Important note: Information in this article was accurate in September 2001. The state of the art may have changed since the publication date.
American Foundation for AIDS Research, September 2001
Dave Gilden
Last July a National Institute of Allergy and Infectious Diseases committee issued a report reviewing what is known about condom efficacy in blocking disease transmission. Entitled "Scientific Evidence on Condom Effectiveness for Sexually Transmitted Disease (STD) Prevention," the report summarized the results of a workshop held in July, 2000 at the request of then-Representative Tom Coburn and several other conservative representatives. Except for HIV and the transmission of gonorrhea to men, the report held that there was no definitive evidence that condoms protect one from STDs. The result was cries from the right denouncing the "safe-sex myth," as Tom Coburn put it.
The NIAID report held condoms to too high a standard of proof, a standard that is unachievable in the types of studies feasible in real life. From the report itself, it seemed clear that condoms also have a protective role at least in chlamydia and in protecting women from cervical dysplasia, if not HPV infection itself. (That is possibly because condoms guard the cervix, but not the entire genital region.) As for herpes, a report last spring was arguably conclusive in finding that condoms reduce male-to-female herpes transmission (A Wald et al., JAMA 2001 Jun 27;285(24):3100-6. (Herpes transmission to the men in this study was too low to draw a conclusion on condoms.) HPV and herpes are the two STD microbes transmissible by skin-to-skin contact. They are the kind that condoms are least likely to prevent.
In its overall tone, the NIAID report was not really hostile to condoms. In its second paragraph, the 49-page document states, "Primary prevention of STD infection is an important health priority. Unfortunately there are no STD vaccines, except for hepatitis B vaccine, and topical microbicides to prevent STDs are not available. Beyond mutual lifelong monogamy among uninfected couples, condom-use is the only method for reducing the risk of HIV infection and STDs available to sexually active individuals."
It is striking that both the NIAID committee and the Surgeon General’s "Call to Action to Promote Sexual Health and Responsible Sexual Behavior," released just three weeks earlier, came to the same general conclusion about safe sex’s effectiveness. They both held that condoms are protective for certain diseases (HIV at the very least) and that some evidence indicates that they are protective for many others. Both thought that condoms are important and that more research is necessary. But the Surgeon General strongly advocated safer sex education in the schools. The NIAID report in its conclusions had little to say about sex education. Yet, the NIAID document became an instrument for countering the Surgeon General and advocating abstinence outside of marriage.
Advocating abstinence over safe sex has extremely pernicious implications. This sexually repressive message implies that most people contract HIV through their own misdeeds. In particular, if there is no permissible sex outside of marriage, and gay people can’t marry, then gay sex is always wrong. Not only is there no need to tell the uninfected sinners about condoms, but society need not make heroic efforts to support the people who are infected.
Everybody ignores the near absence of sexually transmitted HIV among gay men exclusively practicing oral sex or among lesbians. That observation is not convenient for fundamentalists’ morality. But then, of the eight STDs examined by the NIAID panel, five are easily detectable and curable (chancroid, syphilis, gonorrhea, trichomoniasis, chlamydia) and two are largely manageable, either medically or by the immune system (genital herpes and human papilloma virus). Vaccines for herpes and HPV are now in advanced testing. Except for HIV, then, these other diseases could be controlled and eliminated – or soon could be – by standard medical practice. Syphilis and chancroid already are rather rare in industrialized countries. Whether condoms protect against these diseases is not that important.
The eighth disease that the NIAID panel considered was HIV, which is, of course, usually fatal after a long asymptomatic phase. Treatment is lifelong and highly toxic. Its ultimate ability to stave off AIDS has yet to be demonstrated. An effective vaccine is still far off. HIV is the only microbe for which condoms are a critical part of current prevention efforts. And the NIAID panel did concede condoms’ demonstrated protective effect for this virus.
