CD4 cell count and viral load-specific rates of AIDS, non-AIDS and deaths according to current antiretroviral use

TY - JOUR

T1 - CD4 cell count and viral load-specific rates of AIDS, non-AIDS and deaths according to current antiretroviral use

AU - Mocroft, Amanda

AU - Phillips, Andrew N

AU - Gatell, Jose

AU - Horban, Andrej

AU - Ledergerber, Bruno

AU - Zilmer, Kai

AU - Jevtovic, Djordje

AU - Maltez, Fernando

AU - Podlekareva, Daria

AU - Lundgren, Jens D

AU - EuroSIDA in EuroCoord

AU - van Lunzen, Jan

PY - 2013/3/27

Y1 - 2013/3/27

N2 - BACKGROUND: CD4 cell count and viral loads are used in clinical trials as surrogate endpoints for assessing efficacy of newly available antiretrovirals. If antiretrovirals act through other pathways or increase the risk of disease this would not be identified prior to licensing. The aim of this study was to investigate the CD4 cell count and viral load-specific rates of fatal and nonfatal AIDS and non-AIDS events according to current antiretrovirals.METHODS: Poisson regression was used to compare overall events (fatal or nonfatal AIDS, non-AIDS or death), AIDS events (fatal and nonfatal) or non-AIDS events (fatal or nonfatal) for specific nucleoside pairs and third drugs used with more than 1000 person-years of follow-up (PYFU) after 1 January 2001.RESULTS: Nine thousand, eight hundred and one patients contributed 42372.5 PYFU, during which 1203 (437 AIDS and 766 non-AIDS) events occurred. After adjustment, there was weak evidence of a difference in the overall events rates between nucleoside pairs (global P-value = 0.084), and third drugs (global P-value = 0.031). As compared to zidovudine/lamivudine, patients taking abacavir/lamivudine [adjusted incidence rate ratio (aIRR) 1.22; 95% CI 0.99-1.49] and abacavir and one other nucleoside [aIRR 1.51; 95% CI 1.14-2.02] had an increased incidence of overall events. Comparing the third drugs, those taking unboosted atazanavir had an increased incidence of overall events compared with those taking efavirenz (aIRR 1.46; 95% CI 1.09-1.95).CONCLUSION: There was little evidence of substantial differences between antiretrovirals in the incidence of clinical disease for a given CD4 cell count or viral load, suggesting there are unlikely to be major unidentified adverse effects of specific antiretrovirals.

AB - BACKGROUND: CD4 cell count and viral loads are used in clinical trials as surrogate endpoints for assessing efficacy of newly available antiretrovirals. If antiretrovirals act through other pathways or increase the risk of disease this would not be identified prior to licensing. The aim of this study was to investigate the CD4 cell count and viral load-specific rates of fatal and nonfatal AIDS and non-AIDS events according to current antiretrovirals.METHODS: Poisson regression was used to compare overall events (fatal or nonfatal AIDS, non-AIDS or death), AIDS events (fatal and nonfatal) or non-AIDS events (fatal or nonfatal) for specific nucleoside pairs and third drugs used with more than 1000 person-years of follow-up (PYFU) after 1 January 2001.RESULTS: Nine thousand, eight hundred and one patients contributed 42372.5 PYFU, during which 1203 (437 AIDS and 766 non-AIDS) events occurred. After adjustment, there was weak evidence of a difference in the overall events rates between nucleoside pairs (global P-value = 0.084), and third drugs (global P-value = 0.031). As compared to zidovudine/lamivudine, patients taking abacavir/lamivudine [adjusted incidence rate ratio (aIRR) 1.22; 95% CI 0.99-1.49] and abacavir and one other nucleoside [aIRR 1.51; 95% CI 1.14-2.02] had an increased incidence of overall events. Comparing the third drugs, those taking unboosted atazanavir had an increased incidence of overall events compared with those taking efavirenz (aIRR 1.46; 95% CI 1.09-1.95).CONCLUSION: There was little evidence of substantial differences between antiretrovirals in the incidence of clinical disease for a given CD4 cell count or viral load, suggesting there are unlikely to be major unidentified adverse effects of specific antiretrovirals.

KW - Acquired Immunodeficiency Syndrome

KW - Adult

KW - Anti-Retroviral Agents

KW - CD4 Lymphocyte Count

KW - Cohort Studies

KW - Female

KW - Humans

KW - Incidence

KW - Male

KW - Middle Aged

KW - Prospective Studies

KW - Survival Analysis

KW - Viral Load

U2 - 10.1097/QAD.0b013e32835cb766

DO - 10.1097/QAD.0b013e32835cb766

M3 - SCORING: Journal article

C2 - 23698060

VL - 27

SP - 907

EP - 918

JO - AIDS

JF - AIDS

SN - 0269-9370

IS - 6

ER -