The Washington Blade - December 15, 2000

A study from Rome of 1,251 people with HIV found they experienced "similar efficacy" whether they were taking the protease inhibitor ritonavir or indinavir in combination with nucleoside analogs.

The study was reported in the Nov. 20 issue of AIDS Research and Human Retroviruses.

The researchers, led by Stefano Vella, president of the International AIDS Society, did notice that viral loads seemed to decline more with indinavir. They also noted that patients on ritonavir were more likely to experience a significant negative side effect.

But the two treatments, noted the report, "were not different in terms of number of definitive discontinuations because of treatment failure" and the study result "suggests similar efficacy of the two treatments in patients who can tolerate them." Lab companies defining resistance test 'cutoffs' Two companies providing "resistance testing," which helps doctors determine what anti-HIV drugs their patients are most likely to respond to, announced in the past few weeks that they have defined important and previously unknown "cutoff levels" on the effectiveness of several drugs.

One company, ViroLogic, reported that the increasingly popular protease inhibitor ABT-378 (lopinavir, marketed by Abbott as Kaletra) loses its clinical effectiveness when a phenotype resistance test shows the virus has mutated to a 10-fold reduction of its susceptibility to the drug. With the Glaxo Wellcome nucleoside analog abacavir (marketed as Ziagen), said ViroLogic, this "cutoff" level is 4.5-fold.

At an AIDS conference in Scotland in October, the British lab company Virco reported that the nucleoside analogs ddI and d4T have "the lowest frequency of resistance," that ddC had "infrequent resistance," and that AZT and 3TC "appeared most frequently" to develop resistance.

Generally, noted Virco, nucleoside analogs have significantly less benefit at a cutoff level of 3 to 4.5-fold decreased susceptibility; protease inhibitors have a cutoff at 2.5 to 4-fold; and non-nucleoside analogs have a cutoff at 6 to 10-fold.

Both companies are continuing their work in defining the specific cutoff for each drug, but David Ho of New York's Aaron Diamond AIDS Research Center said the definition of these cutoff levels is an "important achievement" that will help doctors make "more informed" decisions about drug choices.

In brief ...

NONOXYNOL-9 REMOVED FROM "WET": The manufacturer of a popular brand of lubricant announced last month that it has removed the spermicide nonoxynol-9 from its products. Trigg Laboratories, the maker of WET products, said the company's move was in response to a warning issued by the U.S. Centers for Disease Control and Prevention in August. The warning came following a report at the International Conference on AIDS that women using spermicides with nonoxynol-9 became infected with HIV at about a 50 percent higher rate than women using a spermicide without the substance. According to the CDC notice, "anyone currently using N-9 as a microbicide to protect themselves from HIV transmission during anal intercourse should be informed of the ineffectiveness of this agent and warned of the potential risk of this practice. ... If given the choice, condoms without N-9 may be a better option for HIV prevention." TRIPLE-DRUG PILL APPROVED: The U.S. Food and Drug Administration approved an anti-HIV pill Nov. 16 that combines three nucleoside analogs. The pill - called Trizivir - combines three drugs produced by Glaxo Wellcome: AZT-3TC-abacavir. With increasing emphasis on the use of a combination of drugs to suppress the virus, the combination, which is taken twice a day, is expected to ease the pill-taking burden for at least some patients. The FDA also recently approved a new "coated" version of Bristol-Myers' nucleoside analog ddI (marketed as Videx). The new form, Videx EC, includes an enteric coat that prevents the drug from being released into the system until it hits the small intestine where it is absorbed. With the standard version of ddI, patients must take antacids simultaneously to prevent the pill from being dissolved too quickly. The new version also relieves the patient of the need to chew the tablet, which has a taste that many find unpleasant.

NON-NUKE WARNING STRENGTHENED: The FDA "strengthened" its warning last month about the risk of life-threatening liver toxicities associated with the use of the non-nucleoside analog nevirapine, especially in the first three months of use. The drug is marketed as Viramune by the Boehringer Ingelheim/Roxane Laboratories. The early warning signs of trouble, noted the FDA, include fatigue, malaise, anorexia, and nausea, followed by jaundice and an enlarged liver. Patients taking nevirapine who experience these symptoms are advised to see their doctors "immediately."