Pharmac. & Ther. Vol. 55: 201-277, 1992
AIDS ACQUIRED BY DRUG CONSUMPTION AND OTHER NONCONTAGIOUS
Department of Molecular and Cell Biology, 229 Stanley Hall, University
of California at Berkeley, Berkeley, CA 94720, U.S.A.
2. Definition of AIDS
2 Epidemics, Sub-Epidemics and 25
AIDS includes 25 previously known diseases and two clinically
and epidemiologically very different AIDS epidemics, one in America and
Europe, the other in Africa (Table 1) (Centers for
Disease Control, 1987; Institute of Medicine, 1988; World Health Organization,
1992a). The American/European epidemic falls into four sub-epidemics: the
male homosexual, the intravenous drug user, the hemophilia and the transfusion
recipient epidemics (Table 1).
2.1.1. The Epidemics by Case Numbers, Gender
The American/European AIDS epidemics of homosexuals and
intravenous drug users are new, starting with drug-using homosexual AIDS
patients in Los Angeles and New York in 1981 (Centers for Disease Control,
1981; Gottlieb et al., 1981; Jaffe et al., 1983a). By December
1991, 206,392 AIDS cases had been recorded in the U.S. and 65,979 in Europe
(Table 1) (World Health Organization, 1992a; Centers
for Disease Control, 1992b). The U.S. has reported about 30,000-40,000
new cases annually since 1987, and Europe reports about 12,000-16,000 cases
annually (World Health Organization, 1992a; Centers for Disease Control,
Remarkably for a presumably infectious disease, 90% of
all American and 86% of all European AIDS patients are males. Nearly all
American (98%) and European (96%) AIDS patients are over 20 years old;
the remaining 2% and 4%, respectively, are mostly infants (Table 1) (World
Health Organization, 1992a; Centers for Disease Control, 1992b). There
is very little AIDS among teenagers, as only 789 American teenagers have
developed AIDS over the last 10 years, including 160 in 1991 and 170 in
1990 (Centers for Disease Control, 1992b).
Since 1985, 129,066 AIDS cases have been recorded in Africa
(World Health Organization, 1992b), mainly from the people of Central Africa
(Blattner, 1991). Unlike the American and European cases, the African cases
are distributed equally between the sexes (Quinn et al., 1986; Blattner
et al., 1988; Institute of Medicine, 1988; Piot et al., 1988;
Goodgame, 1990) and range "in age from 8 to 85 years" (Widy-Wirski
et al., 1988).
An AIDS crisis that was reported to "loom" in
Thailand as of 1990 (Anderson, 1990; Smith, 1990) and that was predicted
to "explode" now (Mann and the Global AIDS Policy Coalition,
1992) has generated only 123 AIDS patients from 1984 until June 1991 (Weniger
et al., 1991).
2.1.2. AIDS Diseases
The majority of American (62%) and European (75%) AIDS
patients have microbial diseases or opportunistic infections that result
from a previously acquired immunodeficiency (World Health Organization,
1992a; Centers for Disease Control, 1992b). In America these include Pneumocystis
pneumonia (50%), candidiasis (17%) and mycobacterial infections such as
tuberculosis (11%), toxoplasmosis (5%), cytomegalovirus (8%) and herpes
virus disease (4%) (Table 1) (Centers for Disease Control, 1992b). Pneumocystis
pneumonia is often described and perceived as an AIDS-specific pneumonia.
However, Pneumocystis carinii is a ubiquitous fungal parasite that
is present in all humans and may become active upon immune deficiency like
many others (Freeman, 1979; Pifer, 1984; Williford Pifer et al.,
1988; Root-Bernstein, 1990a). Since bacterial opportunists of immune deficiency,
like tuberculosis bacillus or pneumococcus, are readily defeated with antibiotics,
fungal and viral pneumonias predominate in countries where antibiotics
are readily available. This is particularly true for risk groups that use
antibiotics chronically as AIDS prophylaxis (Callen, 1990; Bardach, 1992).
Indeed, young rats treated for several weeks simultaneously with antibiotics
and immunosuppressive cortisone all developed Pneumocystis pneumonia
spontaneously (Weller, 1955).
