Traditional Medicine

Traditional medicine is a tightly controlled system of regulations, ac­creditation, approval, and licenses. Providers of health care—physi­cians, midlevel practitioners, nurses—must be licensed, and their li­censes depend on training, postgraduate education, and certifying examinations.

This system of controls is set up to safeguard the public. The con­trols are meant to stop people or programs or institutions from claim­ing to offer services or cures that are in fact unnecessary, useless, or un­proven.

The health care providers and the health care facilities of traditional medicine are discussed in chapter 7, and financing health care is dis­cussed in chapter 9.

Traditional Medicine's Drugs

Most of the drugs offered by traditional medicine have been tested by a scientific method that starts with studying the drug in a test tube and ends an average of twelve years later after studying the drug in thou­sands of people (see below, “Experimental Drugs and Clinical Trials”). The results of those tests are analyzed statistically, to see if some appar­ent benefit is actually due either to simple chance or to “outliers,” those rare and exceptional cases that lie far outside the average case.

The important part of this process is the rules by which the study was done in the first place. Certain protocols are now standardized for HIV treatment. The number of participants, or sample size, needs to be adequately large. The participants need to be randomized, that is, as­signed randomly to either the new drug regimen or the standard drug regimen for comparison. The study must be long enough, usually 24 to 48 weeks. The study’s end point—usually measurements of the viral load, the CD4 cell count, and/or the presence of HIV-related complica- tions—needs to be clearly defined. Information about the drugs’ safety also needs to be clearly defined.

If the results survive the peer review process, they are published in medical journals and presented at meetings, especially the HIV/AIDS medical meetings attended by 3,000 to 6,000 people whose careers are committed to HIV. This entire process ensures that physicians learn about new treatments and reassess old ones. The process by now has a twenty-year history and has become thoroughly standardized.

A second way that drugs get reviewed is the FDA’s regulatory process. The FDA licenses new drugs for sale in the United States. Other countries have similar agencies. The FDA’s purpose is to assure the safety and efficacy of new drugs; to let doctors and patients know that drugs sold in the United States are safe, within reasonable and well-defined lim­its; and to make sure drugs work for selected and well-defined condi­tions.

FDA reviews are tedious, expensive, and time-consuming, but the need to assure safety and efficacy is an incredible demand. For the aver­age drug, the total cost of development is around $1 billion; three thou­sand patients need to be studied; and the review takes six to twelve months. The length, extent, and cost of this process may be appropriate and necessary for new drugs for non-life-threatening conditions like si­nusitis, headache, and joint pain. But it may be unnecessarily rigid and slow for serious conditions that kill people, like AIDS and cancer. Be­cause of this argument, the FDA has developed a fast-track review of drugs for critical medical conditions, including AIDS. By the start of 2006, 21 of 22 drugs submitted in the past twenty years by pharmaceu­tical companies for the treatment of HIV were approved. The time re­quired for review after submission was generally three to six months, and the sample size required was substantially lower than for other drugs. This fast review process has helped create a rich pipeline of new drugs, thereby drastically improving HIV care. The process remains rig­orous, using the same protocols for clinical trial design to establish safety and efficacy.

Approved Drugs

The drugs used in traditional medicine can be classified into approved and unapproved drugs. An approved drug is a drug that is approved by the FDA and that can be sold to the public (see below, under “Experi­mental Drugs and Clinical Trials”). Approved drugs are further divided into nonprescription drugs, prescription drugs, and controlled drugs. Nonprescription drugs, like aspirin and cold remedies, can be bought by anyone—that is, they are “over the counter” drugs. Prescription drugs can be bought only with a prescription or with a licensed physician’s tele­phone call to a pharmacy.

Most approved drugs have two names: a generic name, which is usu­ally also the medical name (like pentamidine), and a trade name, which is usually selected by the drug’s manufacturer (like Pentam). Drugs that have been patented by a single manufacturer have only one trade name. Once that manufacturer’s patent runs out, many manufacturers can make the drug, and each manufacturer now puts a different trade name on the drug. As a result, there can be several trade names for a single generic drug (trimethoprim-sulfamethoxazole is called both Bactrim and Septra).

Unapproved drugs, often called underground drugs, are drugs that are neither approved by the FDA nor in the process of being approved. They are widely taken without prescription by people with HIV infec­tion. They are discussed further below, under “Alternative Medicine.”

Types of Drugs Used for HIV Infection

People with HIV infection take three kinds of drugs: drugs against the virus, drugs and vaccines to prevent the complications of HIV infection, and drugs to relieve unpleasant symptoms.

