Relationship between antiretrovirals used as part of a cART regimen and CD4 cell count increases in patients with suppressed viremia

Abstract

It is unknown if the CD4 cell count response differs according to antiretroviral drugs used in combination antiretroviral therapy (cART) in patients with maximal virological suppression [viral load (VL) < 50 copies/ml]. To compare the change in CD4 cell count over consecutive measurements with VL < 50 copies/ml at both time-points according to nucleoside backbones and other antiretrovirals used. Generalized linear models, accounting for multiple measurements within patients, were used to compare CD4 cell count changes after adjustment for antiretrovirals, time from starting cART, age, CD4 at first VL < 50 copies/ml, prior antiretroviral treatment, and change in CD4 cell count since starting cART. We studied 28418 instances of VL < 50 copies/ml in 4041 patients. The mean annual change in CD4 cell count was +45.5/microl [95% confidence interval (CI) +39.4 to +51.6/microl). Comparing two drug nucleoside backbones, there was a lower annual change in CD4 cell count for zidovudine/lamivudine (n = 13038; -15.4/microl; P = 0.012) and for those on tenofovir (n = 1809; -27.3/microl; P = 0.029) compared to lamivudine/stavudine (n = 7339). Compared to the boosted-protease inhibitor regimen (n = 5915), use of an abacavir-based triple-nucleoside regimen was associated with a lower annual change in CD4 cell count (n = 2504 pairs; -26.1/microl; P = 0.011). A nucleoside backbone of zidovudine/lamivudine or any tenofovir-based backbone was associated with significantly poorer increases in CD4 cell count compared to a nucleoside backbone of stavudine/lamivudine, as was an abacavir-based triple nucleoside regimen compared to a boosted protease inhibitor regimen. Long-term studies are needed to determine whether the differences in immunological response seen here translate into differences in the risk of clinical disease.