~HIV and AIDS

~HIV and AIDS
Reprinted with permission of Life Extension®.



A Brief History of HIV/AIDS

In June 1981, the Centers for Disease Control published a report on five cases of P. carinii pneumonia (CDC 1981). At that time, P. carinii was a very unusual form of pneumonia. All five cases occurred in gay men who had other unusual infections and abnormal lymphocyte (white blood cell) ratios. Subsequently, researchers discovered that there was evidence of human immunodeficiency virus (HIV) prior to 1981. Later investigations of European recipients of Factor VIII (the clotting factor missing in hemophiliacs and used in intravenous [IV] replacement to control bleeding episodes) showed that HIV was present in some plasma donors from the United States in 1977. Antibodies against HIV were found in specimens collected from the Belgian Congo in 1959. HIV probably spread from the Congo to Brussels, Belgium, to New York, to the gay male population in Los Angeles, CA, and then to San Francisco, CA. Comparisons of HIV to very similar chimpanzee viruses showed that HIV ancestors crossed over the species line from chimpanzee to human several times from 1910-1950.

After the initial report in the CDC medical journal, the ensuing 20 years saw the development of a worldwide epidemic involving both sexes (termed a horizontal epidemic by infectious disease language), as well as mothers and children (vertical epidemic). During this time, procedures for "universal precautions" in handling blood and other body fluids became standard procedure. The wisdom of universal precautions is now exceedingly clear, even obvious; but in the 1980s, blood banks in the United States and other countries lost credibility because of contaminated blood bank pools. In France and Japan, officials were publicly chastised and prosecuted; some were given jail sentences as representatives of blood bank facilities that failed to protect hemophiliac patients from contaminated blood. (Factor VIII, the clotting factor missing in the most common form of hemophilia, is composed of pooled plasma from multiple donors and, as such, had the highest risk of HIV transmission of any blood product. A single dose of Factor VIII cryoprecipitate contains contributions from 1000-20,000 donors.)

The United Nations named HIV and acquired immune deficiency syndrome (AIDS) a major threat to developing countries. In this time period, the disease orphaned 13.2 million children, infected 60 million people worldwide, and killed a worldwide total of almost 22 million people, rivaling the 25 million death count from the Black Death (bubonic plague) of the 14th century (Gottlieb 2001; Sepkowitz 2001; Steinbrook 2001).

In the last 20 years, we have seen waves of nearly mass hysteria about HIV, long periods of dashed hopes regarding treatment, resurgence of optimism with the development of the newer treatments of highly active antiretroviral therapy (HAART), frustrated efforts at vaccine development, and global rates of infection at crisis proportions, especially involving transmission from mothers to children.

AIDS activists made definite helpful reforms regarding the availability of newer drugs and the drug approval process. In 1986, it took an average of 34.1 months to push a drug through the FDA approval process. In 1999, this time frame decreased to an average of 12.6 months. Rather than following the established rules of lobbying, other novel approaches were used, such as drug buyers' clubs, civil disobedience, and telephone "zaps" during which the telephone switchboard of a targeted company was incapacitated by a barrage of incoming coordinated calls. Because of AIDS activism, patients are now routinely consulted in drug study design. Community-based research efforts are conducted all across the country, and new drugs are made available more quickly.

In the United States, after the development of protease inhibitors, one of the drug classes used to treat AIDS (see the Treatment of HIV/AIDS section for more complete definitions of drug types), the death rate from AIDS declined in 1996. With adequate insurance, people infected with HIV in the United States can afford the $10,000 a year required for HIV therapy and monitoring. With the newer therapies, the face of AIDS is changing from that of the grim reaper into a manageable chronic condition--at least in the United States and Western Europe.

High cost and difficulty in monitoring the disease process still keep infection rates from HIV in developing countries incredibly high. Interestingly, because we now have treatments that have improved survival, the HIV problem in affluent countries is changing to a feeling of complacency regarding the disease. In addition to this complacency, patients and the medical community face problems related to drug resistance, toxicity to pharmacologic regimens, and the development of new drug protocols, including when to start and stop therapy or change a particular protocol.

Etiology

In the early years of HIV, many causes of AIDS were proposed. Some of these now seem quite eccentric, although they were plausible at the time. Prior theories, now discarded, include: (1) the disease was caused by CMV (cytomegalovirus, which was found with very high frequency in those with AIDS); (2) HIV was caused by amyl nitrite or isobutyl nitrite, both of which were used as sexual stimulants and were known immunosuppressants; (3) repeated exposure to another's sperm triggered an immune response, resulting in eventual suppression of immunity; and (4) the disease was caused by a non-HIV virus, not yet discovered.

As more and more evidence accumulated through reports of transmission via blood products, less doubt existed about a viral cause. In some quarters, doubt still persists that HIV causes AIDS. One remaining theory is that the long-term use of recreational drugs is linked to causation, which is exacerbated by nucleoside analogs, another drug type used in treatment (see the Treatment section for complete definition). The improvements made in retroviral therapy have actually intensified this debate (Sepkowitz 2001).

The 13th International AIDS Conference convened in July 2000 in Durban, South Africa. The Durban Declaration, written and signed by more than 5000 leading researchers, physicians, and directors of research institutions from around the world, was published in Nature (Anon. 2000) and summarized as follows: "The evidence that AIDS is caused by HIV is clear-cut, exhaustive, and unambiguous, meeting the highest standards of science. The data fulfill exactly the same criteria as for other viral diseases, such as polio, measles and smallpox. (The article goes on to list compelling scientific evidence.) . . . . Patients with AIDS, regardless of where they live, are infected with HIV. . . Further compelling data are available. HIV causes AIDS. It is unfortunate that a few vocal people continue to deny the evidence. This position will cost countless lives."