Drugs directed against HIV are called antiviral or antiretroviral drugs. Antiretroviral drugs come in three groups, defined by how they act against HIV. See also chapter 3.

Nucleoside analogs (“nukes”). This group of drugs attacks HIV by in­terfering with one of HIV’s enzymes, called reverse transcriptase. HIV uses reverse transcriptase to change its RNA to RNA’s mirror image, DNA. The viral DNA then becomes part of the DNA of an infected cell like the CD4 cell. So when the CD4 cell reproduces, it produces more HIVs and is itself eventually destroyed. When the nukes interfere with reverse transcriptase, they therefore interfere with HIV’s takeover of the CD4 cell’s DNA.

Protease inhibitors (PIs). These were introduced in late 1995. PIs at­tack HIV at a different place in its reproductive cycle. Once HIV is inside the cell and has taken over the cell’s DNA, it uses the enzyme called protease to help make the complete virus. So by inhibiting protease, the PIs inhibit HIV from ever completing the virus’s life cycle. The PIs are more potent than the nukes, both in the test tube and in the body (see table 4).

Nonnucleoside reverse transcriptase inhibitors (NNRTIs). As the name implies, these drugs, like the nukes, inhibit reverse transcriptase, but they are not chemically or biologically like nucleosides (see table 4).

Entry inhibitors. A fourth class of anti-HIV drugs, the entry inhibitors, block HIV’s entry into the CD4 cell. The first entry inhibitor was enfu- virtide (T20, Fuzeon), approved by the FDA in 2003. Enfuvirtide needs to be injected twice daily. Several more entry inhibitors, to be taken by mouth, are being developed. Many experts feel that this new class of drugs will have an important impact on HIV infection and its manage­ment.

Aside from all the antiretroviral drugs, another category of drug taken by people with HIV infection prevents complications. A multitude of drugs prevent the most frequent and serious of the complications, pneumocystis pneumonia. Other drugs prevent other frequent compli­cations such as tuberculosis, toxoplasmosis, and Mycobacterium avium complex (MAC). Vaccines prevent influenza and pneumococcal pneu­monia. We know that these prevention strategies work, because proper clinical trials have shown that they do. For these complications, we know ways to detect who is most susceptible: for pneumocystis pneu­monia, a CD4 count under 200; for toxoplasmosis, a CD4 count under 100 coupled with a positive blood test; for MAC, a CD4 count less than 50; and for tuberculosis, a positive skin test.

The third type of drug taken by people with HIV infection provides relief from unpleasant symptoms, including insomnia, anxiety, depres­sion, fever, aches, problems with sleep and appetite, nausea, diarrhea, and pain. These drugs don’t cure the problem causing the symptoms, but they do reduce the person’s suffering. Relieving symptoms is the strat­egy used for most noninfectious diseases.

A fourth type of drug is used to treat the side effects of the drugs listed above. For example, the high levels of blood cholesterol that many antiviral drugs cause can be treated with statins. Diarrhea can be treated with loperamide. Sometimes the best treatment is simply to switch drugs, but if the side effect is not serious, if the goals of treatments are achieved, and if the alternative options are limited, our tendency is to press on and continue treatment aimed just at the symptoms of the side effect.

Side Effects of the Drugs

Many of these drugs have side effects, referred to by physicians as ad­verse drug reactions, ADRs for short. The ADRs of most drugs are well known and well defined, based on the experience of thousands of peo­ple who took the drug during its clinical trials, and on the experience of everyone who took the drug once it was on the market. Although any­one can develop ADRs, for some reason ADRs are more common in peo­ple with HIV infection. For instance, trimethoprim-sulfamethoxazole (Bactrim or Septra) causes ADRs in 10 percent of the people without HIV infection and 50 percent of those with HIV infection.

ADRs are classified as either allergic or toxic. Allergic reactions mean that the cells of the immune system have recognized the drug as foreign and have responded by causing a rash, a fever, or both—like the rashes that penicillin causes in some people. In allergic reactions, the dose of the drug is unimportant: the immune system will respond simi­larly regardless of the dose. Serious allergic reactions often imply that neither that drug nor any related drugs should be taken again.

Toxic reactions are caused not by the immune system but directly by the drug itself. An example is the drowsiness caused by Dramamine or other antihistamines or the kidney damage and anemia caused by am­photericin B. Toxic reactions are usually dose-related; lowering the dose will relieve the symptoms.

