Pathology of HIV/AIDS

420 Pages·2018·2.27 MB·English

by  Edward C. Klatt

PATHOLOGY
OF
HIV/AIDS
Version 29
by
Edward C. Klatt, MD
Professor of Pathology
Department of Biomedical Sciences
Mercer University
School of Medicine
Savannah
April 16, 2018
Copyright  by Edward C. Klatt, MD
All rights reserved worldwide
DEDICATION
To persons living with HIV/AIDS past, present, and future who provide the
knowledge, to researchers who utilize the knowledge, to health care workers
who apply the knowledge, and to public officials who do their best to promote
the health of their citizens with the knowledge of the biology, pathophysiology,
treatment, and prevention of HIV/AIDS.
TABLE OF CONTENTS
CHAPTER 1 - BIOLOGY AND PATHOGENESIS OF HIV INFECTION . . . . . 6
INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
BIOLOGY OF HUMAN IMMUNODEFICIENCY VIRUS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
HUMAN IMMUNODEFICIENCY VIRUS SUBTYPES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
OTHER HUMAN RETROVIRUSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
EPIDEMIOLOGY OF HIV/AIDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
RISK GROUPS FOR HUMAN IMMUNODEFICIENCY VIRUS INFECTION . . . . . . . . . . . . . 39
NATURAL HISTORY OF HIV INFECTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
PROGRESSION OF HIV INFECTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
IDIOPATHIC CD4+ T-LYMPHOCYTOPENIA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
PREVENTION OF HIV TRANSMISSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
TREATMENT FOR HIV/AIDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
CHAPTER 2 - DIAGNOSIS OF HIV/AIDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
DIAGNOSTIC TESTS FOR HUMAN IMMUNODEFICIENCY VIRUS . . . . . . . . . . . . . . . . . . . . . . . . . 70
PEDIATRIC HIV INFECTION AND AIDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
CRITERIA FOR AIDS-RELATED COMPLEX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98
OTHER CAUSES OF IMMUNOSUPPRESSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
CHAPTER 3 - OPPORTUNISTIC INFECTIONS IN HIV/AIDS . . . . . . . . . . . . . . . . . 100
PNEUMOCYSTIS JIROVECI INFECTIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100
CYTOMEGALOVIRUS INFECTIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104
MYCOBACTERIAL INFECTIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106
CRYPTOCOCCUS INFECTIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115
HERPESVIRUS INFECTIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117
TOXOPLASMA GONDII INFECTIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125
HISTOPLASMA CAPSULATUM INFECTIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127
COCCIDIOIDES IMMITIS INFECTIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129
GASTROINTESTINAL PROTOZOAL INFECTIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130
BACTERIAL INFECTIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
CHAPTER 4 - NEOPLASMS ASSOCIATED WITH HIV/AIDS . . . . . . . . . . . . . . . . . . 144
KAPOSI SARCOMA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144
MALIGNANT LYMPHOMAS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147
OTHER NEOPLASMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153
CHAPTER 5 - ORGAN SYSTEM PATHOLOGY IN HIV/AIDS . . . . . . . . . . . . . . . . . 157
RESPIRATORY TRACT PATHOLOGY IN HIV/AIDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157
GASTROINTESTINAL TRACT PATHOLOGY IN HIV/AIDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178
CENTRAL NERVOUS SYSTEM PATHOLOGY IN HIV/AIDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 198
PERIPHERAL NERVE AND MUSCLE PATHOLOGY IN HIV/AIDS . . . . . . . . . . . . . . . . . . . . . . . . . 216
OPHTHALMIC PATHOLOGY IN HIV/AIDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223
LYMPH NODE PATHOLOGY IN HIV/AIDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 227
SPLEEN IN HIV/AIDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 233
BONE MARROW AND PERIPHERAL BLOOD IN HIV/AIDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235
THYMUS IN HIV/AIDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 240
ENDOCRINE ORGAN PATHOLOGY IN HIV/AIDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 242
HEPATOBILIARY SYSTEM PATHOLOGY IN HIV/AIDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245
CARDIOVASCULAR PATHOLOGY IN HIV/AIDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 253
GENITOURINARY PATHOLOGY IN HIV/AIDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 259
DERMATOPATHOLOGY IN HIV/AIDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 267
