Trends and Treatments in AIDS
This report was reviewed for medical and scientific accuracy by Mark B. Feinberg, MD, PhD , Associate Professor of Medicine and Microbiology and Immunology, Emory University School of Medicine; Attending Physician, HIV/AIDS Service, Grady Memorial Hospital, Atlanta, Georgia.
Experts at the 7th Conference on Retroviruses and Opportunistic Infections recently agreed that future advances in the treatment of AIDS are likely to come in increments. Fourteen drugs have been approved by the FDA for the treatment of HIV infection, and dozens more are currently under development. Of course, not all of the drugs now being studied in the laboratory or in early-phase clinical trials will pass the hurdles for drug approval required by the FDA, but a number of new treatments are likely to become available over the next few years.
As recently as five years ago, available treatments for HIV infection were unable to substantially delay progression to AIDS or death for HIV-infected persons. However, the advent of potent antiviral drugs and the deviation of more effective treatment strategies that use antiviral drugs in combination, has enabled many HIV-infected individuals to live substantially longer and healthier lives. As a result, the number of deaths due to AIDS has been drastically reduced since these drugs became available about four years ago. Longer follow-up of treated individuals will be necessary to determine the duration of benefit of available regimens of antiviral drugs.
While the antiviral treatments now in widespread use can significantly extend the length, and improve the quality of life of HIV-infected people, they also have a number of undesirable side effects that have become evident as longer-term experience with these new drugs has been gained. At first, HIV researchers thought these side effects were primarily the result of treatment with a specific class of drugs known as protease inhibitors; more recent studies presented at the meeting indicate that all classes of drugs used to treat HIV infection can be associated with these undesirable side effects. Some of the side effects observed include redistribution of body fat-a "buffalo hump" that develops on the neck, accumulation of fat in the belly and visceral organs, while the limbs and face become thinner, and changes in lipid profiles (elevation of the "bad" cholesterol-LDL cholesterol and triglycerides-as well as reduction in the "good" HDL cholesterol). These lipid changes could potentially place treated individuals at an increased risk for the development of heart disease, and HIV treatment researchers are now watching patients undergoing anti-HIV treatment closely in this regard.
Two studies presented at the meeting described a previously unrecognized side effect of the life-prolonging drugs known as protease inhibitors: the loss of bone density (known as osteoporosis). One study showed that bone mineral density, or bone mass, was significantly decreased among 21% of 122 men taking protease inhibitor-containing therapy, compared with 6% of people with AIDS who were not taking these drugs and with healthy uninfected men. A second study of 80 HIV-infected men being treated with combination antiviral therapy demonstrated that 28.4% had some bone thinning and a further 9.5% had a significant degree of osteoporosis. All men in the second study also had changes in total body fat composition described above and were responding to their HIV drug treatment. This second study was unable to determine whether the osteoporosis was specifically related to the use of protease inhibitors or to the other changes in overall metabolism associated with the body-fat syndrome.
Trends in Treatment and Prevention
People with AIDS currently have to cope with a complicated treatment regimen, involving a large number of pills taken at different times of the day. Some of these medications must be taken with food, while others need to be taken on an empty stomach. Significant efforts are being made to simplify these treatment regimens so that patients will be more likely to take their prescribed drugs as directed. New protease inhibitors are being studied with encouraging results; one of these new agents can be taken once a day (BMS-23262) and a second can be taken twice a day (ABT-378/r). Also, new pills are being introduced that combine two or three of the older drugs, again streamlining treatment regimens. It now appears likely that effective and far more convenient once-a-day regimens of combination antiviral therapy will become available in the next 1 to 2 years.
AIDS Vaccine A Distant Hope
Unfortunately, the availability of an effective AIDS vaccine remains a distant hope. Although several studies have shown some promise with experimental AIDS vaccine approaches in studies conducted on monkeys, some of these approaches may not be easily translated to or applicable for human use. Furthermore, demonstrating the safety and effectiveness of other vaccine strategies in clinical trials in humans will likely take a number of years to accomplish. Researchers may have to change their definition of what a vaccine does, at least in the near future, explained Gary Nabel, MD, director of the new center for vaccine research being constructed at the National Institutes of Health. Dr. Nabel told listeners that while significant progress is being made in HIV vaccine research, it would likely be a number of years before a vaccine that can prevent the spread of HIV infection is available. Researchers now anticipate that the first available HIV vaccines will not be able to completely prevent HIV infection, but will hopefully allow the newly-infected individual to live longer and be less likely to transmit the virus to others. Should this prediction be borne out, it could still mean that an incompletely effective HIV vaccine would be able to play an important role in helping to contain the continued spread of the AIDS epidemic.
"Morning After" Pill Prevents AIDS
On another front, a "morning after" treatment (also known as post-exposure prophylaxis or PEP) may decrease the chance of becoming infected with the virus for people who have been exposed to the HIV during sexual contact. A study of 401 women and men who had unsafe sex with either an intravenous drug user, a homosexual, or a person known to be infected with HIV, came to a San Francisco clinic for a 4-week treatment course of Combivir®, a pill that combines two common AIDS drugs (AZT and 3TC). These people learned about the opportunity for preventive treatment through a local advertising campaign. Because of the design of this study, it was not possible to determine how effective such post-exposure prophylaxis was in decreasing an exposed individual's risk of becoming infected with HIV. Indeed, it was not possible to tell whether all individuals studied had actually been exposed to an HIV-infected person. Forty-three percent knew that their partners were HIV-positive, but 57% were unsure. The treatment proved to be safe, and the side effects included mostly nausea, headache, and diarrhea. The physicians who conducted this study were concerned that people would use post-exposure prophylaxis as an alternative to practicing safe sex. However, most of the people were one-time-only users of this service. Only 12% returned to the clinic within six months for a second treatment after unsafe sex.
