Dataset Information

Measures of Longitudinal Immune Dysfunction and Risk of AIDS and Non-AIDS Defining Malignancies in Antiretroviral-Treated People With Human Immunodeficiency Virus.

ABSTRACT:

Background

Human immunodeficiency virus (HIV) infection leads to chronic immune activation/inflammation that can persist in virally suppressed persons on fully active antiretroviral therapy (ART) and increase risk of malignancies. The prognostic role of low CD4:CD8 ratio and elevated CD8 cell counts on the risk of cancer remains unclear.

Methods

We investigated the association of CD4:CD8 ratio on the hazard of non-AIDS defining malignancy (NADM), AIDS-defining malignancy (ADM) and most frequent group of cancers in ART-treated people with HIV (PWH) with a CD4 and CD8 cell counts and viral load measurements at baseline. We developed Cox proportional hazard models with adjustment for known confounders of cancer risk and time-dependent cumulative and lagged exposures of CD4:CD8 ratio to account for time-evolving risk factors and avoid reverse causality.

Results

CD4:CD8 ratios below 0.5, compared to above 1.0, were independently associated with a 12-month time-lagged higher risk of ADM and infection-related malignancies (adjusted hazard ratio 2.61 [95% confidence interval {CI }1.10-6.19] and 2.03 [95% CI 1.24-3.33], respectively). CD4 cell counts below 350 cells/μL were associated with an increased risk of NADMs and ADMs, as did infection, smoking, and body mass index-related malignancies.

Conclusions

In ART-treated PWH low CD4:CD8 ratios were associated with ADM and infection-related cancers independently from CD4 and CD8 cell counts and may alert clinicians for cancer screening and prevention of NADM.

SUBMITTER: Chammartin F

PROVIDER: S-EPMC11006099 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature

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Publications

Measures of Longitudinal Immune Dysfunction and Risk of AIDS and Non-AIDS Defining Malignancies in Antiretroviral-Treated People With Human Immunodeficiency Virus.

Chammartin Frédérique F Mocroft Amanda A Egle Alexander A Zangerle Robert R Smith Colette C Mussini Cristina C Wit Ferdinand F Vehreschild Jörg Janne JJ d'Arminio Monforte Antonella A Castagna Antonella A Bailly Laurent L Bogner Johannes J de Wit Stéphane S Matulionyte Raimonda R Law Matthew M Svedhem Veronica V Tallada Joan J Garges Harmony P HP Marongiu Andrea A Borges Álvaro H ÁH Jaschinski Nadine N Neesgaard Bastian B Ryom Lene L Bucher Heiner C HC

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20240401 4

<h4>Background</h4>Human immunodeficiency virus (HIV) infection leads to chronic immune activation/inflammation that can persist in virally suppressed persons on fully active antiretroviral therapy (ART) and increase risk of malignancies. The prognostic role of low CD4:CD8 ratio and elevated CD8 cell counts on the risk of cancer remains unclear.<h4>Methods</h4>We investigated the association of CD4:CD8 ratio on the hazard of non-AIDS defining malignancy (NADM), AIDS-defining malignancy (ADM) and ...[more]

