S. Agency for International Development. “Look at Nigeria, a country with a high level of sexually transmitted disease, but a low rate of HIV [4 percent]. In Nigeria, they circumcise.”

Circumcision is the surgical removal of the prepuce, or foreskin, the highly vascularized sheath of tissue that surrounds, lubricates and protects the tender glans, or head of the penis. Ritual removal of the prepuce, like that practiced in Mandela’s Xhosa (pronounced KO-sah) tribe, is a rite of passage common in many African cultures. The presence or lack of a foreskin is sometimes linked to tribal identity, although many circumcising cultures have abandoned the painful and potentially unsanitary rituals, opting instead for a sterile procedure performed in a modern medical setting.

Infant circumcision in the United States was not widespread until the beginning of the century, when it was promoted as a medical procedure with an odd variety of purposes: to enchance cleanliness, prevent disease and discourage masturbation.

Since then, support for the medical benefits of circumcision has eroded. In 1971, the American Academy of Pediatrics declared there were “no valid medical indications” for infant circumcision, a position that has been debated and restated with various degrees of ambiguity ever since. But AIDS could change all that.

Predictably, anti-circumcision advocates are outraged by this latest push to promote the procedure in developing countries. “The foreskin is not dangerous,” insisted Marilyn Milos, a nurse and founder of NOCIRC, an organization based in San Anselmo, Calif. She said circumcision has been justified for more than a century by dubious scientific theories. “The scare tactics are always consistent with the dreaded disease of the times. There was a penile cancer scare in the ’30s; a cervical cancer scare in the ’50s; and the sexually transmitted disease scare of the ’60s.” HIV is no different, she said.

Author David Gollaher, whose medical history of circumcision dubs it “the world’s most controversial surgery,” argues that the evidence for an HIV link is not strong enough to warrant such an invasive and permanent medical fix. “This whole argument has surfaced in America, a nation with one of the highest circumcision rates, and also the highest HIV rate in the industrialized world,” he said. In Europe, he added, there is a low rate of circumcision, and a low rate of HIV.

Moreover, Gollaher believes that the symbolic significance that circumcision rituals play in various cultures make it a poor candidate for a public health measure. “Even if the link to HIV were well established, people would not accept it,” he said. “The social and cultural meanings of the surgery are vastly more important than any single scientific argument.”

Gollaher and other critics complain that pro-circumcision researchers are ignoring a range of factors among religious and ethnic groups that can muddy results, including differing sexual practices, hygienic standards, levels of sanitation, endemic diseases, economic status and consistency in condom use.

But the evidence is not limited to arcane epidemiology. There are biological reasons that suggest the foreskin is especially vulnerable to HIV. Initially, the fragility of tissue was suspected. The foreskin can tear and bleed during sex, providing a pathway for pathogens into the bloodstream. Circumcision proponents have long argued that the procedure reduces susceptibility to a variety of sexually transmitted diseases, particularly those that form soft sores, such as syphilis. There is ample evidence that men who have a history of STDs, particularly ulcerative forms, run a higher risk of HIV infection.

More recent research has determined that the prepuce is exceptionally rich in a specialized white blood cell that acts as a sentry for the human immune system. These blood cells, known as Langerhans cells, lodge in the fragile mucosal tissue of the inner lining of the foreskin, an environment similar to that found in the vagina, cervix or rectum. When Langerhans’ cells encounter invading microbes, they churn out a variety of chemical signals that, like a bugler’s call, rally the bloodstream’s various immunological warriors. But the problem is that HIV has a particular affinity for these cells. The virus can lock onto a specific receptor on their surface.

Designed to protect the tender prepuce from microbial attack, these specialized white blood cells make the foreskin the port of entry for HIV infection of males. Cultures that do not engage in the ancient practice of foreskin removal may therefore become more vulnerable, proponents say. Although the protective effect of male circumcision directly affects men, it also carries over to women, who are often infected by male partners.

