Chapter 6
HIV/AIDS Costs and Treatment

FINANCING HEALTH CARE DELIVERY

Care for HIV/AIDS patients is expensive. Newer drug treatments, most prominently highly active antiretroviral therapy (HAART), have high per-unit costs. Nonetheless, their introduction in 1996 reduced total health care spending on AIDS by reducing the rate of hospitalization and use of outpatient care. According to a study conducted by the Rand Corporation and published in the March 15, 2001, issue of the New England Journal of Medicine, the average HIV patient incurred costs of about $1,410 per month in 1998. Extended over the full year, a patient's drug treatment for HIV could cost as much as $18,000. People with AIDS could spend up to $77,000 a year on treatment.

Longer survival periods following an AIDS diagnosis lead to even greater costs for care and treatment. For example, according to statistics from New York City released in an August 11, 2005, report from the Independent Budget Office, Department of Health and Mental Hygiene, the average survival time of AIDS patients in that city increased from five months in 1981 to eighty-two months in 2003.

Figures from the same report, published in the August 11, 2005, issue of Newsday, illustrate the effects of the increasing treatment costs and enhanced survival. The amount spent by the city's HIV/AIDS Services Administration rose from $117 million in fiscal year 1999 to $193 million in fiscal year 2004.

Some HIV/AIDS patients rely on health insurance to help pay these costs. But many patients are not insured. And many policies exclude or deny coverage to people with preexisting conditions, and, as a result, many HIV-positive people are denied private health insurance.

According to the Office of National AIDS Policy, a White House agency, approximately half of all adults and nearly 90% of children living with HIV/AIDS in the United States have the costs of their treatment paid for by Medicaid. Medicaid is an entitlement program run by state and federal governments to provide health care insurance to patients younger than sixty-five who cannot afford to pay for private health insurance. Medicaid eligibility requirements vary from state to state. Generally, however, the program covers people with incomes of less than $700 per month who cannot support themselves financially due to a physical or mental impairment—an impairment that is expected to last at least one year or result in death. The operation of Medicaid programs also varies widely by jurisdiction. Many states supplement federal funding with their own funds, and each state determines its eligibility criteria and benefits—the number and type of treatments provided through the program.

The toll of AIDS on the Medicaid program is huge. For example, during 2004 the Medicaid program paid for services for an estimated 195,000 people living with AIDS at a cost of $5.4 billion. Between 1986 and 2000 the number of people living with AIDS who received Medicaid benefits increased by about 215%, and Medicaid expenditures increased by more than 1,860%. For example, in fiscal year 1995 Medicaid spending for HIV/AIDS care was $1.5 billion. In fiscal year 2003 it had risen to $8.5 billion, according to the Centers for Medicare and Medicaid Services.

A Reverse in Federal Policy

In early 1997 the administration of President Bill Clinton announced that it hoped to expand Medicaid to cover all low-income HIV-infected people. The administration had hoped to give low-income HIV-positive people access to HAART drugs that slow the onset of AIDS. By the end of the year, however, the administration announced that it could not follow through because such a nationwide plan would increase government spending. Both the Clinton administration and the administrations of George W. Bush forbade the federal government and states to change the Medicaid rules if that change would increase spending over a five-year period. As of 2005, only patients who have been diagnosed with AIDS, not those who are HIV-positive, are covered by Medicaid.

Domestic spending cuts announced by President George W. Bush in February 2005 included trimming $45 to 60 billion from the Medicaid budget over the next ten years, which will further limit the number of AIDS patients who receive treatment through Medicaid.

State Programs to Provide Drugs

In the late 1980s state-administered programs were established to help AIDS patients pay for azidothymidine (now called zidovudine, or ZDV), the newest effective drug at the time. The programs give free drugs to AIDS patients who are not poor enough to qualify for Medicaid coverage but who do not have private health insurance coverage, or patients who have used up their prescription drug coverage. The federal government provides two-thirds of the funding for the state programs, and the balance comes mostly from the states. In fiscal year 1996 federal and state drug program expenditures totaled about $145 million. These costs have risen dramatically. For example, Medicaid expenditures for HIV antiretroviral drugs in fiscal year 2003 were approximately $630 million.

Until recently, these programs did not attract many participants, primarily because ZDV alone was not very effective against the disease. In the late 1990s, however, with the development of a new class of antiretroviral drugs—called protease inhibitors (PIs)—that seem to reduce the amount of virus in the blood, more patients wanted to take advantage of the programs. (The typical three-drug "cocktail"—one new PI combined with two other HIV/AIDS medications—costs at least $12,000 per year per patient.)

This growing demand has put a financial strain on the programs, and many states have to ration HIV/AIDS drugs or turn patients away in order to remain solvent. Some states are making it harder for people to qualify for the programs, and a few are beginning to charge small copayments (a percentage of the total cost that the patient is responsible for paying) to offset the cost of the drugs. Several states do not offer the new drugs through their programs. More than thirty states offer at least one PI, but seventeen states do not provide any. Even after cutbacks in their AIDS drug programs, some states may run out of money before they receive more federal funds.

By 2004 the number of uninsured people with HIV and AIDS who were on waiting lists for state AIDS Drug Assistance Programs (ADAPs) had climbed into the thousands. North Carolina had the nation's longest waiting list, at 940 people. Among the states with waiting lists were Alabama, Alaska, Idaho, Iowa, Kentucky, Montana, South Dakota, and West Virginia.

ADAPs, which operate in all fifty states, provide medications to approximately 136,000 people each year. But funding is state-controlled and discretionary. This can lead to capping the enrollment of eligible people in the program, as was done in 2004 in Utah, Arizona, and Indiana, or reducing the funds provided for aid, as was done in 2004 in Idaho and in 2005 in Massachusetts, Nebraska, New Hampshire, New Jersey, and Oregon.

Costs to the Insurance Industry

Some employers, largely those that are self-insured and paying premiums to third-party insurers as protection against catastrophic health care claims, have put caps on expenditures for HIV/AIDS treatments. In some cases these employers have reduced their policies from million-dollar lifetime coverage to $10,000, which does not cover a year's worth of treatment. Because self-insured plans are exempt from most states' insurance regulations, employees covered by such plans who acquire HIV have no protection from insurance caps.

NEW LIFE INSURANCE AVAILABLE

In 1997 Guarantee Trust Life Insurance Company, a small Midwestern company, began to offer life insurance to some HIV-positive people. Company president Richard S. Holson III said the company decided to offer the coverage because it believes that many HIV-positive people are otherwise healthy and should be viewed as having a treatable chronic illness rather than a terminal disease. With new treatments available, affected people are living longer.

The policies provide up to $250,000 coverage and are offered to those who acquired the virus through sexual activity or accidental needle sticks. Applicants must be between the ages of twenty-one and forty-nine, have previous and current CD4 tests of 400 or greater, and never have been diagnosed with AIDS. Coverage is not offered to people who acquired the disease through the injection of drugs because drug use increases the company's risks, including the chance that prescribed medications will not be taken. The coverage is expensive: a typical thirty-year-old nonsmoking male who is HIV-positive pays $1,500 per month for the $250,000 policy.

Following this lead, Dutch insurance companies are poised to begin offering life insurance policies to some people infected with HIV. The Union of Insurers in the Netherlands, which represents more than 80% of the Dutch market, has decided to begin offering coverage in 2005. Coverage will be offered to those who have responded positively to treatment with antiretroviral drugs.

Changes to the Health Care System

Since the 1960s U.S. government spending on health services has consistently increased. Federal health expenses rose from 15% of the federal budget in 1990 to 20% in 2005. At the same time health care providers—doctors, hospitals, and other health-related institutions and professions—have watched as payments for Medicare, Medicaid, and private insurance coverage, once easily obtained in the 1960s and 1970s, were increasingly laden with restrictions and limits. In the 1990s providers also encountered a greater resistance among private insurers to pay. Bureaucratic management, increasing amounts of paperwork to document medical care and claims, and slow reimbursement rates prompted some physicians to stop caring for Medicare/Medicaid patients. Managed-care programs, which often restrict physicians' professional decisions and patient choices, were initially designed to control medical care costs.

