Aids Panel Report

Studiengruppe für AIDS-Therapie
Study group for AIDS therapy
c / o Felix A. de Fries
Eglistrasse 7 CH-8004 Zürich Switzerland
Tel./FAX: 0041 (0)1 401 34 24
felix.defries@bluewin.ch

Zürich, 8th April 2001

President Mbeki's advisory panel on the causes of AIDS-defining
illnesses and appropriate mesures on 6-7 Mai and 3-4 July in
Johannesburg assembled leading promotors of the HIV-AIDS-modell such as
Jean Luc Montagnier and Helene Gayle (CDC) and critics of this modell
such as Peter Duesberg, Eleni Papadopulos Eleopulos, Etienne de Harven,
and Joseph A. Sonnabend. (To call in question the HIV-AIDS- modell was
later criticised by the signatories of the Durban declaration, that
disqualified the critics as deniers of aprooved scientific facts.)

The report on this panel with the discussion on the aetiology and
transmission of AIDS, the HIV-tests and their accuracy, the treatment of
AIDS and the use of anti-retroviral drugs, the preventive and
prophilactic mesures, the socio-economic factors and the recommendations
and proposed research projects is now available at
http://www.gov.za/events/aidspanel.htm .

It shows, that the question if the HIV-virusparticles and the emergence
of AIDS defining illnesses are the product of a transmittalbe new
retrovirus or if they are the effect of epigenetic mechanisms induced by
malnutrition, frequent inflamation (due tu dirty water and hurts), the
misuse of antibiotics and by toxic substances (in the environment) has
to be asked furthermore. (Articles from international medical pappers,
that you find enclosed, illustrate the role of infant malnutrition, the
accuracy of HIV-tests and the causes and the emergence of AIDS defining
illnesses in developped countries.)

In regard of the facts presented at the presidential advisory panel the
requested broad administration of nucleosid analog drugs in developping
countries will have to be discussed again.

Yours faithfully

Felix de Fries

Study group for AIDS therapy.

NUTRITION AND IMMUNITY
----------------------------------------

History of nutritional immunology: introduction and overview.

Beisel WR.

Department of Immunology and Infectious Diseases,
School of Hygiene and Public
Health, Johns Hopkins University, Baltimore, MD 21205.

Nutritional immunology is a newly recognizedsubdiscipline of vast clinical
and public health importance.
Its history began in 1810 with recognition of lymphoid tissue atrophy due to
malnutrition. Discovery of vitamins in the early 1900s was followed by reports
on their contribution to immunity and other host defenses. A hiatus in
immunonutritional progress occurred during World War II and the "antibiotic era,"
but a worldwide rebirth of interest began in the 1960s and early 1970s.

The current logarithmic growth of nutritional immunology was triggered by
increased medical interest, plus the introduction of new concepts and investigative
research methodologies from both parent sciences.

1: J Nutr 1996 Oct; 126(10 Suppl): 2611S-2615S
RelatedArticles, Books, LinkOut

Nutrition in pediatric HIV infection: setting the research agenda.
Nutrition and immune function: overview.

Beisel WR.
Department of Immunology and Infectious Diseases,
Johns Hopkins University,
School of Hygiene and Public Health,
Baltimore,
MD,
USA.

Malnutrition can have adverse, even devastatingeffects on the antigen-specific
arms of the immune system and on generalized host defensivemechanisms.
Protein/energy malnutrition and/or deficiencies of single nutrients
that assist in nucleic acid metabolism generally lead to atrophy of lymphoid
tissues and dysfunctions of cell-mediated immunity. Deficiencies of single
nutrients can impair production of key proteins. Trace element deficiencies
are often multifactorial. Essential fatty acid deficiencies can reduce or perturb
the synthesis ofcytokine-induced eicosanoids. Arginine deficiency can diminish
the production of nitric oxide, and deficiencies of antioxidant nutrients can allow
increases in the damaging effects of free oxygen radicals. Humoral immunity
continues to be maintained, although new primary responses to T-cell-dependent
antigens are generally subnormal in both magnitude and quality.

