       TreatmentUpdate57, Vol. 7, No. 3 - March 1995
       *************************************************
       published by Community AIDS Treatment Information
       Exchange, Suite 420 - 517 College St., Toronto,
       Ontario, Canada M6G 4A2
       *************************************************

       INFECTION FIGHTERS

       A. Mepron or iv pentamidine for PCP

       * BACKGROUND

       The life-threatening infection PCP is one of the more common
infections seen in patients in North America and Western Europe.
Symptoms can include fever, shortness of breath and dry cough.
Standard therapy is Bactrim(R)/Septra(R) or iv (intravenous)
pentamidine. Alternatives may include clindamycin-primaquine,
dapsone-trimethoprim, trimetrexate-dapsone and Mepron(R) (atovaquone,
Wellvone(R)). There are problems associated with every therapy as some
patients cannot tolerate sulfa drugs. Mepron is a relatively new
treatment for PCP, and the manufacturer, Glaxo-Wellcome, has been
conducting trials comparing it to standard therapy.

       * STUDY DETAILS

       In one experiment, researchers tested Mepron against iv
pentamidine. Although 144 subjects (139 men and 5 women) entered the
trial the company used data on 56 subjects who received Mepron and
53 who received pentamidine. Only subjects with mild-to-moderate
documented PCP entered the study. Researchers assigned subjects at
random to one of 2 arms of the study; either 750 mg Mepron "3 times
daily with food" or one daily dose of pentamidine of either 3 or 4
mg/kg of body weight. Subjects were supposed to receive either drug
for 3 weeks. Those subjects with "moderately severe PCP also
received oral [corticosteroids]" to reduce inflammation. Subjects
and doctors knew which drugs subjects received.

       * RESULTS

       According to the printed analysis,

       - 57% of subjects who received Mepron and 40% of who received
         iv pentamidine "were successfully treated." This
         difference was not statistically significant.

       - More subjects receiving Mepron (29%) were likely not to
         improve than subjects receiving pentamidine (17%). This
         difference was not statistically significant.

       - Subjects given pentamidine were more likely to stop
         recovering because of drug toxicity than subjects given
         Mepron.

       * SIDE EFFECTS

       Among subjects who received pentamidine, serious side effects
included low blood sugar, nausea and vomiting. Among subjects
receiving Mepron the most serious side effect was "rash". Subjects
receiving Mepron reported "increased cough."

       * CONTESTED CONCLUSIONS

       The study doctors concluded that "oral [Mepron compared to iv
pentamidine] have similar rates for successful treatment of mild to
moderate PCP..."

       Doctors not associated with this study warn that

       "[subjects] in this study had a treatment failure rate that
       was 71% higher if they received Mepron than if they received
       iv pentamidine." Other doctors noted that within the first 4
       weeks of treatment more subjects assigned to Mepron (13%)
       died than subjects assigned to pentamidine (8%). This
       difference was not statistically significant. By the 8th week
       the rates of death were similar.

       Although Mepron is less effective than standard treatment
(Bactrim/Septra or iv pentamidine) it remains an option,
particularly for patients who cannot tolerate sulfa drugs.

       REFERENCES:

              1. Dohn MN, Weinberg WG, Torres RA, et al. Oral
       atovaquone compared to iv pentamidine for Pneumocystis
       carinii pneumonia in patients with AIDS. Annals of Internal
       Medicine 1994;121(3):174-180.

              2. Lederman MM, and Van der Host C; Stoeckle M
       and Tannenberg A. Atovaquone for Pneumocystis carinii
       pneumonia. Annals of Internal Medicine 1995;122(4):314-315.

              3. Hughes WT. The role of atovaquone tablets in
       treating pneumocystis carinii pneumonia. Journal of Acquired
       Immunodeficiency Syndromes and Human Retrovirology
       1995;8(3):247-252.

       II TESTING

       A. Pregnancy and the immune system

       * BACKGROUND

       Researchers studying pregnancy have found a relationship
between the mother's immune system and the placenta (the 'organ'
that develops around the fetus). The placenta is rich in blood
vessels from the mother and fetus so that the fetus can received
oxygen and nutrients from the mother. In order for the fetus to
survive, it must be protected from the mother's immune system. It
appears that the placenta produces chemicals that alter the mother's
immune system.

