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                         Editor: David Dodell, D.M.D.
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Date: Fri, 15 Apr 94 22:01:15 MST
From: mednews (HICNet Medical News)
To: hicnews
Subject: AIDS Daily News Summaries
Message-ID: <[e-mail]>

                        AIDS Daily Summary
                          April 12, 1994

The Centers for Disease Control and Prevention (CDC) National AIDS
Clearinghouse makes available the following information as a public
service only. Providing this information does not constitute endorsement
by the CDC, the CDC Clearinghouse, or any other organization. Reproduction
of this text is encouraged; however, copies may not be sold, and the CDC
Clearinghouse should be cited as the source of this information.
Copyright 1993, Information, Inc., Bethesda, MD


            "Diarrhea Associated With Clostridium Difficile
                 in AIDS Patients Receiving Rifabutin"
        Lancet (Great Britain) (02/12/94) Vol.343,No.8894,P 417
                      (McBride, Michael O. et al.)

     A recent report described the benefits of prophylaxis for
mycobacterium avium complex (MAC) infection in HIV/AIDS patients, but
failed to discuss an important factor, say McBride et al. of St. Mary's
Hospital in London.  Antibiotic-associated diarrhea and colitis have been
reported with most broad-spectrum antibiotics, including rifampicin.
Although it has not been named in any published report on these symptoms,
rifabutin is a derivative of rifamycin S which displays a wide range of in
vitro activity against bacteria similar to that seen with rifampicin.
McBride et al. used rifabutin to treat 22 HIV-positive patients known or
thought to have MAC infections.  Four of the patients developed Clostridium
difficile-associated diarrhea; in two, the condition culminated in pseudo-
membranous colitis.  The occurrence of this complication has serious
implications for prophylactic regimens.  MAC infections are common among
immunocompromised patients, and there appears to be an increase in the
incidence of C difficile-associated diarrhea in patients receiving
rifabutin compared with a group of as severely immunocompromised patients
not taking the drug.  Because the incidence of antibiotic-associated
diarrhea/colitis with rifabutin is unknown, McBride et al. caution against
its widespread use until this association is clarified.

               "AIDS Threat to Hospital Workers--Study"
                           Reuters (03/03/94)

     London--Doctors screened the blood and urine of 875 people treated in
the emergency department of a busy London hospital, and found many more
cases of  HIV infection than anticipated.  According to doctors at St.
Mary's Hospital, one in 40 young or middle-aged people treated in the
facility's emergency ward was infected with HIV--four times the number
presented in a previous London study.  The study found that 2.4 percent of
St. Mary's emergency ward patients between the ages of 16 and 45 were
HIV-positive, and warned of the high risk of exposure to hospital emergency
workers.  "Our findings should alert authorities in inner cities to the
prevalence of HIV infection in patients attending accident and emergency
departments, even in a hospital with a large HIV clinic," the study said.
"There is a continuing risk of HIV infection to health care workers,
particularly inexperienced senior house officers practicing emergency
medicine in an environment that is often frenetic."

        "Rheumatoid Arthritis Advance May Be Relevant to AIDS"
              AIDS Treatment News (02/18/94) No.193,P 5
                           (James, John S.)

     London researchers report promising results in treating rheumatoid
arthritis with a monoclonal antibody against tumor necrosis factor (TNF),
a condition that is found naturally in the body but is often too high in
HIV/AIDS patients.  TNF can stimulate HIV growth directly, and is
suspected to be an important contributing element of wasting syndrome.
Pentoxifylline and thalidomide, two drugs being tested as potential AIDS
therapies, reduce the levels of TNF in the body.  The monoclonal antibody,
produced by Philadelphia's Centocor company, may also be highly effective
in blocking TNF.  All of the 50 or so volunteers, who had failed standard
treatments for rheumatoid arthritis, have had apparent success when
treated with the monoclonal antibody, according to reports on the British
Broadcasting Corporation.  While this drug is not yet widely available,
the results of the study--if confirmed--may advance the research on
other drugs with a similar mechanism of action.

      "High-Purity Factor Concentrates in Prevention of AIDS"
      Lancet (Great Britain) (02/19/94) Vol.343, No.8895, P.478
                         (Schwarz, H.P.)