Table 1. AIDS Statistics*
Epidemics American European African
AIDS total 1985-1991 206,000 66,000 129,000
AIDS annual since 1990 30-40,000 12-16,000 ~20,000
HIV carriers since 1985 1 million 500,000 6 million
Annual AIDS per HIV carrier 3-4% 3% about 0.3%
AIDS by sex 90% male 86% male 50% male
AIDS by age, over 20 years 98% 96% ?
AIDS by risk group
male homosexual 62% 48%
intravenous drugs 32% 33%
transfusions 2% 3%
hemophiliacs 1% 3%
general population 3% 13% 100%
AIDS by Disease:
Microbial 50% Pneumocystis pneumonia 75% opportunistic infections
11% mycobacterial disease fever
including 3% tuberculosis diarrhea
5% toxoplasmosis tuberculosis
8% cytomegalovirus slim disease
4% herpes virus
Microbial total 62% 75% about 90%
(sum > 62% due to overlap)
Non-Microbial 19% wasting 5% wasting
10% Kaposi's 12% Kaposi's
6% dementia 5% dementia
3% lymphoma 3% lymphoma
Non-microbial total 38% 25%
* Data from references cited in Section 2. There are small
(± 1%) discrepancies between some numbers cited here and the most
recent surveys cited in the text, because some calculations are based on
Contrary to its name, AIDS of many American (38%) and European
(25%) patients does not result from immunodeficiency and microbes (Section
3.5.8). Instead, these patients suffer dementia (6%/5%), wasting disease
(19%/5%), Kaposi's sarcoma (10%/12%) and lymphoma (3%/3%) (Table
1) (World Health Organization, 1992a; Centers for Disease
The African epidemic includes diseases that have been
long established in Africa, such as fever, diarrhea, tuberculosis and "slim
disease" (Table l) (Colebunders et al.,
1987; Konotey-Ahulu, 1987; Pallangyo et al., 1987; Berkley et
al., 1989; Evans, 1989a; Goodgame, 1990; De Cock et al., 1991;
Gilks, 1991). Only about 1% are Kaposi's sarcomas (Widy-Wirski et al.,
1988). The African AIDS definition is based primarily on these Africa-specific
diseases (Widy-Wirski et al., 1988) "because of limited facilities
for diagnosing HIV infection" (De Cock et al., 1991).
2.1.3. AIDS Risk Groups and Risk-group
Specific AIDS Diseases
Almost all American (97%) and European (87%) AIDS patients
come from abnormal health risk groups whose health had been severely compromised
prior to the onset of AIDS: 62% of American (47% of European) AIDS patients
are male homosexuals who have frequently used oral aphrodisiac drugs (Section
4), 32% (33%) are intravenous drug users, 2% (3%) are critically ill recipients
of transfusions and 1% (3%) are hemophiliacs (Institute of Medicine, 1988;
Brenner et al., 1990; Centers for Disease Control, 1992b; World
Health Organization, 1992a). About 38% of the American teenage AIDS cases
are hemophiliacs and recipients of transfusions, 25% are intravenous drug
users or sexual partners of intravenous drug users and 25% are male homosexuals
(Centers for Disease Control, 1992b). Approximately 70% of the American
babies with AIDS are born to drug-addicted mothers ("crack babies")
and 13% are born with congenital deficiencies like hemophilia (Centers
for Disease Control, 1992b). Only 3% of the American and 13% of the European
AIDS patients are from "undetermined exposure categories," i.e.
from the general population (Table 1) (World Health
Organization, 1992a; Centers for Disease Control, 1992b). Some of the differences
between European and American statistics may reflect differences in national
AIDS standards between different European countries and the U.S. and differences
in reporting between the World Health Organization (WHO) and the American
Centers for Disease Control (CDC) (World Health Organization, 1992a). By
contrast to the American and European AIDS epidemics, African AIDS does
not claim its victims from sexual, behavioral or clinical risk groups.
The AIDS epidemics of different risk groups present highly
characteristic, country-specific and sub-epidemic-specific AIDS diseases
(Table 1 and Table 2):
1. About 90% of the AIDS diseases from Africa are old
African diseases that are very different from those of the American/European
epidemic (Section 2.1.2, Table 1). The African diseases
do not include Pneumocystis pneumonia and candidiasis (Goodgame,
1990), although Pneumocystis and Candida are ubiquitous microbes
in all humans including Africans (Freeman, 1979; Pifer, 1984).