While the official government agencies remained silent about the uses to which the condom report was put, the Centers for Disease Control and Prevention (CDC) held its second National HIV Prevention Conference this August. There, amid all the talk of social marketing, community education and individual counseling schemes, condoms’ worth in preventing HIV was assumed. Meanwhile, condoms were not the only answer: Alternatives and supplements to condoms appeared whenever the implications of medical science were explored. Preventing HIV goes beyond the simple ABCs – abstinence, betrothal and condoms – to veritable alphabet soup.
One recurrent controversy that is now a step closer to settlement is the safety of oral sex. It has long been observed that HIV is infrequently transmitted through oral sex. There have been occasional reports of individuals who have contracted HIV in this way, but the significance of such reports is debatable. For one thing, people will omit mention of acts they may feel guilty about, such as unprotected anal sex. For another, various conditions such as receiving seminal fluid in the mouth and oral lesions (including those from dental flossing!) may increase the risk.
At the CDC conference, Kimberly Page Shafer of the University of California San Francisco (UCSF) Center for AIDS Prevention Studies described her innovative study that was able to account for these objections (abstract 975). Page Shafer’s study took advantage of a new type of HIV test, the "detuned" ELISA, which is able to distinguish old HIV infections from ones contracted in the past six months.
Investigators tested 194 gay men of unknown HIV status who claimed that they had had no anal or vaginal sex and no injection drug use in the previous six months. Nearly all said that they had practiced unprotected receptive oral intercourse. The participants acknowledged a median of two receptive oral intercourse (ROI) partners during this period. A fifth had partners known to have HIV. Of that group, 89% did not use a condom, and 40% swallowed ejaculate. No new HIV infections were found in the entire 194-man cohort. (One person with an older infection was detected.)
Nobody is arguing that HIV is never transmitted through oral sex, only that it is very rare. Given that condoms sometimes break and, more often, are forgotten, unprotected oral sex may well be safer than anal sex with condoms. (The NIAID report granted that condoms reduced HIV transmission by 85%.)
There is no reason to be fatalistic when the condom does break or is missing altogether. Persons do have a second chance to prevent HIV. It is called PEP, or postexposure prophylaxis, and interest in it is growing. PEP consists of HIV drugs, usually two nucleoside analogs like AZT and 3TC, administered for four weeks after exposure to HIV. Studies in monkeys indicate that this regimen should start within three days of exposure – and preferably within 24 hours – for there to be hope of blocking HIV.
The CDC does not recommend PEP except in healthcare workers exposed to HIV through on-the-job accidents. Nonetheless, there were three PEP presentations at the CDC prevention conference, covering programs in Massachusetts and Australia (abstracts 265, 429 and 441). Official PEP programs now exist in US hospitals located in Atlanta, Chicago, Los Angeles, New York City, San Francisco and throughout Massachusetts.
Of the approximately 400 PEP patients described in the conference presentations, none became infected. The same was true in the 375 San Francisco patients in another recent study (JO Kahn et al., Journal of Infectious Diseases, March 1 2001; 183(3)707-14).
Michelle Roland, a lead investigator in the San Francisco study, pointed out that her study (and the others, as well) are not designed to prove the efficacy of nonoccupational PEP. "It is virtually impossible to do efficacy studies because the transmission rate is so low," she said. The rate of transmission from even the highest-risk unprotected sex (acting as the receptive partner in anal intercourse with a known HIV-positive person) is only one to five in a thousand. Most of the PEP patients in these studies did not know their partner’s HIV status. It is likely that many of these partners did not have HIV at all.
Beyond these studies, which can be classified as suggestive, the one fairly solid bit of data on PEP comes from a retrospective CDC study of healthcare workers exposed to HIV through such occupational accidents as being stuck with contaminated syringes. In an examination of such incidents occurring before 1994, CDC investigators inferred that PEP with AZT alone reduced HIV transmission by 81% (DM Cardo et al., N Engl J Med 1997 Nov 20;337(21):1485-90.