As of 2005 many managed-care programs, also known as health maintenance organizations (HMOs) and preferred provider organizations (PPOs), are having administrative and financial problems. These programs, which rely heavily on primary care practitioners (general and family physicians), are shifting the focus of treatment they provide for HIV/AIDS patients. Beginning around the year 2000, a large number of HIV-infected people enrolled in managed-care networks. This is in part because more companies are placing all employees in HMOs and PPOs, and in part because government insurance programs are also directing Medicaid recipients to such programs.

A NEW MANAGED-CARE PROGRAM FOR HIV/AIDS PATIENTS: THE TENNESSEE "CENTERS OF EXCELLENCE" PROGRAM

On January 1, 1994, Tennessee withdrew from the federal Medicaid program and began to implement a state health care reform plan called Tennessee Medicaid (TennCare). In May 1998 TennCare introduced a voluntary managed-care program for its members with HIV or AIDS. The model program features "Centers of Excellence" providers—practitioners with high levels of expertise in the care of HIV/AIDS patients. The providers must agree to adopt and adhere to a clinical protocol (set of rules) developed by a committee composed of providers, consumers, managed-care organizations, and public health officials. The protocol committee meets up to twice a month to discuss and recommend new drug therapies as they become available and to inform participating providers about new treatments.

Providers may be individual practitioners with access to needed services or full-service clinics composed of a group of practitioners. There are no financial incentives to participate in the program. However, providers who meet the Centers of Excellence criteria do not have to obtain prior authorization when they prescribe drugs or treatments that fall under the clinical protocols.

The Centers of Excellence program frees managed-care organizations (MCOs) from the clinical and administrative responsibility of keeping close tabs on HIV and AIDS care. It also allows MCOs to remain confident that providers are capable and have access to a wide range of services needed by members. MCO members know that participating providers meet high standards of HIV/AIDS clinical care. Other managed care programs are developing comparable programs to meet the unique health and social service needs of people living with HIV/AIDS.

The program, which costs $5.1 billion a year, has endured criticism since its beginning. Doctors and hospitals have complained that it has been underfunded, forcing them to carry an unfair proportion of the costs. But despite its rocky history, TennCare was renewed on July 1, 2002, in a five-year agreement with the federal government.

CHALLENGES FOR THE DELIVERY SYSTEM

HIV/AIDS poses a major challenge to health care institutions, health care professionals, and others who provide direct health care services. HIV/AIDS is a relatively new disease, whereas most medical knowledge is acquired over many years or generations. The health care system cares for about one million people in the United States suffering from a disease that is still only partly understood. The system must also plan to deliver services to the tens of thousands of people in the United States who are HIV-positive and will require specialized health care services during the coming years, although only a small proportion will need intensive medical care at any one time.

The number of indigent people in need of HIV/AIDS care, particularly those who bring the added complications of drug addiction, homelessness, and other socioeconomic problems, has strained public hospitals in particular. Patients in public hospitals are often different from those in private hospitals. They generally seek care later in the course of the disease's progression and are, therefore, sicker. The scarcity of resources—trained personnel, hospital beds, and support services—in the community, combined with inadequate funding and reimbursement for HIV/AIDS care, are significant obstacles to effective health care delivery for poor HIV/AIDS patients.

Office Visits

Some physicians, particularly those who handle many HIV/AIDS patients, have extended their office hours or hired counselors to deal with these patients because their visits are time-consuming. Physicians polled by the Centers for Disease Control and Prevention (CDC) reported more than 2.5 million patient visits for HIV in 2000. (See Table 6.1.) While this represented only about 0.3% of the estimated 824 million visits for all causes in 2000, it did not reflect the growing amount of time spent on diagnostic and screening services in each office or the increase in the number of visits devoted to counseling and educating HIV/AIDS patients. According to the same survey, 5.2 million office visits provided counseling for and education about HIV and sexually transmitted disease transmission (0.6% of all patient visits). (See Table 6.2.)

Hospital Care

The nation's approximately seven thousand hospitals are also feeling the pinch of Medicare rate limits, reduced payments from MCOs, and intense competition from other providers, such as ambulatory surgical centers and hospices. Many are struggling to remain profitable institutions. During the 1970s and 1980s the steady growth of "for-profit" hospitals lured many privately insured, middle-class patients away from community hospitals, leaving most of the uninsured, sicker patients to seek care from inner-city public hospitals.

Most HIV/AIDS patients are cared for in inner-city public hospitals that are already overburdened with inadequate revenues, staff shortages, lack of referral facilities, and emergency rooms used by many poor neighborhood residents as sources of primary medical care. Many health care professionals praise San Francisco's model of care. This California city was hit hard in the early days of the epidemic and developed a range of innovative, effective programs in response to acute need during the early 1990s. This model of care relies on extensive outpatient services and volunteer social support services provided by the well-established and well-organized gay and lesbian community.

Changes in Health Care Delivery

Although fewer people are acquiring HIV/AIDS, the evolution of HIV care is altering the ways in which health care is delivered. In the late stages of AIDS most patients require intermittent hospitalization and home health care. Those who are not as severely affected and have symptoms or conditions that once required intravenous therapy (which had to be administered in a hospital or by home health professionals) are now able to self-medicate at home. Many drugs are now available for oral administration in pill or liquid form. These home care and community-based measures lessen the burden on the health care delivery system and make it easier for HIV/AIDS patients to care for themselves.

People with AIDS (PWAs) who receive informal home health care (such as care from friends and family) often use fewer hospital services, perhaps reflecting a greater desire to remain at home. PWAs with strong social support systems and who prefer to remain at home may also be less likely to demand an aggressive approach to treating their illness. Those who receive formal home health care (visits from physicians, nurses, therapists, social workers, case managers, and other paid caregivers) often use more hospital services. This may reflect a greater use of all types of health services by PWAs with weaker social support systems and/or an aggressive approach to treatment by medical professionals.

An AIDS Care Alternative

In 1993, in an effort to offer Atlanta's 4,400 uninsured AIDS patients treatment equal to that available to patients with private insurance, Grady Memorial Hospital opened a $7 million outpatient HIV/AIDS clinic. Since that time the clinic and its 150-member staff have provided emergency care, dental services, mental health counseling, social and support services, HIV research and education, case management, and babysitting. The clinic is partially financed under a provision of the Ryan White Comprehensive AIDS Resources Emergency (CARE) Act of 1990 (PL 101-381), which was enacted to provide funding to improve the quality and availability of care for HIV-infected people. In 1994 the clinic began asking patients to pay nominal fees based on their incomes. Under the CARE Act, providers may charge up to 10% of a patient's wages.

Hospice Care

The AIDS epidemic has had a significant impact on hospices. Hospice care, both in the home and in specialized centers, offers care aimed at comfort rather than cure. This includes expert pain relief, along with emotional, psychological, and spiritual support for patients, their families, and friends. The majority of hospice patients are older adults who suffer from terminal diseases such as cancer and face imminent death.

At the beginning of the AIDS epidemic patients did not fit well into the hospices of the day. AIDS patients were younger than traditional hospice patients, and the progression of their disease was less predictable than many cancers. Furthermore, as one hospice administrator noted, because many people with AIDS were accustomed to prejudice, they initially mistrusted the motivation and altruism of hospice workers. In the early 2000s, more than two decades after the first cases of AIDS were identified, home-based hospice programs designed to meet the needs of AIDS patients, their partners, and families have gained acceptance in the medical community as well as among HIV-infected people and the voluntary social service agencies organized to support them.

HEALTH CARE PROVIDERS

Physicians

AIDS physicians have been defined as doctors who perform a wide variety of services in addition to providing care to AIDS patients. Many are also AIDS activists and may be involved in developing policies, planning for care needs, and dealing with the media.

One challenge in the training of physicians to treat AIDS patients is that AIDS care requires skills and training in the multitude of conditions known to be part of HIV/AIDS. However, the amount of experience—rather than the kind of training—may be a better predictor of the quality of care the physician is able to deliver.