Immunological dysfunctions associated with malnutrition have been termed Nutritionally
Acquired Immune Deficiency Syndromes (NAIDS). Infants and small children
are at great risk because they possess only immature, inexperienced immune systems
and very small protein reserves. The combination of NAIDS and common childhood
infections is the leading cause of human mortality. NAIDS can generally be corrected
by appropriate nutritional rehabilitation, but from a viewpoint highly important to
this Workshop, AIDS and NAIDS are intensely synergistic.
AIDS-induced malnutrition can lead to the secondary development of NAIDS, with
its much broader array of additional immunological dysfunctions. The complex and
far reaching insults to the immune system caused by NAIDS, and the synergistic
combination of NAIDS and AIDS, thereby hasten the demise of many victims of
AIDS. Aggressive nutritional support for children with HIV infections could delay,
or lessen, the development of NAIDS and avoidance of NAIDS would improve both
quality and length of life.

Fatal infections in protein-calorie malnourished
children with thymolymphatic atrophy.

Comment in: J Infect Dis. 1995 Feb;171(2):502-4

Purtilo DT, Connor DH.

The clinicopathological features of 25 children who died with protein-calorie
malnutrition were studied.
All but four subjects were found at necropsy to havenutritional thymectomy
and all but 3 died ofinfectiousdiseases.
The infectious agents were chiefly intracellular micro-organisms including
miliary tuberculosis, Herpes simplex, varicella, measles, Pneumocystis carinii,
and Plasmodium falciparum.
Staphylococcal infections, salmonellosis, shigellosis, strongyloidiasis, and
hookworm were other significant infectious agents.
Nutritionally acquired defective immunity, especially cell-mediated immunity,
probably permitted these infectious agents to multiply and to disseminate widely.

PMID: 805568 [PubMed - indexed for MEDLINE]

AIDS IN DEVELOPED COUNTRIES

Heterosexual transmission of human immunodeficiency
virus (HIV) in northern California: results from a ten-year study.

Padian NS, Shiboski SC, Glass SO, Vittinghoff E.

Department of Obstetrics,
Gynecology and ReproductiveSciences,
University of California,
San Francisco,
USA.

To examine rates of and risk factors for heterosexual
transmission of human immunodeficiency virus (HIV), the authors conducted a
prospective study of infected individuals and their heterosexual partners who have
been recruited since 1985.
Participants were recruited from health care providers, research studies, and health
departments throughout Northern California, and they were interviewed and examined
at various study clinic sites. A total of 82 infected women and their male partners and
360 infected men and their female partners were enrolled. Over 90% of the couples
were monogamous for the year prior to entry into the study; < 3% had a current
sexually transmitted disease (STD). The median age of participants was 34 years,
and the majority were white. Over 3,000 couple-months of data were available for
the follow-up study. Overall, 68 (19%) of the 360 female partners of HIV-infected
men (95% confidence interval (CI) 15.0-23.3%) and two (2.4%) of the 82 male
partners of HIV-infected women (95% CI 0.3-8.5%) were infected. History of
sexually transmitted diseases was most strongly associated with transmission.
Male-to-female transmission was approximately eight-times more efficient than
female-to-male transmission and male-to-female per contact infectivity was estimated
to be 0.0009 (95% CI 0.0005-0.001). Over time, the authors observed increased
condom use (p < 0.001) and no new infections.
Infectivity for HIV through heterosexual transmission is low, and STDs may be the
most important cofactor for transmission. Significant behavior change over time in
serodiscordant couples was observed.

PMID: 9270414 [PubMed - indexed for MEDLINE]

Redefining the growth of the heterosexual HIV/AIDS
epidemic in Chicago.

Murphy JT, Mueller GE, Whitman S.

Epidemiology Program,
Chicago Department of Public Health,
Illinois 60604,
U.S.A.

A dramatic shift in the relative distribution of the five categories of heterosexual
transmission for AIDS cases diagnosed in Chicago since 1991 prompted a
mode-of-transmission validation study of what had become the most frequently
reported heterosexual exposure: heterosexual relations with a person with AIDS
(PWA) or documented HIV infection whose risk is not specified.

METHODS: For 395 cases with originally reported heterosexual exposure,
one or more of three supplemental data sources were employed: medical
records were reviewed, medical providers were interviewed, and patients or
proxies (i.e., spouse, significant other, or family member) were interviewed
when possible. When reported HIV exposure could not be validated or reclassified,
the transmission category employed was "no identifiable risk" (NIR).

RESULTS: Eighty-five percent (336 of 395 cases) were reclassified into different
transmission categories. Most notably, 69% (272 of 395 cases) were reclassified
into transmission categories that did not involve heterosexual contact, including NIR.
The cumulative percentage of cases attributable to heterosexual contact declined from
8% to 5% as a result of reclassification.
Additionally, reclassification resulted in a reduction of nearly 50% in the number of
AIDS cases attributable to heterosexual contact diagnosed in 1993 and 1994.

