Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Jul 31;24(12):1877-86.
doi: 10.1097/QAD.0b013e32833b1b26.

Immunodeficiency and the risk of serious clinical endpoints in a well studied cohort of treated HIV-infected patients

Amit C Achhra  1 , Janaki Amin, Matthew G Law, Sean Emery, Jan Gerstoft, Fred M Gordin, Michael J Vjecha, James D Neaton, David A Cooper; INSIGHT ESPRIT & SILCAAT study groups
Collaborators, Affiliations

Immunodeficiency and the risk of serious clinical endpoints in a well studied cohort of treated HIV-infected patients

Amit C Achhra et al. AIDS. .

Abstract

Objective: To investigate the relative predictive value of CD4(+) metrics for serious clinical endpoints.

Design: Observational.

Methods: Patients (3012; 20 317 person-years) from control arms of ESPRIT and SILCAAT were followed prospectively. We used Cox regression to identify CD4(+) metrics (latest, baseline and nadir CD4(+) cell count, latest CD4(+)%, time spent with CD4(+) count below certain thresholds and CD4(+) slopes) independently predictive of all-cause mortality, non-AIDS deaths, non-AIDS (cardiovascular, hepatic, renal and non-AIDS malignancy) and AIDS events. Akaike information criteria (AIC) were calculated for each model. Significant metrics (P < 0.05) were then additionally adjusted for latest CD4(+) cell count.

Results: Non-AIDS deaths occurred at a higher rate than AIDS deaths [rate ratio: 6.48, 95% confidence interval (CI) 5.1-8.1], and non-AIDS events likewise (rate ratio: 1.72, 95% CI 1.65-1.79). Latest CD4(+) cell count was strongly predictive of lower risk of death (hazard ratio per log2 rise: 0.48, 95% CI 0.43-0.54), with lowest AIC of all metrics. CD4(+) slope over seven visits, after additional adjustment for latest CD4(+) cell count, was the only metric to be an independent predictor for all-cause (hazard ratio for slope <-10 cells/microl per month vs. 0 +/- 10: 3.04, 95% CI 1.98-4.67) and non-AIDS deaths (hazard ratio for slope <-10 cells/microl per month vs. 0 +/- 10: 2.62, 95% CI 1.62-4.22). Latest CD4(+) cell count (per log(2) rise) was the best predictor across all four endpoints and predicted hepatic (hazard ratio 0.46, 95% CI 0.33-0.63) and renal events (hazard ratio 0.39, 95% CI 0.21-0.70), but not cardiovascular events (hazard ratio 1.05, 95% CI 0.77-1.43) or non-AIDS cancers (hazard ratio 0.78, 95% CI 0.59-1.03).

Conclusion: Latest CD4(+) cell count is the best predictor of serious endpoints. CD4(+) slope independently predicts all-cause and non-AIDS deaths.

PubMed Disclaimer

Figures

Figure-1
Figure-1. Rates by latest CD4+ counts
Rates of non-AIDS events and deaths and AIDS events and deaths by CD4+ category. Non-AIDS events include fatal or non-fatal events only in one of the four categories: cardiovascular, renal, hepatic and non-aids malignancy.
Figure-2
Figure-2. Latest CD4+ counts and specific non-AIDS events categories
(a to e): Adjusted Hazard ratios (per log2 rise in CD4+ counts, with 95% CI) for the association between latest CD4 count and categories of serious non-AIDS diseases. For fatal events, CD4+ and RNA were lagged by 6-months in the model and adjusted hazard per log2 rise in CD4+ counts plotted.
Figure-2
Figure-2. Latest CD4+ counts and specific non-AIDS events categories
(a to e): Adjusted Hazard ratios (per log2 rise in CD4+ counts, with 95% CI) for the association between latest CD4 count and categories of serious non-AIDS diseases. For fatal events, CD4+ and RNA were lagged by 6-months in the model and adjusted hazard per log2 rise in CD4+ counts plotted.
See this image and copyright information in PMC

References

    1. Mocroft A, Vella S, Benfield TL, Chiesi A, Miller V, Gargalianos P, et al. EuroSIDA Study Group. Changing patterns of mortality across Europe in patients infected with HIV-1. Lancet. 1998;352:1725–1730. - PubMed
    1. Pacheco AG, Tuboi SH, Faulhaber JC, Harrison LH, Schechter M. Increase in non-AIDS related conditions as causes of death among HIV-infected individuals in the HAART era in Brazil. PLoS One. 2008;3:e1531. - PMC - PubMed
    1. Sackoff JE, Hanna DB, Pfeiffer MR, Torian LV. Causes of death among persons with AIDS in the era of highly active antiretroviral therapy: New York City. Ann Intern Med. 2006;145:397–406. - PubMed
    1. Smit C, Geskus R, Walker S, Sabin C, Coutinho R, Porter K, et al. Effective therapy has altered the spectrum of cause-specific mortality following HIV seroconversion. AIDS. 2006;20:741–749. - PubMed
    1. Burgi A, Brodine S, Wegner S, Milazzo M, Wallace MR, Spooner K, et al. Incidence and risk factors for the occurrence of non-AIDS-defining cancers among human immunodeficiency virus-infected individuals. Cancer. 2005;104:1505–1511. - PubMed

Publication types

MeSH terms