Q-A 1

Q (t) I'm a student in science and I'm doing a research on Bactrim.
I would be very grateful if you could give me informations on its chemical composition and its biological and chemical effects on human body.

A (t) Bactrim® is composed of two antibiotics that act in synergy : sulfamethoxazole and trimethoprime (respectively 400 and 80 mg, and for the strong presentation, 800 and 160 mg) and excipients.

Sulfamethoxazole belongs to the sulfamide antibiotics family ; trimethoprime belongs to the diaminopyrimidines antibiotics family. These two antibiotics block, at two consecutive levels, the metabolic chain that lead to the bacterian nucleoproteins.

Bactrim® has a wide antibacterian action, especially on Pneumocystis carinii, Toxoplasma gondii, Salmonella, Shigella, Haemophilus, E. Coli, Klebsiella, Enterobacter, Proteus, Citrobacter, Vibrio cholerae, Listeria...

Concerning its metabolism after absorption : maximal plasmatic concentrations are reached between 2 and 4 hours (for a strong Bactrim® tablet, between 40 and 60 mg/ml for the sulfamethoxazole and from 1 to 2 mg/ml for the trimethoprime); half life is respectively 9 -11 hours and 10 -12 hours; its diffusion is fast (cerebrospinal fluid, middle ear, tonsil, saliv, lungs, bronchial secretions, prostate, seminal fluid, vaginal secretions, bones); protein binding is respectively 66 and 45%. In the blood, 85% of the sulfamethoxazole is metabolised into glycuroconjugated and N-4 acetyled derived, wich would be bacteriologically unactive. 25% of the trimethoprime is metabolised in active metabolites. 80% of the Bactrim® is eliminated in 72 hours through the urinal duct, metabolised or unchanged (20% for the sulfamethoxazole, 50% for the trimethoprime); a part is excreted by the bile (similar concentration to the plasma), but only a small proportion of trimethoprime (4%) is eliminated in the faeces, because of its intestinal reabsorption.

Bactrim® is often used in the treatment of urinary or prostatic infections, when others antiseptics are not appropriate. Like any antibiotics with wide antibacterian action, it is preferable, in order not to favor the apparition of resistances, only to use it preferable, in order not to favor the apparition of resistances, only to use it for bronchopulmonary, digestive, genital, middle ear infections in case of necessity. Concerning HIV infection, it is used as preventive treatment (primary prophylaxis) in pulmonary pneumocystosis, cerebral toxoplasmosis as well as in curative treatment of pneumocystosis.

The most frequent side effects are nausea, vomiting, epigastralgy, pruriginous cutaneous eruption.

Some other side effects are more rare, but they may require the stop of the treatment (or a desensibilisation technique, that was notably developped for HIV+ patients). It may consists in haematologic effects from an immuno-allergic origine* : thrombopaenia, leukopaenia, medullar aplasia. Concerning old patients and/or deficient in folic acid, mecanism would be toxic, dose and duration dependant.

Hypersensibility signs (anaphylactic shock, Quincke edema, hyperthermia), epidermic necrolysis (polymorphic erythema, Lyell syndrome and Stevens-Jonhson syndrome), hepatitis, pseudomembraneous colitis have been reported. Alterations of the kidney function and neurologic consequences (aseptic meningitis) remain exceptional.

Let's mention that Bactrim® mustn't be used for patients with a G6PD enzymatic deficiency (risk of haemolytic anaemia), end of pregnancy, in case of breast-feeding, for newborn and premature babies (because of the immaturity of the hepatic enzymatic systems); during pregnancy, its use is not recommended, because of its teratogenic effect described on animal; a biological follow-up is necessary in case of long duration treatment, for old patients or folate-deficient, in case of renal or hepatic insufficiency; a particular follow-up is necessary because of possible interactions with coumarin-type anticoagulant, oral sulfonylurea-type antidiabetic, cyclosporin, phenythoïn. (9710)

* These immuno-allergic effects would be more frequent for HIV+ persons, particularly with the strong dose.

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Q-A 2

Q (t) I have been tested HIV+ recently. I would like have informations on official as well as non-official treatments, as complementary treatments seem to be more and more used.

A (t) Indeed we think that it is useful to use so-called complementary treatments, either for patients with or without an official antiretroviral treatment.

Among these treatments, some appear essential to use. Vimanin C (at least 750 mg a day, in tablets or fruits; kiwi is the fruit that contains the most), glucuronamide (Guronsan®, 1 tablet in the morning, or Detoxalgine®, 2 tablet in the morning; these two compounds bring 500 mg vitamin C), vitamin E (Toco 500®, 2 to 3 tablets a day, reimbursed) and Selenium (2 vials in the morning, reimbursed). Some of these treatments (vitamin C and E) are even officially recommended by "official" associations, such as Aides (in its newspaper, Remaides).

Other so-called complementary treatments may have an interest, as more and more researchers consider that HIV is not sufficient to explain the evolution of the infection to AIDS. Cofactors would intervene, maybe in a different manner with the patients (the state of oxidation of the cells is one of the co-factors on which vitamins C and E act).

But, for several among these treatments, further studies should be carried out to confirm or not their interest.

If you could connect to our Internet website <http://www.positifs.org/>, you could have numerous informations on these treatments (this site proposes more than 500 pages of informations, more than half concerning treatments).

Concerning official antiretroviral treatments, they shouldn't be started too soon, neither too late.

New recommandations have been published by international experts in June 1997. A consensus exists, about the idea of treating "soon and strong". But opinions are differing concerning biological values to retain as limit points.

Bitherapies (AZT-ddI, AZT-ddC, AZT-3TC) must'nt be used any longer, as their may provoke resistances, making later tritherapies less efficient.

A tritherapy is now officially recommended in case of clinical signs (opportunistic infection), at any level of CD4 cell count and viral load. Same case, even with a satisfying viral load, if CD4 cells are inferior to 200/mm3, and for more specialists, inferior to 350/mm3, even to 500/mm3. Same case with high count of CD4 cell, if the viral load is superior to 30- 50,000 copies/ml, even for certains specialists, superior to 10,000 or 5,000 copies.

For non treated patients, viral load should be checked every 3 to 6 months.

D4T-3TC-Indinavir association, one of the most interesting tritherapies, in terms of efficiency, should be used in first intention.

The ideal is to reach, with a tritherapy, an undetectable viral load in 6 months, and if possible in 3 months. In case of reapparition of a detectable viral load, this result must imperatively confirmed 15 days after, and lead to a replacement of at least two of the three molecules, if possible. A viral load that would remain superior to 1,000 copies/ml three months after the beginning of a tritherapy would be the sign of a rebound.

We hope that our mail will help you to understand more clearly the domain of official antiretroviral treatments, as well as complementary treatments. (9712)

* Concerning official treatments, Bactrim treatment (1 tablet a day) prevents from pulmonary pneumocystosis or cerebral toxoplasmosis, two of the most frequent opportunistic infections. This primary prevention is advised for people with less than 200 CD4 cells/mm3, or under 15% (in case of allergy, desensibilisation techniques may be used). In some cases, other prophylaxies are also advised (particularly concerning mycobacteria).