While the evidence for a link between lack of circumcision and the spread of HIV in Africa is strong, researchers are also looking for other reasons to explain why some countries have high infection rates, while others are relatively spared. High on the list is a suspicion that certain strains of the virus itself may be more virulent, such as the so-called subtype C strain that is cutting a swath through South Africa. If certain strains are eventually proved to be more virulent, it won’t necessarily rule out a connection to lack of circumcision: the more virulent strains may have a greater affinity for Langerhans’ cells, and thus are more likely to infect men with foreskins, and subsequently their sexual partners.

Long after Reining put her maps together, HIV’s tendency to take hold in non-circumcising cultures seems clearer than ever. Of the 23.3 million people in sub-Saharan Africa believed by UNAIDS to be infected with HIV, the overwhelming majority live in places with low rates of male circumcision, such as Botswana, Mozambique, Uganda and Zimbabwe. The “AIDS Belt” stretches like a question mark across central and eastern Africa, down to South Africa, where the current hot spot for the epidemic is in the province of KwaZulu-Natal. That is the home of the non-circumcising Zulu tribe, where one-third of the women at pregnancy clinics test positive for the virus.

There is little evidence of such high infection rates in Western Africa, where traditions of circumcision date back thousands of years. In Asia, a similar trend is developing. Both Thailand and the Philippines are nations with a thriving commercial sex industry. Yet the HIV rate in Thailand is nearly 40 times the 0.06 percent prevalence rate in the Philippines. In the Philippines, most men are circumsized; in Thailand, they are not.

University of Illinois at Chicago anthropologist Robert Bailey estimates that lack of male circumcision may account for up to 55 percent of HIV infections in nations where fewer than one in five men are circumcised. A program to flip the percentage, raising circumcision rates to four out of five, could save millions of lives, he believes. A pilot program in Kenya is providing circumcisions for about $5.40 each. “If you can have a public health measure that reduces infection or illness by 25 percent to 30 percent, that is considered to be a very successful intervention,” Bailey said. “We’re talking about a 50 percent reduction. That is huge by public health standards. If you could reduce car fatalities by 20 percent, that’s huge. If you can reduce homicides by 20 percent, that’s worthy of headlines.”

Yet from Asia to Africa to North America, the notion that there is a link between circumcision and protection against HIV has met stubborn resistance.

At a fireside meeting with American AIDS reporters, KwaZulu Natal health minister Dr. Zweli Mkhize reflected on the prospects for circumcision in his province. “Very few individuals will do this,” he said.

It was Shaka, the legendary king of the Zulus, who decreed the tradition’s end in the 1820s. Since then, an intact foreskin has been a mark of the proud Zulu male.

“Circumcision is too human a solution,” suggested Daniel Halperin, a medical anthropologist at the University of California at San Francisco, and a leading international proponent of circumcision as a tool in the fight against AIDS. “It’s funky. It’s tribal. It’s not modern medicine. It’s not coming in with a pill,” he said.

Fueling the debate over adding circumcision to the list of HIV prevention programs is the sheer preponderance of evidence from years of research, and a stunning surprise from Uganda’s heavily studied Rakai District. Johns Hopkins University researcher Dr. Thomas Quinn tracked the health of 415 rural Ugandan couples who were sero-discordant, meaning that, at the start of the 30-month trial, one partner was HIV positive, while the other was not. The primary purpose was to prove that the higher a person’s level of virus in the bloodstream, the more likely he or she is to infect someone else. Though criticized on ethical grounds — participants were offered counseling and condoms, but were not told by researchers the serostatus of their partners — the study proved its point: Infectiousness was closely tied to the “viral load” measured in the bloodstream.

But even circumcision proponents were startled by the findings in another part of the Quinn study: Of 137 uncircumcised men with HIV-infected partners, 40 eventually became infected over a two-and-a-half-year period. Among a smaller group of 50 circumcised men with HIV-positive partners, not one contracted the virus.

Since 1988, when the first study was presented on the topic, there have been at least 45 additional studies worldwide examining a link between lack of male circumcision and HIV. The most scientifically rigorous showed that men who were not circumcised ran between 2.3 and 4.5 times the risk of contracting AIDS as men who had the procedure done.

