Enfuvirtide Beneficial Even with High Viral Loads

Enfuvirtide Beneficial

Enfuvirtide offers immunological and clinical benefits for HIV-infected patients who are resistant to several other anti-retroviral drugs, and it seems to help some whose viremia persists during enfuvirtide treatment, according to an international team of researchers.

During treatment with enfuvirtide, which prevents viral and cellular membrane fusion, increased CD4 counts and lower T-cell activation may occur, despite evidence of significant HIV replication.

Researchers from Madrid, Spain, evaluated the immunological and genetic features of four patients who were not responding to antiretroviral therapy. Although they developed resistance to enfuvirtide, they either maintained stable CD4 levels or showed increased CD4 cell counts and experienced a dramatic clinical improvement. All four patients were resistant to several protease and reverse transcriptase inhibitors. They were observed for 80 weeks after enfuvirtide rescue therapy was begun.
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The patients’ immunological responses were compared with those of three control groups: (1) a similar set of multi-drug-resistant patients given salvage therapy without enfuvirtide with similar viral loads; (2) patients receiving highly active antiretroviral therapy (HAART) with no detectable viral load; and (3) untreated HIV patients with viral loads similar to those of the study patients.

In the study group, the viral load declined during the first weeks of enfuvir-tide therapy but eventually rebounded. Two of the patients continued to have stable CD4 counts despite increased viremia, whereas CD4 counts rose in the two other patients.

A mutation in the HR1 region appeared at the same time as treatment failure in the four patients. Changes in the HR2 region also occurred during en-fuvirtide therapy, but it was not clear whether these changes were related to the development of resistance.

Viral replication had a weaker impact on immune activation among the treated patients than in the patients not receiving HAART or enfuvirtide.
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The researchers proposed that the inhibition of fusion by enfuvirtide might weaken the impact of the virus on CD4 cells by promoting compensatory HIV entry into cells via the endocytosis pathway.