Low Viral Levels May Protect Against AIDS Transmission
A study conducted in rural Uganda by Thomas C. Quinn, MD and colleagues from Johns Hopkins University sought to identify factors that determine the efficiency with which HIV infection is transmitted between individuals. It included 415 heterosexual couples in which one partner had HIV and one did not. The couples were given free condoms to help prevent HIV transmission, but rarely used them.
This study found that people with low levels of the HIV in the blood (so-called, low "viral loads") are significantly less likely to spread the infection to others. The study also showed that being circumcised protected against becoming infected with HIV when exposed to an infected sex partner. Although this study was conducted in Africa, it may have important implications for people living in the United States as well. Levels of virus in the blood can decline substantially for HIV-infected people who are responding to antiviral treatment. Therefore, infected people who are being successfully treated with antiviral drugs may be less likely to pass the virus on to others. Experts caution that this study should not be taken as a go-ahead sign to have unsafe sex with someone who is infected with HIV or to practice any other unsafe sex or drug use behaviors.
Simple Inexpensive Pill Prevents Maternal-Fetal Transmission of AIDS
Another study provides hope that many HIV-infected pregnant women in developing countries can decrease (by approximately half) the chances that their babies become infected with HIV during delivery by taking a single dose of an anti-HIV drug called nevirapine (Viramune®) during labor; their babies were also given a very low dose of this drug for the first three days of life. This treatment compared favorably with a more complicated and expensive treatment regimen that involved a dose of AZT given to mothers at onset of labor and then every three hours until delivery, followed by their babies being given AZT twice a day for the first seven days of their lives.
"This simple, easy treatment with limited toxicity costs only $4, which is within a reasonable range for most of the developing world. In the developing world, approximately 700,000 babies are born with AIDS each year. If this treatment were used, more than 300,000 lives would be saved," said Laura A. Guay, MD, of Johns Hopkins University, the lead author of the study. The challenge is how to make this treatment available to HIV-infected pregnant women in poor countries. Most of the countries in the developing world do not have the financial resources to purchase these drugs nor do they have an infrastructure capable of delivering this treatment to the people who need it. UNICEF currently has 21 pilot projects to implement distribution of nevirapine (Viramune®) to HIV-infected women during labor. Unfortunately, even if the babies are successfully protected from HIV infection, many of them are destined to become orphans due to the eventual loss of their parents to AIDS.
Oral Sex Is Not Safe Sex
Another study from the Centers for Disease Control and Prevention presented at the meeting sounded an alarm about the supposed safety of oral sex. The study showed that AIDS infection could be attributed to oral sex in at least 8% of homosexual men with newly-diagnosed HIV infection. Oral sex has been perceived by many as a relatively low-risk practice. However, there has been little data available to support this assumption. This new study suggests that oral sex can be a method of HIV transmission and should be considered a risky behavior. Anal sex among homosexual men is more risky, but "the false assumption that oral sex is safe has led to tragic consequences," said Helene D. Gayle, MD, of the Centers for Disease Control and Prevention.
The study included 102 men, eight of whom stated that they practiced only oral sex without protection. If other risky behaviors were specified by these men, then the oral route was excluded as the cause of infection. It is possible, however, that the rate of transmission via oral sex may have been even higher, because some of the cases that were excluded could have been caused by oral sex. On the other hand, representatives of the gay press said that many men do not like to admit that they practice "receptive" anal sex and some of these men may have lied in the survey and said they only practiced oral sex. Whether the 8% represents an inflated figure or just the tip of the iceberg cannot be determined from this study, but the message is that oral sex should not be considered safe sex behavior among homosexual men.
Drugs that Work May Bring False Assurance
This study followed another troubling report from the Centers for Disease Control and Prevention, showing that 31% of at-risk men in San Francisco were "less concerned" about AIDS transmission because there is now effective treatment for controlling HIV infection, and 17% were "less careful" about sex or drug use. Researchers who presented the studies agreed that these are "deadly misperceptions" and that "prevention is now more critical than in the early days of the AIDS epidemic" because people with AIDS are living longer and have more time to transmit HIV infection to others.
New Techniques for Making the Blood Supply Safe
As a result of the AIDS epidemic and fears about contaminated blood supplies, new sophisticated techniques have been developed to make sure that the blood supply is as safe as possible for people who need transfusions. These techniques-called nucleic acid detection methods-are extremely expensive, explained Michael Busch, MD, of the Blood Center of the Pacific, San Francisco, California. They are associated with a cost of $2 million per quality life year extended (a measure used to assess the cost-effectiveness of treatments), compared to $50,000 for a cardiac bypass operation, he told listeners. The techniques can only identify one in one million HIV-infected blood donors, whereas the yield is much higher among donors infected with hepatitis C, he added. "Right now, we are spending about $100 million to make the blood supply safe, but the benefits of saving lives with a safer blood supply appear to be persisting," said Dr. Busch.