Circumcision may have already prevented around 8 million HIV infections in 15 African and Asian countries, according to Malcolm Potts, an epidemiologist at the University of California at Berkeley’s School of Public Health.

If lack of male circumcision is a major risk factor for the spread of a heterosexual HIV epidemic in developing countries, the future is truly frightful for the heavily populated, non-circumcising cultures of India and China, where HIV is just beginning to make inroads.

But skeptics say the best way to fight the spread of HIV is through prevention education, testing and STD treatment. According to Wisconsin pediatrician Robert Van Howe, studies in Tanzania found that for about 39 cents per person, such a program could reduce HIV infections by 40 percent — the same range of protection claimed by circumcision proponents. “For circumcision to compete, it would have to be done for less than $1.52, and I don’t think you can do that, in a sterile setting, with the education that has to go along with it,” he said.

Advocates of circumcision recognize that promoting it for HIV prevention poses its own set of problems. Circumcision itself is a potentially dangerous operation, particularly if performed in the traditional manner experienced by Nelson Mandela. Each year, the African press carries stories of charlatan circumcisers who botch the operation, causing infection and even amputation for the unfortunate young victims. The use of unsanitary tools and traditional blades, called assegai, on multiple penises could spread HIV rather than stop it. Circumcision rites are also sometimes accompanied by celebratory sex parties, where the virus can be spread to multiple partners by the freshly bloodied organs.

But the biggest fear is that it will be viewed as so protective against HIV that safer sex practices will be jettisoned. Proponents stress that circumcision alone is not the answer. It does not eliminate the risk of HIV infection: It merely may reduce it. And HIV still appears at unacceptably high rates in cities where circumcision is widely practiced. Poor hygiene, lack of condom use, alcohol abuse, promiscuity, commercial sex and the use of vaginal astringents in so-called “dry sex” may all play a role in the spread of HIV. All of these conditions combined, along with the lack of male circumcision, may explain the disproportionately high levels of HIV among Africa’s non-circumcising cultures.

In the western Kenyan city of Kisumu, Population Council researcher Jane Chege has been studying the circumcision and HIV trends among a population of members of the Luo tribe. Chege’s unpublished data showed that the HIV infection rate was 26 percent among those Luo tribesmen who were not circumcised before their first sexual experience, compared to 6 percent among those who were circumcised. The results are part of a UNAIDS study that has found that HIV rates are lower among circumcised populations, even those that showed the highest rates of risky sexual behavior. The studies examined many different factors, including sexual practices, sexually transmitted disease rates and different subtypes of the virus to determine what might explain higher infection rates. The results of the study found that only two factors stood out with statistical significance: infection with a herpes virus and lack of male circumcision.

The impact of AIDS on Kisumu is devastating: Twenty-three percent of girls ages 15 to 19 are HIV positive. Chege shakes her head sadly. “These kids are going to die. But before they do, they are likely to get married, and their children are very likely to be born HIV positive.”

As a member of Kenya’s majority Kikuyu tribe, Chege said she has been accused of “tribal imperialism” for advocating circumcision among the Luo. But she said the epidemiological data are so striking that the issue needs to be addressed.

“This is a big issue. It is not something you can just ignore,” she said. “Even a 5 percent difference in HIV rates is significant, because we are talking about a killer.”

The dream and the coming disaster

AIDS threatens to ravage the hopes of South Africa's young democracy. Don't expect leaders to get excited because a few companies cut the cost of HIV drugs.

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The dream and the coming disaster

In S ward of Hlabisa Hospital, in the heart of Zulu country, women lie two and three to a bed, head to foot. In the men’s medical ward, a skeletal black man, big eyes staring vacantly, shivers in a fetal position. The hospital has 296 beds. One recent day it had 630 patients.

