Indications that US clinicians may be re-thinking previously aggressive approaches to antiretroviral therapy have been strengthened by the publication of one of the strongest attacks yet mounted on early HIV treatment in a peer-reviewed medical journal.
In a review published by the American College of Physicians' journal Annals of Internal Medicine, Dr Keith Henry of the University of Minnesota argues that "an increasing number of clinical studies focus more on what is good for the drug rather than what is good for the patient" and calls for a more patient-focused approach to care.
He condemns the trend towards starting treatment with a CD4 count closer to 500 than 200 cells/mm3, noting: "In my clinic for protease inhibitor failure, some patients who were never at imminent risk for AIDS-related clinical events harbor virus strains that are resistant to all available drugs".
Dr Henry's review of current HIV treatment debates comes two weeks after the Seventh Conference on Retroviruses, at which Dr William Powderley of Washington University, St Louis, a member of the US treatment guidelines panel, surprised his audience by remarking that it may not be unreasonable to delay treatment until the CD4 cell count falls near to 200 cells/mm3, the level at which the risk of AIDS-defining illnesses begins to increase.
Dr Henry urges a similar cautious approach.
"If a risk-benefit analysis determines that the risk for adverse effects and resistance to key classes of drugs outweighs the risk for AIDS-defining illnesses over a 3-year period in an individual patient, conservative use of therapy may be the wiser approach.", he writes.
The midwestern specialist also challenges the notion that when therapy begins, its objective should always be maximal suppression of viral load. He cites ACTG 175 data presented at the 1998 Geneva Twelfth World AIDS Conference, which suggests that individuals maintained on two-drug antiretroviral therapy with viral load below 10,000 copies and CD4 counts above 300 had only a 4% chance of developing an AIDS-defining illness within three years. Henry notes that the use of dual therapy as initial treatment is increasing amongst his colleagues.
He also highlighted:
- Lack of long-term data on the consequences of failing to switch therapy after viral rebound. "Clinicians need to consider [preserving] potent treatment options for later use at times when patients may be at greater risk for AIDS-related clinical events", remarks Dr Henry.
- Growing evidence of metabolic disorders, particularly lipid disorders, in patients with pre-existing risks for heart disease.
- The exacting standards of adherence required to maintain viral suppression. It may be better to wait for less complicated therapies, he concludes.
However, in an accompanying editorial, Dr Oren Cohen, secretary to the US Department of Health and Human Services treatment guidelines panel, argues that delaying therapy may:
- increase the risk of drug resistance by permitting many more replication cycles to take place before the selection pressure of antiretroviral therapy is introduced
- increase the risk that thymic function will be lost, thereby affecting the quality of immune reconstitution
But Dr Cohen concludes that clinical trials examining differing treatment strategies are the future for HIV research, and highlights the recent NIAID call for trial designs addressing issues such as when to start, when to switch and which drugs to use.
Cohen O. Antiretroviral therapy: time to think strategically. 132: 320-22, 2000.
Henry K. The case for more cautious, patient-focused antiretroviral therapy. Annals of Internal Medicine 132: 306-11, 2000.