Worldwide Prevalence of HIV

Initial press coverage was given to the homosexual transmission of the disease because AIDS was first reported in gay men, and this was the most common mode of transmission in developed countries. It is important to remember, however, that now heterosexual transmission is the most common occurrence worldwide. Perinatal (during pregnancy, during delivery, or through infected breast milk) transmission from mother to infant is a huge problem in developing nations. Sexual contact between local populations and HIV-positive truck drivers with multiple partners has greatly magnified the spread of HIV in Africa (Jaffe 2001). Along the Trans-African Highway, approximately 20% of young women are infected with HIV. A 15-year-old who was born in South Africa has a 50% probability of dying from AIDS (Jaffe 2001). However, in Uganda, with a program encouraging safe sex, occurrence declined from 1989-1997.

In 1987, no AIDS cases were reported in Thailand, but by the middle of the following year, 40% of Bangkok IV drug users had the virus, which had also spread to those selling sex. India is second only to South Africa in the total number of persons infected. An article in Science projected 10 million cases in China by 2010 (Normile 2000). In Germany, after the fall of the Berlin Wall, the public health system collapsed and HIV infection surged.

Infection rates in the United States have declined recently, but this has led to concerns about the development of complacency toward the illness as described previously. There is evidence of a decline in safe sex practices that may lead to a new wave of epidemic proportion (Jaffe 2001). In the United States, AIDS is the second leading cause of death in the age group of 25-44. Women are the fastest growing segment of the AIDS population, and more and more persons over 60 are now HIV-positive.

Special Populations and HIV

  • Women
  • Occupational Postexposure Prophylaxis
  • Children
  • Underdeveloped Countries


Women and AIDS. In the United States, women are the fastest growing segment of the population becoming HIV-positive. Worldwide, where HIV incidence rates in females have already been high, this is not the case. Unfortunately, because of low prior incidence of HIV infection in women, the disease is frequently not considered by physicians as a possibility until HIV is in its advanced stages. Women who have abnormal Pap smears (possibly indicating malignancy), vaginal infections, or pelvic infections that are unusual in some way (such as being recurrent or are unusually resistant to treatment) may have HIV. When AIDS is treated, women also present a special problem in the development of drug resistance. Drugs used in the treatment of AIDS diffuse into the female genital tract at concentrations lower than that in the blood, and because of this low-level exposure of HIV to the drug, resistant HIV strains can develop (Si-Mohamed et al. 2000, as reported in Women's Health and can be found at the following link: http://womenshealth.medscape.com/25636.rhtml ). When indicated, cervical and vaginal secretions should be checked for resistant HIV strains. The development of a resistant strain means therapy must be changed, sometimes to a more toxic or less well-tolerated regimen.

Occupational Postexposure Prophylaxis. This therapy applies to occupational exposure, such as to a healthcare worker by a single needle-stick exposure to an HIV-infected individual, as well as to other types of single, unintended needle exposure or sexual exposure. Postexposure prophylaxis is intended to be a rare occurrence and should not be considered as routine treatment for continuous sexual or needle exposure because this type of use more rapidly leads to the development of drug-resistant HIV strains. Therapy in this setting should be a two-drug regimen and continue for 4 weeks. Lab evaluations for possible adverse effects from the drugs used should be considered after 2 weeks of therapy. If the exposure contained a resistant HIV strain, then a more intense regimen of three or more drugs to which the virus is susceptible should be selected (Carpenter 1998). Health care workers who experience HIV exposure may wish to enroll in the CDC registry by telephoning (888) 737-4448.

Children. The general principles of HIV treatment in adults also apply to children. There is a considerable population of hemophiliac children who became HIV-positive via receiving HIV-contaminated Factor VIII concentrate during treatment. The incidence of transmission was high in the early days of HIV, prior to more rigorous blood-banking tests because pooled plasma used for Factor VIII was obtained from such a large number of donors. There have been delays in the development of drug formulations for children, especially the protease inhibitors. Unappealing taste or nonliquid formulation may make the drug difficult for children to take. Young children have higher CD4 counts than adults, and these counts decrease with age (CD4 cells are a subpopulation of T-cells). Thus, it is sometimes difficult to determine if a declining CD4 count is due to disease progression or the natural changes occurring with maturity. In general, children respond well to combination therapy, even though it is more difficult to achieve complete viral suppression in children (Darbyshire 2000).

Underdeveloped Countries. Treatment of AIDS in resource-poor countries certainly relates to cost--not only the cost of the treatment (drugs) but also the cost of monitoring treatment response and drug toxicity with laboratory markers, and the cost of tracking the population that is HIV-positive. A less-than-optimal response in any of these areas can lead to development of drug-resistant HIV strains, which will of course further complicate and threaten the success of therapy. In resource-poor countries, transmission of the virus from mother to infant is the major source of infection. Fortunately, there have been improvements in treatment in the perinatal transmission of AIDS. Two doses of nevirapine, 1 given to the mother in labor and 1 to the baby, decrease the transmission rate by 50% (Guay et al. 1999; Darbyshire 2000). There has been a worldwide philanthropic call to buy nevirapine for developing countries (Renault 1999). AZT (zidovudine) and 3TC (lamivudine) have also been used over longer time periods to decrease perinatal transmission. Drug therapy may not be as effective in populations with generally poor medical compliance or in those who are difficult to track for other reasons.

Continued . . .
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