Relationship Between HAART Regimen and CD4 Cell Count Increases
Relationship Between HAART Regimen and CD4 Cell Count Increases
Background: 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].
Objectives: 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.
Methods: 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.
Results: We studied 28418 instances of VL < 50 copies/ml in 4041 patients. The mean annual change in CD4 cell count was +45.5/μl [95% confidence interval (CI) +39.4 to +51.6/μl). Comparing two drug nucleoside backbones, there was a lower annual change in CD4 cell count for zidovudine/lamivudine (n = 13038; -15.4/μl; P = 0.012) and for those on tenofovir (n = 1809; -27.3/μl; 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/μl; P = 0.011).
Conclusions: 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.
One of the goals of combination antiretroviral therapy (cART) is to suppress HIV-viral load (VL) to < 50 copies/ml. The increase in CD4 cell count in antiretroviral naive patients starting cART is around 100-150/μl in the first year of treatment. There is thought to be an accelerated increase in the initial months of therapy, a steady increase up to 4 years after starting cART and a possible plateau at 3-4 years after starting cART. In patients who respond well to cART and achieve undetectable levels of VL, subsequent annual increases in CD4 cell count are estimated to be around 100/μl. Randomized clinical trials comparing antiretrovirals used as part of cART typically recruit antiretroviral-naive patients with a primary virological endpoint. The immunological response tends to be a secondary analysis. Some randomized studies in antiretroviral-naive patients have found differences in the short term (i.e., 24- or 48-week) immunological response, while the majority have found no differences, even where there was a significant difference in virological response. In all of these clinical trials however, patients studied were not restricted to those with undetectable levels of viremia. To our knowledge, there has been no study comparing the immunological response to cART while VL is suppressed and comparing that response stratified by antiretroviral drugs used. While viral load is suppressed, there could be differences between antiretrovirals in effect on T-cell repertoire, or penetration of latent virus reservoirs. If an antiretroviral, or combination of antiretrovirals, had a better immunological response while VL was suppressed, this could translate into a long-term reduced rate of clinical disease progression.
The aims of this study were therefore to assess the increase in CD4 cell count in patients taking cART and in whom VL was undetectable, and to compare nucleoside backbones and other antiretrovirals used as part of a cART regimen.
Abstract and Introduction
Abstract
Background: 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].
Objectives: 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.
Methods: 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.
Results: We studied 28418 instances of VL < 50 copies/ml in 4041 patients. The mean annual change in CD4 cell count was +45.5/μl [95% confidence interval (CI) +39.4 to +51.6/μl). Comparing two drug nucleoside backbones, there was a lower annual change in CD4 cell count for zidovudine/lamivudine (n = 13038; -15.4/μl; P = 0.012) and for those on tenofovir (n = 1809; -27.3/μl; 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/μl; P = 0.011).
Conclusions: 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.
Introduction
One of the goals of combination antiretroviral therapy (cART) is to suppress HIV-viral load (VL) to < 50 copies/ml. The increase in CD4 cell count in antiretroviral naive patients starting cART is around 100-150/μl in the first year of treatment. There is thought to be an accelerated increase in the initial months of therapy, a steady increase up to 4 years after starting cART and a possible plateau at 3-4 years after starting cART. In patients who respond well to cART and achieve undetectable levels of VL, subsequent annual increases in CD4 cell count are estimated to be around 100/μl. Randomized clinical trials comparing antiretrovirals used as part of cART typically recruit antiretroviral-naive patients with a primary virological endpoint. The immunological response tends to be a secondary analysis. Some randomized studies in antiretroviral-naive patients have found differences in the short term (i.e., 24- or 48-week) immunological response, while the majority have found no differences, even where there was a significant difference in virological response. In all of these clinical trials however, patients studied were not restricted to those with undetectable levels of viremia. To our knowledge, there has been no study comparing the immunological response to cART while VL is suppressed and comparing that response stratified by antiretroviral drugs used. While viral load is suppressed, there could be differences between antiretrovirals in effect on T-cell repertoire, or penetration of latent virus reservoirs. If an antiretroviral, or combination of antiretrovirals, had a better immunological response while VL was suppressed, this could translate into a long-term reduced rate of clinical disease progression.
The aims of this study were therefore to assess the increase in CD4 cell count in patients taking cART and in whom VL was undetectable, and to compare nucleoside backbones and other antiretrovirals used as part of a cART regimen.
Source...