2. The American/European epidemic falls into several sub-epidemics
based on sub-epidemic-specific diseases:
a) American homosexuals have Kaposi's sarcoma 20 times
more often than all other American AIDS patients (Selik et al.,
1987; Beral et al., 1990).
b) Intravenous drug users have a proclivity for tuberculosis
(Sections 4.5 and 4.6).
c) "Crack" (cocaine) smokers exhibit pneumonia
and tuberculosis (Sections 3.4.5 and 4.6).
d) Ninety-nine percent of all hemophiliacs with AIDS have
opportunistic infections, of which about 70% are fungal and viral pneumonias,
but less than 1% have Kaposi's sarcoma (Evatt et al., 1984; Centers
for Disease Control, 1986; Selik et al., 1987; Koerper, 1989).
e) Nearly all recipients of transfusions have pneumonia
(Curran et al., 1984; Selik et al., 1987).
f) HIV-positive wives of hemophiliacs exhibit only pneumonia
and a few other AIDS-defining opportunistic infections (Section 126.96.36.199).
g) American babies exclusively have bacterial diseases
(18%) and a high rate of dementia (14%) compared to adults (6%) (Table
1) (Centers for Disease Control, 1992b).
h) Users of the cytotoxic DNA chain terminator AZT, prescribed
to inhibit HIV, develop anemia, leukopenia and nausea (Section 4.6.2).
3. The Thai mini-epidemic of 123 is made up of intravenous
drug users (20%), heterosexual male and female "sex workers"
(50%) and male homosexuals (30%) (Weniger et al., 1991). Among the
Thais 24% have tuberculosis, 22% have pneumonia and other opportunistic
infections common in Thailand and 10% have had septicemia, which is indicative
of intravenous drug consumption (Weniger et al., 1991).
HIV-AIDS Hypothesis, or the Definition of AIDS
Based on epidemiological data collected between 1981 and
1983, AIDS researchers from the CDC (Centers for Disease Control, 1986)
"found in gay culture-particularly in its perceived "extreme"
and "non-normative" aspects (that is "promiscuity"
and recreational drugs)-the crucial clue to the cause of the new syndrome"
(Oppenheimer, 1992). Accordingly the CDC had initially favored a "lifestyle"
hypothesis for AIDS.
However, by 1983 immunodeficiency was also recorded in
hemophiliacs, some women and intravenous drug users. Therefore, the CDC
adopted the "hepatitis B analogy" (Oppenheimer, 1992) and re-interpreted
AIDS as a new viral disease, transmitted sexually and parenterally by blood
products and needles shared for the injection of intravenous drugs (Francis
et al., 1983; Jaffe et al., 1983b; Centers for Disease Control,
1986; Oppenheimer, 1992). In April 1984 the American Secretary of Health
and Human Services and the virus researcher Robert Gallo announced at a
press conference that the new AIDS virus was found. The announcement was
made, and a test for antibody against the virus-termed the "AIDS test"-was
registered for a patent, before even one American study had been published
on this virus (Connor, 1987; Adams, 1989; Crewdson, 1989; Culliton, 1990;
Rubinstein, 1990). Since then most medical scientists have believed that
AIDS is infectious, spread by the transmission of HIV.
According to the virus-AIDS hypothesis the 25 different
AIDS diseases and the very different AIDS epidemics and sub-epidemics are
all held together by a single common cause, HIV. There are two strains
of HIV that are 50% related, HIV-1 and HIV-2. But as yet only one American-born
AIDS patient has been infected by HIV-2 (O'Brien et al., 1992).
Since nearly all HIV-positive AIDS cases recorded to date are infected
by HIV-1, this strain will be referred to as HIV in this article. The HIV-AIDS
hypothesis proposes: (a) that HIV is a sexually, parenterally and perinatally
transmitted virus, (b) that it causes immunodeficiency by killing T-cells,
but on average only 10 years after infection in adults and two years after
infection in infants-a period that is described as the "latent period
of HIV" because the virus is assumed to become reactivated in AIDS-and
(c) that all AIDS diseases are consequences of this immunodeficiency (Coffin
et al., 1986; Institute of Medicine, 1986, 1988; Gallo, 1987; Blattner
et al., 1988; Gallo and Montagnier, 1988; Lemp et al., 1990;
Weiss and Jaffe, 1990; Blattner, 1991; Goudsmit, 1992).
