T-20: response limited in HIV patients with fewest drug options

Julio Montaner of the University of British Columbia reported on the response to T-20 according to baseline viral load and resistance profile in TORO-1, the North American study of T-20 added to a background regimen chosen after resistance testing in highly treatment-experienced patients.

The median baseline viral load was 158,000 copies/ml, and the median CD4 cell count was 80 cells/mm3. 61% of patients had viral load above 100,000 copies/ml, and 54% had CD4 cell counts below 100 cells/mm3. 69% of patients had phenotypic susceptibility to two or less antiretrovirals (including tenofovir), with an average susceptibility to 1.7 antiretrovirals in the optimised background regimen.

Viral load response according to phenotypic susceptibility score (number of active drugs in the background regimen) ranged from –2.3 log₁₀ copies/ml in T-20 recipients with a PSS of 3 - 4 to 0.2₁₀ log copies/ml in optimised background regimen recipients with a PSS score of 1 or less. In general the added benefit conferred by T-20 treatment amounted to a viral load reduction of approximately 1 log when compared with the optimised background regimen.

Multivariate analysis showed that the magnitude of viral response was related to the following independent factors:

• Treatment with T-20: -1.00 log₁₀ copies/ml reduction in viral load

Lopinavir susceptibility: -0.24 log₁₀ copies/ml

Phenotypic susceptibility score: - 0.33 log₁₀ copies/ml per drug

Baseline CD4 cell count: - 0.19 log₁₀ copies/ml per 100 cells/mm3

Total adherence score: - 0.25 log₁₀ copies/ml

Prior lopinavir experience: +0.83 log₁₀copies/ml

Responses to T-20 were greater in those patients with CD4 cell counts above 100 cells/mm³ or viral load below 100,000 copies/ml (-2 log₁₀ copies/ml).

Speaking at a meeting organised by resistance test company Virologic, which carried out the testing in this study, Dr Joe Eron of the University of North Carolina said that the results of TORO-1 show that phenotypic resistance testing has an important role to play in the optimisation of T-20 salvage regimens. Dr Julio Montaner highlighted the fact that whilst T-20 appears to contribute a 1 log viral load reduction whenever it is used, the chances of durable viral suppression are greater when it is used with at least two other active drugs, including lopinavir. This in turn has implications for when it might be best to use T-20; after failure of lopinavir may be too late.

References

Lalezari J et al. Enfuvirtide (T-20) in combination with an optimised background (OB) regimen vs OB alone: week 24 response among categories of treatment experience and baseline (BL) HIV antiretroviral (ARV) resistance. 42nd ICAAC, San Diego, abstract H-1074, 2002.