       * CYTOKINES FOR SURVIVAL

       Research on pregnant mice and humans suggests that the immune
system of the female parent undergoes a complicated change during
pregnancy. One arm of the immune system called CMI (cell-mediated
immunity) seems to become weaker during pregnancy. The body needs
CMI to fight off certain microbes that tend to 'hide' inside cells.
Examples of these microbes include CMV and SV, the bacteria that
cause TB and related infections and, the parasite that causes the
brain infection 'toxo' (toxoplasmosis). To help fight off these
microbes the immune system releases chemicals such as IL-2 and
interferon-gamma. Interestingly, large doses of these two chemicals
can kill the fetus.

       The other arm of the immune system is called humoral
immunity. Chemicals that strengthen this response include IL-4, -6
and -10. Antibody-producing B cells are an important part of this
arm. In experiments on pregnant mice who are not likely to carry
the fetus for the full length of pregnancy, injections of IL-3 and
GM-CSF (granulocyte macrophage-colony stimulating factor) help
correct this problem. Researchers in Alberta and India found that
the placentas from women prone to abortion tend to release IL-2,
interferon-gamma and TNF (tumour necrosis factor).

       * HELPING THE MOTHER

       It appears that pregnancy seems to strengthen humoral
immunity and weaken CMI. This change seems to help the fetus survive
pregnancy. Another issue is the survival of the mother. To
strengthen humoral immunity may mean that pregnant women may not be
able to maintain a strong defence (CMI) against HIV and other
microbes. Thus pregnancy may further weaken the immune systems of
HIV-infected women. Researchers need to find out more about the
immune systems of women in general and women with HIV/AIDS in
particular.

       REFERENCES:

              1. Wegmann TG, Lin H, Guilbert and Mossman TR.
       Bidirectional cytokine interactions in the maternal-fetal
       relationship: is successful pregnancy a TH2 phenomenon?
       Immunology Today 1993;14(7):353-356.

              2. Clarke AG and Kendall MD. The thymus in pregnancy:
       the interplay of neural, endocrine and immune influences.
       Immunology Today 1994;15(11):545-551.

              3. Moncayo HE, Solder E, Abfalter E and Moncayo R.
       Cytokines and the maternal-fetal interface. Immunology Today
       1994;15(6):295.

       B. Pregnancy and HIV: why some babies escape infection

       * THEORY VERSUS REALITY

       According to the World Health Organization, approximately 1
million children worldwide are infected with HIV. In the USA every
year 7,000 HIV-infected women give birth to between 1,000 and 2,000
infected infants. On average between 75% to 85% of babies are born
without HIV infection although their mothers are infected. Several
research teams are studying infants born to these mothers, but these
teams have produced more theories than clear answers. In general, it
seems that the state of the mother's immune system and severity of
HIV infection may play a role in the outcome of pregnancy. In some
studies it appears that breast feeding may transmit the virus. In
several studies it appears that fetuses' with strong CMI
(cell-mediated immunity) were less likely to be HIV-infected
compared to other fetuses with weak CMI. Women with HIV-2 infection
seem less likely to transmit that virus to the fetus.

       REFERENCES:

              1. Glausiuz J. HIV: The babies who escape. New
       Scientist 16 April, 1994, pages 38 to 42.

              2. Khouri YF, McIntosh K, Cavacini L, et al. Vertical
       transmission of HIV-1: correlation with maternal viral load
       and plasma levels of CD4 binding site anti-gp120 antibodies.
       Journal of Clinical Investigation 1995;95:732-737.

              3. Clerici M, Sison A, Berzofsky JA, et al. Cellular
       immune factors associated with mother-to-infant transmission
       of HIV. AIDS 1993;7:1427-1433.

              4. Kilk SC, Wara DW, Landers DV and Levy JA. Features
       of HIV-1 that could influence maternal-child transmission.
       Journal of the American Medical Association
       1994;272(6):467-474.

              5. Douglas SD. Immunological and virological clues for
       mother-to-child transmission of HIV-1 and HIV-2. Journal of
       the American Medical Association 1994;272(6):487-488.

              6. Rowlands-Jones SL, Nixon DF, Alderhous MC, et al.
       HIV-specific cytotoxic T-cell activity in an HIV-exposed
       but uninfected infant. Lancet 1993;341:860-861.

