A (t) Concerning your
question about the simultaneous rise of the CD4 cells and
the viral load, this rise should be checked by another test
one month after, to determine wether it is significant : the
number of copy/ml doesn't allow to conclude : only an
increase or a decrease of 0.5 log is considered as being
signifiant. Concerning a rise from 5,000 to 8,000 copies/ml,
it is probable that the increase of the log is inferior to
0.5. In that case, the increase in copies/ml doesn't
correspond to a signifiant increase.
Anyway, as a decrease of
the CD4 cells count and an increase of the viral load are
signs of a risk of evolution, there is generally not
discordancy.
A discordancy could be explained by the fact that these
markers are not systematically reliable, and particularly
because off the signification of the mecanisms they
explorate.
The viral load corresponds
to the quantity of virus circulating in the blood; some
think it is not a marker of the total quantity of the virus
in the body (virus is present in the lung cells, brain and
intestine too). We must add that the viral load doesn't
explorate the others factors that would intervene in synergy
with it (indeed, the HIV wouldn't explain the apparition of
the AIDS epidemy in 1981 only by itself, neither the
heterogeneity of the AIDS symptoms in general and among the
patients; cofactors would partially explain why some persons
develop opportunistic infections, and why some situations
evoluate more rapidly. Numerous cofactors have been
suspected, most of them remaining hypothetic; others are
more probable, such as HHV6, which would explain the
developpement of Kaposi's Sarcoma. This herpes virus, very
different from the others communs herpes viruses, make the
object of research works in order to find a complementary
specific treatment).
Concerning the CD4
lymphocytes, one should notice that it is not a specific
marker of the HIV infection, variations secondary to other
reasons may appear. What more, physiological variations
(chronobiological) for asymptomatic seropositive persons
exist (and for HIV negative persons) according to the
seasons, the months, even during the day (variations
reaching 100%, which is not a problem as the blood analysis
are always made at the same hours in the morning).
Concerning your question
about the use of tritherapies during pregnancy, and our
opinion on the most adapted therapy, we haven't
unfortunately more informations to give you, since our first
answer.
You will find
complementary informations in the mail we sent on the 9th of
September to Pr DORMONT from the National Aids Research
Agency (ANRS) in wich we wrote : "So, for now, AZT is the
only officially recommended treatment in France during
pregnancy. Assays are being carried out with AZT + 3TC,
others with AZT + Nevirapine.
Protease inhibitors, because of their hepatic effects on the
fetus, are not studied for the pregnant woman. We read that
D4T would have a good placentar diffusion but for now, there
is no protocole in France using this molecule as a
prevention (information given on telephone by Laboratories
Brystol-Myer Squibb).
We could like to know if you have any other information
concerning other protocoles than AZT as a monotherapy,
concerning prevention of mother-fetus transmission, as well
as preliminary results of these protocoles. We also wish to
know if, following the Greenberg et coll. publication
(Abstract Tu-C. 2592, Vancouver, 1996), wether protocoles
have been considered with a prenatal supply in vitamin
A.
About this subject, we have another series of questions.
The NIH in the States has made eleven recommendations
concerning HIV treatment. The 8th one mentions that "women,
pregnant or not, must have an optimal anti-HIV
treatment".
For now, the optimal anti-HIV official treatment is
represented by the tritherapies including a protease
inhibitor. So, either the NIH recommendation considers that
protease inhibitors have a "tolerable" hepatic toxicity for
the fetus, in regard with the risk of HIV transmission
during the first 3 months of pregnancy (35%), or, wich is
not very probable (because of the risk of an increase of the
virus replication, for the mother and the apparition of
resistances), the protease inhibitor may be stopped during a
few months. Do you have any precisions on that subject, and
what is your opinion ?
We would like to have your opinion on another recommendation
of the NIH. The use of reverse transcriptase nucleosidic
inhibitors analogues during pregnancy rises the problem of
the mutagen risk that could occur, particularly at the
begining of pregnancy.
As you know, the Ames test used for the drawing up of a AMM
file may be negative, even though the result for some
molecules (AZT) may be positive for other tests, for
instance the SOS Chromotest, more sensitive.
The SOS-Chromotest has
been experimented since 1988 (Hoffnung and Quillardet,
Institut Pasteur). An article showed that with this test,
AZT is strongly positive, even with low concentrations,
inferior to 100 ng/ml, closed followed by ddI; D4T and ddC
being the less positive. 3TC had not been tested (Mamber
S.W. et coll., Antimicrob. Agents and Chemotherapy, 34,
1237-1243, 1990).