A 1996 study headed by M. M. Kitahata, published in the New England Journal of Medicine (vol. 334), claims that AIDS patients treated by primary care physicians with no previous experience dealing with the disease died more than a year earlier than those whose doctors had treated at least five AIDS patients. The study also shows that patients had a 46% decrease in relative risk of death at any given time when treated by a physician who had treated other AIDS patients. The difference, according to the researchers, was that the more experienced physicians consulted more frequently with specialists and reported more visits with their AIDS patients. Since that time, the study's findings have been verified by further research (W. E. Cunningham et al., "The Effect of Hospital Experience on Mortality among Patients Hospitalized with Acquired Immunodeficiency Syndrome in California," American Journal of Medicine, vol. 107, no. 2, August 1999; M. M. Kitahata et al., "Primary Care Delivery Is Associated with Greater Physician Experience and Improved Survival among Persons with AIDS," Journal of General Internal Medicine, vol. 18, no. 2, 2003).

MORE PHYSICIANS ARE WILLING TO TREAT HIV PATIENTS

The AIDS epidemic began at a time when many newly graduated physicians were not choosing primary care specialties such as internal medicine, the most fitting for the ongoing care required by HIV-infected patients. Some observers feared that new physicians would avoid practicing in geographic areas where there were large proportions of HIV/AIDS patients.

Fortunately, the CDC finds that most primary care doctors believe that they have an obligation to care for HIV-infected patients and are interested in further professional training to help increase their skill and comfort in caring for HIV/AIDS patients. Among physicians who report they do not provide care to AIDS patients, the majority cite a lack of experience with HIV and note that providers with more expertise are readily available in their communities.

Nurses

The impact of HIV/AIDS on nurses can be more difficult to assess than its effect on doctors. Nurses often have different viewpoints than some physicians about their professional obligations to patients with HIV. As hospital employees, nurses seldom have the option of choosing whether to treat a particular patient (nor do patients have much choice of nurses). Nurses, however, report that caring for HIV/AIDS patients can take an enormous emotional toll since they are often the primary source of continuous physical and emotional care for these patients, who generally require more care and services than other patients.

Nurses, physicians, and other health care professionals must cope with more than simply their fears of contracting the disease from HIV/AIDS patients and keeping abreast of advances in the treatment of the disease. They also face a wide range of emotional issues when caring for these patients, from feelings of failure when treatment is unsuccessful to grief when witnessing the untimely deaths of patients. Support groups and counselors help many health professionals, especially hospice workers, to share and understand these feelings so they are better able to care for HIV/AIDS patients and their families.

CDC Guidelines

In 1992, in response to an incident in which five patients acquired HIV from a Florida dentist, the CDC addressed occupational exposure to blood-borne pathogens. The CDC offered new guidelines to prevent the accidental spread of the infection from health care providers to patients and from patients to health care workers. The recommendations stressed the careful and consistent use, with all patients, of standard infection control procedures for blood-borne agents—the so-called universal precautions—that were published by the CDC in 1987.

The CDC guidelines also recommended that HIV-infected health care workers stop performing what were termed "exposure-prone invasive procedures" and that professional medical and dental groups draw up lists of "exposure-prone procedures" for their disciplines. The CDC recommended that HIV-infected health care workers consult with a panel of experts to determine which, if any, limits should be placed on their medical practices and further advised practitioners to inform patients of their HIV-infection status before performing medical procedures.

The CDC guidelines resulted in some unforeseen consequences. Professional groups, hospital attorneys, state courts, legislatures, and the U.S. Congress reacted with alarm to a perception of dangers to patients posed by HIV-infected health care professionals totally out of proportion to the largely theoretical risk. According to the U.S. Public Health Service, the average risk of HIV infection after skin contact with HIV-infected blood is estimated to be about 0.3%, and the risk for transmission is probably even lower from contact with body fluids or tissues other than blood. Through 1990, forty cases of occupationally acquired HIV were documented. By the end of 2001 fifty-seven documented cases had been reported and 138 additional cases of HIV infection may be linked to occupational exposures (see below).

Most medical professional associations refused to cooperate in developing a list of exposure-prone invasive procedures that carry a higher risk of virus transmission. They did not believe there was enough data to support drawing up such a list. Nonetheless, the CDC did not withdraw its recommendation concerning the exposure-prone procedures list, even after studies of more than fifteen thousand patients cared for by thirty-two health care workers known to be HIV infected found that none of the patients contracted HIV as a result of the care.

The CDC also recommended that the following procedures and philosophies would best serve patients and health care workers:

• The universal and meticulous use of well-understood infection-control procedures, particularly those developed from the study of hepatitis B—another blood-borne infection that is one hundred times more infectious and ten times more common in health professionals—should be applied in all health care settings, whether hospital, office, or home based.
• Operative or other invasive procedures, in which injury to health care professionals occurs with any frequency, should be discontinued or modified to the greatest extent possible. This involves developing new instruments and investigating new operative techniques.
• All health care professionals should consider being tested for HIV. An HIV-positive result, however, should not justify restricting the practice of health care professionals.

The National Commission on AIDS did not agree with all of the CDC guidelines, cautioning against placing too much emphasis on HIV transmission in health care settings. Unwarranted emphasis in the wrong place, the commission noted, distracts the nation from proper attention to sexual transmission, transmission via intravenous drug use, the problems of sexually active teenagers, and an epidemic that needs more committed health care professionals.

The commission also warned that the costs associated with testing all health care professionals and all patients would amount to $1.5 billion and that there was no evidence that such testing would increase patient or worker safety.

Should Doctors Tell Patients?

Since 1991 the American College of Surgeons (ACS), the nation's largest professional organization of surgeons, has, in defiance of CDC guidelines, refused to draw up a list of procedures that might pose a high risk of transmitting HIV from doctor to patient. The group maintains that since not a single documented case of surgeon-to-patient transmission has been established, there is no scientific basis for suggesting that a particular surgical procedure increases the risk of viral transmission. The ACS also notes that surgical patients are at greater risk for other surgery-related infections than for HIV, even from an HIV-infected physician.

The CDC guidelines, published in the July 12, 1991, issue of Mortality and Morbidity Weekly Report ("Recommendations for Preventing Transmission of Human Immunodeficiency Virus and Hepatitis B Virus to Patients during Exposure-Prone Invasive Procedures"), instruct HIV-infected health care workers to avoid contact with patients that could potentially bring the worker's blood into contact with a patient's body cavities or mucous membranes.

HEALTH CARE WORKERS AND INFECTION

Health Care Workers with HIV and AIDS

As of December 2003 the CDC was aware of only fifty-seven documented cases of health care workers other than surgeons in the United States who had become infected with HIV as a result of occupational exposures. The breakdown of those who were infected was as follows: nurses (twenty-four), clinical laboratory workers (sixteen), nonsurgical physicians (six), nonclinical laboratory technicians (three), housekeeper/maintenance workers (two), surgical technicians (two), embalmer/morgue technician (one), health aide/attendant (one), respiratory therapist (one), and dialysis technician (one).

The CDC was also aware of 138 cases of HIV infection or AIDS possibly linked to occupational exposure among health care workers as of December 2003. These workers have not reported other risk factors for HIV infection. They had reported a history of occupational exposure to blood, body fluids, or HIV-infected laboratory material but had not documented infection after a specific exposure.

The known and possible cases of occupational acquisition of HIV undoubtedly represent an underestimate. There are surely unknown numbers of people who acquired their infection through occupational exposures, although, even in 2005, this is conjectural.

As of 2005 twenty-one states had enacted needle-safety legislation to safeguard health care workers from blood-borne pathogen (agents that cause disease) exposures. State laws aim to strengthen and supplement the federal standards mandated by the Occupational Safety and Health Administration. Many of the state laws require the creation of a written exposure plan that is periodically reviewed and updated; protocols for safety device identification and selection; logs to document and report injuries with sharp instruments; and strict requirements and training for workers on how to use safety devices.

In 2001 the Public Health Service updated guidelines for treatment to prevent health care workers with occupational exposure to HIV from becoming infected with the virus. Known as "postexposure prophylaxis" (PEP), the recommendation is that affected workers be given a four-week regimen of two antiretroviral drugs such as zidovudine and lamivudine, with the addition of a third drug for HIV exposures that pose an increased risk of transmission. While the best strategy to protect health care workers is to avoid exposure to HIV and other blood-borne pathogens, PEP has, as of 2005, proven effective in preventing HIV infection in workers who have been exposed.

