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Clinical Overview of HIV Disease

Section 1: Introduction and History

Widespread awareness of HIV disease began with a brief report in 1981, published in the Morbidity and Mortality Weekly Report , of a rare pneumonia caused by Pneumocystis carinii (now known as P jiroveci ) as well as other unusual infections in 5 young homosexual men in Los Angeles.( 1 ) Awareness that a significant epidemic was developing grew as case reports mounted and similar immune deficiency syndromes were described in New York, California,( 2,3 ) and elsewhere among homosexual men, intravenous drug users, Haitians,( 4 ) hemophiliacs,( 5 ) recipients of blood transfusions,( 6 ) infants,( 7 ) female sexual partners of infected men,( 8,9 ) prisoners,( 10 ) and Africans.( 11 ) As researchers began to describe the epidemiology and risk factors in a systematic way, many theories emerged regarding the cause of the mysterious disease. An infectious agent was postulated, and, in 1983, a novel human retrovirus was isolated as the putative etiologic agent.( 12-14 ) That virus was eventually named human immunodeficiency virus, or HIV.( 15 ) Despite dramatic advances in basic virology and clinical management, HIV infection has developed into a worldwide pandemic, with tens of millions of individuals infected by the virus and many millions more affected by it. Clinicians treating HIV are challenged by a clinically complex illness with relatively limited resources for treatment in most settings.

By 1985, serologic assays had been developed to test for HIV infection in asymptomatic persons, to identify new infections by seroconversion, and to screen blood donations.( 16 ) Early trials of antiviral treatments for HIV and immune modulators were fraught with disappointment.( 17-22 ) In 1987, zidovudine (AZT, or azidothymidine) became the first drug approved by the U.S. Food and Drug Administration (FDA) for the treatment of AIDS.( 26 ) Early excitement over the life-extending effects of the drug soon waned, as patients treated with this single-drug therapy began to experience disease progression leading in most cases, to death. However, understanding of the epidemiology, treatment, and prophylaxis of opportunistic infections (OIs) associated with HIV-induced immune deficiency led to significant life-saving advances, particularly in the areas of infection with Pneumocystis jiroveci and Mycobacterium avium complex (MAC).( 27,28 )

The introduction of protease inhibitors (PIs) in the mid-1990s revolutionized the treatment of HIV.( 29 ) Effective combination antiretroviral therapy (ART) became the standard of care in the United States and Western Europe. Very soon thereafter, countries in which effective ART was available began to note sharply declining morbidity and mortality associated with HIV infection.( 30 )

Studies of patients receiving the new therapies shed light on HIV pathogenesis. Patients treated with potent ART showed precipitous decreases in the amount of HIV RNA circulating in their serum, indicating interference with HIV replication (which, unimpeded, can produce more than 10 billion viral particles per day). Additionally, after successful inhibition of viral replication, CD4 T-cell counts began to increase in treated individuals, demonstrating the regenerative capacity of the damaged immune system.( 31 ) Corroborating this understanding of the dynamic interaction between viral replication and the host immune system, studies began to show the value of HIV RNA measurement (viral load) as both a predictor of disease progression and a measure of treatment success.( 32-36 )

Potent therapy was not without complications, however; and the dogma of the late 1990s, "hit early, hit hard," ( 37 ) became balanced by realization that long-term medication toxicity was likely among individuals who were now living longer, healthier lives with HIV infection. Once again, the paradigm of HIV treatment underwent revision, and treatment was now recommended primarily for individuals with more advanced disease.( 38 )

This chapter provides a general overview of issues relevant to clinical practitioners. More extensive discussions on the topics covered here are available in other chapters of the HIV InSite Knowledge Base .