A research on databases for the 1990-1997 period on the
anti-HIV molecules tested with the SOS-Chromotest allowed to
find only one publication, on hydroxyurea. It is very
surprising, as this test is cheap (less then 3,000 FF),
rapid and easy. Some say that it is difficult to extrapolate
results from in vitro to in vivo. This test however keeps
its utility, as for ethics reasons there is no possibility
to practise mutagenicity tests on human beings.
The SOS-Chromotest could help to propose the less positive
molecule for a pregnant woman, if all the anti-HIV molecules
were positive.
The increase of e-mail questionning about the preventive
treatment of HIV transmission from mother to child probably
corresponds to an increase of the seropositive person
desiring to have a child.
Concerning the
mutagenicity of nucleosides analogues, this subject already
worried us and had been evoked after the publication of the
results of the ATCG 076 protocole, in the article "AZT and
procréation". It seems that this risk should be
limited, if AZT is prescribed at the end of the
pregnancy.
At this time, the National
Council for AIDS recommended a follow-up care for children
born from a seropositive mother who took AZT during her
pregnancy, if possible beyond teenagehood.
If tritherapies recommendations were advised during all the
pregnancy, it would be imperative to assure that the used
molecules have no or the most limited possible mutagenic
effect, particularly because more and more seropositive
women wish to have a baby."
Pr DORMONT didn't answer
us, so we transmitted this mail to M. Serge LECOZ, from the
ACTION TREATMENTS association (190 bd de Charonne, 75020
Paris, France; Tel +33 (0)1 43 67 66 00), asking for answers
and precisions on these questions. You could also try to
contact him. (9710)
Results with AZT are
unquestionable, but some authors raised the hypothesis that
AZT could have a negative effect after time, for persons
whose mother took AZT during their pregnancies. We wrote an
article on this particular subject in 1994 ("AZT and
procreation") and a few months later the National AIDS
Council (Conseil
National du Sida
in France) advised in a report to try and assure a follow-up
care of children in that particular case. However they
precised that the risk of side effects was
hypothetic.
Indeed this risk seems be
hypothetic, as AZT in this ATCG 076 protocole is not
prescribed at the begining of the pregnancy, when it would
be major. But we are not completely sure of that, and we
think the National AIDES council either, even if it doesn't
explicitly admit it (let's not forget that it is the first
time in the history of medicine that such a follow-up is
recommended until the adult age; the preceeding case was the
distilbene [Diethylstilbestrol] in the seventies).
We contacted the Brystol-Myers Squibb laboratory to ask if
according to their studies made on D4T, it would be able
alone or in association, to decrease, like AZT, the risk of
HIV transmission. It would be interesting, because D4T is
less toxic than AZT. We have no answer for the
moment.
Other ways of prevention
are being studied : for instance the vaginal wash with
antiseptic product during the delivery.
Concerning the risk of
transmission to the partner, some techniques reducing this
risk exist, such as the determination of the ovulation peak,
or even totally suppress it (artificial
insemination).
Concerning contamined
children, the certainty can only be established a few months
after birth. For most of the children, the HIV infection
slowly evoluates, at a rythm comparable to the adults.
However some situations evoluate more rapidly.
To obtain more
informations on this subject, and particularly to have
testimonies of couples living with this problem, we advise
you to contact the following associations:
International Community of
Women Living with HIV / AIDS
2C, Leroy House, 436 Essex Road, London, N1 3QP, UK
Tel : +44 171 704 0606
Fax : +44 171 704 8070
icw@gn.apc.org
http://www.icw.org
Ikambere
La maison accueillante pour les femmes
5, rue Virgil Grissom, 93200 Saint-Denis, France
Tel : +33 (0)1 42 35 74
02
Fax : +33 (0)1 42 35 76 16
You could also contact the
CRIPS, one of the most important documentation centers:
CRIPS Ile de France
192, rue Lecourbe
75015 Paris France.
Tel +33 (0)1 53 68 88
88
Fax +33 (0)1 53 68 88 89
infos@lecrips.net
http://www.lecrips.net
We think that it would be
useful for you to meet a gynecologic unit in a hospital. It
is indeed the place where doctors are the most used to this
type of pregnancy.
Finally it must be know
that even if more and more doctors consider that the
decision to procreate only belongs to the couple, numerous
doctors still wish to limit the information to the patients,
and among them some consider negatively the procreation for
couples living with the HIV. (9708)