       C. Pregnancy and HIV: a French study

       * A 7-YEAR STUDY IN FRANCE

       In this project, researchers have been keeping track of
babies born to HIV-infected mothers. The mothers were asked not to
breast feed their infants. Here is the subject profile:

       - average age was about 27 years
       - about 1/4 were from Central Africa
       - about 5 % were from the West Indies
       - 80% had either no symptoms or just persistently
         swollen lymph nodes
       - average CD4+ cell count was roughly 600 cells
       - average % of lymphocytes that were CD4+ was 30%
       - average CD8+ cell count was 864 cells
       - average % of lymphocytes that were CD8+ was 44%

       No women used anti-HIV drugs during the study.

       * TRANSMISSION RATE OF 20%

       The researchers reported data on 848 mothers (and their
children). They found that about 20% of babies had HIV infection.
The transmission rate has remained roughly the same since 1986.
Researchers analysed other data to find out what factors might
affect the infection of babies. They found that the following
factors did not have any relation to the infant being HIV-infected:

       - being born in Central Africa
       - cutting open the mother's womb to release the infant
       - whether the mother was infected through needles or
         sex

       The following factors appeared to be associated with
infection of the fetus:

       - breast-feeding
       - age-older mothers
       - low CD4+ cell counts (explained below)
       - detectable p24 antigen
       - symptoms of HIV infection

       On average, women who had a CD4+ cell count of 601 cells or
more had a 15% chance of giving birth to an infected infant. Women
who had less than 200 CD4+ cells had a 43% chance of giving birth to
an infected infant. These differences were statistically
significant; that is, not likely due to chance alone. Women with the
lowest risk of transmission (12%) had more than 500 CD4+ cells and
less than 40% of CD8+ cells. Women with the highest risk (50%) of
transmission had less than 200 CD4+ cells and more than 40% CD8+
cells. The length of time infants were breast fed did not seem to
affect which infants would become HIV-infected. Mothers who were
more than 35 years old had a transmission rate of 30% and those
under the age of 25 had a rate of less than 16%. Subjects with no
symptoms of HIV infection had an 18% risk of transmission while
those with AIDS had a rate of 35%.

       REFERENCES:

              1. Mayaux M-J, Blanche S, Rouzioux C, et al. Maternal
       factors associated with perinatal HIV-1 transmission: the
       French cohort study-7 years of follow-up observation. Journal
       of Acquired Immunodeficiency Syndromes and Human Retro-
       virology 1995;8(2):188-194.

       D. Pregnancy and HIV-studies from Tanzania and Cote d'Ivoire

       * STUDY DETAILS

       Researchers in Sweden and Tanzania conducted a 3 year study
to try and find out factors that might explain why some babies are
born without HIV infection. The researchers tested blood from 3,000
mothers and found that roughly 12% were HIV infected. Data analysis
relied on information from 255 mothers,138 of whom were infected
with HIV, and 117 who were not. The researchers noted CD4+ and CD8+
cells, the HIV protein p24 and beta2-microglobulin (2-m). Blood
levels of 2-m increase as the immune system weakens in subjects
with HIV infection.

       * RESULTS

       On average about 22% of infants born to infected mothers were
also infected. The researchers found that the following factors were
linked to infection in the infants:

       - higher-than-normal blood levels of 2-m
       - detectable p24 antigen
       - low blood levels of CD4+ cells

       * 2-M

       On average, infants born to women with relatively high blood
levels of 2-m (2 mg/litre or greater) had a 34% chance of also
being HIV-infected. In women with less than 2 mg/L of 2-m, the
chance of giving birth to an infected infant was 14%.

       * %CD4+ CELLS

       The researchers did not find any statistically significant
relations between infected infants and CD4+ cell counts. When they
measured the percent of lymphocytes that were CD4+, then low %CD4+
levels were linked to infants being infected. For mothers with %CD4+
cells 20% or less, the chance of an infant being born with HIV
infection was about 33%. Mothers who had more than 20% CD4+ cells
had a transmission rate of 14%. Among mothers with less than 20%
CD4+ cells and blood levels of 2-m greater than 2 mg/L, the rate
of transmission was 54%. Although p24 antigen was more commonly
detected in blood samples from mothers who transmitted the infection
(than in those that didn't), "few mothers had [detectable p24]".

