The AIDS Pandemic

Impact on Science and Society

Kenneth H. Mayer, H.F. Pizer

• Publisher: Academic Press
• Year: 2004
• eBook ISBN: 9780080475806
• Topic: Medicine
• Subtopic: AIDS & HIV

The AIDS Pandemic explores the ways in which HIV/AIDS has, and continues to transform the wide range of related disciplines it touches. Novel perspectives are provided by a unique panel of internationally recognised experts who cover the unprecedented impact onf AIDS on culture, demographics and politics around the world, including how it affected the worlds' economy, health sciences, epidemiology and public health. This important far- reaching analysis uses the lessons learned from a wide array of disciplines to help us understand the current status and evolution of the pandemic, as it continues to evolve.* Unique and timely presentation of new theories and perspectives* Concentrates on the changes that have taken place in a broad array of related disciplines* Provides key contextual information, for those new to the field or at interface areas between disciplines* Includes an international focus on evolving African and Asian experiences* Focuses on the current strategies for developing vaccines and microbicides* Outlines harm reduction and prevention programs* Explores issues related to delivery of life-saving AIDS medications in resource-constrained environments

1

Virology

Phyllis J. Kanki ¹ Director, AIDS Prevention Initiative in Nigeria, Harvard School of Public Health, Boston, USA
¹ Phyllis J Kanki, DVM, ScD is Professor of Immunology and Infectious Disease at the Harvard School of Public Health. She received her DVM degree from the University of Minnesota and D.Sc. degree in virology from the Harvard School of Public Health. She has directed the collaborative AIDS research program between scientists at Harvard and University Cheikh Anta Diop in Dakar, Senegal for over 18 years, leading a prospective study of commercial sex workers in one of the longest studied cohorts of HIV infected women worldwide. In 2000 she initiated the AIDS Prevention Initiative in Nigeria, a multi-site collaborative and evidence based prevention program, and directs the Rapid Expansion of anti-HIV Treatment in Botswana, Nigeria and Tanzania. She has published widely and received numerous awards worldwide. Her research interests include HIV pathogenesis, molecular epidemiology, and intervention studies. Her work has described major biological differences and interactions between HIV-1 and HIV-2.

Myron E. Essex ² AIDS Prevention Initiative in Nigeria, Harvard School of Public Health, Boston, USA
² Myron E Essex, PhD is Chairman of the Harvard AIDS Institute, the Mary Woodard Lasker Professor of Health Sciences at Harvard University and Chairman of the Department of Immunology and Infectious Diseases at the Harvard School of Public Health. He holds doctorates in veterinary medicine and microbiology. He has received numerous awards, including in 1986 the Albert Lasker Medical Research Award (with Drs. Gallo and Montagnier) the highest medical research award given in the United States. Dr. Essex has authored or co-authored more than 450 scientific articles and edited seven books. He was one of the first to link animal and human retroviruses to immunosuppressive disease, suspect that a retrovirus was the agent cause in AIDS, and determine that HIV could be transmitted through blood and blood products. Since 1985, Dr. Essex and colleagues have worked with collaborators in Africa and Asia, where they conduct biological, clinical, and epidemiological studies.

In the early 1980s, our laboratory was involved in the study of retroviruses and their association with cancer. Max Essex had been involved in years of investigation on the biology of feline leukemia virus (FeLV), a retrovirus of cats that was not only associated with cancer but also immunosuppressive disorders. FeLV was only one of many known and well-studied animal retroviruses at the time. Viruses in mice, chickens, cows, sheep, and horses had been studied for years in an effort to better understand and investigate possible viral causes of human cancer. Therefore in 1982, the discovery of human T-cell leukemia virus (HTLV) seemed to be the ‘holy grail’ that had been searched for. However, within a few years, descriptions of a new disease or syndrome in young male homosexual populations prompted the search for the causative agent. Infectious disease specialists involved with these populations, epidemiologists, and virologists were drawn into the investigation of this new disease. In the Boston area in the mid-1980s, investigators from the Harvard School of Public Health combined expertise with clinical investigators at Mass General Hospital, Beth Israel, and the New England Deaconess hospitals to conduct studies of suspect cases and controls in a search for the etiologic agent. Small scientific meetings were held at increasing frequency to stay ahead of the new data that were being generated. These meetings brought together investigators from many different disciplines, which in retrospect promoted the public health perspective of the field. New funding opportunities also encouraged multidisciplinary groups that would study this new disease entity.

Once human immunodeficiency virus (HIV) was recognized as the etiologic agent of the acquired immune deficiency syndrome (AIDS), the field recognized some of the technical challenges of further characterizing the viral infection and therefore implementing clinical care. Retrovirus infection had only been relatively recently described in humans with HTLV-I and HTLV-II, and methods for diagnosis through antibodies or virus isolation were relatively new and distinct from other viral systems. Therefore the need for new technologies to address this virus infection was recognized early in the epidemic. In later years, the use of polymerase chain reaction (PCR) technology to detect and quantitate virus provided the foundation for clinical management of this disease. As epidemiologists recognized the alarming increase of HIV/AIDS cases across the globe, the use of PCR-based sequencing techniques allowed the realization of the tremendous diversity of HIV viral strains that compose what we now recognize as the global HIV/AIDS pandemic.

