Problems with Combination Drug Therapy

Despite good news of the increased health and prolonged lives of HIV-infected people undergoing combination drug therapy, there are some problems with this approach. Combination drug therapy is expensive, often results in severe and unpleasant side effects, and most importantly, is difficult to follow. Patients may have to take dozens of pills per day, some of which have very different requirements (for instance, some pills must be taken on an empty stomach, while others need to be taken with food or significant amounts of water). All of this effort is to control an infection that initially may not seem to have any symptoms. As a result of the difficulty of combination drug therapy, it is common for individuals to skip doses, or take themselves off the drugs for a period of time. The side effect of these breaks in treatment is an increase in HIV replication, which increases the risk of developing drug-resistant varieties. Patients who do not follow the drug treatment schedule carefully can find themselves with large virus populations that are multiply drug resistant. Even if this resistant virus is less able to infect cells, few people can live with high loads of HIV for long. To control the virus over the long term, individuals with multiply drug-resistant variants must change and perhaps increase the number of drugs in their cocktail—some patients take 10 to 15 different drugs several times per day. Many scientists fear that the rapid rate of HIV evolution will eventually outpace their ability to both develop new drugs and prolong the asymptomatic period of HIV infection.

Perhaps more troublesome than the evolution of HIV within a patient is the potential evolution of the HIV epidemic in response to combination drug therapy. The rate of transmission of HIV has not significantly changed in the United States for a decade—about 40,000 new infections are reported every year. However, many of the HIV strains that are being transmitted today already carry some degree of drug resistance. Currently, between 10-30% of new infections are of drug-resistant HIV. This means that potentially as many as one-third of newly infected people have fewer options for controlling their virus. As the transmission of drug-resistant HIV increases, our ability to control AIDS in the U.S. population will decline. Worse yet, there is some evidence that combination drug therapy has made HIV and AIDS appear to be less of a threat, leading to decreased prevention efforts and an upswing in infection rates. Combination drug therapy does not cure HIV infection—at best it is an expensive and long-term commitment to increase an individual's ability to live with this disease. Increases in transmission and drug resistance will erode the benefits of this powerful therapy.

Combination drug therapy is also not available to all of the 42 million HIV-infected individuals around the world. Currently, combination drug therapy costs $1,000 to $2,000 per month. As discussed in Essay 9.3, HIV continues to disproportionately affect the poorest and most vulnerable members of our society and the global community. The gap between the resources of the most-affected

Essay 9.3

The Global Impact of HIV

AIDS and HIV no longer dominate the headlines in the United States—apparently for a good reason. According to the Centers for Disease Control (CDC), the number of AIDS-related deaths in the United States has plummeted from over 51,000 in 1995 to less than 16,000 in 2001, mostly due to the effectiveness of combination drug therapy. This is a remarkable 70% drop, and as a result AIDS no longer ranks as a leading cause of death in the United States. Currently, nearly twice as many Americans die from gunshot wounds as from the results of HIV infection.

However, the overall death rate due to AIDS obscures some of the important details of this epidemic in the United States. Data collected by the CDC indicate that AIDS is now the fifth leading cause of death among Americans aged 25 to 44, the third leading cause of death among Hispanic males in this age group, and the leading cause of death for black males in this age group. Nearly 14% of new HIV infections are to injection-drug users, and 59% of new HIV infections reported in teenagers are in girls, most of them African-American. In the United States, HIV and AIDS is becoming a disease of the impoverished and marginalized; people with the least access to adequate health care.

The inequity of AIDS is even more profound on a global scale (Figure E9.3). According to the United Nations Joint Program on HIV/AIDS (UNAIDS), 90% of all HIV infections occur in the developing world—an astonishing 70% of all HIV infections occur in Sub-Saharan Africa. In impoverished countries such as Zimbabwe and Botswana, over one-third of all adults are infected with HIV. The scale of the epidemic is almost impossible to fathom—nearly 30 million people infected, nearly all of whom will die within the decade. Only a tiny fraction of the infected individuals receive anti-HIV drug therapy, and few of them receive basic medical treatment for opportunistic infections. The epidemic in Africa could soon be matched in other impoverished areas of Asia and eastern Europe—in countries whose economies and healthcare systems are sure to be seriously stressed by it.

The devastation caused by AIDS in Africa is exemplified by the country of Malawi, whose people face widespread famine as well as high numbers of AIDS deaths and HIV infections. Adverse weather and changes in government policy contributed to the food crisis, but the impact of AIDS has been substantial. A study performed in central Malawi in 2002 indicated that nearly 70% of households had lost laborers due to illness, and 50% of families delayed planting crops to take care of ill family members or the orphaned children of their relatives. The epidemic is also sapping the ability of the government of Malawi to provide agricultural support for these small farmers because many employees of the government are themselves ill, or must care for ill relatives, and also because government resources are stretched thin by the public-health crisis caused by AIDS.

Rays of hope exist in this bleak landscape, however. According to UNAIDS, prevention programs that emphasize the use of condoms and promote abstinence have helped decrease the number of new HIV infections among young women in Ethiopia, Uganda, and South Africa; and several African governments have begun addressing the AIDS crisis at the highest level. In 2001, the United Nations made a strong commitment to slowing and cushioning the impact of the epidemic around the world, but without resources from wealthy countries, the loss of life and the disruption caused by this disease could be without precedent in human history.

populations and the cost of this promising therapy means that AIDS will continue to kill people by the millions for years to come.

In reality, the best "treatment" for AIDS is to avoid becoming infected with HIV at all (Figure 9.14). HIV is a fragile virus that is only transmitted through direct contact with bodily fluids—primarily blood, semen, vaginal fluid, or occasionally to newborns via breast milk. There is no evidence that the virus is spread by tears, sweat, coughing, or sneezing. It is not spread by contact with an infected person's clothes, phone, or toilet seat. It is not transmitted by insect bite. And it is unlikely to be transmitted by kissing (although any kissing that allows the commingling of blood could lead to HIV transmission). HIV is frequently spread through needle sharing among injection-drug users, but the primary mode of HIV transmission is via unprotected sex, including oral sex, with an infected partner. So, what is the best way to avoid HIV infection? Do not use injection drugs, and if you are sexually active, know your partner's HIV status, drug habits, and sexual activities. According to the Centers for Disease Control,

North America

Eastern Europe and Central Asia

North America

Eastern Europe and Central Asia

Latin America

Latin America

Sub-Saharan Africa

Australia and New Zealand

Figure E9.3 The AIDS crisis. HIV infections are not evenly distributed around the world—in general, poorer areas have more cases. In addition, the rate of spread of infections in various areas is not equal. Whereas developed countries have a rate of new infections of 4-5%, areas of Asia have seen a growth in infections of over 20% in the past several years.

about one-quarter of the approximately one million HIV-infected people in the United States do not know that they carry this deadly virus. If your partner might be at risk for HIV infection, practice safer sex—that is, use a condom.

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