Risks to Patients

Health care officials are not the only ones worried about HIV transmission in the health care setting. Patients also fear that infected health care workers could transmit the virus to them. The CDC developed a model of the risk of HIV transmission to patients, estimating that the risk of a patient becoming infected by an HIV-positive surgeon during a single operation is anywhere from one in 42,000 to one in 420,000. This risk is considerably less than the risks associated with many other medical procedures.

Ongoing studies by the CDC of more than 15,700 patients of thirty-two HIV-infected health care workers found no documented evidence that HIV infections found in these studies could be attributed to medical or dental care, with the exception of the five patients of a Florida dentist in 1990. Medical researchers have tried without success to determine how the dentist infected his patients and whether the exposure was accidental or deliberate. One theory is that he did not properly sterilize his dental tools; another is that he accidentally cut his finger or jabbed himself with a hypodermic needle, did not notice it, and bled into the patients' mouths. Prior to his death in 1990, the dentist denied intentionally exposing his patients.

In 1990 Rudolph Almarez, a Baltimore breast surgeon who performed operations on as many as two thousand patients, died from AIDS. The nature of his death stirred up such concern that shortly after he died a Baltimore law firm solicited clients to seek legal advice, whether they were infected or not. The law firm told clients that they might be reimbursed for the emotional distress they now suffered if they sued the hospital where Almarez had practiced. Two separate legal complaints based on the fear of HIV exposure were dismissed by a Baltimore judge. The judge further stated that there were no allegations that Almarez had not followed recommended safety procedures or that any accident had taken place during surgery. None of the patients alleged infection from Almarez. A later study failed to find any HIV-positive patients among those Almarez had treated (Rossi v. Almarez, Faya v. Almarez, Baltimore City Cir. Ct. Nos. 90344028 CL123396; 90345011 CL12345g, May 23, 1991).

WHAT DOES IT COST TO TREAT HIV/AIDS PATIENTS?

In 2004 all federal government spending for HIV-related activities exceeded $16 billion. Federal spending for HIV/AIDS care alone totaled $11 billion. A full-scale clinical trial for a new drug costs between $9 and 18 million. The per-patient cost of HIV/AIDS drugs is between $12,000 and $70,000 a year depending on the severity of the patient's condition. Costs are expected to increase due to the rising costs of hospitalization, home care, insurance premiums and copayments, and physician services. Additionally, federal and state programs such as Medicaid have been forced to operate under tighter budgets and have eliminated certain treatments from insurance coverage. In 2000 certain drugs (including Bristol-Myers Squibb's enteric-coated formulation of didanosine and Abbott Laboratories' protease inhibitor ABT-378) rose substantially in price. Since then, concern over the rising price led to a self-imposed freeze in pricing by some manufacturers in 2002. But in February 2003 Roche Pharmaceuticals announced that the price for Fuzeon, at the time the most expensive AIDS treatment on the market, will more than double in Europe.

Some expenses, however, have actually been reduced by relocating services from the hospital to a variety of outpatient settings. Examples of cost-saving services include outpatient transfusions and outpatient treatment for opportunistic infections such as Pneumocystis carinii pneumonia and cryptococcal meningitis. Increased volunteer-based social service programs that enable patients to be cared for at home also can prevent expensive hospital stays.

Federal government spending on HIV-related care and activities has increased steadily since 1985, when about $2 million was spent. In 2003 the budget office of the U.S. Public Health Service estimated that federal spending for HIV-related expenses was $16.7 billion, $10.2 billion of which was spent on medical care. Other government costs included research ($2.8 billion), education and prevention ($1.9 billion), and cash assistance ($1.7 billion), which is provided through the Social Security Administration and the Department of Housing and Urban Development. (See Table 6.3.)

The Ryan White Comprehensive AIDS Resources Emergency Act

In 1998 the Ryan White Comprehensive AIDS Resources Emergency (CARE) Act (PL 101-381) was the only federal program providing funds specifically for medical and support services to individuals with HIV and AIDS. The Act was named after Ryan White, who died of AIDS in 1990. White was an Indiana teenager with hemophilia who became infected through a blood transfusion. Shunned by his community because many people feared becoming infected through any kind of contact with him, White fought to attend school and attain rights for those infected with HIV/AIDS. White's efforts helped change the way the world treated those with the disease. The CARE Act was signed in 1990 and reauthorized in 1996 and 2000. The 2000 reauthorization addressed additional initiatives including improving access to care for vulnerable populations (such as women, minorities, and those with addictions or mental health disorders), increased accountability of providers, and improving services in underserved rural and urban regions.

CARE Act funds are appropriated using four formulas (Titles I-IV). The Title I formula provides emergency assistance to metropolitan areas disproportionately affected by the HIV epidemic. To qualify for Title I funds, eligible metropolitan areas (EMAs) must have more than two thousand cumulative AIDS cases reported during the preceding five years and a population of at least five hundred thousand. (The population provision does not apply to any EMA named and funded before fiscal year 1997.) In fiscal year (FY) 1991, the first year Title I grants were available, there were only nineteen EMAs. In FY 2004 there were fifty-one EMAs in twenty-two states, the District of Columbia, and Puerto Rico. More than $4.8 billion in Title I funding has been allotted from FY 1991 through 2003. In FY 2004 EMAs received $595.3 million. New York ($122.1 million), Los Angeles ($36.6 million), Washington, D.C. ($30 million), and San Francisco ($29.8 million) received the largest grants. (See Table 6.4.)

In fiscal year 2005, the total amount of the Title I awards declined to $587.4 million. The proportionate amounts awarded to some of the EMAs has also declined. New York is slated to receive $117.9 million, San Francisco $28.3 million, and Washington $29.4 million. However, the amount received by Los Angeles has increased to $36.8 million. (See Table 6.4.)

Title II funds are provided to state governments. Ninety percent of Title II funds are distributed on the basis of AIDS patient counts, while 10% are distributed through competitive grants awarded to public and nonprofit agencies. More than $6.7 billion in Title II funding was allotted from FY 1991 through 2003. (States that have more than 1% of all AIDS cases reported nationally during the preceding two years must match the federal grant with their own resources. The amount is based on an annual formula.) The totals increased from $845.7 million in FY 2001 to $1.03 billion in 2004. (See Table 6.5.) The states use their Title II funds to contract with service providers for ambulatory (outpatient) health care, insurance coverage, residential and in-home hospice care, transportation to and from appointments, food banks, and home-delivered meals.

In addition to the base award granted under Title II, states receive funds to support AIDS Drug Assistance Programs (ADAPs). ADAPs provide medication to low-income HIV-positive people who are either uninsured or underinsured. (The states may elect to use their Title II funds for their ADAPs.) Beginning in 1996, extra funds were made available for the ADAPs. In FY 1999 a total of $709.9 million (including $461 million for ADAP funding) was allocated for improved health care and support services for people living with HIV/AIDS. Additionally, 1999 was the first year that Guam and the U.S. Virgin Islands received ADAP funding. For FY 2001 the amount earmarked for ADAP was $589 million. FY 2001 also was the first year that 3% of the ADAP allocation was directed to fund supplemental drug grants to states demonstrating severe need.

Title III of the CARE Act funds grants to provide early intervention services and outpatient treatment for low-income, medically underserved people and supports development of quality HIV primary care programs. During 2002 Title III grants served 150,000 patients; 70% were people of color and 30% were women. In fiscal year 2005 the Title III funding will total $25.7 million. Title IV funds link primary health care and social services for women, infants, and children to HIV research and clinical drug trials. For FY 2002, $193.9 million was allocated to Title III programs and $70.9 million for Title IV programs.

As of August 2005, the CARE Act was facing funding reallocation. The U.S. Department of Health and Human Services proposed reauthorizing the act, which would reduce funding to metropolitan areas that have pioneered AIDS treatment efforts and redirect money to states that have been less timely in their response to HIV/AIDS. If approved, the reauthorization would reduce funding in AIDS-intensive states, including New York and California.

Private Insurance and Medicaid

The financing of HIV/AIDS care is increasingly becoming the responsibility of Medicaid, a government program designed to provide medical care for people who fit the criteria for funding. Greater reliance on Medicaid funding is due in large part to the increase in the number of HIV/AIDS cases among intravenous drug users and poor people who are unlikely to be covered by private health insurance. In addition, many patients who once had private insurance through their workplace lost their coverage when the illness made them too sick to work, forcing them to turn to Medicaid and other public programs.

