UZH-Logo

Maintenance Infos

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


Mocroft, A; Phillips, A; Gatell, J; Horban, A; Ledergerber, B; Zilmer, K; Jevtovic, D; Maltez, F; Kirk, O; Lundgren, J (2012). CD4 count and viral load specific rates of AIDS, non-AIDS and deaths according to current antiretroviral use. Journal of the International Aids Society, 15(6):18191.

Abstract

Background: CD4 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 negatively affect the risk of disease this would not be identified prior to licensing. The aims of this study were to investigate the CD4 and viral load specific rates of fatal and non-fatal AIDS and non-AIDS events according to current antiretrovirals. Methods: Poisson regression was used to compare overall events (fatal or non-fatal AIDS, non-AIDS or death), AIDS events (fatal and non-fatal) or non-AIDS events (fatal or non-fatal) for specific nucleoside pairs and third drugs used with>1000 person-years of follow-up (PYFU) after January 1st 2001. Results: 9801 patients were included. The median baseline date was January 2004 (interquartile range [IQR] January 2001-February 2007), age was 40.4 (IQR 34.6-47.3 years), and time since starting cART was 3.3 (IQR 0.9-5.1 years). At baseline, the median nadir CD4 was 162 (IQR 71-257/mm3), baseline CD4 was 390 (IQR 249-571/mm3), viral load was 1.9 (IQR 1.7-3.3 log10copies/ml) and 2961 (30.2%) had a prior AIDS diagnosis and 6.4 years) prior to baseline. During 42372.5 PYFU, 1203 (437 AIDS and 766 non-AIDS) events occurred. The overall event rate was 2.8 per 100 PYFU (95% confidence interval [CI] 2.7-3.0), of AIDS events was 1.0 (95% CI 0.9-1.1) and of non-AIDS events was 1.8 (95% CI 1.7-1.9). Of the AIDS events, 53 (12.1%)were fatal as were 239 (31.2%) of the non-AIDS events. 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). Compared to zidovudine/lamivudine, patients taking abacavir/lamivudine (adjusted incidence rate ratio [aIRR] 1.22; 95% CI 0.99-1.49) and abacavir plus 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 to those taking efavirenz (aIRR 1.46; 95% CI 1.09-1.95)(Figure). Conclusions: There was little evidence of substantial differences between antiretrovirals in the incidence of fatal and non-fatal AIDS and non-AIDS events for a given CD4 or viral load, suggesting there are unlikely to be major unidentified adverse effects of specific antiretrovirals, although confounding by indication cannot be ruled out.

Background: CD4 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 negatively affect the risk of disease this would not be identified prior to licensing. The aims of this study were to investigate the CD4 and viral load specific rates of fatal and non-fatal AIDS and non-AIDS events according to current antiretrovirals. Methods: Poisson regression was used to compare overall events (fatal or non-fatal AIDS, non-AIDS or death), AIDS events (fatal and non-fatal) or non-AIDS events (fatal or non-fatal) for specific nucleoside pairs and third drugs used with>1000 person-years of follow-up (PYFU) after January 1st 2001. Results: 9801 patients were included. The median baseline date was January 2004 (interquartile range [IQR] January 2001-February 2007), age was 40.4 (IQR 34.6-47.3 years), and time since starting cART was 3.3 (IQR 0.9-5.1 years). At baseline, the median nadir CD4 was 162 (IQR 71-257/mm3), baseline CD4 was 390 (IQR 249-571/mm3), viral load was 1.9 (IQR 1.7-3.3 log10copies/ml) and 2961 (30.2%) had a prior AIDS diagnosis and 6.4 years) prior to baseline. During 42372.5 PYFU, 1203 (437 AIDS and 766 non-AIDS) events occurred. The overall event rate was 2.8 per 100 PYFU (95% confidence interval [CI] 2.7-3.0), of AIDS events was 1.0 (95% CI 0.9-1.1) and of non-AIDS events was 1.8 (95% CI 1.7-1.9). Of the AIDS events, 53 (12.1%)were fatal as were 239 (31.2%) of the non-AIDS events. 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). Compared to zidovudine/lamivudine, patients taking abacavir/lamivudine (adjusted incidence rate ratio [aIRR] 1.22; 95% CI 0.99-1.49) and abacavir plus 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 to those taking efavirenz (aIRR 1.46; 95% CI 1.09-1.95)(Figure). Conclusions: There was little evidence of substantial differences between antiretrovirals in the incidence of fatal and non-fatal AIDS and non-AIDS events for a given CD4 or viral load, suggesting there are unlikely to be major unidentified adverse effects of specific antiretrovirals, although confounding by indication cannot be ruled out.

Altmetrics

Downloads

30 downloads since deposited on 24 Jan 2013
13 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Infectious Diseases
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2012
Deposited On:24 Jan 2013 09:42
Last Modified:17 Nov 2016 15:52
Publisher:BioMed Central
ISSN:1758-2652
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.7448/IAS.15.6.18191
PubMed ID:23228785
Permanent URL: https://doi.org/10.5167/uzh-71231

Download

[img]
Preview
Content: Published Version
Filetype: PDF
Size: 312kB
View at publisher
Licence: Creative Commons: Attribution 3.0 Unported (CC BY 3.0)

TrendTerms

TrendTerms displays relevant terms of the abstract of this publication and related documents on a map. The terms and their relations were extracted from ZORA using word statistics. Their timelines are taken from ZORA as well. The bubble size of a term is proportional to the number of documents where the term occurs. Red, orange, yellow and green colors are used for terms that occur in the current document; red indicates high interlinkedness of a term with other terms, orange, yellow and green decreasing interlinkedness. Blue is used for terms that have a relation with the terms in this document, but occur in other documents.
You can navigate and zoom the map. Mouse-hovering a term displays its timeline, clicking it yields the associated documents.

Author Collaborations