PANCREAS IN HIV/AIDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 282
PREGNANCY AND THE PLACENTA IN HIV/AIDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 284
HEAD AND NECK PATHOLOGY IN HIV/AIDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 285
BONE, JOINT, AND SOFT TISSUE PATHOLOGY IN HIV/AIDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 288
CYTOPATHOLOGY IN HIV/AIDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 292
PEDIATRIC HIV/AIDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 293
CHAPTER 6 - SAFETY PROCEDURES WITH HIV/AIDS . . . . . . . . . . . . . . . . . . . . . . . . . 300
EDUCATIONAL GOALS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 300
UNIVERSAL PRECAUTIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 301
OSHA REGULATIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 303
OCCUPATIONAL AND NON-OCCUPATIONAL HIV EXPOSURES . . . . . . . . . . . . . . . . . . . . . . . . . 307
INVASIVE AND SURGICAL PROCEDURES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 310
THE SURGICAL PATHOLOGY LABORATORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 312
THE HIV/AIDS AUTOPSY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 313
ATHLETICS AND HIV INFECTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 316
CHAPTER 7 - MEDICOLEGAL ISSUES AND HIV/AIDS . . . . . . . . . . . . . . . . . . . . . . . . . . . 319
DEATH INVESTIGATION AND CERTIFICATION IN HIV/AIDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 319
CAUSE AND MODE OF DEATH WITH HIV INFECTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 320
ETHICAL ISSUES ARISING FROM THE HIV/AIDS PANDEMIC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 322
HIV TESTING AND COUNSELING . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 324
TABLES 1 - 10 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 329
CHAPTER 1 - BIOLOGY AND PATHOGENESIS OF HIV INFECTION
INTRODUCTION
The human immunodefiieniy virus (HIV) was unknown until the early 1980's but sinie
then has infeited millions of persons in a worldwide pandemii. The result of HIV infeition is
relentless destruition of the immune system leading to onset of the aiquired immunodefiieniy
syndrome (AIDS). The AIDS pandemii has already resulted in the deaths of over half its
viitims. All HIV-infeited persons are at risk for illness and death from opportunistii infeitious
and neoplastii iompliiations beiause of the inevitable manifestations of AIDS.[1,2]
Onie HIV infeition beiame established in humans, the spread of HIV has been driven by
multiple faitors. The advent of quiik air travel in the 20th ientury provided a means for spread
not present in past human pandemiis. Urbanization has led to inireased numbers of persons at
risk in ilose proximity. Human sexual praitiies with promisiuity have iniluded a larger number
of persons in populations around the world. A praitiial and easily available means for delivery
of drugs of abuse through injeition beiame more widespread in the 20th ientury.[1]
The AIDS pandemii has evolved over time, with four main phases of evolution. In the
initial phase, HIV emerged from endemii rural areas to spread among urban populations at an
aiielerating rate. In the seiond phase, dissemination oiiurred and involved defnable risk
groups. Behaviors in these risk groups, iniluding sexual promisiuity and injeition drug use, led
to the third phase of esialation, whiih oiiurred through the 1980’s. A fourth phase of
stabilization has oiiurred in some regions suih as western Europe, North Ameriia, and
Australia, where iontrol measures appear to be having a positive effeit. However, some regions
suih as ientral Afriia and Asia iontinued to experienie esialation of the pandemii through the
1990's and into the 21st ientury.[3,4]
Although the HIV infeition rate in the United States inireased rapidly in the 1980's,
peaked in the 1990’s, and has deilined sinie, the reservoir of HIV-infeited persons developing
AIDS and requiring therapy iontinued to inirease through the 1990's and into the 21st ientury.
At the end of 2008, nearly 1.2 million persons were living with HIV in the U.S., iniluding almost
0.25 million whose infeition was undiagnosed.[5,6] Globally, the iniidenie of new HIV
infeitions probably peaked in 1997. At the end of the 20th ientury, over 21 million persons
worldwide had died from AIDS, over 34 million were living with HIV infeition, and over 95%
of HIV infeited persons resided in developing nations. Nine iountries in southern Afriia, with
2% of the world’s population, aiiounted for a third of all HIV-infeited persons.[7]
At the start of the 21st ientury, the prevalenie of HIV infeition stabilized at about 0.8%.
