Q-A 1

Translation in plan

Q-A 2

Q (t) I am seronegative.

My girlfriend is seropositive since 1990, her clinical state is : asymptomatic viral load = 8,000 copies/ml in April 1997, CD4 cells are 1,150 (800 in April 1997).

We wish to have a child, and we would like to know the state of knowledge concerning a tritherapy during pregnancy, which one is the most adapted (type, beginning, side effects on the child...).

Last question, what do you think of a simultaneous increase of the viral load and the CD4 cells? Isn't it contradictory?

To finish, we would like to thank your team for the time and energy you dedicated to a preceeding request from our part, and to congratulate for your disponibility.

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)