Added to this list are those whose employment or economic status would normally ensure them insurance coverage, but who became virtually ineligible for private health insurance coverage once they tested positive for HIV. Others need assistance because some insurance companies consider HIV infection a "preexisting condition," making it ineligible for payment of claims. Even insurance companies that do cover HIV treatment often impose caps, limiting coverage to relatively small dollar amounts.

The HIV/AIDS epidemic has prompted private insurers to add an HIV antibody screening test for people who are not joining insurance programs through groups or employers. These "individual enrollees"—who make up 15% of all people in the insurance market—are required to take medical exams to prove they are "insurable." In the early 1990s California, Massachusetts, and the District of Columbia initially banned the use of HIV antibody testing for private insurance purposes but reversed the ban in the storm of resulting controversy.

Death Benefits

Since 1988 an industry has developed that offers dying AIDS patients the opportunity to collect a portion of their life insurance benefits before they die, either to pay for their treatment or to spend as they wish during their remaining time. These viatical (money for necessities given to a person dying or in danger of death) settlements are reached when an insured person sells his or her life insurance policy to an independent insurance company at a reduced or discounted price. This enables the patient to have some cash from the policy while he or she is still alive. After the patient dies, the company that bought the policy is paid the full death benefits. Regulators with the Securities and Exchange Commission are scrutinizing some practices that they say may victimize AIDS patients.

Some larger companies such as Prudential offer policy holders more than 90% of their policy payouts, but only with a physician's certification that they have less than six months to live. Smaller companies usually pay 50 to 80% of the benefit payable at death, although they will pay benefits to people who still have up to five years to live. The longer the person is expected to live, the less the cash disbursement they receive.

Most insurers will not write new life insurance policies for people known to have AIDS. But the insurance industry had paid out more than $640 million in death benefits by 2002 on policies of already-insured people who died of AIDS. At least one company does offer life insurance policies to some people infected with HIV, provided they meet certain eligibility requirements.

TREATMENT RESEARCH

Medical and pharmaceutical research to develop and conduct clinical trials of antiretroviral drugs is expensive. In 2002 the National Institutes of Health (NIH) spent an estimated $2.7 billion on AIDS research, while it spent approximately $630 million to investigate breast cancer and $263 million for research on strokes.

Decisions about how much is spent to research a particular disease are not based solely on how many people develop the disease or die from it. Rightly or wrongly, economists base the societal value of an individual on his or her earning potential and productivity—the ability to contribute to society as a worker. The bulk of the people who die from heart disease, stroke, and cancer are older adults. Many have retired from the workforce and their potential economic productivity is often minimal. This economic measure of present and future financial productivity should not be misinterpreted as a "casting-off" of older adults; instead, it is simply an economic measure of present and future financial productivity.

In contrast, AIDS patients are usually much younger and die in their twenties, thirties, and forties. Until they develop AIDS the potential productivity of these people, measured in economic terms, is high. The number of work years lost when they die is considerable. Using this economic equation to determine how disease research should be funded, it may be considered economically wise to invest more money to research AIDS since the losses, measured in potential work years rather than lives, are so much greater.

The primary goals of HIV/AIDS therapy are to prolong life and improve its quality. While in the early days of AIDS research a cure for the disease was envisioned, few researchers by the early 2000s realistically expected any drug to cure HIV infection. The bottom-line objective became making the virus less deadly by foiling its efforts to reproduce within the body.

A major obstacle to the discovery of such treatments is the cost of drug research and development. Pharmaceutical manufacturers spend millions of dollars researching and developing new medicines. According to the Pharmaceutical Research and Manufacturers of America, since 1992 U.S. pharmaceutical companies have consistently spent more money each year on research and development (R&D) activities than the annual budget of the National Institutes of Health. For example, in 2002 the estimated pharmaceutical R&D budget was $32 billion, while the entire NIH budget (research and other activities) was $24 billion. Furthermore, private-sector spending has been growing faster than government spending since 1995.

As of 2005, pharmaceutical companies were testing seventy-nine medications for HIV/AIDS and associated conditions. The successful candidates will complement the eighty-two medications that were approved since the 1980s.

A pharmaceutical manufacturer must cover the cost not only of R&D for the approximately three out of ten drugs that succeed, but also for many of the drugs—seven out of ten—that fail to make it to the marketplace. Because of this cost, once a new drug receives U.S. Food and Drug Administration (FDA) approval, its manufacturer ordinarily holds a patent or gains exclusivity rights, which guarantee it will be the sole marketer for a specified time (usually from three to twenty years) in order to recoup its investment. During this time, the drug is priced much higher than if other manufacturers were allowed to compete by producing generic versions of the same drug. In contrast to the original manufacturer, the generic manufacturer does not have to pay for the successes and failures that occurred in the drug development pathway or pursue the complicated, time-consuming process of seeking FDA approval. The producer of generic drugs has the formula and must simply manufacture the drugs properly. Because of the lower cost of the generic drug after the original patent or exclusivity period has expired, competition among pharmaceutical manufacturers generally lowers the price. HIV/AIDS drugs are granted seven years of exclusivity under legislation aimed at encouraging research and promoting development of new treatments.

The issue of patent protection for HIV/AIDS drugs is understandably contentious. Pharmaceutical manufacturers and others argue that patent protection is necessary to allow for the financial investments necessary to breed innovation. However, to those directly affected by HIV/AIDS, and those governments or health care systems that provide care, the enormous costs can be infuriating, especially with the knowledge that generic drugs carrying a lower price tag are possible. In the developing world, the need for less expensive HIV/AIDS drugs is urgent. Indeed, reflecting this urgency, a November 2002 meeting of the World Trade Organization (WTO) adopted a resolution affirming the right of WTO member countries to do whatever they deem necessary to protect public health, including overriding pharmaceutical patents. In May 2003 the government of Zimbabwe declared a national emergency for six months over the HIV/AIDS pandemic, enabling it to purchase and make available generic versions of HIV/AIDS drugs that are still under patent protection. Prior to this, the passage of the Kenya Industrial Property Bill 2001 allowed the importation and production of more affordable medicines for HIV/AIDS in that country.

FDA-APPROVED DRUGS

The first drug thought to delay symptoms was zidovudine (ZDV; formerly known as azidothymidine, or AZT). While initially promising, ZDV's effects were found to be temporary at best. Several other drugs work on the same principle as ZDV—exclusion of HIV from the host chromosome. A new class of drugs called protease inhibitors (PIs) appears to keep HIV already in the host cells from reproducing. PIs block the ability of HIV to mature and infect new cells by suppressing a protein enzyme of the virus, called protease, which is crucial to the progression of HIV. One study conducted by Merck shows that a combination of Crixivan and two other AIDS drugs reduces virus load by more than 99% in patients with T cell counts between 50 and 400 virus particles per cubic millimeter.

Even if the effectiveness of PIs proves to be transient, they should improve patients' prospects simply by creating more roadblocks for HIV, which mutates so rapidly that it becomes resistant to most drugs when the drugs are used alone. Even if a cure is never found, new and better drugs used in various combinations may make HIV infection a chronic but manageable disease, much like diabetes.

The cost, however, is high. PIs range from about $4,800 to $8,000 for a year's supply. When combined with ZDV or any of the other commonly used antiretroviral drugs, such as lamivudine (3TC), zalcitabine (ddC), didanosine (ddI), or stavudine (d4T), the cost is approximately $18,000 per year. Government programs and private insurers alike are looking for ways to pay for, and in some cases avoid paying for, these new therapies. As Moises Agosto of the National Minority AIDS Council in Washington, D.C., notes, though the drugs may be approved, people may still not be able to use the new treatments if programs cannot afford them.

Types of Antiretroviral Agents

As of 2005 the FDA accepted the following classes of antiretroviral agents for treatment of HIV/AIDS.

