Chapter 5
The Future of STDs

Starting with the discovery of antibiotics by Alexander Fleming in 1929, the last century has uncovered an unprecedented number of cures for human diseases, including STDs. As a result, the fatality rates for STDs such as syphilis and gonorrhea have plummeted. Significant advances have also been made in the diagnosis and treatment of many STDs. Yet, in spite these successes, the number of people infected with STDs has never been higher, and the emergence of AIDS has made STDs one of the fastest-growing and most well-funded focuses of medical research.

There are good reasons for seeking new and more effective treatments for STDs. One is the appearance of new strains of drug-resistant organisms against which previously successful treatments have less and less effect. Because bacteria are extremely adept at transferring their drug-resistant abilities to their drug-sensitive neighbors, antibiotic resistance is occurring more and more frequently among the bacteria that cause gonorrhea, syphilis, chlamydia, and chancroid. Overuse of these drugs has contributed to this problem. For example, penicillin used to be commonly taken by prostitutes to ward off possible infection by gonorrhea. Taking this antibiotic as a precaution, rather than a cure, encouraged the growth of drug resistant organisms. As a result, most strains of gonorrhea are now resistant to penicillin, and it is not uncommon to find strains with resistance to two or three antibiotics.

Although there are still a number of antibiotics that can be effectively used against gonorrhea and other bacterial STDs, over the last decade bacteria that are resistant to every known antibiotic have been isolated from sick patients. Infections of this type are difficult to treat and often impossible to cure and are on the rise. According to Hazel Mitchell, an expert in the epidemiology of human disease at the University of New South Wales in Sydney, Australia, "There is a great need for new antibiotics which act in a novel manner. If new treatments are not found soon, we may see a regression back to the days where a cut on a finger could result in a fatal infection."⁴⁰

New Drugs Are Rare

Finding new drugs to use against STDs is difficult, sometimes extraordinarily so. For every one that works, tens of thousands of synthetic and naturally occurring chemical compounds may have been considered. Clement Stone, a former senior vice president of research for Merck, a pharmaceuticals giant, says, "Each drug has its own way of being born. Often we consciously search for a drug for a specific use, but more often it is serendipity."⁴¹ The use of AZT, the first antiviral drug to have a substantial effect on HIV, is a case in point. This drug was originally examined as a treatment for cancer in 1964 but did not turn out to be useful. It was not until the 1980s, some twenty years later, that AZT was found to slow the progression of HIV infection to AIDS.

Even after a drug is found to be effective in the laboratory, it must go through a rigorous and lengthy testing process to prove that it is safe in humans. According to the Pharmaceutical Research and Manufacturers of America organization, out of five thousand compounds that enter preclinical testing, only five will make it to human trials and approximately one out of those five will be found to be effective and safe enough to be approved for public use. On average, it takes 8.5 years of testing to get a drug to market. This is a very long time when compared to the rate at which germs are becoming drug resistant.

Relatively accelerated approval of AIDS drugs is the one exception to the lengthy process of drug approval. Realizing that many people facing a certain death are willing to gamble on the success of an unproven and possibly dangerous treatment, the Food and Drug Administration issued new guidelines that loosen the strict controls on safety in humans that are part of the drug-testing process. Fully informed of possible health risks, HIV-positive individuals can participate in clinical trials of experimental drugs that otherwise might not have reached the human trial stage for years. The benefits are two-fold; people with HIV gain early access to the latest treatments, while the assessment of new drugs is accelerated by a large supply of volunteers.

Immunotherapy: An Untapped Resource

Not all of the new treatments rely on the discovery of conventional drugs. Some of the most exciting new prospects for treating STDs are based on the knowledge of ways that the body itself can be prompted to fight an existing infection. A new line of treatment, called immunotherapy or therapeutic vaccination, is being devised to make use of this untapped resource. It works by the topical application or injection of substances that trigger a change in the immune system, causing it to eliminate the infection from the body or render the germs inactive.