CONCLUSIONS: In Chicago, an emerging problem in AIDS surveillance appears to
be the use of an ambiguous heterosexual exposure category as a default when other
information is not readily available. This study has found the growth in AIDS cases
among persons exposed to HIV through heterosexual contact to be much slower than
previously perceived. This finding may have important implications for the national
debate over the extent to which heterosexual people are being infected and how
funding and prevention strategies should be prioritized.

PMID: 9358107 [PubMed - indexed for MEDLINE]

AETIOLOGY

Induction of antibody to asialo GM1 by spermatozoa and
its occurrence in the sera of homosexual men with the
acquired immune deficiency syndrome (AIDS).

Witkin SS, Sonnabend J, Richards JM, Purtilo DT.

Compared to healthy homosexual and heterosexual men,
homosexual men with acquired immune deficiency syndrome (AIDS) possessed
significantly higher levels of IgG antibody to the neutral glycolipid asialo GM1
(ganglio-N-tetraosylceramide) (P less than 0.01). Of 31 homosexuals with AIDS, 36%
possessed levels of this antibody that were at least two standard deviations
above the mean of the healthy men. Furthermore, asialo GM1 antibody could be removed
from serum by adsorption with spermatozoa. Weekly rectal insemination of male
rabbits with rabbit semen also led to the appearance of antibody to asialo GM1 by 15
weeks. These results suggest that asialo GM1 is a component of ejaculated
spermatozoa and demonstrate that rectal insemination by itself can lead to the
production of antibodies to this glycolipidin the rabbit. In addition, asialo GM1 antibodies
may be of value as a serological marker for the early detection of individuals with
AIDS.

PMID: 6652964 [PubMed - indexed for MEDLINE]

Acquired immunodeficiency syndrome, opportunistic
infections, and malignancies in male homosexuals.
A hypothesis of etiologic factors in pathogenesis.

Sonnabend J, Witkin SS, Purtilo DT.

The acquired immunodeficiency syndrome (AIDS) occurs
in a subgroup of male homosexuals having sexual contact with a large number
of partners. Uncommonly, AIDS has also been diagnosed in Haitians,
hemophiliacs, and intravenous drug users and their infants. Manifestations
include autoimmune disturbances, opportunistic infections, Kaposi's sarcoma,
chronic lymphadenomegaly, non-Hodgkin's lymphoma, or squamous cell carcinoma.
The hypothesis receiving most consideration is that a yet-to-be-identified virus
causes AIDS. An alternative view is that repeated sexual nvolvement with multiple
partners, in a subgroup of male homosexuals, exposes the men to the
immunosuppressive impact of cytomegalovirus (CMV) and allogeneic
semen. Antibody to asialo-Gm1 and other antigens on sperm react with and impair
lymphoid cells. We propose a biphasic process.
First, a reversible acquisition phase of impaired T-cell immunoregulation permits
reactivation of Epstein-Barr virus (EBV), and autoantibodies are produced by the
activated B cells. If sexual activity continues at a high level, accumulating immune
defects, including destruction of thymic epithelium, lead to a second, self-sustaining
phase wherein cytotoxic lymphocytes fail to eliminate herpesvirus-infected
cells. Evidence is mounting that Kaposi's sarcoma is caused by CMV and that EBV is
responsible for the B-cell lymphomas in these patients. Multiple factors, rather
than a novel virus, probably induce AIDS in male homosexuals. If this hypothesis is
correct, then rational bases for prevention and intervention can be designed.

PMID: 6300480 [PubMed - indexed for MEDLINE]

VIRAL LOAD
------------------

T cell telomere length in HIV-1 infection: no evidence
for increased CD4+ T cell turnover.

Wolthers KC, Bea G, Wisman A, Otto SA, de Roda Husman
AM, Schaft N, de Wolf F, Goudsmit J, Coutinho RA, van der Zee AG,
Meyaard L, Miedema F.

Department of Clinical Viro-Immunology,
Central Laboratory of the Netherlands
Red Cross Blood Transfusion Service,
Amsterdam,
TheNetherlands.
clbkvi@xs4all.nl

Progression to acquired immunodeficiency syndrome (AIDS) has been
related to exhaustion of the regenerative capacity of the immune
system resulting from high T cell turnover. Analysis of telomeric terminal
restriction fragment (TRF) length, a marker for cellular replicative history,
showed that CD8(+) T cell TRF length decreased but CD4(+) T cell TRF
length was stable during the course of human immunodeficiency virus
type-1 (HIV-1) infection, which was not explained by differential telomerase
activity. This observation provides evidence that turnover in the course of HIV-1
infection can be increased considerably in CD8(+) T cells, but not in CD4(+) T
cells. These results are compatible with CD4(+) T cell decline in HIV-1 infection
caused by interference with cell renewal.