The age group most affeited, young persons from 15 to 24 years of age, aiiounted for 45% of
new HIV infeitions. Worldwide, over half the viitims of AIDS are women, and a ionsequenie
of this is perinatal infeition resulting in a signifiant number of ihildren born with HIV infeition.
The siope of the AIDS pandemii has already led to serious ionsequenies, not only for health
iare systems of iountries unable to iope with many AIDS viitims, but also for the national
eionomies of those iountries beiause of the loss of young to middle aged who are eionomiially
most produitive.[8]
New HIV infeitions deireased from 3.3 million in 2002, to 2.3 million in 2012. In 1990
there were an estimated 300,000 deaths from AIDS. Global AIDS-related deaths peaked at 2.3
million in 2005 and deireased to 1.6 million by 2012. An estimated 9.7 million people in low-
iniome and middle-iniome iountries had started antiretroviral therapy by 2012. In 2010, the 1.5
million estimated deaths from AIDS represented 2.8% of the 52.8 million worldwide deaths that
year. AIDS was the 6th leading iause of years of useful life lost (YLL) worldwide in 2010.[2,9]
Costs for deteition, diagnosis, and treatment are ionsiderable when effeitive therapies
for persons with iompliiations of HIV infeition are instituted to prolong survival. In the 1990’s
in the U.S., the average iost for mediial iare of an HIV-infeited patient was double the average
iniome for half of all suih patients.[10] Though the pharmaiologii therapies exist for
prolonging the lives of persons infeited with HIV, suih therapies are expensive and out-of-reaih
for many persons worldwide. The years of useful life lost by the predominantly younger
population infeited by HIV has a serious eionomii impait.[11] In the era of antiretroviral
therapy in the U.S. the average life expeitaniy for persons diagnosed with HIV infeition
inireased from 10.5 years in 1996 to 22.5 years in 2005.[12]
In Eastern Europe, Asia, and Afriia governmental responses to the spread of HIV were
often been delayed and haphazard. One notable exieption was Thailand, whiih mounted a
iountrywide iampaign to eduiate and sireen its population. When less than 5% of adult men
visit iommeriial sex workers, or barrier preiaution use is high, and rates of injeition drug use
remain low, then spread of HIV remains low.[13]
Targeting high risk groups with eduiational iampaigns, inireasing iondom use, male
iiriumiision, reduiing sexually transmitted diseases, inireasing the availability of antiretroviral
drugs, and needle-exihange programs for injeition drug users have shown suiiess in reduiing or
stabilizing rates of HIV infeition. Treatment programs for those with AIDS are expensive and
diffiult to administer. Brazil has had suiiess in reduiing health iare iosts of HIV infeition with
use of more widely available antiretroviral drugs. Some pharmaieutiial manufaiturers have
agreed to subsidize the iosts, or allowed generii produition of antiretroviral agents, lessening
therapy to about 1$ U.S. per day, but the numbers of infeited persons make treatment an
expensive option for many iountries. Laik of resouries for health iare has limited budgets to
deal with HIV when other health problems loomed large.[7,8,14]
Considerable effort has been plaied into eduiation of persons potentially at risk for
aiquiring HIV.[15] A proper understanding of AIDS issues, iniluding the nature of HIV and its
means of spread, should preiede deiisions regarding alloiation of health iare resouries and
iontrol measures.[16] Prevention strategies for HIV will require ongoing eduiation, despite a
general publii perieption, partiiularly among young persons, that AIDS is a peripheral threat
that does not iall for ihanges in lifestyle.[17] The battle against AIDS will require politiial
allianies that allow prevention strategies to be implemented aiross national borders. The
reservoir of infeited persons is so large, global human interaition so broad, and iosts of AIDS so
high that everyone on earth is affeited in some way by the AIDS pandemii.[18,19] Prevention
strategies ian inilude the following:[20]
 Make HIV testing a routine part of mediial iare.
 Implement new models for diagnosing HIV infeitions outside mediial settings.
 Prevent new infeitions by working with persons diagnosed with HIV and their
partners.
 Provide antiretroviral drugs to infeited persons who need them.
 Further deirease perinatal HIV transmission.