There are few places in South Africa where the looming AIDS catastrophe is more apparent, or more frightening, than in this hamlet built around an old Catholic medical mission. The HIV infection rate among women who come to prenatal clinics here is 30 percent. Tuberculosis is soaring — there were 2,000 cases last year — and 70 percent of TB patients are also HIV positive.

“The people in the upper echelons don’t appreciate the size of the tidal wave that is coming,” said Dr. Sean Drysdale, who recently stepped down as the hospital’s superintendent, and seems burned out by the experience. Asked what was broken that he could not afford to fix, he muttered: “Everything.”

Last week, in response to the growing AIDS crisis throughout southern Africa, five leading pharmaceutical firms offered to slash the price of HIV drugs in developing countries, in some cases by as much as 85 percent to 90 percent off U.S. prices. AIDS activists around the globe were jubilant. But in South Africa the reaction is far more complicated. The government has had a sluggish, strange and downright scary response to the AIDS disaster about to wash over the country. And that’s not likely to change because of long-overdue price concessions from the West.

Ten years ago, AIDS barely existed here. Now, more than 4 million people, roughly 10 percent of the population, are infected. Treating those people — in particular, making available the lifesaving anti-retroviral drugs that have dramatically changed AIDS care in the West — is simply not a government priority. For one, leaders will not readily accept a program that brings drugs to South Africans with AIDS, but not to those with malaria or TB or other rampant, devastating illnesses. On a deeper level, leaders fear that high-priced AIDS treatment will derail precious economic development in a country finally emerging from oppression. Faced with a choice of AIDS drugs or new water systems, AIDS drugs or housing, AIDS drugs or health clinics, schools and highways, the drugs fall short.

“People with AIDS expect you to drop everything for AIDS,” Dr. Manto Tshabalala-Msimang, South Africa’s health minister, recently told reporters. “As my daughter said to me, ‘You are the minister of health, not the minister of AIDS.”’

It is a rational, yet cold-blooded calculation. And it helps explain some of the baffling actions taken by leaders in recent months.

Just as the eyes of the world began turning to South Africa, which will host the 13th International AIDS Conference in July, President Thabo Mbeki created a spectacle of disregard for nearly two decades of science. He revived old complaints about the toxicity of the frontline anti-retrovirals, such as AZT. And he convened an international panel to air the views of dissident scientists, including Peter Duesberg of Berkeley, Calif., who cling to the discredited view that HIV is not the cause of AIDS.

Mbeki’s stance was all the more puzzling because his country had appeared to be leading the international crusade to bring down the price of AIDS drugs in the developing world. American AIDS activists, energized by the success of the anti-retroviral drug cocktails, thought they were joining that campaign. Last year, they badgered the Clinton administration into reversing a little-known policy to impose trade sanctions on any nation that sidestepped patent protections on AIDS drugs.

As it turns out, all this official questioning of basic AIDS science, and all this talk of toxic drugs, is just dissembling for domestic consumption. The real issue with anti-retroviral drugs is that leaders honestly believe South Africa can’t afford them, even at a discount. The government also doesn’t want to craft a health policy that favors some people over others, let alone a policy that allows multinational drug manufacturers to call the shots.

“The guiding principal is access to health care … Equal access to health care,” Tshabalala-Msimang said.

That attitude has angered AIDS doctors, researchers and activists who believe that millions of people in South Africa could benefit from anti-retroviral drugs. “South Africa is becoming paralyzed by the issue of equity,” said Dr. James McIntyre, director of the HIV Research Unit at Chris Hani Baragwanath Hospital, the sprawling public medical center in Soweto.

As the international furor over Mbeki’s public slap at AIDS researchers carried on this month, his ministers were slowly owning up to the real issue. Forget about the questions about the cause of AIDS, and the toxicity of AZT. Mbeki is grappling with a horrible choice: pay for the drugs or pay to bring running water to remote villages in KwaZulu-Natal. “We just can’t afford AZT,” Tshabalala-Msimang said.