       * COTE D'IVOIRE

       Another study in C8te d'Ivoire analyzing data from over 600
poor HIV-1 infected women, found that pregnant women had a 25%
chance of giving birth to an infected infant. For women with HIV-2,
the equivalent figure was 1%.

       REFERENCES:

              1. Bredberg-Raden U, Urassa W, Urassa E, et al.
       Predictive markers for mother-to-child transmission of HIV-1
       in Dar es Salaam, Tanzania. Journal of Acquired
       Immunodeficiency Syndromes and Human Retrovirology
       1995;8(2):182-187.

              2. Adjorlolo-Johnson G, De Cock D, Dkpini E, et al.
       Prospective comparison of mother-to-child transmission of
       HIV-1 and HIV-2 in Abidjan, Cote d'Ivoire. Journal of the
       American Medical Association 1 994;272(6):462-466.

       E. French-American study on AZT for pregnant HIV-infected
          women

       * STUDY DETAILS

       We now report results from the study ANRS 024/ ACTG 076.
Researchers randomly assigned subjects to one of 2 arms in the
study; either AZT or placebo. Those assigned to AZT received 500
mg/day orally before giving birth and during birth they received iv
AZT 2mg/kg of body weight for 1 hour, "followed by 1 mg/kg/hour
until birth." After birth the infant received AZT 2 mg/kg every 6
hours for 6 weeks. Subjects and their infants received regular
monitoring. For their analysis, researchers used data from 205 women
assigned to receive AZT and 204 women assigned to placebo. Neither
doctors nor subjects were supposed to know who received AZT and who
did not. At least 1/2 of the subjects:

       - were 25 years old
       - had 550 CD4+ cells
       - were pregnant for 6 months before entering the
         study
       - received AZT for 11 weeks before giving birth

       * EFFECT(S) OF AZT

       Researchers made decisions about the effect of AZT or placebo
in a number of ways. In one calculation, 180 mothers and their
infants received AZT while 183 others did not. Roughly 8% of infants
born to mothers in the AZT arm were infected as were 26% of those
born to mothers in the placebo arm. Since 8% of infants born to
mothers who used AZT were also HIV-infected, treatment with AZT
does not provide 100% protection.

       * TOXICITY--THE MOTHERS

       Roughly the same proportion of women reported side effects in
each arm of the study. There were no deaths among the mothers in
either arm during the study. Six months after birth, 95% of women
in both arms of the study had CD4+ cell counts "greater than 300
CD4+ cells".

       * TOXICITY--THE INFANTS

       Five deaths occurred in subjects receiving AZT and 3 others
in those assigned to placebo. None of these deaths appeared to be
caused by AZT or placebo. Doctors detected a variety of physical
defects in 33 infants but these were evenly divided between the 2
arms of the trial. Nearly twice as many infants given AZT had
reduced blood levels of haemoglobin (needed for moving oxygen) than
others not given the drug. Six weeks after birth (when they stopped
using AZT) haemoglobin rose. References appear in section F below.

       F. AZT and pregnancy-unanswered questions and difficult
          decisions

       * WHAT NEXT?

       Despite the apparent benefit of AZT in ANRS 024/ACTG 076
(details of which appear above) many questions remain unanswered .

       * TIMING OF 'TREATMENT'

       It appears that HIV infection of the fetus happens late in
the course of pregnancy; before, during and possibly after birth
(via breast milk). In making an attempt to protect the fetus,
researchers gave women oral and iv AZT, and later their infants
received the drug as well. One issue arising from this research is
the timing of treatment. Can shorter exposure to AZT late in
pregnancy also provide the same or better protection from HIV?

       * AZT: DELIVERY AND DOSE

       Women in this trial received oral AZT at a dose of 500
mg/day. Can the fetus of pregnant women benefit from a reduced dose
of AZT-300 mg/day? The women in the trial also received iv AZT, is
this always needed? AZT is supposed to work by interfering with the
viral enzyme RT (reverse transcriptase); it works only once a cell
has already been infected by HIV. In experiments on health care
workers and patients accidentally infected with HIV, treatment with
AZT by itself or the related drug ddI and interferon-alpha has not
protected people from HIV infection. As well, it is not clear what
might happen to the fetus if the mother develops virus that is
resistant to AZT.