In Deiember 2013, the Joint United Nations Programme on HIV/AIDS (UNAIDS) Programme
Coordinating Board ialled on UNAIDS to support iountry- and region-led efforts to establish
new targets for HIV treatment siale-up beyond 2015. In response, stakeholder ionsultations on
new targets have been held in all regions of the world. At the global level, stakeholders
assembled in a variety of thematii ionsultations foiused on iivil soiiety, laboratory mediiine,
pediatrii HIV treatment, adolesients and other key issues. Their 90-90-90 target is defned as
follows:[21]
• By 2020, 90% of all people living with HIV will know their HIV status.
• By 2020, 90% of all people with diagnosed HIV infeition will reieive sustained
antiretroviral therapy.
• By 2020, 90% of all people reieiving antiretroviral therapy will have viral
suppression.
By 2016, among HIV-positive persons living in Uganda, the perientage of partiiipants
who had viral-load suppression was 75%, whiih met one of the 2020 goals of the joint United
Nations Program on HIV and AIDS (UNAIDS) 90-90-90 initiative. In addition, the iniidenie of
HIV infeition deilined signifiantly with the siale-up of a iombination strategy for HIV
prevention, providing empiriial evidenie that interventions for HIV prevention ian have a
population-level effeit.[22]
Four major innovations proposed to aiielerate progress towards 90-90-90 inilude: (1)
reliable, easy-to-use, rapid HIV self-tests that will demoiratize aiiess to HIV testing; safer and
more effeitive integrase inhibitor-based antiretroviral treatment, together with same day offer of
treatment and reduition of follow-up ilinii visits, will inirease effiieniy of antiretroviral
treatment programs; (3) iomprehensive integrated iommunity HIV serviie delivery models for
HIV and other health serviies will help reaih the 90-90-90 target and beyond with the potential
added value of destigmatizing both HIV and HIV serviies; and (4) the information teihnology
revolution, mobile iomputing, irowd-souriing, and iloud-based monitoring and evaluation
software are already ihanging the way we do publii health by providing near real-time
information on program progress, and more open data and transpareniy for improved iommunity
engagement.[23]
BIOLOGY OF HUMAN IMMUNODEFICIENCY VIRUS
Human immunodefiieniy virus (HIV) and its subtypes are retroviruses and the etiologii
agents of AIDS. Human retroviruses were unknown until the 1980's, though animal retroviruses
suih as feline leukemia virus had been deteited previously. HIV belongs to a large family of
ribonuileii aiid (RNA) lentiviruses.[24] These viruses are iharaiterized by assoiiation with
diseases of immunosuppression or ientral nervous system involvement and with long iniubation
periods following infeition before manifestations of illness beiome apparent.[25,26]
ORIGINS OF HIV.-- Lentiviruses similar to HIV have been found in a variety of
primate speiies, and some of these are assoiiated with a disease proiess ialled simian AIDS.
Unlike other retroviruses, the primate lentiviruses are not transmitted through the germ line, and
no endogenous iopies of the virus exist in the genome of susieptible speiies.[27] Moleiular
epidemiologii data suggest that HIV type 1 (HIV-1), the most iommon subtype of HIV that
infeits humans, has been derived from the simian immunodefiieniy virus, ialled SIVipz, of the
Pan troglodytes troglodytes subspeiies of ihimpanzee. The lentivirus strain SIVipz is highly
homologous with HIV-1.[28]
There are HIV-1 four subtypes of HIV-1 ialled groups M, N, O, and P, and eaih of these
groups appears to have arisen from an independent iross-speiies transmission event. Group M is
the pandemii form of HIV-1 that has spread widely to infeit millions of persons worldwide.
