AIDSWEEKLY Plus; Monday, October 15, 2001
Michael Greer, Senior Medical Writer

NewsRx -- The nucleotide analog adefovir dipivoxil (ADV) can affect the frequency of HIV reverse transcriptase mutations conferring increased drug resistance although the impact may not be significant, according to researchers in the United States.

Michael D. Miller and colleagues at Gilead Sciences, Inc. in Foster City, California, and SUGEN, Inc. in San Francisco conducted a study to "determine whether genotypic changes in HIV-1 (HIV) reverse transcriptase (RT) occur during adefovir dipivoxil (ADV) therapy that may alter the susceptibility of HIV to adefovir or the related nucleotide inhibitor, tenofovir."

Adefovir does not appear to have a greater influence on the HIV RT genotype than other similar drugs, Miller and coworkers reported.

Almost one-third (32%) of the patients treated with adefovir as part of an antiretroviral therapy (ART) regimen developed nucleoside-associated RT mutations within 24 weeks, they said. The prevalence of RT mutations in adefovir-treated patients was similar to that seen in control patients (28%), however, and many of these mutations were linked to the combination of zidovudine and stavudine.

Patients who developed RT mutations during adefovir treatment displayed slight reductions in adefovir sensitivity, accompanied by a small loss in average viral control after 24 and 48 weeks, study data showed. Neither of these trends was statistically significant. Tenofovir susceptibility was virtually unaffected, the researchers noted.

Surprisingly, none of the mutations seen during in vitro adefovir research was observed in this study cohort ("Adefovir and tenofovir susceptibilities of HIV-1 after 24 to 48 weeks of adefovir dipivoxil therapy: Genotypic and phenotypic analyses of study GS-96-408," J Acquir Immune Defic Syndr 2001 Aug 15;27(5):450-8.

"HIV RT changes that arose during ADV therapy appear attributable to the patient's background ART," Miller and colleagues concluded. "ADV therapy may have influenced the pattern of ZDV [zidovudine]-associated resistance mutations that developed, but this did not result in an observed loss of viral load suppression."

The corresponding author for this report is Michael D. Miller, Gilead Sciences Inc., 353 Lakeside Drive, Foster City, CA 94404 USA.

Key points reported in this study include:

• Adefovir may have a limited effect on the frequency of HIV reverse transcriptase mutations conferring increased drug resistance
  
  
• However, many of the mutations seen were more likely to have resulted from other drugs and drug combinations, particularly zidovudine and stavudine
  
  
• Adefovir-treated patients had slightly reduced drug sensitivity and impaired viral control after 24 and 48 weeks, although the loss was not statistically significant.
  

This article was prepared by AIDS Weekly editors from staff and other reports.

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