While immunotherapy commonly makes use of drugs, it differs from conventional treatments because the body does most of the work and the drugs only need to be administered once or infrequently. This makes it ideal for improving the treatment of STDs that currently require long-term, daily doses of medication. According to a senior scientist in charge of therapeutic vaccine development for a large pharmaceutical company:

Market research shows that many people with STDs do not like to take pills to control their condition. It reminds them day in and day out that they are infected with an STD. There is also the worry that their pills will be discovered by other people. Cutting down on the demands of a treatment by swapping a daily dose of pills for infrequent injections or a cream that is rubbed into the skin makes it more appealing and solves the problem of people forgetting to take their medicine or taking the wrong amount.⁴²

This change in how some STD drugs are administered could have a major impact on the current epidemic by increasing compliance as well as relieving infected people of their symptoms and making them less contagious to others.

Immunotherapy research for several STDs is well under way. Two such treatments for genital herpes are in the later stages of development and are showing great promise. In recent clinical trials, both treatments, one that is given by injection and the other that works as a topical gel, were found to stop or reduce the frequency of recurrent herpes outbreaks for up to six months following treatment. This is a substantial advance over the daily oral doses of antiviral drugs taken by many people to keep their symptoms under control. Positive data has also been reported for an immunotherapy agent for genital warts in males, clearing warts and reducing the chances of relapse in a high percentage of men who participated in a trial.

Hope that a therapeutic vaccine is possible for HIV stems from the fact that a small percentage of people infected with HIV are so-called long-term nonprogressors, meaning that they have lived with the infection for two decades or more without getting sick and without treatment. Some especially powerful immune response in these people is preventing the virus from causing harm, and researchers are trying to identify the chemical or genetic factors that contribute to that response in hopes of duplicating it in the laboratory.

Several therapeutic vaccines for HIV are being tested in clinical trials with human subjects. The most promising results have come in subjects whose viral loads have already been reduced with antiviral drugs, but a therapeutic vaccine has already been shown to benefit monkeys infected with SIV, a virus that is closely related to HIV, and results from ongoing trials in humans are expected in 2003. Another therapeutic vaccine developed against chlamydia has not yet been tested in humans, but it has been found to work in mice, and researchers are hopeful that it will also work in primates.

An Ounce of Prevention Is Worth a Pound of Cure

New treatments for STDs may be on the way, but past experience shows that they may not be sufficient to halt the current epidemic. The problem is that STDs spread from person to person so rapidly that even when a cure exists, it cannot be administered quickly enough to counteract the number of new infections.

Relying on cures alone is problematic from an economic stand-point as well. The development and licensing of new drugs is so costly that few new drugs can be priced affordably in the poor countries of the developing world, where the incidence of STDs is highest and the treatments are most sorely needed. Aside from the moral issues that this raises, cures that are only available to a fortunate few will not be of great benefit in reducing the incidence of STDs because they do little to stop the diseases from circulating throughout the population. A separate economic issue is the vast amount of money that could be saved on health care if STDs were avoided in the first place. For all these reasons, finding new ways to prevent STDs is every bit as important as finding cures.

On the forefront of STD prevention is the move to produce topical creams or gels that can kill the germs that cause STDs. Over sixty of these products, also called microbicides, are currently under development. Most of these are being designed to work by the preintercourse application of the product within the vagina, preventing the transmission of STDs. The fact that these microbicides can be used without the knowledge or consent of a male partner is seen as a bonus since females in many cultures are prevented from using protective devices, such as condoms, by their male partners. Yet in some ways, microbicides are not a great improvement over existing forms of prevention. Like condoms, they can only be effective if they are used for every act of intercourse. Forgetting to use them or using them incorrectly even once is enough to contract an STD.

Vaccines to Protect Against STDs

Vaccines are some of the best forms of disease prevention because they deliver effective, long-lasting protection with only one or a limited series of injections and can be administered to healthy populations before any infection occurs. Most of the major health organizations see the development of vaccines as essential for bringing the STD epidemic and other diseases under control. According to Anthony S. Fauci, the director of the National Institute of Allergy and Infectious Diseases, "Our commitment to developing new and better vaccines to prevent the world's most serious infectious diseases has never been stronger."⁴³