     Seremetis et al. conclude that high-purity products should be
preferred for treating HIV-positive hemophiliacs.  They base their
recommendation on a study which showed that stabilization of CD4 cells
with high-purity concentrates is the most striking seen with any AIDS
treatment or prevention approach.  If these findings are valid, say
Schwarz et al. of Immuno AG in Austria, high-purity factor VIII
concentrates would also have to be considered for treatment of HIV-
positive patients who are not hemophiliacs.  To prevent false hopes for
these patients, Schwarz et al. suggest that the findings of Seremetis
and colleagues be confirmed.  In their opinion, the Seremetis study has
several serious flaws.  According to Schwarz et al., the methods of
analysis did not properly consider the potential for bias in patient
selection and use of antiretrovirals, the questionable endpoint, and
selective withdrawal.

         "World AIDS Chief Warns China Time Is Running Out"
                       Reuters (03/08/94)

     Beijing--The World Health Organization's top AIDS official warned
China that rapid social change could fuel the AIDS epidemic in the world's
most populous country if measures are not taken to prevent the spread of
the disease.  With only 1,200 official HIV infections and a handful of
AIDS cases, China is statistically far behind regional centers of AIDS
like India and Thailand, but the numbers are increasing.  Michael Merson,
head of WHO's global program on AIDS, predicted that this trend would
likely continue as economic change alters Chinese society.  Greater
mobility spurred by greater affluence, as well as changing sexual
attitudes and behavior are boosting the risks for infection. "The
potential here for a serious epidemic certainly exists," according
to Merson.  "China needs to make this a priority."  While he has observed
a measure of improvement on the part of the Chinese government to muster
support in the battle against AIDS, Merson said more needs to be done
to prevent the country from being overwhelmed by the wave of infection
now spreading across Southeast Asia.  He said China's main hope for
avoiding AIDS was education and a concerted government effort to change
people's attitudes about what is still widely perceived as a "foreigner's
disease."

                    "Human Herpesvirus 6 in AIDS"
             Lancet (03/05/94) Vol.343, No.8897, P.555
                (Lusso, Paolo and Gallo, Robert C.)

     Robert C. Gallo and Paolo Lusso of the National Cancer Institute
first isolated human herpesvirus 6 (HHV-6) in the laboratory in 1986
from patients with lymphoproliferative disorders and AIDS.  New research,
conducted by Knox and Carrigan, show that HHV-6 infection is active and
disseminated in AIDS patients.  HHV-6 was expressed in the lung, liver,
kidney, spleen, and lymph node tissues taken from all nine patients
studied.  Gallo and Lusso found similar data via a polymerase chain
amplification.  The results of these two studies, they say, provide
in-vivo evidence that suggest that HHV-6 has a catalytic role in the
progression of HIV infection.  With the latest data, it is now known that
HHV-6 stimulates the release of HIV-activating cytokines and induces de
novo expression of the major HIV receptor CD4 in mature CD8 T lymphocytes
and natural killer cells, thus increasing the range of cells vulnerable
to infection.  There is now little doubt that HHV-6 can be reactivated in
people with compromised immune systems and may sometimes act as a
legitimate opportunistic pathogen.  It is further implied that HHV-6,
once reactivated in the course of HIV infection, may have a negative
impact on the immune system and hasten progression of the disease.
Longitudinal studies of HHV-6 replication in HIV patients are critical
to establish a solid connection with disease progression, say Lusso and
Gallo.

     "Disseminated Active HHV-6 Infections in Patients With AIDS"
             Lancet (03/05/94) Vol. 343, No. 8897, P. 577
            (Knox, Konstance Kehl and Carrigan, Donald R.)

     Human herpesvirus 6 (HHV-6) can reactivate in immunocompromised
hosts and cause severe pneumonitis and marrow suppression in bone
marrow transplant recipients.  HIV patients now represent an immuno-
compromised population at risk for developing serious HHV-6 infections,
and HHV-6 is now being considered as a cofactor in the pathogenesis of
AIDS.  Konstance K. Knox and Donald R. Carrigan of the pathology
department at the Medical College of Wisconsin found HHV-6 infected cells
in the lung, lymph-node, spleen, liver, and kidney tissues obtained at
necropsy from nine AIDS patients.  The infection rate was significantly
higher than that for cytomegalovirus.  Lung infection with HHV-6 was
severe enough in one patient to account for fatal pneumonitis.  The
findings reflect the potential for HHV-6 to cause fatal pneumonitis
in adults with AIDS.  Respiratory failure is the primary cause of
mortality among AIDS patients and idiopathic pneumonitis is the main
cause of death in 5-10 percent of these patients.  HHV-6 may account for
some of these deaths, say Knox and Carrigan.  They conclude that HHV-6
is an important pathogen for people with AIDS, but note that HHV-6
infections are treatable with ganciclovir and foscarnet.