       * OTHER PREGNANT WOMEN

       Readers cannot assume that the results from this study mean
that fetuses of other pregnant HIV-infected women will 'benefit'
from AZT treatment of their mother. The subjects in this trial were
a "select group of women", having

       - few, if any, symptoms of HIV infection
       - little past use of AZT
       - relatively high CD4+ cell counts

       Based on results from ANRS 24/ACTG 076, it is not clear what
might happen to the fetuses of other pregnant HIV-infected women who
have lower CD4+ cell counts, used AZT for long periods of time
and/or have serious symptoms.

       * TOXIC FOR SOME BUT NOT OTHERS?

       Results from the French-American study suggest that toxicity
from AZT to infants is minor, but it is not clear what will happen
to mothers and infants over the long term. Mothers may be
understandably wary given the interim results from the American
study ACTG 152. In that trial hundreds of infants-most aged between
3 and 30 months-received AZT or ddI or a combination of both drugs.
An independent safety monitoring board recommended that the trial be
stopped because babies receiving AZT alone, compared to the other 2
groups, had:

       - stopped growing
       - more life-threatening infections
       - brain damage
       - higher rates of death

       Given that 75% to 85% of pregnant HIV-infected women give
birth to healthy, non-HIV-infected babies, there are concerns about
giving all such women (and their fetuses) AZT. Perhaps research
using less toxic drugs such as nevirapine might be useful.

       * HOW DOES AZT WORK?

       Doctors associated with this study do not know why AZT
treatment apparently reduced the chance of HIV infection of the
fetus. Experiments on baby monkeys infected with SIV suggests that
AZT may delay the appearance of AIDS. Researchers think that the
anti-viral effects of AZT may be the source of its benefit--but
this has not been formally proven. Indeed, researchers do not have a
precise and clear understanding of exactly why most babies born to
HIV-infected mothers do not have HIV infection.

       REFERENCES:

              1. Connor EM, Sperling RS, Gelber R, et al. Reduction
       of maternal-fetal transmission of Human Immunodeficiency
       Virus type 1 with Zidovudine treatment. New England Journal
       of Medicine 1994;331(18):1173-1180.

              2. Rogers MF and Jaffe HW. Reducing the risk of
       maternal-infant transmission of HIV: a door is opened.
       [Editorial] New England Journal of Medicine
       1994;331(18):1222-1223.

              3. Palmer DL, Njelle BL, Wiley CA, et al. HIV-1
       infection despite immediate combination antiviral therapy
       after infusion of contaminated white blood cells. American
       Journal of Medicine 1994;97:289-295.

              4. Glick ME. Interim results lead to discontinuation
       of AZT-only study arm. Press release. February, 1995.

              5. Bayer R. Ethical challenges posed by Zidovudine
       treatment to reduce vertical transmission of HIV. New England
       Journal of Medicine 1994;331(18):1223-1225.

              6. Van Rompay KKA, Otsyula MG, Marthas ML, et al.
       Immediate Zidovudine treatment protects Simian
       Immunodeficiency Virus-infected new born macaques against
       rapid onset of AIDS. Antimicrobial Agents and Chemotherapy
       1995;39(1):125-131.

              7. Dabis F, Mandelbrot L, Msellati P and van de Perre
       P. Zidovudine to decrease mother-to-child transmission of
       HIV- 1: is it a good thing for developing countries? AIDS
       1995;9(2):204-206.

              8. Michie CA and Hyer W. When does HIV cross the
       placenta? Lancet 1995; 345(8948): 517-518.

              9. Kesson AM, Fear WR, Williams L, et al. HIV
       infection of placental macrophages: their potential role in
       vertical transmission. Journal of Leukocyte Biology
       1994;56:241-246.

             10. Bryson YJ, Pangs, Wei LS, et al. Clearance of HIV
       infection in a perinatally infected infant. New England
       Journal of Medicine 1995;332(13):833-838.