Although the concept for vaccines is not new, hepatitis B is the only STD for which a vaccine is currently available. While it would be ideal to develop a vaccine for every STD, limited resources mean that priority is given to the STDs that pose the greatest threat. Vaccines to protect against cervical cancer, genital warts, genital herpes, and HIV have received the most attention since there are no cures for these diseases. A vaccine for genital herpes is within reach, with the final stage of clinical trials under way in the United States. One study shows that the vaccine gives good protection, preventing genital herpes infection in 73 percent of uninfected women over the nineteen-month duration of the study. However, the vaccine has several limitations. One is that the vaccine does not work well in women who are already infected with a related strain of herpes that causes cold sores. Another is that, for reasons researchers do not understand, it also does not work in men. Despite these shortcomings, researchers feel that use of this vaccine will provide powerful ammunition against the herpes epidemic. Lawrence R. Stanberry, one of the developers of the vaccine, says, "If you did universal vaccination of 11- and 12-year-old women you would eventually see an impact on the spread of herpes in both men and women."⁴⁴ According to Stanberry, the vaccine will also be beneficial for decreasing the number of babies infected by the genital herpes virus at birth.

A significant breakthrough is being hailed in the development of vaccines against HPV, the virus responsible for cervical cancer and genital warts. In recent clinical trials, a vaccine that targets the strain of HPV that causes most cases of cervical cancer protected 100 percent of the nearly twenty-four hundred women that received it. In an editorial that accompanied the published results of the trials, physician Christopher Crum wrote that the new HPV vaccine heralds "the beginning of the end for cervical cancer."⁴⁵ An even more potent version of the vaccine, aimed at two cervical-cancer-causing strains and two strains that cause genital warts, is currently in clinical trials in thirteen different countries. The vaccine, which may be widely available in as little as five years, will be given to females before they become sexually active.

Advances in HIV Vaccine Development

The devastating effects of HIV and the lack of affordable drug treatment has resulted in the development of a phenomenal number of experimental HIV vaccines reaching the stage of human trials. Since 1987 there have been over fifty-two clinical trials involving over twenty-seven different vaccines. Thus far, however, not one has been found to be effective for preventing infection by HIV.

The reason for this difficulty is that HIV has a high mutation rate that gives rise to numerous new strains of HIV, each with unique surface structures. Because preventative vaccines work by preparing the body to identify and attack germs based on their specific surface structures, it is a major challenge to produce a single vaccine that will reliably prevent infection by all strains of HIV. However, trying to turn this feature to their advantage, some researchers are working to devise a vaccine that can outwit the virus by causing it to mutate so rapidly that it can no longer survive. Such a vaccine has been shown to protect laboratory monkeys from subsequent exposure to SIV, and human trials are presently being conducted in the United States, Thailand, Trinidad, Haiti, Brazil, and Uganda.

Genome Sequencing Technology Assists in the Fight Against STDs

Perhaps the greatest contribution to the fight against STDs has been the development of revolutionary genetic technology that makes it possible to map the entire DNA sequence, or genome, of an organism. The genomes of organisms that cause STDs were among the first to be sequenced. Genomes from the germs that cause chancroid, gonorrhea, syphilis, and chlamydia, as well as herpes, genital warts, hepatitis B, and HIV have been completed. Encoding all of the instructions for the growth and function of an organism, the genome sequence is viewed as an invaluable tool in the design of new cures, treatments, and methods of prevention.

The benefits of gene sequencing for drug development can already be seen for HIV. Completion of this genome in the mid-1990s allowed two critical steps in the viral life cycle to be identified. Drugs were then found that blocked these steps, interfering with viral replication. The end result was the development of the effective treatment known as HAART, which has greatly improved the health and longevity of people infected with HIV.

Gene sequencing also speeds the process of trying to develop effective vaccines against STDs. Because a vaccine is derived from proteins that exist on the surface, or exterior, of the infectious organism's "body," knowing which proteins exist on the surface and which exist in its interior tells researchers specifically which proteins to target for vaccine development. Genome data gives researchers that knowledge. Although no vaccine has yet been developed to prevent syphilis, the generation of the complete genome of Treponema pallidum, the organism that causes syphilis, has been hailed as a promising step in this direction. NIAID director Anthony S. Fauci says, "Completion of this project is an extraordinary boost for efforts to develop a protective vaccine."⁴⁶

In April 2003 the Human Genome Project announced the completion of the mapping of the entire human genome. This much-heralded achievement means STD researchers can focus as never before on the mechanism of infection in the human host as well as the way the STD germs work. It may be possible to determine, for example, that some humans are genetically more susceptible to STD infection than others, and someday to medically remedy that vulnerability. Understanding STDs from the perspective of both disease germs and the humans that they infect will shed light on the best ways to fight them and the most effective ways to bring the STD epidemic under control.