       "High Incidence of Anal Cancer Among AIDS Patients"
          Lancet (03/12/94) Vol. 343, No. 8898, P. 636
    (Melbye, Mads; Cote, Timothy R.;  Kessler, Larry et al.)

     Until recently, Kaposi's sarcoma and non-Hodgkin lymphoma were
the only cancers strongly linked to AIDS.  Melbye et al. used a linkage
between AIDS and cancer registries in seven American health departments
to investigate the possibility of a connection between HIV infection and
epidermoid anal cancer.  The study documented a dramatically increased
risk of anal cancer among AIDS patients after diagnosis.  The data
conformed to a previously hypothesized association between HIV and the
development of cancer.  Because gay men were at an increased risk of anal
cancer even before the AIDS epidemic, however, Abrams et al. could not
determine precisely how much of the increased risk was attributable to
HIV infection.  Nevertheless, the researchers stress that clinicians
should be alerted to the fact that AIDS patients do have an increased
risk of anal cancer.

             "Finding of AIDS Virus-Cancer Link Offers
                     Possibility of Treating Both"
                    Washington Post (04/08/94) P. A4

     Researchers in San Francisco say HIV directly causes cancer--a
discovery that could mean better treatment for both diseases, but
one that raises doubts about the safety of some forms of gene therapy.
Cancers such as Kaposi's sarcoma and lymphoma have long been linked to
AIDS, but most researchers assumed they were opportunistic infections
taking advantage of the compromised immune systems of AIDS patients.
The new study, however, suggests that the cancers are caused by the virus
itself.  When HIV inserted its genetic material into a cell's DNA, the
researchers say it apparently activated a nearby cancer-causing gene,
thus starting up a less common form of lymphoma known as B-cell lymphoma.
After two years spent reviewing 30 lymphoma cases, they found four in
which HIV inserted itself into the same locale in the host cell's DNA.
According to study co-author Michael McGrath, the researchers now have
additional examples and estimate that as many as a third of non-B-cell
lymphomas in AIDS patients show similar results.  While the findings
have implications for the treatment of both cancer and HIV infection,
they cast doubt over the goal of creating an AIDS vaccine from live virus.
The study authors and others fear such a vaccine could halt AIDS, but
would trigger cancer genes in the process.  Related Stories: Philadelphia
Inquirer (04/08) P. A10; Baltimore Sun (04/08) P. 7A; New York Times
(04/08) P. A13; USA Today (04/08) P. 1D

                 "Report on AIDS Drug Released"
               Washington Times (04/08/94) P. A8
                         (Fox, Maggie)

     The AIDS drug AZT does not prevent development of the fatal
disease in people who are infected with HIV, but remain asymptomatic,
conclude British and French researchers in the long-awaited Concorde
report.  Published in the Lancet medical journal, the report supports
initial findings that the drug has little or no value in preventing the
onset of AIDS in HIV-positive patients.  AZT, also known as zidovudine,
has been shown to effectively prolong the lives of patients with
full-blown disease.  The researchers found that, of 1,749 HIV-positive
individuals enrolled in the study, as many developed AIDS when given
AZT as those who received placebos.  "The results of Concorde do not
encourage the early use of zidovudine in symptom-free HIV-infected
patients," they conclude.  The group published preliminary results last
year that came to the same conclusions.  At that time, the British
pharmaceutical group Wellcome PLC, which markets AZT under the brand
name Retrovir, challenged the findings and said it was certain the drug
could delay progression from HIV to AIDS.  Although the drug company
participated in the study, it declined to sign the final report.
Related Story: Financial Times (04/08) P. 7

  "HIV-1 Detection in Endocervical Swabs and Mode of HIV-1 Infection"
              Lancet (04/02/94) Vol. 343, No. 8901, P. 852
                (Zorr, B.;  Dilger, I.;  Kosh, M. et al.)