PROTEASE INHIBITORS

The following are PIs:

• Indinavir, manufactured by Merck and sold under the brand name Crixivan
• Ritonavir, manufactured by Abbott Laboratories and sold under the brand name Norvir
• Saquinavir, manufactured by Roche Pharmaceuticals and sold under the brand names Invirase and Fortovase
• Nelfinavir, manufactured by Agouron Pharmaceuticals and sold under the brand name Viracept
• Amprenavir, manufactured by GlaxoSmithKline and sold under the brand name Agenerase
• Atazanavir, manufactured by Bristol-Myers Squibb and sold under the brand name Reyataz
• Fosamprenavir calcium, manufactured by GlaxoSmithKline and Vertex Pharmaceuticals and sold under the brand name Lexiva

Drugs formulated with combinations of two or more protease inhibitors also have received FDA approval:

• Lopinavir and ritonavir, manufactured by Abbott Laboratories and sold under the brand name Kaletra; for use in adult and pediatric patients
• Abacavir, retrovir, and lamivudine in a fixed dose combination, manufactured by GlaxoSmithKline and sold under the brand name Trizivir

NUCLEOSIDE ANALOGS

Nucleoside analogs (NAs) were among the first compounds shown to be effective against viral infections. Research in the 1970s led to the development of the drug acyclovir, which is still being used to treat herpes infections. The first four anti-HIV drugs to be approved—ZDV (at one time called AZT), didanosine, dideoxycytosine, and stavudine—were NAs.

As their name implies, NAs exert their action based on their three-dimensional structure, which mimics the structure of the nucleoside building blocks of DNA. By becoming incorporated into DNA as the molecule is replicated, the analogs can preserve the structure of DNA but make it impossible for the HIV to use its reverse transcriptase to hijack the host replication machinery to make new viral copies.

As of 2005, the following NAs have received FDA approval for use with HIV/AIDS:

• ZDV, manufactured by GlaxoSmithKline and sold under the brand name Retrovir
• Didanosine (also called dideoxyinosine, or ddI), manufactured by Bristol-Myers Squibb and sold under the brand name Videx

• Zalcitabine (also called dideoxycytosine, or ddC), manufactured by Roche Pharmaceuticals and sold under the brand name Hivid
• Stavudine (D4T), manufactured by Bristol-Myers Squibb and sold under the brand name Zerit
• Lamivudine (3TC), manufactured by GlaxoSmithKline and sold under the brand name Epivir
• Abacavir succinate, manufactured by GlaxoSmithKline and sold under the brand name Ziagen
• A combination of lamivudine and abacavir, manufactured by GlaxoSmithKline and sold under the brand name Epizicom
• A combination of emtricitabine and tenofovir disoproxil fumarate, manufactured by Gilead Sciences and sold under the brand name Truvada

NONNUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS

Another class of antiretroviral drugs approved in the late 1990s is nonnucleoside reverse transcriptase inhibitors (NNRTIs). NNRTI compounds slow down the process of the reverse transcriptase enzyme that allows the virus to become part of the infected cell's nucleus. The compounds accomplish this by binding to the viral enzyme, which blocks the ability of the enzyme to function. As of 2005 there were three NNRTIs approved for use by the FDA:

• Nevirapine, manufactured by Boehringer Ingelheim and sold under the brand name Viramune
• Delavirdine, manufactured by Pfizer and sold under the brand name Rescriptor
• Efavirenz, manufactured by Bristol-Myers Squibb and sold under the brand name Sustiva
• Amprenavir, manufactured by GlaxoSmithKline and sold under the brand name Combivir
• Emtricitabine, manufactured by Gilead Sciences and sold under the brand name Emtriva

NUCLEOTIDE ANALOGS

Like nucleoside analogs, nucleotide analogs also inhibit the HIV reverse transcriptase. However, the molecular mechanism of this inhibition is different from nucleoside analogs. Specifically, nucleotide analogs are active without modification, while the nucleoside inhibitors only work in cells that have the machinery to add a phosphorus group to the compounds. This may allow nucleotide analogs to be active in a wider range of HIV-infected cells than nucleoside inhibitors. Nucleotide analogs have the advantages of only needing to be taken once a day and show some effectiveness against resistant HIV. However, serious side effects such as kidney damage and eye inflammation have been reported with some nucleotide analogs.

In October 2001 the FDA approved Viread (tenofovir disoproxil fumarate) as the first and, as of 2005, only nucleotide analog for HIV treatment. Intended for use in combination with other antiretroviral drugs, the new drug has been shown to reduce HIV replication. But there are not yet long-term study results to demonstrate whether Viread effectively inhibits the clinical progression of HIV.

AN ANTI-FUSION DRUG

As of 2005, one drug that interferes with the fusion of HIV with the host cell membrane has been approved by the FDA. Enfuvitide, which is manufactured by Roche and Trimeris, is sold under the brand name Fuzeon.

Aggressive Treatment

With new drugs in the anti-HIV/AIDS arsenal, many people with HIV/AIDS who had given up hope of effective treatment returned to clinics and doctors' offices. While treatment guidelines previously promoted early intervention with ZDV, recommended treatment now combines PIs with other antiretroviral drugs. Treatment recommendations change rapidly in response to the development of new drugs and clinical trials indicating the effectiveness of different combinations of antiretroviral drugs. Researchers are acting quickly to develop new mixtures of the recently approved and older drugs. Because HIV mutates to resist any drug it faces, including all PIs, researchers find that varying the combination of drugs prescribed can "fool" the virus before it has time to mutate.

Another approach to treatment, presented in an article published in the February 15, 2000, issue of the Annals of Internal Medicine by Keith Henry, suggests that overly aggressive antiretroviral therapy in the early stages of the disease may expose patients to unpleasant side effects and cause their systems to build resistance. Henry recommends a more cautious strategy: a long-term, patient-focused approach that includes delaying initial therapy, planned interruptions in drug dose administration, therapy switching, and immune-based therapy. In October 2003 the European Medicines Agency advised doctors not to start HIV patients on the aggressive didanosine-lamivudine-tenovir triple-drug combination, since no compelling improvement had been noted in those receiving the treatment.

Patients undergoing therapy with new drugs or drug combinations must be highly disciplined. For instance, Crixivan must be taken on an empty stomach, every eight hours, not less than two hours before or after a meal, and with large amounts of water to prevent development of kidney stones. Patients must also be careful to never skip doses of Crixivan, otherwise HIV will quickly grow immune to its effect. (Crixivan has been found to generate cross-resistance, meaning it made patients resistant to other PIs.) Invirase must be taken in large doses. Norvir must be carefully prescribed and administered because it interacts negatively with some antifungals and antibiotics used by AIDS patients. Because there are numerous minor and serious risks associated with use of these drugs, patients must be closely monitored.

The difficulty of dealing with a complicated regimen of daily medication and maintaining the personal resolve to continue the regimen are issues for HIV/AIDS patients. Henry argues that more support should be given to those health care professionals (such as nurses and pharmacists) who educate patients and assist them in maintaining their complicated daily medication schedules. During 2000 many combined HIV/AIDS medication regimens could be administered two to three times per day, and once-a-day regimens may be possible in the near future. Such a possibility, according to the researchers, may lead to improved adherence to treatment and quality of life for people with HIV/AIDS.

Lingering Questions

As observed earlier, the success of PIs may prove transient. Studies conducted by drug companies that produce the PIs show that viral loads decrease to undetectable levels for at least a few months whether the patients have been HIV-positive for a few weeks or a few years. Because the drugs were allowed to be used under the FDA's accelerated approval program—a fast-track approval after safety and efficacy are demonstrated in a single clinical trial—some investigators question their long-term efficacy. If each PI is able to suppress HIV for only a little while, critics ask, then are HIV/AIDS patients any better off?

Other questions persist. Even though HIV patients treated with PIs may have no detectable HIV in their blood, might it still be present in their tissue? Will drug-resistant strains of the virus emerge over time? Will these powerful drugs cause harmful side effects if taken for long periods? Is it safe to switch from one drug to another once there is resistance? Studies are underway and more are planned to determine the optimal therapy and when it should begin.

AIDS and Marijuana

Marijuana (Cannabis sativa ) is an herb that has become infamous for the "high" it can cause, due to a constituent chemical called tetrahydrocannabinal (THC). Until the late 1930s the beneficial properties of marijuana to relieve pain and increase appetite were recognized, and the drug was used medically in the United States. By the 1970s, however, marijuana's medical benefits were considered to be far outweighed by the potential for abuse, and laws banning its use were enacted in the United States and other countries.

