The Pharmaceutical Journal
Vol 271 No 7258 p76
19 July 2003

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Annals of Internal Medicine abstract (more)

Switching anti-HIV regimen could delay onset of resistance

Switching anti-HIV drug regimens every few months rather than continuing the same regimen until it stops working could delay the development of resistance, suggest Spanish and Argentinian researchers. However, they say that further research is needed before such a strategy is used in clinical practice (Annals of Internal Medicine 2003;139:81).

The researchers assigned 161 patients infected with HIV to stavudine, didanosine and efavirenz (regimen A) or zidovudine, lamivudine and nelfinavir (regimen B) until the treatment failed or to alternate between regimen A and B every three months.

They found that patients treated with regimen A or B had similar rates of treatment failure. However, treatment failure was delayed in patients who alternated between the two regimens (incidence rate, 1.2 events/1,000 person-weeks versus 4.8 events/1,000 person-weeks, P=0.01).

Patients treated with regimen A or B until treatment failure had similar CD4 cell counts, adverse events, reported adherence and quality of life as patients treated with the alternating regimen.

Writing in an accompanying editorial, Dr Michael Saag, of the University of Alabama, Birmingham, suggests that a subtle improvement in adherence (not picked up by the researchers) may be behind the reduced rate of treatment failure seen for the alternating regimen. "Alternating the regimens every three months may have minimised the degree of subclinical, low-grade toxicity that may have accumulated in the continuous-therapy arms and thereby led to improved adherence," he says.

He points out that more skipped doses mean more viral replication in the presence of inadequate drug levels. This, in turn, means more chance of resistant viruses developing (ibid, p148).