PMID: 38092042

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Project description:HIV-1 infection leads to chronic inflammation and to an increased risk of non-AIDS mortality. Our objective was to determine whether AIDS-defining events (ADEs) were associated with increased overall and cause-specific non-AIDS related mortality after antiretroviral therapy (ART) initiation. We included HIV treatment-naïve adults from the Antiretroviral Therapy Cohort Collaboration (ART-CC) who initiated ART from 1996 to 2014. Causes of death were assigned using the Coding Causes of Death in HIV (CoDe) protocol. The adjusted hazard ratio (aHR) for overall and cause-specific non-AIDS mortality among those with an ADE (all ADEs, tuberculosis (TB), Pneumocystis jiroveci pneumonia (PJP), and non-Hodgkin's lymphoma (NHL)) compared to those without an ADE was estimated using a marginal structural model. The adjusted hazard of overall non-AIDS mortality was higher among those with any ADE compared to those without any ADE (aHR 2.21, 95% confidence interval (CI) 2.00 to 2.43). The adjusted hazard of each of the cause-specific non-AIDS related deaths were higher among those with any ADE compared to those without, except metabolic deaths (malignancy aHR 2.59 (95% CI 2.13 to 3.14), accident/suicide/overdose aHR 1.37 (95% CI 1.05 to 1.79), cardiovascular aHR 1.95 (95% CI 1.54 to 2.48), infection aHR (95% CI 1.68 to 2.81), hepatic aHR 2.09 (95% CI 1.61 to 2.72), respiratory aHR 4.28 (95% CI 2.67 to 6.88), renal aHR 5.81 (95% CI 2.69 to 12.56) and central nervous aHR 1.53 (95% CI 1.18 to 5.44)). The risk of overall and cause-specific non-AIDS mortality differed depending on the specific ADE of interest (TB, PJP, NHL). In this large multi-centre cohort collaboration with standardized assignment of causes of death, non-AIDS mortality was twice as high among patients with an ADE compared to without an ADE. However, non-AIDS related mortality after an ADE depended on the ADE of interest. Although there may be unmeasured confounders, these findings suggest that a common pathway may be independently driving both ADEs and NADE mortality. While prevention of ADEs may reduce subsequent death due to NADEs following ART initiation, modification of risk factors for NADE mortality remains important after ADE survival.

Project description:BACKGROUND:The differential effects of commonly prescribed combined antiretroviral therapy (cART) regimens on AIDS-defining neurological conditions (neuroAIDS) remain unknown. SETTING:Prospective cohort studies of HIV-positive individuals from Europe and the Americas included in the HIV-CAUSAL Collaboration. METHODS:Individuals who initiated a first-line cART regimen in 2004 or later containing a nucleoside reverse transcriptase inhibitor backbone and either atazanavir, lopinavir, darunavir, or efavirenz were followed from cART initiation until death, lost to follow-up, pregnancy, the cohort-specific administrative end of follow-up, or the event of interest, whichever occurred earliest. We evaluated 4 neuroAIDS conditions: HIV dementia and the opportunistic infections toxoplasmosis, cryptococcal meningitis, and progressive multifocal leukoencephalopathy. For each outcome, we estimated hazard ratios for atazanavir, lopinavir, and darunavir compared with efavirenz via a pooled logistic model. Our models were adjusted for baseline demographic and clinical characteristics. RESULTS:Twenty six thousand one hundred seventy-two individuals initiated efavirenz, 5858 initiated atazanavir, 8479 initiated lopinavir, and 4799 initiated darunavir. Compared with efavirenz, the adjusted HIV dementia hazard ratios (95% confidence intervals) were 1.72 (1.00 to 2.96) for atazanavir, 2.21 (1.38 to 3.54) for lopinavir, and 1.41 (0.61 to 3.24) for darunavir. The respective hazard ratios (95% confidence intervals) for the combined end point were 1.18 (0.74 to 1.88) for atazanavir, 1.61 (1.14 to 2.27) for lopinavir, and 1.36 (0.74 to 2.48) for darunavir. The results varied in subsets defined by calendar year, nucleoside reverse transcriptase inhibitor backbone, and age. CONCLUSION:Our results are consistent with an increased risk of neuroAIDS after initiating lopinavir compared with efavirenz, but temporal changes in prescribing trends and confounding by indication could explain our findings.

Dataset Information

Measures of Longitudinal Immune Dysfunction and Risk of AIDS and Non-AIDS Defining Malignancies in Antiretroviral-Treated People With Human Immunodeficiency Virus.

Background

Methods

Results

Conclusions

Publications

Measures of Longitudinal Immune Dysfunction and Risk of AIDS and Non-AIDS Defining Malignancies in Antiretroviral-Treated People With Human Immunodeficiency Virus.

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