The Body Covers: The 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy
Probability and Durability of Achieving Less Than50 Copies/mL of HIV RNA by Treatment Intensification With Tenofovir DF (TDF)
September 28, 2002
There were several predictors of which type of patient was likely to establish a VL of less than 50 copies: baseline viral load, the presence of mutations associated with thymidine analogs (TAMS) as well as the 184V mutation associated primarily with use of lamivudine (3TC, Epivir). Baseline viral load showed a clear relationship with this outcome: the higher the viral load, the less likely someone was going to have their VL get to less than 50 copies. For example, those whose viral load was less than 1,000 copies had a 43 percent chance of having it decrease to less than 50 copies, while those who had a VL of greater than 5,000 copies were only this successful 6 percent of the time. In addition, the more thymidine analog (AZT, d4T)-related mutations, the less likely someone was able to get to less than 50 copies. The researchers noted that in those who had no TAM mutations, 49 percent were able to get to less than 50 copies. The presence of the 184V mutaton was also somewhat helpful in getting to less than 50 copies.
In terms of maintaining this degree of suppression, the researchers noted that after one year, about 20 percent of patients rebounded from less than 50 copies to greater than 500 c/mL. This rebound was not associated with the development of the K65R mutation, one which is associated with high-level tenofovir resistance, implying that other drugs in the regimen were "giving out," leading to this rebound. This also suggests that this strategy, even if not successful, does not "burn out" the potency of tenofovir. Of interest, there were eight patients in the overall study who developed the K65R mutation, and 5/8 were on a thymidine analog at that time. This sheds some light on the potential relevance of maintaining a thymidine analog to "protect" against developing this mutation.
These data increase the ability to guide clinicians and patients in the circumstance of managing a regimen that is not fully suppressive. It would be reasonable to consider adding tenofovir for patients who have low-level breakthrough, and/or have genotypic evidence of a high likelihood of response. It is noted, as with all agents, that there is an improved response with this approach if one uses the drug before cross-resistance mutations develop from other drugs. While adding a single drug is controversial and generally not standard of care, it is reasonable to consider these data to inform the approach called "intensification" (i.e., adding a single drug to a partially suppressive regimen before high-level resistance has set in).
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