As recently as June 2005, the U.S. Supreme Court ruled that the medical use of marijuana is illegal under federal law. However, some states have passed laws that permit the use of the drug for medically approved reasons, such as relief for pain and nausea. In Canada marijuana use for cancer and AIDS patients is legal; in fact, the patients obtain the drug from federal government-grown plants.

In 1992 the FDA approved a version of marijuana for medical use. The product, called Marinol, contains synthetic THC and is available by prescription. Administration of THC in a pill form allows patients to avoid the inhalation of marijuana smoke, which can contain many potentially noxious chemicals. Many AIDS patients, however, claim that Marinol is too weak to alleviate their symptoms.

Marijuana's ability to stimulate appetite and suppress nausea have made it an attractive adjunct to HIV/AIDS therapy. Nonetheless, opposition to the medical use of the drug still exists. This is particularly true of the proposal to make the traditional cigarette (or reefer) form of marijuana available for medical use. In August 2005 the U.S. Drug Enforcement Administration heard presentations from advocates and critics of a proposal to allow the FDA to decide if marijuana should be reclassified as a prescription drug.

THE DISCOVERY OF AN HIV-RESISTANT GENE

In August 1996 scientists working independently at the Aaron Diamond AIDS Research Center in New York City and the Free University of Brussels, Belgium, announced that some white people have genes that may protect them from HIV no matter how many times they are exposed to the virus. The researchers hope the findings could lead to new HIV/AIDS therapies or to the development of pills or injections to prevent HIV.

The researchers discovered that a gene called CCR5 is associated with HIV resistance. The gene codes for a protein called CC chemokine receptor 5 (CCR5) that is located on the surface of host cells including macrophages, monocytes, and T cells. HIV exploits this protein by using it as a receptor to bind to, and subsequently infect, cells such as T cells. The CCR5 mutation blocks the manufacture of CCR5. Thus, HIV loses its surface target and cannot invade the immune system.

Subsequent studies conducted in the United States found that one in one hundred people inherits two copies of this gene—one from each parent—and is completely immune to HIV infection. One in five people with only one copy of the CCR5 gene can become infected, but remains healthy two to three years longer than those without the altered gene. This may be because he or she has half as many CCR5 receptors as is normal, which limits or slows the spread of the virus.

Research studies in the United States have found that the gene is most common in white Americans (10 to 15% of the population). It is rarely found in black Americans and almost never in Africans or Asians, perhaps reflecting the origins of the mutation.

Certain populations appear to be resistant to HIV because they lack or have a mutated form of the CCR5 receptor. Most populations that carry the mutant CCR5 gene come from Europe, and there are indications that the mutation arose only about seven hundred years ago. For a mutation to be sustained in a population at a rate of 10%, there must be some benefit bestowed by the mutation. It is likely nothing to do with HIV, since HIV did not appear until the middle of the twentieth century.

Exactly what the selective pressure was that caused the appearance of the CCR5 mutation is debatable. A prevailing theory has been that the selective pressure was the bubonic plague. But new research leads to the proposal that smallpox was the trigger. Which of these, if either, is true remains to be determined.

Research is also underway to learn more about another gene—CCR2—that, when expressed dominantly, appears to slow the progression of AIDS.

NEW RESEARCH

The Thymus Gland and the Immune System

One of the next major challenges in the fight against HIV/AIDS is reviving a deteriorated immune system. Without a healthy immune system, HIV/AIDS patients will not be able to recover from the disease, even if a cure is found. Researchers theorize that it may be possible to rejuvenate a wasted immune system. The key to this is the thymus gland, which is located next to the heart behind the breastbone. The thymus gland is where T cells mature. When mature, the T cells fight infections in the body. But when HIV invades the body, the virus uses the T cell to replicate itself. The T cell does not survive this process and the whole immune system collapses, leaving the HIV-infected patient susceptible to rare and often deadly opportunistic infections.

Until the late 1990s it was thought that the thymus gland was only active during the first thirty years of life and that no new T cells were made thereafter. In recent years researchers have observed that the new drug combinations, often called "cocktails," seem to be able to boost the number of T cells. No one, however, knows where these new cells are coming from. Currently, doctors use artificial means to increase the number of T cells in HIV-infected persons. If the adult body can indeed manufacture new T cells, it may be possible to restore the immune system.

Morning-After Treatment

HIV has now been classified as a communicable sexually transmitted disease in the United States. A few doctors are beginning to prescribe some of the drugs used to treat established infections as "morning-after" pills in an attempt to prevent transmission of the virus after risky sexual encounters. As of 2005, there is no scientific consensus on the validity of this approach, and the medications are not licensed for this use. But other forms of HIV are halted by prompt use of the drugs, encouraging some doctors to give it a try. For example, an antiretroviral drug regimen given to hospital personnel following an accidental needle stick from an HIV-infected patient seems to reduce the one in two hundred risk of transmission by about 80%. Similarly, antiretroviral treatment given to HIV-infected pregnant women reduces the risk of transmission to the newborn baby from one in four to less than one in ten.

This "off-label" use of potent PIs in an attempt to prevent the spread of HIV, however, is controversial. All drugs used in the treatment of HIV have side effects, some of which may be potentially life threatening. Furthermore, some researchers fear that if people believe morning-after treatment will prevent HIV infection, they may stop taking precautions, such as using condoms, to prevent exposure to HIV. Others feel that the treatment is not appropriate as a preventive measure for people exposed to ongoing risk, such as relationships where only one partner is infected, because the drugs are too toxic. Other methods, such as the continued use of condoms, would be much safer.

Finally, post-exposure treatment is expensive. The costs of two or three drugs taken for a month, plus laboratory tests and visits to the doctor, may run as high as $1,000. Of course, this is a fraction of the cost for lifetime treatment of HIV infection and certainly money well spent if it prevents a person from acquiring the virus.

Some researchers say the morning-after treatment could save lives. The drugs themselves will save some lives, and the offer of treatment will bring people who are at high risk for acquiring HIV into environments where they can get counseling and care. In San Francisco, California, post-exposure treatment is offered to victims of rape as a matter of course. Some doctors feel that if the treatment does not work to prevent the disease, it may work to at least treat it as early as possible. Though there is disagreement about the effectiveness and wisdom of widespread use of post-exposure treatment, nearly all researchers and health care providers agree that for sexually active people the best prevention is the use of condoms.

Additional Research

There are several promising directions in HIV/AIDS treatment and research. Simplified medication regimens may improve adherence to treatment, and structured treatment interruptions allow the body to recover from the effects of medications. Structured treatment interruptions might, according to the theory, allow the body to regain immunity to HIV during breaks from the medication schedule. Other studies focus on better understanding of HIV-specific immunity and how to retain or restore it, as well as research into nutritional deficiencies that might accelerate the disease among some patients.

IN SEARCH OF A VACCINE

Some pharmaceutical companies claim that the high costs of research and development and the relatively low return on their investments (since the period of patent protection is limited to seven years) leave little financial incentive to develop new HIV/AIDS drugs. And development of such drugs is, for better or worse, an economically driven, rather than strictly humanitarian, enterprise. Similarly, the companies allege that they have little economic motivation to research and develop HIV vaccines. In February 1996 Anthony Fauci, the head of NIAID, released guidelines to promote cooperation between the government and private industry. The plan's goal was to overcome the alleged unfavorable market forces that have caused some companies to abandon research of potential HIV vaccines.

Such vaccine efforts continue. At the beginning of 2003 NIAID and the international HIV Vaccine Trials Network announced an agreement with Merck & Co., a leading manufacturer of anti-HIV compounds, to support the evaluation of promising HIV vaccines. To date, thirty potential vaccines have been evaluated.

In 2005 fifteen vaccine trials involving more than thirty-six hundred participants were in progress, according to the HIV Vaccine Trials Network and the Pharmaceutical Manufacturers of America. (See Table 6.6.) One of the candidate vaccine trials is taking place in the countries of Brazil, Haiti, Peru, and Trinidad and Tobago. Two vaccine trials are underway in South Africa and Botswana. Two other trials are international in scope. Finally, thirteen vaccine trials are ongoing in the United States. While most of the trials are small-scale (phase I) trials, two large-scale phase III trials are underway and two other trials may enter phase III testing.

