Drug Strategy Won't Stop HIV Resistance
Interrupting Drug Treatment Won't Outwit Drug-Resistant AIDS Virus
Aug. 27, 2003 -- A strategy called structured treatment interruption (STI) won't outwit drug-resistant HIV, a new study shows.
The finding crushes hope for a bold plan to help patients for whom all existing anti-HIV drugs are failing. The idea was to extend the life of these drugs by stopping treatment for a while. Evidence suggested that patients' HIV infections would revert to a drug-sensitive form.
Now a large clinical trial shows this doesn't happen. Drug-sensitive virus does indeed appear -- but that doesn't mean drug-resistant virus goes away. Patients who interrupt treatment don't suddenly do better. In fact, says researcher Jody Lawrence, MD, they do worse than those who continue treatment.
"Patients with HIV and multidrug-resistant virus should avoid STI," Lawrence tells WebMD. "In our study, those who remained on optimized standard treatment did better than those who tried STI."
Lawrence's report appears in the Aug. 28 issue of The New England Journal of Medicine.
Looking for New Options When Time Is Running Out
The study enrolled 270 patients who were running out of options. The HIV in their blood had developed resistance to all existing AIDS drugs. Even though they were getting the best possible treatment, there was more and more virus in their blood, and fewer and fewer life-preserving CD4 T cells.
"We embarked on this study because we are seeing more and more patients in this predicament," says Lawrence, a clinician at San Francisco General Hospital. "The patients are asking, 'Are these drugs doing me any good? Am I getting more harm from the drugs than good?' As a primary care provider, I didn't have any good answers."
In the study, half the patients continued with state-of-the-art therapy. In such patients, doctors keep testing the virus to see which drugs work best -- and continue giving them powerful combinations. Even in the face of mounting resistance, this works for a surprisingly long time -- but not forever. Eventually, AIDS appears.
That's why half the patients were willing to try something new. They stopped all AIDS drugs for four months. Drug-resistant HIV isn't as fit as drug-sensitive HIV. The hope was that once the drug-sensitive HIV returned, it would push out the drug-resistant form. Then drug treatment could begin again, with much more potent effect.
After about a year, the patients who interrupted treatment were worse off than those who hadn't. They had more virus -- and fewer T cells -- in their blood.
Two smaller trials are also looking at STI in this patient population. One, called the Retrogene study, got pretty much the same disappointing results. The other, called GIGHAART, showed a benefit when STI was followed by massive treatment with all available drugs -- seven drugs, on average. But few patients are able to stay on such a toxic regimen for long.
In an editorial accompanying the Lawrence study, Bernard Hirschel of Geneva University Hospital agrees with Lawrence. Patients with drug-resistant HIV should not try STI.
Other STI Strategies
Earlier in the course of HIV infection, there may still be a role for STI.
One idea is to stop HIV treatment for short periods of time, possibly in combination with immune-boosting treatments. The idea is to let the immune system see enough HIV to allow it to help the drugs fight the virus.
The other idea is to take anti-HIV drugs only on alternate weeks. This idea, currently being tested at the NIH, would greatly reduce drug-related side effects and toxicity. And it would cut the cost of expensive AIDS drugs in half -- a boon to resource-poor countries, if it works.