People usually develop ADRs after they have been taking the drug for one or two weeks. Some people, however, will have a serious ADR after one dose; others will have no ADRs until after they have taken the drug for months or years; some develop ADRs after repeated courses of the same drug. Therefore, ADRs are unpredictable: because a drug was taken once and tolerated does not mean that it can be taken later and cause no ADR.

Sorting out and controlling ADRs will be done by a physician. The physician will either give the person with a suspected ADR what is called a drug holiday—discontinuation of all drugs—or will stop drugs one at a time, starting with those that are most likely to cause ADRs and those that are most dispensable.

Table 9 lists the prescription drugs commonly taken by people with HIV infection, their generic and trade names, their doses, the conditions they treat, and their side effects.

Costs of the Drugs

The costs of the drugs differ, depending on the pharmacy and whether they are generic or trade-name drugs. Nearly all people with HIV infec­tion taking HIV drugs get those drugs from a prescription plan through an HMO, a commercial insurance company, Medicaid, Medicare, or the Ryan White Care Act funds. Few people can afford the full price of these drugs, so some prescription plan is nearly always necessary. Some peo­ple prefer mail order pharmacy services for convenience, cost savings, and anonymity. Ask your physician to write prescriptions, when appro­priate, for drugs under their generic rather than their trade names. Many drugs required by people with HIV infection still have a patent; these tend to be expensive, usually $2,000 to $10,000 yearly if continuous use is re­quired. The patent protects the exclusive right of the drug company that discovered the drug to sell it. This protection means that the company can charge what the market will bear—even if the drug is easy to make— and is the reason that drugs are so expensive. The situation angers con­sumers and insurance companies. Nevertheless, patent protection is the reason we have such progress in drug development in this field, the rea­son people with HIV infection now live fifteen years longer, and the

Table 9. Drugs Commonly Taken by People with HIV Infection

225

Cost/Week or

226

Common infections: pneumonia, infectious diarrhea

227

228

ulcers on penis)

229

rash, hair loss: all are dose-related

Cost/Week or

230

231

Cost/Week or

232

sweat (Rare—liver damage, rash); causes liver to eliminate some drugs faster, so doses of those drugs must in­crease; one of these drugs is methadone—and consequence can be

withdrawal symptoms—and another is birth control pills

233

*The cost figure is the approximate wholesale price of the indicated drug for 2005; the cost to the consumer will usually be higher.

reason they’re likely to live even longer in the future. Once the drug goes off patent, the price drops precipitously. AZT, for instance, went from $12 per day to $.50 per day in one month. The cost of the standard therapy, Highly Active Antiretroviral Treatment (HAART), is $10,000 to $15,000 yearly. Many people question our ability as a society to pay this high price, especially with 800,000 candidates for the therapy. One method to evaluate price is by cost-effective analysis—a method by which we can compute the amount of money required to preserve life for one year. Computing the cost of a year of life preserved balances all costs of tests, treatment, hospitalization, medication, and physicians’ fees. For treatment in the HAART era, the cost is $15,000 to $20,000 per year of life preserved. By comparison, the cost of a year of life pre­served for mammography is $40,000, and for coronary bypass, it is $113,000 per year of life preserved. The point is that on the basis of other well-accepted, standard treatments, the cost of HAART seems justified.

Paying for the Drugs

The question of who pays for drugs is complicated and controversial. All insurers, public or private, differ in whether they pay for drugs, how much they pay, and which drugs they pay for. Medicaid and the Veter­ans Administration both provide coverage for prescription drugs; Medi­care, through its prescription drug plans, covers only some drugs. Com­mercial insurance companies’ plans and Blue Cross/Blue Shield’s plans vary in their coverage. Medicaid is a state-based program, so that cov­erage depends to some extent on where you live. In New York and Mary­land, coverage is generous; in most southeastern states, coverage is fru­gal. The Ryan White Care Act (Title II) funding for medications is also state-based, and again, availability and the extent of coverage depend on where you live. Title II has three criteria for access: limited income and assets, lack of an alternative source of payments, and a formulary that includes the requested drugs.

In general, where Medicaid has frugal coverage, the Title II funds will be not be extensive because a frugal Medicaid plan places demands on the Title II funding. The frugal states have people waiting for access to Title II support, and drug availability is limited.

The companies and plans that do cover drugs sometimes put limits on their coverage. They will pay only for FDA-approved drugs. Non­prescription drugs and drugs used in alternative treatments are not cov­ered by any insurer.

For more information on what insurers do and do not pay for, see chapter 9.