             11. Schwartz DH, Sharma UK, Perlman EJ and Blakemore K.
       Adherence of Human Immunodeficiency Virus lymphocytes to fetal
       placental cells: a model of maternal->fetal transmission.
       Proceedings of the National Academy of Sciences USA 1995;
       92:978-982

       III  VACCINES

       A. Vaccines for HIV

       * BACKGROUND

       During the past 10 years researchers have been constructing a
number of potential anti-HIV vaccines. Most of these vaccines were
designed to stimulate one arm of the immune system (humoral
immunity) and cause the body to make anti-HIV antibodies. The
theory supporting this design relied on a number of now outdated
ideas, one of which was that anti-HIV antibodies would protect
people from HIV infection. Unfortunately most people with HIV/AIDS
make these antibodies which do not appear to protect them from
infection or further damage to the immune system. It appears that
the other arm of the immune system--CMI (cell-mediated immunity)--
weakens over time. Many of the life-threatening infections seen in
AIDS occur because CMI has declined. Researchers in France, Montral
and California studying monkeys with AIDS have reached the same
conclusion. They are trying to design vaccines that can boost CMI
against SIV (the virus that causes AIDS in some monkeys) and HIV.
These vaccines may also be used to help the immune systems of people
with HIV/AIDS.

       * HELPING VACCINES WORK

       Usually vaccines have 2 parts. The first part (called the
adjuvant) is designed to enhance the immune response to the vaccine
(the second part). Adjuvants generally used in vaccines include:

       - alum (aluminum hydroxide)
       - CFA (complete Freunds adjuvant made with light mineral oil)
       - extracts of bacteria such as MDP (muramyl dipeptide)

       Most adjuvants stimulate production of antibodies and favour
humoral immunity. Scientists working on developing HIV/AIDS vaccines
are trying to find adjuvant that can help T cells respond to a
vaccine. Researchers experimenting on humans with cancer are testing
a number of chemicals designed to boost CMI. Reviewing their early
results, it is not clear which chemicals are best for boosting CMI.
Here are several chemicals that are being tested for their ability
to boost T cells so that they will be stimulated by vaccines:

       - interleukins 2 and 12
       - DTC (Immuthiol(R) )
       - MIMP (methyl inosine monophosphate)
       - thymic hormones such as thymosin alpha 1,
         thymopentin, thymic humoral factor
       - levamisole (Ergamisol(R)
       - indomethacin (Indocid(R)
       - complete Freunds adjuvant (CFA)

       REFERENCES:

              1. Hadden JW. T-cell adjuvants. International Journal
       of Immunopharmacology 1994; 16(9):703-70.

              2. Vaslin B, Le Grand R, Vogt G, et al, Induction of
       Humoral and cellular immunity to simian immunodeficiency
       virus: what are the requirements for protection? Vaccine
       1994;12(12):1132-1140.

              3. Chan WL, Rodgers A, Grief C, et al. Immunization
       with class 1 human histocompatibility leukocyte antigen can
       protect macques against challenge infection with SIVMAC-32H
       AIDS 1995;9(3):223-228.

       B. The Salk HIV vaccine-results from several
          studies

       * BACKGROUND

       Learning that CMI (cell-mediated-immunity) was reduced in
patients with AIDS a research team led by Dr. J. Salk (creator of
the polio vaccine) designed a potential anti-HIV vaccine called the
immunogen. To make this vaccine, technicians attacked HIV with
chemicals and radiation so that it could not cause any infection.
They then removed the HIV-protein gp120. This protein can impair the
ability of the immune system to fight HIV. To boost the response of
the immune system to the vaccine, researchers used an adjuvant
called IFA (incomplete Freunds adjuvant) using light mineral oil and
other ingredients. IFA appears to stimulate both CMI and humoral
immunity. The researchers also used a small amount of another HIV
protein called p24 with the adjuvant.

       * STUDY DETAILS

       All subjects in this study were adults, had CD4+ cell counts
of at least 600 cells, and had no symptoms of HIV infection. As
well, subjects did not have B-cells producing high levels of
unnecessary antibodies. Researchers randomly assigned subjects to
receive 3 injections of the vaccine or just the adjuvant over six
months.