History of the Discovery of HIV

AIDS was first recognized as a new and distinct clinical entity in 1981 (Gottlieb et al., 1981; Masur et al., 1981; Siegal et al., 1981). The first cases were recognized because of an unusual clustering of diseases such as Kaposi sarcoma and Pneumocystis carinii pneumonia (PCP) in young homosexual men. Although such unusual diseases had previously been observed in distinct subgroups of the population – such as older men of Mediterranean origin in the case of Kaposi sarcoma or severely immunosuppressed cancer patients in the case of PCP – the occurrence of these diseases in previously healthy young people was unprecedented. Since most of the first cases of this newly defined clinical syndrome involved homosexual men, lifestyle practices were first implicated and intensively investigated. These included the exposure to amyl or butyl nitrate ‘poppers’ or the frequent contact with sperm through rectal sex, which might have acted as immunostimulatory doses of foreign proteins or antigens.

However, AIDS cases were soon reported in other populations as well, including injection drug users (IDUs) (Anonymous, 1982) and hemophiliacs (Davis et al., 1983; Poon et al., 1983; Elliott et al., 1983). Similar to investigations of male homosexual populations, these new risk groups were exposed to doses of foreign proteins and antigens but through the blood. In the case of IDUs, this would occur through intravenous injection of drugs and needle sharing, and in the case of hemophiliacs through the therapeutic infusion of Factor VIII. Asymptomatic hemophiliacs and IDUs were often found to have unusual immunological tests, such as the inverted T lymphocyte helper:suppressor ratios (i.e. less than the normal 1:1 ratio of helper to suppressor cells). These abnormal tests suggested a problem with the cellular immune system, with low numbers of helper T lymphocytes, also referred to as CD4+ lymphocytes, a finding similar to that observed in many AIDS patients.

Three new categories of AIDS patients were soon observed, including blood transfusion recipients (Curran et al., 1984; Jaffe et al., 1984), adults from Central Africa (Clumeck et al., 1983; Piot et al., 1984; Van de Perre et al., 1984), and infants born to mothers who had AIDS or were IDUs (Rubinstein et al., 1983; Oleske et al., 1983; Scott et al., 1984). The transfusion-associated cases had received blood donated from an AIDS patient at least three years before they began showing symptoms (Curran et al., 1984; Jaffe et al., 1984). Based on the disparate populations afflicted with this new malady and the emerging epidemiology of the disease, the possible infectious etiology for AIDS was considered (Francis et al., 1983).

Multiple studies were initiated to determine the possible role of various microorganisms, especially viruses, in causing AIDS. These studies measured and compared seroprevalence rates for suspect viruses in AIDS patients and controls. The shortlist of candidate viruses included: cytomegalovirus, which was already associated with immunosuppression in kidney transplant patients; Epstein–Barr virus, which was a lymphotropic virus; and hepatitis B virus, which was known to occur at elevated rates in both homosexual men and recipients of blood or blood products. However, based on the unique clinical syndrome and unusual epidemiology of AIDS, if one of these viruses was to be etiologically involved, it would presumably have been a newly mutated or recombinant genetic variant.

At the same time, our group (Essex et al., 1983), Gallo and his colleagues (Gelmann et al., 1983), and Montagnier and his colleagues (Barre-Sinoussi et al., 1983) postulated that a variant T lymphotropic retrovirus (HTLV) might be the etiologic agent of AIDS. Indeed, HTLV, discovered by Gallo and his colleagues in 1980, was the only human virus known to infect T helper (CD4+) lymphocytes at that time (Poiesz et al., 1980). This seemed reasonable since it was already clear that T helper lymphocytes were selectively depleted by the causative agent in clinical AIDS (Rubinstein et al., 1983; Ammann et al., 1983; Fahey et al., 1984; Lane et al., 1985). In addition, HTLV was known to transmit through the same routes as the etiologic agent of AIDS: sexual contact (with transmission apparently more efficient from males), by blood, and from mother to baby (Essex, 1982). Finally, HTLV-I was also known to induce immunosuppression (Essex et al., 1984), as we had previously recognized in animal retrovirus systems (Essex et al., 1985).

AIDS patient blood samples were repeatedly cultured in an attempt to find a virus related to HTLV-I or HTLV-II (Kalyanaraman et al., 1982). Although antibodies cross-reactive with HTLV-I and HTLV-related genomic sequences were found in a minority of AIDS patients (Gelmann et al., 1981; Barre-Sinoussi et al., 1983; Essex et al., 1983), the reactivity was weak, suggesting either AIDS patients were also infected with an HTLV, or that a distant, weakly reactive virus was the causative agent. Soon after, Gallo and his colleagues obtained proof that AIDS was linked to an HTLV (Popovic et al., 1984; Gallo et al., 1984; Schupbach et al., 1984). Further characterization of the agent – now termed HIV-1 – revealed that ...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Contributors
• Preface
• About the Editors
• Dedications
• Introduction
• 1: Virology
• 2: Immunology in the Era of HIV/AIDS
• 3: Quantitative Science
• 4: The Public Health Response to HIV/AIDS: What Have We Learned?
• 5: AIDS and Sexually Transmitted Disease Prevention and Control
• 6: HIV Treatment Meets Prevention: Antiretroviral Therapy as Prophylaxis
• 7: Challenges in Developing HIV Vaccines
• 8: Microbicides
• 9: AIDS Behavioral Prevention: Unprecedented Progress and Emerging Challenges
• 10: The Evolution of Comprehensive AIDS Clinical Care
• 11: The Ever-changing Face of AIDS: Implications for Patient Care
• 12: Economics
• 13: Expanding Global Access to ARVs: The Challenges of Prices and Patents
• 14: The African Experience
• 15: Asia: Health Meets Human Rights
• 16: How HIV/AIDS Changed Gay Life in America – And What Others Can Learn from Our Experience
• 17: Drug Use
• 18: Management of HIV/AIDS in Correctional Settings
• 19: Medical Ethics and the Law
• Index