The preference of the South African government, a 6-year-old democracy built from the wreckage of apartheid, is to fight AIDS with a lower-cost, lower-tech approach. Instead of anti-retrovirals for the infected, the Mbeki administration wants education-oriented AIDS prevention programs. The government is demanding deeper discounts on lower-cost antibacterial and antifungal drugs to treat the opportunistic infections that occur when — yes — HIV wears down the body’s natural defenses.

Stripped of the “HIV may not cause AIDS” arguments, the strategy makes more sense. It acknowledges that trade-offs may be necessary. The government, moreover, uses arguments against anti-retrovirals that the pharmaceutical industry itself has made. Until South Africa has the clocks, running water and refrigerators needed to maintain 24-hour combination drug therapies, the industry lobby has said, it makes little sense to sink resources into such medications.

“Drugs are not going to help because we won’t be able to use them properly,” said Sean Drysdale, the Hlabisa doctor. “While they are feeling well, we’d be asking them to take a concoction that would make them feel terrible.”

South Africa’s government was not a party to the negotiations that led to the anti-retroviral price cuts announced last week. That deal was struck among manufacturers, the World Health Organization and UNAIDS, bargaining on behalf of all Africans. The combination of drugs needed to fight the virus costs about $1,000 a month in the United States. It would cost about $150 a month in poor countries.

But it will take more than steep discounts on a few AIDS drugs to bring the Mbeki administration aboard the anti-retroviral bandwagon. Only a full regime of anti-retroviral drugs, including nucleoside analogs such as AZT and protease inhibitors such as Saquinavir, will pull off the miracle seen in gay white American men. Even with drugs at a fraction of U.S. prices, it is difficult to imagine miracles for Hlabisa.

Tshabalala-Msimang spent much of May negotiating another astonishing, if less publicized, price concession: Pfizer Inc.’s pledge to provide the antifungal drug fluconazole free to South African clinics capable of prescribing and dispensing it to patients suffering from cryptococcal meningitis, a common and devastating opportunistic infection.

It turns out that the South African government’s lengthy battle with international drugmakers over the right to make cheap knockoffs — which Americans perceived as an effort to make anti-retrovirals affordable — may be targeted at the less glamorous medications. South Africa needs these drugs to treat not only AIDS-related infections, but also malaria, tuberculosis and diarrhea, which are prevalent among the impoverished majority.

At the government sees it, to follow wealthy Western nations down the anti-retroviral path would sink South Africa in a money pit, and destroy the deferred dreams of economic development. Affluent gay men may give the epidemic its public face; AIDS is, arguably, a disease of poverty. Alleviate poverty, the reasoning goes, and AIDS will decline. Meanwhile, the overall health of the population will improve.

“We need to remind ourselves that we are within a country with one of the greatest development agendas of any country in the world,” said Malcolm Steinberg, chief executive of the consulting firm Abt Associates in South Africa.

Yet critics point out that without a dramatic push to deal with AIDS, the young nation stands at another precipice. According to a forthcoming report by the University of Pretoria, statisticians have lowered the average life expectancy in South Africa from 65.4 years to 55.7 years. In the province of KwaZulu-Natal, the HIV-positive rate for pregnant women is estimated at more than 32 percent. University of Natal demographer Karen Michels reports that “deaths now outstrip births,” and that by 2005, “only 13 percent of the population could live to celebrate their 40th birthday.”

South Africa is taking a big gamble by placing AIDS lower on its list of priorities. No doubt, money diverted from development to treat AIDS could harm efforts to stem poverty. But effective AIDS drugs have the potential to lower the cost of treating infection, and, theoretically, to make patients less infectious. Research has already shown that the drugs can reduce the transmission from mother to child at birth.

AIDS, which spared South Africa during its first decade ravaging sub-Saharan Africa, is now crashing down on this nation. If the demographers are correct, the Hope of Africa may slip into a chasm — where civil society breaks down for want of workers. Where death presides over a land of orphans. Overwhelmed by AIDS, South Africa would not be able to grow itself out of the epidemic. Economic development, and the aspirations of her people, would be just another casualty of AIDS.

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