The design of the vaccines currently under trial is varied. Eight of the vaccines use a weakened and medically safe version of viruses as a delivery vehicle to carry various HIV genes into the human participants. The hope is that antibody production to the HIV critical proteins encoded by these genes will occur, and that this production will offer protection from HIV infection. Six other vaccines use a DNA plasmid to ferry HIV genes into the human participants; the aim again is to stimulate antibody production.

There are problems of experimental design and ethical considerations involved in vaccine trials using human volunteers. Most volunteers for the vaccine have behaviors that put them at risk for contracting HIV. Some may mistakenly believe that participating in the clinical trial of an experimental vaccine—which may be a vaccine or a placebo—protects them and, with a false sense of security, they may resume high-risk behaviors.

If these volunteers contract HIV during the clinical trial, scientists cannot be sure whether it is from risky behaviors or from the experimental vaccine (some vaccines may contain live HIV because a weakened version of the virus itself is used to stimulate the body's immune system to act against the virus). When volunteers contract HIV during trials, the testing is abandoned. On the other hand, volunteers may reduce their risks so successfully that they are never exposed to HIV, leaving the vaccine nothing to fight. This paradox is unique to HIV/AIDS research and frustrates scientists.

Despite optimistic projections in the early 1990s that a vaccine would be found by 1995, a considerable number of promising experimental HIV vaccines have proven ineffective against strains of HIV taken from infected people. Researchers reported developing antibodies that worked successfully against HIV grown in test tubes, but in every case they failed when used against HIV in human beings. NIAID head Anthony Fauci commented that the results of the initial vaccine research were "cause for some sober reflection." As of 2005, none of the candidate vaccines has shown sufficient promise to warrant manufacture, approval, and use.

Nonetheless, Robert Gallo, one of the co-discoverers of HIV and the director of the Institute of Human Virology at the University of Maryland, Baltimore, is cautiously optimistic about the development of the HIV vaccine. Speaking at the first World Congress on Men's Health in Vienna, Austria, in October 2001, Gallo predicted that one of the vaccines then under investigation would likely be successful. Still, those in need will have to wait for this optimism to bear fruit. At that time Gallo said he believed an effective HIV vaccine was "realistically at least five years away."

The First Large-Scale Human Test

In June 1998 the FDA granted permission to VaxGen Inc. of San Francisco to conduct the world's first full-scale test of a vaccine to prevent HIV infection. The VaxGen vaccine—a genetically engineered molecule designated AIDSvax—had been found safe in tests involving twelve hundred volunteers in March 1992, with more than 99% of the vaccinated participants producing antibodies. The 1998 test involved five thousand volunteers in forty clinics throughout the United States and Canada, and twenty-five hundred volunteers in sixteen clinics in Thailand.

AIDSvax is made from part of HIV's outer coat, specifically a molecule called gp120. The molecule functions in the attachment of the virus to host cells. The vaccine did not contain the intact virus, only the gp120 protein from two strains of HIV. (Previous vaccines had used one strain.) The two strains of the vaccine that were tested in North America are made with strains common in North America. The vaccine used in Thailand contained strains common to that part of the world. Participants in the North American study were men who have sex with men and uninfected partners of HIV-positive people. In Thailand, volunteers were uninfected intravenous drug users. Two-thirds of the North American volunteers were given the vaccine, and the rest received a placebo. In Thailand, half the group received the vaccine and half were given a placebo. The four-year trial ended in 2002.

The trial results were reported on February 23, 2003. Unfortunately, AIDSvax was determined to be a failure, as the comparison of those who received the vaccine versus those receiving a placebo demonstrated a meager 3.8% reduction in new HIV infections in the vaccine population. This result is statistically insignificant. Surprisingly, Asians and blacks who received the vaccine displayed an astounding 67% lower rate of infection than their racial counterparts who received the placebo. Considerable debate has arisen concerning these latter observations. Was this a statistical fluke? Or did AIDSvax display demographically specific protection, and if so, why?

Although health officials and AIDS activists are hopeful, scientists are divided over when and which experimental vaccines should be approved for full-scale testing. Some favor trying any promising vaccine while others advise waiting until the vaccine is completely understood before testing it. The results of the AIDSvax trial could sway the argument toward the latter camp.

One potential problem with AIDSvax, and perhaps a partial explanation of the poor overall results, is that previous tests indicated that it boosted only one part of the immune system—the component of the immune system responsible for antibody production. It is generally believed that a truly effective anti-HIV vaccine must boost another part of the immune system—the killer T cells that destroy virus-infected cells. Some experts consider the vaccine a long shot, but others point out that a failed vaccine does not mean that the experiment failed. Negative results can teach researchers what not to do in the future.

Vaccince Research Center

In 2000 the Dale and Betty Bumpers Vaccine Research Center (VRC) opened on the NIH campus in Bethesda, Maryland. The $34 million facility is overseen by Anthony Fauci and brings together private companies and federal agencies to research, develop, and produce vaccines. Though VRC is not exclusively devoted to HIV research and will eventually begin efforts to develop vaccines for other diseases, VRC director Gary Nabel says HIV is a first target for the facility, which had $40 million in funding in 2002.

The first testing at VRC began in October 2001 and is a study of VRC-001-VP, a DNA vaccine that contains tiny amounts of reengineered HIV DNA. The clinical trial of VRC-001-VP involves volunteers who are not necessarily at risk for HIV infection and seeks to answer questions about how the immune system responds to the vaccine and the best timing for administering second and third doses of the vaccine.

The results were encouraging and demonstrated that the vaccine was safe, well-tolerated by the volunteers, and could induce immune responses. Beginning in December 2003, a larger clinical trial of the vaccine began. The encouraging results from the trial prompted a larger, ongoing clinical trial, which began in January 2005.

While most researchers are optimistic that an effective vaccine will be developed, many believe it may take as long as ten years to perfect a vaccine. As of 2005, researchers at the VRC believe that more than one vaccine formulation, or a vaccine that works two ways—to boost immunity provided by T cells and to produce antibodies to attach to HIV and mark it for destruction—may be necessary to provide complete protection.

A Dissenting View on Why There Is No Vaccine

A small group of researchers who call themselves the Group for the Scientific Reappraisal of the HIV/AIDS Hypothesis dispute the view widely held by the rest of the world's scientific community, namely that AIDS is caused by HIV. The two champions of this very controversial view are Peter Duesberg, who discovered the first cancer-related gene in 1970 and is a professor of molecular and cell biology at the University of California, Berkeley, and Kary Mullis, winner of the 1993 Nobel Prize in chemistry. Duesberg and Mullis disagree on exactly what causes AIDS, but they do agree that HIV is not the cause. In Inventing the AIDS Virus (Washington, DC: Regnery, 1996), Duesberg observed that despite huge efforts—more than one hundred thousand research papers published and $35 billion in taxpayer dollars spent—the HIV/AIDS hypothesis has failed to produce any public health benefits.

Duesberg bases his hotly disputed, highly controversial hypothesis, in part, on the fact that existing theories concerning the cause of AIDS rely on epidemiological, or circumstantial, evidence—that HIV is found in all people who have AIDS—and not on scientific proof that directly connects HIV with AIDS. If an infectious agent caused AIDS, Duesberg argues, it would exhibit five distinct qualities:

1. It would spread randomly between the sexes.
2. AIDS would appear quickly, in a matter of weeks or months instead of years.
3. Active and plentiful HIV microbes would be identifiable in all cases.
4. Cells would decrease or be impaired to the extent that the immune system could not replace them.
5. There would be a logical and consistent pattern of symptoms in AIDS patients.

Duesberg's reasoning is compelling to some: none of these qualities has been observed with HIV. Infection in men is far more common than in women, though this is changing; the onset of AIDS can take up to eleven years; the virus is difficult to isolate; cells in AIDS patients are replaced; and symptoms vary among patients.

Duesberg's detractors contend that the overwhelming body of research links HIV to AIDS. Even some of the critics, however, still agree with his basic observation: because more than twenty years have passed since AIDS was first described and research has failed to substantially change the fate of people with HIV/AIDS, new paths of investigation may be in order.