Because of this belief, 25 previously known, and in part
entirely unrelated diseases have been redefined as AIDS, provided they
occur in the presence of HIV. HIV is in practice only detectable indirectly
via antiviral antibodies, because of its chronic inactivity even in AIDS
patients (Section 3.3). These antibodies are identified with disrupted
HIV, a procedure that is termed the "AIDS test" (Institute of
Medicine, 1986; Rubinstein, 1990). Virus isolation is a very inefficient
and expensive procedure, designed to activate dormant virus from leukocytes.
It depends on the activation of a single, latent HIV from about 5 million
leukocytes from an antibody-positive person. For this purpose the cells
must be propagated in vitro away from the virus-suppressing immune
system of the host. Virus may then be detected weeks later in the culture
medium (Weiss et al., 1988; Duesberg, 1989c).
Antibodies against HIV were originally claimed to be present
in most (88%) AIDS patients (Sarngadharan et al., 1984), but have
since been confirmed in no more than about 50% of the American AIDS patients
(Institute of Medicine, 1988; Selik et al., 1990). The rest are
presumptively diagnosed based on disease criteria outlined by the CDC (Centers
for Disease Control, 1987; Institute of Medicine, 1988). Because of confidentiality
laws more tests are probably done than are reported to the CDC.
Since the "AIDS test" became available in 1985,
over 20 million tests have been performed annually in the U.S. alone on
blood donors, servicemen and applicants to the Army, AIDS patients and
many others, and millions more are performed in Europe, Russia, Africa
and other countries (Section 3.6). On the basis of such widespread testing,
clearly the most comprehensive in the history of virology, about 1 million,
or 0.4% of mostly healthy Americans (Curran et al., 1985; Institute
of Medicine, 1988; Duesberg, 1991a; Vermund, 1991; Centers for Disease
Control, 1992a), 0.5 million, or 0.2% of Western Europeans (Mann et
al., 1988; Blattner, 1991; World Health Organization, 1992a), 6 million,
or 10% of mostly healthy Central Africans (Curran et al., 1985;
Institute of Medicine, 1988; Piot et al., 1988; Goodgame, 1990;
Blattner, 1991; Anderson and May, 1992) and 300,000 or 0.5% of healthy
Thais (Weniger et al., 1991) are estimated to carry antibodies to
HIV (Table 1). According to the CDC the incidence of HIV-2 is "relatively
high" in Western Africa with a record of 9% in one community, but
"exceedingly low" in the U.S. where not even one infection was
detected among 31,630 blood donors (O'Brien et al., 1992).
Alternative Infectious Theories of AIDS
In view of the heterogeneity of the AIDS diseases and
the difficulties in reducing them to a common, active microbe, several
investigators have proposed that AIDS is caused by a multiplicity of infectious
agents such as viruses and microbes, or combinations of HIV with other
microbes (Sonnabend et al., 1983; Konotey-Ahulu, 1987, 1989; Stewart,
1989; Cotton, 1990; Goldsmith, 1990; Lemaitre et al., 1990; Root-Bernstein,
1990a,c; Balter, 1991; Lo et al., 1991).
However, the proponents of infectious AIDS who reject
HIV as the sole cause or see it as one of several causes of AIDS have failed
to establish a consistent alternative to or cofactor for HIV. Instead,
they typically blame AIDS on viruses and microbes that are widespread and
either harmless or not life-threatening to a normal immune system, such
as Pneumocystis, cytomegalovirus, herpes virus, hepatitis virus,
tuberculosis bacillus, Candida, mycoplasma, treponema, gonococci,
toxoplasma and cryptosporidiae (Section 3.5.7) (Freeman, 1979; Mims and
White, 1984; Pifer, 1984; Evans, 1989c; Mills and Masur, 1990; Bardach,
1992). Since such microbes are more commonly active in AIDS patients than
in others, they argue that either chronic or repeated infections by such
microbes would generate fatal AIDS (Sonnabend et al., 1983; Stewart,
1989; Mills and Masur, 1990; Root-Bernstein, 1990a,c).
Yet all of these microbes also infect people with normal
immune systems either chronically or repeatedly without causing AIDS (Freeman,
1979; Mims and White, 1984; Evans, 1989c; Mills and Masur, 1990). It follows
that pathogenicity by these microbes in AIDS patients is a consequence
of immunodeficiency acquired by other causes (Duesberg, 1990c, 1991a).
This is why most of these infections are termed opportunistic.