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Early immunologic failure is associated with early mortality among advanced HIV-infected adults initiating antiretroviral therapy with active tuberculosis.

ABSTRACT: The relationship between antiretroviral therapy (ART) response and early mortality after ART initiation is unknown. We hypothesized that early mortality is associated with decreased early immunologic response to ART.We prospectively determined the association between changes in plasma human immunodeficiency virus type 1 (HIV-1) RNA and CD4(+) T-cell counts (CD4 count) after 4 weeks of ART and early mortality in adults with pulmonary tuberculosis and pre-ART CD4 counts ? 125 cells/µL. Purified protein derivative (PPD)-specific immune recovery was determined by interferon-? enzyme-linked immunosorbent spot assays. Levels of interleukin 6, C-reactive protein, and soluble CD14 were assessed. Patients with CD4 count and viral load values at baseline and week 4 were analyzed using multiple logistic regression.Early immunologic response, but not pre-ART CD4 counts or virologic response, was related to early mortality (8 [interquartile range {IQR}, -18 to 43] vs 68 [IQR, 24-131] cells/µL, P = .002). In a logistic regression model, every 20 cells/µL increase in the CD4 count from baseline to week 4 was independently associated with a 40% reduction in the odds of death (odds ratio, 0.59 [95% confidence interval, .41-.87]). PPD-specific immune recovery was lower, whereas levels of immune activation were higher, among deaths.Early immunologic failure despite virologic suppression is associated with early mortality after ART initiation in advanced HIV/tuberculosis.

SUBMITTER: Ravimohan S

PROVIDER: S-EPMC3814836 | biostudies-other | 2013 Dec

REPOSITORIES: biostudies-other

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Early immunologic failure is associated with early mortality among advanced HIV-infected adults initiating antiretroviral therapy with active tuberculosis.

Ravimohan Shruthi S Tamuhla Neo N Steenhoff Andrew P AP Letlhogile Rona R Makutu Didimalang Kgomotso DK Nfanyana Kebatshabile K Rantleru Tumelo T Tierney Ann A Nkakana Kelebogile K Schwartz Adam B AB Gross Robert R Macgregor Rob Roy RR Bellamy Scarlett L SL Frank Ian I Weissman Drew D Bisson Gregory P GP

The Journal of infectious diseases 20130801 11

<h4>Background</h4>The relationship between antiretroviral therapy (ART) response and early mortality after ART initiation is unknown. We hypothesized that early mortality is associated with decreased early immunologic response to ART.<h4>Methods</h4>We prospectively determined the association between changes in plasma human immunodeficiency virus type 1 (HIV-1) RNA and CD4(+) T-cell counts (CD4 count) after 4 weeks of ART and early mortality in adults with pulmonary tuberculosis and pre-ART CD4 ...[more]

PMID: 23908475

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Project description:BackgroundA decline in mortality rates during the first 12 months of antiretroviral therapy (ART) has been mainly linked to increased ART initiation at higher CD4 counts and at less advanced World Health Organization (WHO) clinical stages of HIV infection; however, the role of improved patient care has not been well studied. We estimated improvements in early mortality due to improved patient care.MethodsWe conducted a retrospective cohort study of HIV-infected individuals ages 18 and older who initiated ART at the Mengo HIV Counseling and Home Care Clinic between 2006 and 2016. We conducted a mediation analysis using generalized structural equation models with inverse odds ratio weighting to estimate the natural direct and indirect effects of ART initiation time on early mortality.FindingsAmong 6,847 patients, most were female (69%), with a median age of 32 (interquartile range [IQR] = 28-38), versus a median age of 38 (IQR = 32-45) for males. The median CD4 count at ART initiation increased from 142 cells/ul (95% confidence interval [CI] = 135-150) in 2006-2010 to 302 cells/ul (95% CI = 283-323) in 2015-2016 (p < 0·001). The number of patients at WHO clinical stages I/II increased from 52% in 2006-2010 to 78% in 2015-2016 (p < 0·001). Annual early mortality decreased from 8·8 deaths/100 person years (PYS) in 2006 to 2.5 deaths/100 pys in 2016 (p < 0·001). Mediation by CD4 counts and WHO clinical stages accounted for 54% of the total effect of ART initiation timing on early mortality. In comparison, 46% remained as the direct effect, reflecting the contribution of improved patient care.InterpretationImproved patient care practices should be promoted as a strategy for reducing early mortality after ART initiation, above and beyond the effects from ART initiation at higher CD4 counts and less advanced WHO clinical stage alone.FundingThis research was supported by the President's Emergency Plan for AIDS Relief (PEPFAR), the National Institute of Allergy and Infectious Diseases Division of Intramural Research, and the National Cancer Institute.

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Early immunologic failure is associated with early mortality among advanced HIV-infected adults initiating antiretroviral therapy with active tuberculosis.

Publications

Early immunologic failure is associated with early mortality among advanced HIV-infected adults initiating antiretroviral therapy with active tuberculosis.

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