SEPTEMBER 1998

International AIDS Conference: what's news?
Over 13,000 persons attended the 12th World AIDS Conference in Geneva (28 June - 3 July, 1998). The effectivness of triple therapy and a continued emphasis of reducing viral load as much as possible were both confirmed. However, relatively new side-effects raised many questions (see Remaides 29 p.6). Also, news drugs are under investigation. This article outlines some new discoveries. For a broader view on anti-HIV treatments, please see Remaides 29 p.12.   Viral load New tests are capable of detecting HIV levels down to 50 copies/ml, whereas the limit of detection with the previous generation of tests was only 500 copies/ml. It has been shown that the efficacy of a treatment is more durable when your viral load gets down to less than 50 copies/ml although it may take several weeks or months after starting treatment to get this low. As this is recognised to be important more biological laboratories are using these new ultra-sensitive tests. The aim of treatment is to reach the lowest possible viral load. However, some people have tried different treatmens without achieving reductions in their viral load for sustained periods. Even under these circumstances, studies have shown that treatments slow down the rate at which HIV would otherwise progress.   High viral load Before treatment starts, some people have higher viral load levels (above100,000 copies/ml). If this is the case, triple therapy is less likely to get your viral load to undetectable levels. Therefore, some doctors are start treatment with four drugs in these patients.   Triple therapy without protease inhibitor The efficacy of protease inhibitors has been shown, amongst other things, by both a decrease in opportunistic infections and in an improvement of life expectancy. In spite of this, two issues arose at this conference: whether it would be better to keep them as a second-line option and whether the side effects which are just being recognised (increase in blood fat levels, etc. see Remaides 29 p. -) will have serious long or medium term consequences. In this context, several triple therapy combinations which do not include a protease inhibitor have been studied. Retrovir + Videx + Viramune, investigated for several years, has shown an interesting level of efficacy, although lower than that of a triple therapy combination which includes a protease inhibitor. Triple therapies including Sustiva (efavirenz) or Ziagen (abacavir) though do seem to be as effective as those which include a protease inhibitor. You should remember that these results are only relevant for patients who have never taken any previous anti-HIV treatment before and that these trials only lasted for a few months. They will need to be confirmed with long-term results. Sustiva is a new drug which belongs to the same family as Viramune (see Remaides 28, p.26). Ziagen is from the same family as Retrovir, Videx, etc. but it is more powerful than its predecessors. Several comparative trials with and without protease inhibitors are underway. Their results should be available in 1999.   Hydroxyurea (Hydrea) Hydroxyurea is a drug used to treat certain types of cancer. In HIV infection, hydroxyurea boosts the effectiveness of Videx or Videx+Zerit' (it makes your viral load go down lower), even in patients for whom Videx had stopped working. However, hydroxyurea does not result in large CD4 count rises as the drug has a certain degree of toxicity for bone marrow (where your white and red blood cells are produced).   Simplify one's treatment ? We already know that starting with three or four anti-HIV drugs and then reducing back to two (called 'reduction' therapy) does not maintain your viral load as the necessary low levels. However, a new trial is starting which looks at whether it is possible to start with a quadruple therapy (four anti-HIV drugs) and then switch to a triple therapy (with or without protease inhibitor).   Fewer doses to take ? New dosing schedules are also being studied. At the moment, the safety of none them has been definitely proved, but a few new things were reported: Viracept's efficacy when taken twice a day (5 tablets in the morning and 5 again in the evening, both times with meals) produces results very similar to when it is taken three times a day (see Remaides 29, p. 4). no new data is available regarding taking Crixivan twice (rather than three times) a day. a study is still ongoing comparing Fortovase, a new formulation of the old saquinavir (Invirase), twice a day (8 capsules in the morning and in the evening during or after meals). Viramune once a day (2 tablets) is also being tested. Videx is being tested under the same conditions. In addition, this drug should, some time next year, be available as a capsule (no need to dilute, no more doughy taste !).   Other protease inhibitors ? Norvir slows down the time that many other drugs' take to leave your the body. This feature of ritonavir can be used to increase the potency of the other drugs or simplify the way they have to be taken: the combination of Norvir + Invirase is well known (Invirase twice a day, during meals, with two Norvir capsules in the morning and the evening). Some people also report using much lower Norvir doses (only one capsule morning and evening), which results in them being better tolerated It is a pity that the results of a more formal study are not available to check this. the Norvir (4x100mg capsules in both the morning and in the evening) and Crixivan (2x200 mg capsules in both the morning and in the evening) combination has been looked at in a small number of patients. The main advantages of this combination are that both drugs can be taken twice a day, during meals, without the need to drink large quantities of water. Its efficacy seems to be as good as that of combinations which use Crixivan as the only protease inhibitor. also under investigation: Norvir + Viracept, Viracept + Invirase, Viracept + Crixivan.   Pregnant seropositive women For women using Retrovir or Retrovir + Epivir, the risk of HIV transmission to the child can be reduced by delivering the child by Cesarean section. Nevertheless Cesarean section is not systematically performed since it is sometimes associated with risks of it's own. In addition, it is not certain that the procedure benefits women who are also using triple therapy, since the likelihood of the transmitting HIV to their children is much lower if the mother is on treatment and has an undetectable viral load.   Available soon Agenerase (amprenavir), a new protease inhibitor from Glaxo-Wellcome should be available by end 1998. Preveon (adefovir) from Gilead (one 120 mg tablet a day) should also be available by end 1998. This drug is also effective against Hepatitis B (see Remaides 29 p. 20). As a reminder, Sustiva (efevirenz) and Ziagen (abacavir) are already available in France (see Remaides 28 p. 24).   Not available before next year Two new protease inhibitors are, in theory, effective against HIV strains which are resistant to other protease inhibitors: ABT-378 (Abbott) and tipranavir (formerly PNU-140690, Pharmacia-Upjohn). We are eagerly awaiting more news! FTC (close relative of Epivir) and Fdda (close relative of Videx) are under investigation. New drugs from the same family as Viramune and Sustiva are also being prepared: MKC-422 and S-1153. T-20 blocks the entry of HIV into cells. It seems promising, but needs, for the time being to be given by the intravenous route. A trial is starting in the US very shortly.   Bound for the future Current treatments offer little hope of totally eradicating HIV from someone who is HIV-positive. Nevertheless, a renewed interest exists for drugs which act on the immune system and in particular interleukin-2 (which is currently available only within a clinical trial, see Remaides 27, p 22). Also, the first trial using Remune, an anti-HIV vaccine intended for HIV-positive persons shows that it may improve the immune system's strength and efficiency. It is therefore hoped that HIV infection can be brought under control in two ways: reduce the amount of virus in the body by as much as possible, by using combination therapy with several anti-HIV drugs. use drugs which could then re-activate the immune system, and inparticular your bodies own ability to "kill" virus-infected cells. If these treatments work as well as expected, it may be possible to stop them all together after a certain amount of time (one year? two years?). The evolution of infection would then be followed, and treatments would only be started again if necessary (i.e. if your viral load became detectable or you had a fall in your CD4 count).   Emmanuel Trénado