Taking medical prevention one step farther leads one back to the source of the virus, to the sex partner with HIV. There are increasing signs that reducing viral load through treatment reduces the risk of HIV transmission during sex. At the CDC conference (abstract 1024), Thomas Quinn of Johns Hopkins University presented a model for predicting the relationship between viral load and HIV transmission during penile-vaginal intercourse. The model was based on his team’s findings during a study of 174 self-described monogamous, HIV-discordant couples (RH Gray et al., Lancet 2001 Apr 14;357(9263):1149-53. It took place in the Rakai region of Uganda, where investigators followed these couples for 30 months. The researchers calculated an overall HIV transmission rate of 1.1 per thousand coital acts. When the source partner had a viral load (HIV RNA level in blood plasma) below 1,500 copies/mL, there was no transmission. Above that figure, HIV transmission increased 2.5 fold for every one log (tenfold) increase in HIV viral load.
This population did not have access to anti-HIV medication. For Quinn’s conference presentation, the researchers calculated that to have a major impact, such therapy would have to be provided to everyone with viral loads over 10,000.
A major stumbling block is the uncertain success of current anti-HIV drugs due to HIV’s propensity to develop resistance to those drugs. Fear of increasing the amount of drug-resistant HIV was one consideration that led HIV specialist Kenneth Mayer of Brown University to oppose the use of treatment as a public health anti-transmission measure. Mayer gave a major plenary address on the topic.
As things now stand, Sally Blower of the UCLA estimated that over 40% of the HIV in San Francisco could be drug-resistant by 2004 (abstract 1025 and S Blower, Nat Med 2001 Sep;7(9):1016-20. Comparatively little drug-resistant HIV would be transmitted, according to Blower’s estimates. But the limited transmissibility of drug-resistant HIV partially depends on the amount of sexual risk-taking that the community indulges in.
The high-treatment rates in San Francisco and elsewhere so far have not reduced the rate of new HIV infections – quite the opposite since unprotected sex has increased with the availability of the new highly active antiretroviral therapies. In a 1998 to 1999 survey of 13,000 Seattle men, 51% admitted to unprotected anal sex in the previous six months (abstract 828). This figure is up from 43% four years earlier. It remains to be seen whether increasing the availability of PEP will prove counterproductive because it encourages still further risk-taking.
Another issue is that viral load in the blood, the usual lab indicator, does not always agree with viral load in genital secretions. Susan Fiscus of the University of North Carolina reported that one reason for this is genital infections (abstract 1026). In her study, urethritis raised genital viral loads eightfold. Gonorrhea increased them 11 times. Curing these diseases brought HIV back to the levels observed in the HIV-positive controls.
In his talk, Thomas Quinn estimated that in persons with plasma viral loads greater than 12,000 and genital ulcers, the risk of heterosexual HIV transmission becomes an astounding one in 100 coital acts. The problem here goes beyond the HIV in genital secretions: Over half the genital ulcer disease seen in the Rakai study was herpes. Other researchers have found that HIV is frequently shed from genital herpes sores. Two newly published epidemiological studies have related the extremely high HIV incidence found in particular African communities to the high frequency of genital herpes in those same areas (A Lagarde et al., AIDS 2001 May 4;15(7):877-84 and B Auvert et al., AIDS 2001 May 4;15(7):885-98.
The importance of genital health in reducing HIV transmission extends to both HIV-positive and HIV-negative individuals. In persons with HIV, the inflammation increases the concentration and shedding of HIV. For the HIV negative, inflamed sores make them more vulnerable to contracting the virus. Condoms help protect against sexually transmitted diseases, but they are under the control of the insertive sexual partner and are widely considered cumbersome and disruptive of the sexual experience. This is why less intrusive microbicidal substances, which could be used by women and male receptive partners, would be highly desirable.