PMID: 8929418 [PubMed - indexed for MEDLINE]

HIV- ANTIBODY TESTS
--------------------------------

Binding of glycoprotein 120 and peptides from the HIV-1 envelope
by autoantibodies in mice with experimentally induced systemic
lupus erythematosus and in patients with the disease.

Bermas BL, Petri M, Berzofsky JA,
Waisman A, Shearer GM, Mozes E.

Experimental Immunology Branch,
National Cancer Institute,
NIH,
Bethesda,
Maryland 20892.

Systemic lupus erythematosus (SLE) and infection with the human
immunodeficiency virus type 1 (HIV) are diseases that are characterized
by immune dysregulation and autoantibody production. In this article we
identify and characterize IgG antibodies from mice with SLE and SLE
patients that bind HIV gp120 and HIV envelope-derived peptides.
SLE can be induced insusceptible mouse strains by immunization with
a human monoclonal anti-DNA antibody that bears a common idiotype
designated 16/6 Id. We tested sera from various strains of mice in which
experimental SLE was induced by this method, as well as from 93 patients
with SLE and 31 controls (17 healthy controls, 14 patients with other
autoimmune diseases) for the presence of antibodies reactive to gp120 by an
ELISA. Antibodies reactive with gp120 were produced by BALB/c, C3H.SW,
AKR, and DBA/2 mice, all of which were 16/6 Id immunized and had
experimental SLE. C57BL/6 mice, which are resistant to induction of SLE by
this method, did not produce antibodies reactive with gp120 despite 16/6
immunization. Forty-three percent of SLE patients made antibodies that
bound to gp120 at titers greater than 1:40, whereas 12% of healthy
control sera (p < or = 0.02) and 14% of patients with other autoimmune diseases
contained such antibodies (p < or = 0.05). We delineated the specificity of this
antibody activity by testing for reactivity to six HIVenvelope peptides. In both
mice and SLE patients, sera reactive with gp120 recognized the same three
envelope peptides. Removal of the anti-DNA antibodies from thesera by
DNA-agarose affinity purification did not change anti-gp120 specificity.

PMID: 7826694 [PubMed - indexed for MEDLINE]

1: Am J Epidemiol 1997 Aug 15;146(4):350-7
Related Articles, Books, LinkOut

Infection with human immunodeficiency virus type 1 (HIV-1) and
human T cell lymphotropic viruses among leprosy patients and
contacts: correlation between HIV-1 cross-reactivity
and antibodies to lipoarabinomannan.

Kashala O, Marlink R, Ilunga M,
Diese M, Gormus B, Xu K,
Mukeba P, Kasongo K, Essex M.

Department of Cancer Biology,
Harvard School of Public Health,
Boston,
Massachusetts 02115.

To determine the association between leprosy and human
retroviral infections, 57 leprosy patients, 39 leprosy contacts, and 500
pregnant women were investigated serologically for antibodies to
human immunodeficiency virus type 1 (HIV) and human T cell
lymphotropic virus (HTLV) types I and II.
Antibodies to Mycobacterium leprae phenolic glycolipid I (PGL-I),
and lipoarabinomannan (LAM) were also analyzed. A low prevalence
of HIV-1infection was observed among leprosy patients (3.5%),
leprosy contacts (0), and pregnant women (3.6%).
Antibodies to HTLV-I but not -II were found more often
in leprosy patients (8.7%) and contacts (12.8%) than in pregnant women (0).
Sera from leprosy patients and leprosy contacts were often false-positive for
HIV-1 by ELISA and were indeterminate by Western blot. LAM IgM and PGL-I IgM
antibodies in sera from leprosy patients yielded significant cross-reactivities with
HIV-1 pol and gag proteins. These data suggest that mycobacterial cell
wall antigens may share common epitopes with HIV.

Caution should be exercised when interpreting HIV-1 ELISA and
Western blot data from regions where leprosy or other mycobacterial diseases are
endemic.

PMID: 7906291 [PubMed - indexed for MEDLINE]

1: Cancer Res 1990 Sep 1;50(17 Suppl):5628S-5630S