More Support for Starting ART Earlier

More Support for Starting ART Earlier
In a group of patients who achieved long-term virologic control on ART, immune restoration was more common among those with pretreatment CD4 counts > 200 cells/mm than among those with lower pretreatment counts.

Summary

Most patients who achieve sustained virologic suppression on potent antiretroviral therapy (ART) also experience restoration of immune function (defined as a CD4-count increase to > 500 cells/mm). In some patients, however, CD4-cell counts fail to normalize, even after years of otherwise effective therapy, and this continued immunodeficiency increases risk for both AIDS-defining and non-AIDS-defining illnesses. A new report, based on long-term data from five clinical cohorts in the U.S., describes the prevalence and predictors of immunologic nonresponse in the setting of virologic control.

The analysis involved 366 HIV-infected patients who maintained low or undetectable viral loads (< 1000 copies/mL) on potent ART for at least 4 years. Per inclusion criteria, none of the patients had used hydroxyurea, interleukin-2, interferon alfa, or the combination of tenofovir and ddI (all of which can influence CD4-cell counts). Changes in antiretroviral regimens were allowed as long as viral loads remained < 1000 copies/mL. Median CD4 counts were 201 cells/mm before ART initiation and 560 cells/mm at year 4 of ART. Median duration of follow-up was 7.5 years.

Most patients achieved immune restoration by year 4 of ART, but a substantial proportion (41%) did not -- and many of these patients (60%) continued to have CD4 counts < 500 cells/mm throughout follow-up. Pretreatment CD4-cell count was an important predictor of immune restoration: 95% of patients with pretreatment CD4 counts > 300 cells/mm achieved CD4 counts > 500 cells/mm during follow-up, compared with only 75% of those with pretreatment counts of 100 to 200 cells/mm and 56% of those with pretreatment counts < 100 cells/mm. Interestingly, the proportion of visits at which viral load was detectable ("blips" < 1000 copies/mL) was associated with CD4-cell-count changes prior to, but not after, year 4. Higher-magnitude blips were often accompanied by smaller CD4-cell-count increases, but the association was not significant.

Comment

Although most patients who achieve virologic control on ART also achieve immune restoration, a subset of patients, primarily those with pretreatment CD4 counts < 200 cells/mm, do not reach CD4 counts > 500 cells/mm. Perhaps the most interesting observation in this study is that even in this select group of patients with optimal virologic responses to therapy, those who did not achieve desirable immune responses by year 4 of treatment were unlikely to do so with continued therapy. This finding supports early initiation of ART, before irreparable damage to the immune system occurs.


CLICK HERE for AIDS Clinical Care subscription information.