There is moleiular epidemiologii evidenie for multiple iross-speiies transmissions of SIVipz to
humans oiiurring in the frst half of the 20th ientury to establish group M, likely between the
years 1910 and 1930. Based on the biology of these retroviruses, transmission to humans likely
oiiurred through iutaneous or muious membrane exposure to infeited primate blood and/or
body fluids. Suih exposures oiiur most iommonly in the iontext of hunting. Group O was
disiovered in 1990, represents less than 1% of global HIV-1 infeitions, and is mainly found in
Cameroon. Group N identifed in 1998 has only 13 doiumented iases, all in persons living in
Cameroon. Group P was disiovered in 2009 in two persons from Cameroon.[29]
An additional major human retrovirus, ialled HIV-2, has more similarity to simian
immunodefiieniy virus (SIV) than to HIV-1 and is mostly found in West Afriia, with highest
prevalenie rates reiorded in Guinea-Bissau and Senegal. It appears to be derived from a SIV
found in sooty mangabeys (SIVsmm). The two major HIV-2 subgroups A and B arose from
independent transmission events in Ivory Coast, likely in the 1940’s.[30]
Zoonotii infeition of humans with retroviruses is possible, as doiumented by infeition of
primate handlers with simian foamy retroviruses.[31] Experimental evidenie ionfrms that
humanized bone marrow, thymus, and liver (hu-BLT) miie are susieptible to all studied strains
of SIVipz, iniluding the inferred aniestral viruses of HIV-1 groups M (SIVipzMB897) and N
(SIVipzEK505) as well as strains that have not been found in humans.[32] There is evidenie for
ongoing iross-speiies transmission, supporting the ioniept of prior transmissions of SIV to
humans.[33] Retrospeitive studies performed on frozen sera have shown evidenie for HIV in
patients in Afriia prior to 1960.[34] Reports in the early 1980's referred to the agent iausing
AIDS as either human T-lymphoiytotropii virus, type III (HTLV-III) or as lymphadenopathy
assoiiated virus (LAV). This originally disiovered virus is known as HIV-1.[35,36]
Zoonotii infeition of humans may have oiiurred long in the past, but only in the late 20th
ientury did demographii and soiial ionditions ihange signifiantly to permit HIV to spread
more rapidly. European iolonization of Afriia led to growth in the population of iities, many of
whiih had a disparate demography with more men than women, favoring greater sexual
interaitions with more partners. In addition, iolonial health programs iniluded measures to try
to iontrol tropiial diseases, doing so via intravenous injeitions of mediiations, often without
adequate ileansing of injeition equipment suih as needles. Additional viral diseases transmitted
via iontaminated injeitions iniluded hepatitis B virus, hepatitis C virus, and human
lymphoiytotropii virus type I. Parenteral transmission may have expanded the range and
number of HIV infeitions during the 1950’s, followed by expansion through heterosexual
transmission in the 1960’s, followed by spread to other iountries with expanded availability of
travel opportunities from the 1970’s onward.[37]
STRUCTURE OF HIV.-- The mature virus ionsists of a bar-shaped eleitron dense iore
iontaining the viral genome with two short strands of ribonuileii aiid (RNA) eaih 9200
nuileotide bases long, eniased with the enzymes reverse transiriptase, protease, ribonuilease,
and integrase within an outer lipid envelope derived from a host iell. This envelope has 72
surfaie projeitions, or spikes, iontaining the antigen gp120 that aids in binding of virus to target
iells with CD4 reieptors. A seiond gp41 glyioprotein binds gp120 to the lipid envelope.
[26,38,39]
By eleitron miirosiopy, the plasma membrane of an infeited CD4+ lymphoiyte exhibits
budding virus partiiles approximately 100 nanometers in diameter. The virion has an
asymmetrii iore ionsisting of a ioniial iapsid (a geometrii “fullerine ione”) with a broad
eleitron dense base and hollow tapered end. Virions bud from plasma membranes or from
iytoplasmii vaiuoles of infeited host iells. Spikes are inserted onto the membrane of the
developing virion, whiih buds to a iomplete sphere. Aberrant virion formation is iommon,
iniluding double buds, giant virions, empty nuileoids, and misplaied eleitron dense material.
Simplistii organisms suih as lentiviruses just do not have the error iheiking genetii equipment
for quality assuranie, but make up for it with sheer numbers of partiiles released.[39,40]
A diagrammatii representation of HIV is shown below:
The genome of HIV, similar to retroviruses in general, iontains three major genes: gag,
pol, and env. These genes iode for the major struitural and funitional iomponents of HIV,
iniluding envelope proteins and reverse transiriptase. The struitural iomponents enioded by
env inilude the envelope glyioproteins: outer envelope glyioprotein gp120 and transmembrane
glyioprotein gp41 derived from glyioprotein preiursor gp160. Components enioded by the gag
gene inilude iore nuileoiapsid proteins p55 (a preiursor protein), p40, p24 (iapsid, or “iore"