     While it is generally accepted that HIV is a systemic disease,
there are other viral infections in which the dose and route of
infection dictate the course of disease.  Such a "local" component of
viral infections is common, and primarily determined by the cell tropism
of the virus.  To determine whether there is a local element for HIV,
Zorr et al. used polymerase chain reaction methods to examine extracted
DNA of endocervical swabs to prove the existence of HIV 1-specific DNA.
In 48 percent of the 25 cases examined, HIV-1 specific-DNA was identified.
Those 12 patients were then categorized by assumed mode of transmission.
In patients who contracted the virus through sexual contact, 75 percent
showed HIV-1 DNA on the endocervical swabs.  The detection rate of HIV-1
was lower, however, in patients with assumed intravenous transmission of
HIV.  Because the clinical state of illness can also influence the
detection rate, Zorr et al. looked at the number of CD4 cells, and
observed HIV 1-specific DNA in CD4 cell counts higher than 200.  However,
they could find no significant correlation between declining level of
CD4 cells and HIV-1 detection rate.  The differences in local detection
rate of HIV may be closely related to the pathogenesis of the infection.
The results support the possibility that HIV-1 persists in virus-permissive
cells in cases of sexual transmission, meaning that women with HIV-1 have
a high incidence of other sexually transmitted organisms, which could
result in an increase in inflammatory cells and lead to a possible
enhancement of viral concentration.

    "The Dental AIDS Cases--Murder or an Unsolvable Mystery?"
              JAMA (04/06/94) Vol. 271, No. 13, P. 983
                          (Pepper, David R.)

     Precisely how Florida dentist Dr. David Acer infected six of his
patients with HIV still has authorities puzzled, but David R. Pepper from
the University of California at San Francisco offers a theory that does
not place the blame on contaminated dental equipment.  Pepper says that,
since all six cases had identical DNA sequences in the HIV, Acer himself
was the source of infection.  Because there are no other documented cases
of dental or medical patients who became infected through routine
procedures, Pepper says it is logical to presume that the infections were
the result of an intentional act on Acer's part. Previously published
discussion implies that the virus could have been transmitted or
deliberately injected by the dentist to the six patients.  A more obvious
and more infective source, Pepper speculates, would be semen--which could
be more easily mixed with lidocaine or substituted for lidocaine to be
blended with the anesthetic in preparation for dental procedures.  As a
white or colorless substance, Pepper says semen would be less obvious to
patients and dental assistants than the injection of a red material.  And
semen is known to have an infectivity rate higher than that of random blood.
Although this would mean Acer acted with intent to cause death, it may be
comforting to many patients and physicians to know that it was not an
accidental infection.

                  "AIDS Scientists Suffer Setback"
                 Washington Times (04/12/94) P. A3
                           (McKie, Robin)

     American and European scientists have concluded that preliminary
AIDS vaccines are powerless in stimulating HIV antibodies, and hopes for
creating an effective vaccine before the end of the century have crumbled.
In the laboratory, candidate AIDS vaccines appeared successful in raising
neutralizing antibodies that bound to HIV particles and inhibited their
growth.  The vaccines failed, however, to neutralize the virus when
researchers used "wild" strains of HIV found in the blood of AIDS patients.
Scientists had developed products that were effective against laboratory
strains of HIV, but were useless in blocking strains patients encounter
in reality.  The setback was first reported by researchers at U.S.
biotechnology firm Chiron Corp., and was soon confirmed by other scientists.
"We seemed to be doing so well in developing vaccines, but this has rocked
us," said Marc Girard, head of France's AIDS vaccine research program. "It
has put us back years."  James Neil, an AIDS vaccine researcher at Glasgow
University, said part of the problem has "something to do with the preparation
of specimens in the laboratory.  We have got to find out what is the problem
and put it right before we think about taking human trials further."

       "Genetically Transformed Cells Resist Infection by HIV"
    Chemical & Engineering News (04/04/94) Vol. 72, No. 14, P. 24

     In hopes of developing gene therapy against AIDS, a team of French
researchers genetically transformed three human cell populations to
produce interferon.  According to Viellard et al. of the Institut Curie
in Paris, interferon production in the transformed cells caused them to
resist HIV infection at an early stage of viral entry--either by
preventing HIV from attaching to the CD4 receptor, or by hindering
penetration of the virus into cells.  Introducing interferon sequence
into the genetic material of three human cell lines creates "stable
antiviral expression without impeding cell survival and replication,"
the researchers concluded.



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End of HICNet Medical News Digest V07 Issue #12
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