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HIV Medicine 2007
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1. Introduction

Bernd Sebastian Kamps and Christian Hoffmann

The first reports of homosexual patients suffering from previously rare diseases such as pneumocystis pneumonia and Kaposi's sarcoma were published in May 1981 (Centers for Disease Control 1981a, 1981b, 1981c). It soon became clear that the new disease affected other population groups as well, when the first cases were reported in injecting drug users. However, it took almost two years until, in 1983, the human immunodeficiency virus type I (HIV-1) was defined as the primary cause of the acquired immunodeficiency syndrome (Barré-Sinoussi 1983, Broder 1984, Gallo 1984).

Almost 25 years have now elapsed. Twenty-five years, in which HIV infection has changed from a fatal condition to a manageable chronic illness. Twenty-five years, in which the development of antiretroviral therapy (ART) has been one of the dramatic advances in the history of medicine. However, for the vast majority of people living with HIV/AIDS, ART is still light years away - largely inaccessible in resource-poor countries where HIV continues to devastate families, communities and societies, especially the poor and the socially marginalized.

In the following 800 pages, we present a comprehensive overview of the treatment of HIV infection and its complications. As in previous years, all chapters have been thoroughly revised, and most parts of the book were available on the Internet (www.HIVMedicine.com) months before they were printed here. The philosophy that governs the publication of HIV Medicine 2006 has recently been published at www.freemedicalinformation.com. We firmly believe that that is the way medical textbooks should be handled in the 21st century.

Transmission routes

There are several ways in which someone can become infected with HIV. These transmission routes are well defined (see also Chapter "Post-Exposure Prophylaxis"). HIV infection can be transmitted through:

  • unprotected sexual intercourse with an infected partner;

  • injection or transfusion of contaminated blood or blood products (infection through artificial insemination, skin grafts and organ transplants is also possible);

  • sharing unsterilized injection equipment that has been previously used by someone who is infected;

  • maternofetal transmission (during pregnancy, at birth, and through breastfeeding).

Occupational infections of healthcare or laboratory workers may occur; however, a 1995 study estimated that although 600,000 to 800,000 needlestick injuries occurred among healthcare workers every year in the USA, occupational infection was not frequent. The risk of occupational HIV transmission from contaminated needles to healthcare workers was found to be 0.3 % in case series performed prior to the availability of potent ART.

There are sometimes concerns that there may be alternative routes of HIV transmission. It must be explicitly stated that HIV is NOT transmitted by mosquitoes, flies, fleas, bees, or wasps. HIV is NOT transmitted through casual every day contact. No case of HIV infection has been documented to arise from contact with non-bloody saliva or tears. Since HIV is not transmitted by saliva, it is not possible to contract it through sharing a glass, a fork, a sandwich, or fruit (Friedland 1986, Castro 1988, Friedland 1990). In the opinion of leading experts, exposure of intact skin to HIV-contaminated body fluids (e.g. blood) is not sufficient to transfer the virus.

Sexual intercourse

Unprotected sexual intercourse is the most important transmission route of HIV infection worldwide. Although receptive anal sex is estimated to produce the highest risk of infection, infection after a single insertive contact has also been described. The presence of other sexually transmitted diseases markedly increases the risk of becoming infected with HIV.

The lower the viral load, the less infectious the patient. A prospective study of 415 HIV-discordant couples in Uganda showed that of 90 new infections occurring over a period of up to 30 months, none was from an infected partner with a viral load below 1,500 copies/ml. The risk of infection increased with every log of viral load by a factor of 2.45 (Quinn 2000). It should be noted that the levels of viral load in blood and other body fluids do not always correlate with one another. Thus, individual risk remains difficult to estimate. In addition, HIV-infected patients are not protected from superinfection with new viral strains.

The higher the viral load, the more infectious the patient. This is especially true for patients during acute HIV infection. During acute HIV-1 infection, the virus replicates extensively in the absence of any detectable adaptive immune response, reaching levels of over 100 million copies of HIV-1 RNA/ml (see Chapter "Acute HIV-1 infection").

Intravenous drug use

Sharing unsterilized injection equipment that has been previously used by someone who is infected is an important route of HIV transmission in many countries with a high prevalence of intravenous drug users. In contrast to the accidental needlestick injury (see also Chapter "Post-Exposure Prophylaxis"), the risk of transmission through sharing injection equipment is far higher: the intravenous drug user ensures the proper positioning of the needle by aspiration of blood.

Maternofetal

In the absence of any intervention, an estimated 15-30 % of mothers with HIV infection will transmit the infection during pregnancy and delivery. In approximately 75 % of these cases, HIV is transmitted during late pregnancy or during delivery. About 10 % of vertical HIV infections occur before the third trimester, and 10-15 % are caused by breastfeeding.

In Western countries, perinatal (vertical) HIV infection has become rare since the introduction of antiretroviral transmission prophylaxis and elective cesarean section. For more details, see Chapter "Pregnancy and HIV".

Injection or transfusion of contaminated blood products

In most Western countries, administration or transfusion of HIV-contaminated blood or blood products has become a rare event. With current testing methods (for details see also Chapter "HIV Testing"), the risk of acquiring HIV from a unit of transfused blood is about 1:1,000,000. However, while Western European countries, the United States, Australia, Canada, and Japan have strict and mandatory screening of donated blood for HIV, not all countries do.