The CDC conference held two sessions on such microbicides, including one dealing with their application to anal sex. In response to a NIAID workshop on anal microbicides this spring, the CDC described an action plan for further researching the subject. Traditionally, though, microbicide research has focused on vaginal use. The first phase II trial of Carraguard (carrageenan), a seaweed derivative with broad-spectrum antiviral activity, will end this fall. According to Polly Harrison of the Alliance for Microbicide Development, Carraguard "may be the first one out of the box. We’re all hoping to see some efficacy."
The Alliance estimates that US government research on microbicides will amount to $49 million in the coming fiscal year. That is more than twice the amount spent in the 1997 fiscal year. Still, it is only about a tenth of what the government spends on vaccine research for HIV alone.
While waiting for a feasible microbicide, Nancy Padian of UCSF points out in the September 7, 2001 edition of the journal AIDS that the relatively fragile lining in the cervical canal – and the aspiration of fluids through that canal into the uterus – are what make women more vulnerable to STDs than men. A diaphragm coated on both sides with microbicide would provide a large measure of cervical and upper genital tract protection even in the absence of condoms.
"The diaphragm is prototype for other products that might be massively distributed," Padian commented. What would a mass-produced, presumably disposable, device look like? How much extra protection would it provide? Research and development are only beginning in this area.
Thomas Quinn pointed out at the CDC conference that a similar vulnerable area exists under men’s penile foreskins. Circumcision eliminates the sensitive tissue. In Quinn’s study, none of the circumcised HIV-negative men acquired the virus from their spouses. In contrast to the research on women’s cervixes, a number of studies have been done on the protective effect of circumcision on African men. Male circumcision was a widely practiced coming-of-age ceremony in Africa before Christian missionaries made their influence felt. A recent op-ed column in the Washington Post noted that 35 African studies have been conducted on the protective effect of circumcision. It appears to reduce HIV transmission by more than half (Daniel Halperin and Brian Williams, Washington Post, Sunday, August 26 2001; B01).
None of these measures – including use of condoms – will prove perfect in the real world. Together, though, they provide a range of options that allow individuals to build a personal prevention program. In one conference presentation, Richard Wolitsky of the CDC described the use of relative-risk models to fit personal strategies with one’s acceptable level of risk (abstract 1044). These calculations are not obvious: Protective methods that seem less efficacious may turn out to be more so because they are easier to apply consistently than condoms or abstinence might be.
By Wolitsky’s calculations, use of a condom, assurance that a partner has tested HIV-negative, or receptive oral intercourse each bring down the risk of acquiring HIV to almost one in 100,000 for gay men. Combining all three brings the risk of HIV down to one in 100 million.
Personal risk-reduction strategizing is about to become much more straightforward. A variety of rapid HIV tests (RTs) are coming on the market that have accuracy comparable to standard tests (abstracts 166, 802 and 1009). "Voluntary testing and counseling" (VTC) centers could then combine testing and risk-reduction planning in a single session. This would greatly enhance their ability to identify and work intensively with those who are HIV-positive and those most likely to become so. At present, testing and final counseling are separated by the week or two needed to receive the test results. Many people are lost when they fail to return for their test results.
000910
AM010901
Copyright © 2001 by the American Foundation for AIDS Research (amfAR) and first displayed on amfAR's Treatment Directory web site (http://www.amfar.org/gl). They appear on AEGIS with amfAR's permission. Organizations wishing to reprint or redistribute these materials should request authorization from amfAR's Department of Treatment Information Services (212/806-1600).
AEGiS is made possible through unrestricted grants from Boehringer Ingelheim, iMetrikus, Inc., the National Library of Medicine, and donations from users like you. Always watch for outdated information. This article first appeared in 2001. This material is designed to support, not replace, the relationship that exists between you and your doctor.
AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.
Copyright ©1990, 2001. AEGiS & the Sisters of Saint Elizabeth of Hungary. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS and the Sisters of Saint. Elizabeth of Hungary, or the party credited as the provider of the content.