       * MEASURING T CELLS

       Different labs have different procedures for reporting a
person's CD4+ cell count. Sometimes the actual number of CD4+ cells
is computed. Sometimes it is not. CD4+ cells are lymphocytes, and
lymphocytes are white blood cells. The white blood cells are
expressed as an estimate of the actual number of white blood cells
in 1 cc of blood. CD4+ cells are usually expressed as percentages.
For example, usually lymphocytes make up between 25% and 50% of all
white blood cells. Normally, CD4+ cells make up 30% to 45% of all
lymphocytes. This is an actual measurement. To find out the CD4+
cell count some small calculations are needed. Thus CD4+ cell counts
are calculated while the %CD4+ are actual measurements. Thus %CD4+
and %CD8+ are more accurate than the calculated number of cells. In
a future issue of TreatmentUpdate we will provide details on how to
find out the number of CD4+ and CD8+ cells

       * RESULTS--CD4+ CELLS

       At the time subjects entered the study their average %CD4+
(the proportion of lymphocytes that were CD4+ cells) was roughly
31%. Subjects who received the immunogen had a slower rate of loss
of CD4+ cells compared to subjects who received IFA. This difference
between the two groups was statistically significant that is, not
likely due to chance alone.

       * RESULTS--ANTIBODIES

       Both groups of subjects produced increased amounts of
antibodies against the HIV protein p24. Subjects who received the
immunogen made more antibodies. This difference was also
statistically significant.

       * RESULTS--CMI, VIRUS AND TOXICITY

       To measure CMI technicians inject a small amount of protein
from yeast or bacteria under the skin. In people with good CMI there
is usually a reaction within 48 hours-swelling and redness at the
injection site. The greater the reaction the higher the level of
CMI. Among the subjects given the immunogen, CMI apparently
increased by 21% while subjects in the IFA group had their CMI fall
by 28%.

       It appeared that subjects who received the vaccine had a
slower increase in production of HIV compared to who subjects
received IFA. Again this difference was also statistically
significant. Although some subjects used AZT while in the study, it
did not appear to reduce production of H[V during the study.
Researchers reported no serious side effects in people in both
groups.

       REFERENCES:

              1. Trauger RJ, Ferre F, Daigle AE, et al. Effect of
       immunization with inactivated gp120-depleted Human
       Immunodeficiency Virus type 1 (HIV-1) immunogen on HIV-1
       immunity, viral DNA and percent of CD4+ cells. Journal of
       Infectious Diseases 1994;169:1256-1264.

              2. Moss RB, Ferre F, Trauger R, et al. Inactivated
       HIV-1 immunogen: impact on markers of disease progression.
       Journal of Acquired Immunodeficiency Syndromes 1994;7
       (Supplement l):s21-s27.

              3. Smith GW. Calculating your absolute T4+ count. IN:
       Testing AIDS 1989; page 4.

       C. Salk HIV vaccine--immune boosting effects

       * STUDY DETAILS

       In this study researchers focused on the effect of the
immunogen on CMI. Subjects in this were symptom-free, had at least
a minimal level of CMI and at least 600 CD4+ cells. Researchers
enrolled 46 men and 2 women, and divided them up at random and
placed subjects into 5 groups, each receiving a different dose (50,
100, 200 or 400 mcg (micrograms) of the vaccine or just IFA.
Subjects received at least 1 injection of the vaccine or IFA.
Technicians then tested subjects regularly for CMI. If the results
of the tests suggested that CMI was weak then the subject received a
booster shot of the vaccine (to a maximum of 6 boosters).
Researchers monitored subjects for up to 2 years. They have just
released data on the results of the first 9 months.

       * RESULTS

       At the beginning of the study subjects had various levels of
CMI. Over time, subjects who received the vaccine had higher and
sustained levels of CMI against H1V compared to subjects who
received IFA. For each dose of the vaccine this effect was
statistically significant. It appeared that the 100 mcg dose was "as
effective as the 400 mcg dose in [boosting CMI against HIV] over the
course of the study."

       Based on these preliminary and promising results, the Immune
Response Corporation is planning larger studies.

       REFERENCES:

              1. Turner JL, Trauger RJ, Daigle AE and Carlo DJ.
       HIV-1 Immunogen induction of HIV-1-specific delayed-type
       hypersensitivity: results of a double-blind, adjuvant-
       controlled, dose-ranging trial. AIDS 1994;8(10):1429-1435.

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