Natural history

The "natural history" described in the following refers to HIV infection in the absence of HAART.

The acute viral syndrome of "primary" HIV infection (which is defined as the time period from initial infection with HIV to the development of an antibody response) shows symptoms that often resemble those of mononucleosis. These appear within days to weeks following exposure to HIV (see Chapter "Acute HIV-1 Infection"). However, clinical signs and symptoms may not occur in all patients. During acute HIV infection, there is usually a high plasma viremia and frequently a marked decrease in CD4+ T-cells. The CD4+ T-cell count later increases again, normally to levels inferior to the pre-infection values (see Figure 1).

After the acute infection, equilibrium between viral replication and the host immune response is usually reached, and many infected individuals may have no clinical manifestations of HIV infection for years. Even in the absence of antiretroviral treatment, this period of clinical latency may last 8-10 years or more. However, the term "latency period" may be misleading, given the incredibly high turnover of the virus and the relentless daily destruction of CD4+ T-cells.

At the end of the "latency period", a number of symptoms or illnesses may appear which do not fulfill the definition of AIDS. These include slight immunological, dermatological, hematological and neurological signs. Many of them are listed in the Category B of the CDC classification system (see Table 1). Constitutional symptoms, such as fever, weight loss, night sweats, and diarrhea may also develop. In this situation, the level of 200 CD4+ T-cells/µl is an important cut-off, below which the risk of many AIDS-defining illnesses increases, among them several opportunistic infections and certain neoplasms (see Table 1). Above 200 CD4+ T-cells/µl, most AIDS-defining illnesses are rare events (see also Chapter "AIDS").

However, the course of infection may vary dramatically, and in some cases, the progression to AIDS occurs rapidly. Host factors mainly determine whether or not an HIV-infected individual rapidly develops clinically overt immunodeficiency, or whether this individual belongs to the group of long-term non-progressors, who represent about 5 % of all infected patients (for details, see "Pathogenesis of HIV-1 Infection").

CDC classification system

The most widely accepted classification system of HIV infection, initially published by the U.S. Centers for Disease Control and Prevention (CDC) in 1986, is based on certain conditions associated with HIV infection (see Table 1). This classification system was intended for use in conducting public health surveillance and it has been a useful epidemiological tool for many years. In 1993, the CDC classification was revised (CDC 1993b). Since then, the clinical definition of AIDS has been expanded in the USA (not in Europe) to include HIV-infected patients with a CD4+ T-cell count of less than 200 cells/µl or less than 14 % of all lymphocytes, even in the absence of the listed conditions.

Thus, the current CDC classification categorizes persons on the basis of clinical conditions and CD4+ T-lymphocyte counts. There are three clinical categories (A, B, C - see Table 1) and three CD4+ T-lymphocyte categories (1, 2, 3 - see Table 2). For example, a patient with oropharyngeal candidiasis and a CD4+ T-cell count of 250/µl would be classified as B2; someone with asymptomatic infection and a CD4+ T-cell count of 550/µl would be in category A1. Categorization of the CD4+ T-cells should be based on the lowest accurate CD4+ T-cell count ("CD4 nadir") and not on the most recent one.

For children less than 13 years of age, there is a modified and revised classification system for HIV infection (see chapter "Antiretroviral Therapy in Children"). It should also be noted that, besides the CDC classification, the World Health Organization (WHO) has also published a staging system for HIV infection. The WHO classification is an approach for use in resource-limited settings and is widely used in Africa and Asia.

Epidemiology

New estimations have recently resulted in substantial changes in estimates of numbers of persons living with HIV worldwide (UNAIDS 2007). The estimated number of persons living with HIV worldwide is now assumed to be 33.2 million, a reduction of 16% compared with the estimate published in 2006 (Table 3).

The prevalence and incidence of HIV/AIDS vary considerably from continent to continent, from country to country, from region to region. Several countries in sub-Saharan Africa report infection rates of 30 %, especially in urban areas. In other countries, HIV prevalence still remains low. However, low national prevalence rates can be misleading. They often disguise serious epidemics that are initially concentrated in certain localities or among specific population groups and that threaten to spill over into the wider population.

The joint United Nations program on HIV/AIDS (UNAIDS) provides by far the best and most comprehensive overview. The annual AIDS epidemic update of UNAIDS reports on the latest developments in the global HIV/AIDS epidemic. With maps and regional summaries, it provides the most recent estimates of the epidemic's scope and explores new trends in the epidemic's evolution. It can be found at the Website http://www.unaids.org/. Table 1 provides an overview of the devastating situation of the HIV pandemic.

Conclusion

HIV cannot be transmitted as easily as the influenza virus. Compared to other viral diseases, the prevention of HIV infection is therefore easier. In rich countries, individuals who don't want to be infected with HIV may protect themselves and avoid HIV infection. The same people will not be able to avoid the influenza virus of the next pandemia.

HIV infection has become a treatable disease - at least in countries that can afford widespread health coverage. The following chapters describe how patients should be managed in these countries.

Outside these havens of material well-being, things have not changed since the early years of the HIV epidemic 25 years ago. Many people live in a world where no medical progress seems to have been made. This is a shameful situation, and future generations will hopefully do better than we did.

 

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(15th edition, 818 pages, PDF, 3.7 MB)


     
 

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