Viracept and diarrhoea

Viracept, a protease inhibitor, may cause diarrhoea but this can often decrease or subside after the first two or three weeks of treatment. However these symptoms can also persist, and sometimes be severe. Doctors can prescribe several drugs to control diarrhoea - their efficacy varies from person to person:

- Imodium decreases bowels' movements. Most people start with one or two capsules, then one capsule after each soft stool. Some people need as many as 10 to 12 Imodium capsules a day, but for others a low dose is sufficient (some adults use the paediatric liquid form).

- Smecta coats the inside of the gut walls, which are often damaged by diarrhoea. The usual dose is one sachet, three times a day. For a better efficacy, Smecta and Imodium can be taken together. Smecta must be taken at least two hours before or half an hour after other drugs (to avoid decreasing their gut absorption, hence their efficacy).

- Mucilage drugs are usually prescribed against constipation. However, they appear to have a certain efficacy against Viracept-induced diarrhoea (they absorb water present in the gut; when used to treat diarrhoea, they should be taken with very little water). Many drugs belong to this family : Spagulax, Transilane, Psylia, etc.

- Some foods such as coffee or milk, in some people, can aggravate diarrhoea - they should be avoided if this seems to occur.

Finally, not all diarrhoea is due to drugs and some tests can be performed to check that it is not being caused by something else (stool analyses, etc.)

Testing drug levels in blood

Anti-HIV drugs levels can be tested in blood. This can be helpful if a treatment is not working as well as it should be, if major side-effects appear or when interactions between drugs exist. All doctors, from Paris or the provinces, may call the Hôpital Claude Bernard Pharmacy in Paris for further information (phone: 01 40 25 80 17).

Hepatitis C

Active chronic hepatitis C is usually treated with alpha interferon injections (see Remaides n°29, p. 20). Recent studies suggest that a treatment associating interferon and ribavirine (Rébétol) may be more efficacious than interferon alone.

Viagra : never take with poppers !

Viagra is a drug intended to treat erection dysfunctions. It is available from pharmacies, with a prescription, but it is not reimbursed by the Sécurité Sociale (a 50 mg tablet costs approximately 70FF).

Viagra was shown to be effective and well tolerated in more than 3000 men with erection problems. Nevertheless, several deaths occurred. Pfizer, Viagra's manufacturer had to remind users that this drug must not be used in people with serious heart problems.

In addition, it should never be taken with nitrates (which are found in some drugs used for heart conditions, but also in poppers) since this can lead to severe drops in blood pressure followed by shock and possibly, death. According to Pfizer, there is no major interaction problem with other drugs (in particular anti-HIV drugs); theoretically, blood levels should not be affected by Viagra, although this has not been formally studied. Conversely, some drugs are known to increase Viagra blood levels, including : cimetidine-based drugs (used to treat stomach ulcers), Nizoral (used in fungal infections) and erythromycin-containing antibiotics. Interactions with protease inhibitors have not been formally studied, but there is a possibility that some of them (particularly Norvir) may increase Viagra blood levels. Increases in Viagra blood levels should remain moderate and not present great dangers but it is nevertheless advisable to use the lowest dose of Viagra (25 mg) when taking one of the drugs mentioned above.

Trials with T-20

T-20 is a new anti-HIV drug which prevents viruses from entering cells. A first trial in 16 people suggests an interesting level of efficacy. T-20 must currently be given by infusions, but sub-cutaneous injections will be studied. T-20 is at present only available through clinical trials in the US.

Gynaecological follow-up

Uterus neck lesions are frequent in HIV-positive women. Often caused by the papilloma virus, they can become worse if they are left untreated and can, sometimes, become cancerous. However, a recent study has shown that triple anti-HIV therapy appears to stabilise or decrease these lesions. In all cases, a gynaecological follow-up (usually every 6 months) remains necessary.

Interleukin 2

Interleukin 2 (or IL-2) stimulates CD4 cells production. It is currently under investigation (see Remaides n° 27, p 22). IL-2 may soon become available under a named-patient Autorisation Temporaire d' Utilisation ("ATU nominative") procedure, based on a doctor's request to the Agence du Médicament.

IL-2 can also be available through a different channel as it is approved for use in certain types of cancer. Doctors can therefore prescribe IL-2 to HIV-positive patients.

Norvir

Abbott, its manufacturer, are experiencing difficulties making Norvir. They hope to be able to design new capsules which could be available in the spring of 1999 and would not require being stored at cold temperatures. In the meantime, patients who require it need to resort to the liquid formulation. Some tricks may help hide its taste - ask your pharmacist for a Norvir brochure (see also Remaides n°29, p.5).

Megatherapy

Some researchers recommend "megatherapies" (if not "gigatherapies") to people whose viral load goes up in spite of sequential anti-HIV treatments. These "megatherapies" consist in associating 6,7, sometimes 8 or 9 anti-HIV drugs, including some of the drugs the patient already tried. Efficacy seems to be often interesting (viral load goes down), but side-effects often leave no choice but to stop these treatments for most patients. Under these circumstances, resistance tests (see Remaides n°28, p. 44) may help identify which drugs retain efficacy. Unfortunately, these tests are very rarely available outside of clinical trials.

Medical assistance to procreation

For couples with an HIV-positive man and an HIV-negative woman who want a child, some semen treatment methods dramatically reduce the risk of contamination for the woman (see Remaides n° 28, p. 10). Nevertheless, despite all predictions, this is not readily available at the moment, although it should become available through a clinical trial framework. In Paris, an Hôpital Cochin team has submitted a proposal for this to the ANRS (Agence Nationale de Recherches sur le Sida).

Norms for jellies

When buying lubricating jelly, it is advisable to check that it bear the mention "Norme NF" : this guarantees its compatibility with condoms.

Easier to take protease inhibitors ?

A twice a day dosing regimen of Viracept (5 tablets in the morning and in the evening) is under investigation. Based on currently available 48 week follow-up data, a twice a day dosing regimen is as efficacious as a three times a day regimen. Please remember that Viracept needs to be taken during meals (see Remaides n°29, p. 4). This helps its absorption through the gut, and decreases cases of diarrhoea. In addition, Viracept should preferably be taken with a cold drink as hot drinks make the tablets melt in the mouth and more difficult to swallow.

It also seems possible to take Fortovase twice a day (8 capsules twice a day). A 24 week trial shows that a twice a day dosing regimen is as efficacious as a three times a day regimen. Please remember that Fortovase needs to be taken with a high fat-containing meal (meaning a plentiful breakfast !).

Important note : these data regarding Viracept and Fortovase will need to be confirmed by larger studies.

Agénérase (amprenavir), a new protease inhibitor should be taken twice a day, with no restrictions regarding timing of meals (see below).

On the other hand, Crixivan is still recommended to be taken three times a day as recent data show a better efficacy with this regimen than with a twice a day regimen.

Early data suggest that Norvir (low dosage) plus Crixivan could be taken twice a day. Efficacy studies with this association are ongoing.