Determinants of long-term survival in late HIV presenters: The prospective PISCIS cohort study

Raquel Martin-Iguacel; Juliana Reyes-Urueña; Andreu Bruguera; Jordi Aceitón; Yesika Díaz; Sergio Moreno-Fornés; Pere Domingo; Joaquín Burgos-Cibrian; Juan Manuel Tiraboschi; Isik Somuncu Johansen; Hortensia Álvarez; Josep M. Miró; Jordi Casabona; Josep M. Llibre; PISCIS study group

doi:10.1016/j.eclinm.2022.101600

Determinants of long-term survival in late HIV presenters: The prospective PISCIS cohort study

Raquel Martin-Iguacel^*, Juliana Reyes-Urueña, Andreu Bruguera, Jordi Aceitón, Yesika Díaz, Sergio Moreno-Fornés, Pere Domingo, Joaquín Burgos-Cibrian, Juan Manuel Tiraboschi, Isik Somuncu Johansen, Hortensia Álvarez, Josep M. Miró, Jordi Casabona, Josep M. Llibre, PISCIS study group

^*Kontaktforfatter

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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Abstract

Background: Late HIV diagnosis (i.e CD4≤350 cells/µL) is associated with poorer outcomes. However, determinants of long-term mortality and factors influencing immune recovery within the first years after antiretroviral treatment (ART) initiation are poorly defined. Methods: From PISCIS cohort, we included all HIV-positive adults, two-year survivors after initiating ART between 2005–2019. The primary outcome was all-cause mortality according to the two-year CD4 count. We used Poisson regression. The secondary outcome was incomplete immune recovery (i.e., two-year CD4<500 cells/µL). We used logistic regression and propensity score matching. Findings: We included 2,719 participants (16593·1 person-years): 1441 (53%) late presenters (LP) and 1278 non-LP (1145 non-LP with two-year CD4 count >500 cells/µL, reference population). Overall, 113 patients (4·2%) died. Mortality was higher among LP with two-year CD4 count 200–500 cells/µL (aMRR 1·95[95%CI:1·06-3·61]) or <200 cells/µL (aMRR 4·59[2·25-9·37]). Conversely, no differences were observed in participants with two-year CD4 counts >500 cells/µL, regardless of being initially LP or non-LP (aMRR 1·05[0·50-2·21]). Mortality rates within each two-year CD4 strata were not affected by the initial CD4 count at ART initiation (test-interaction, p = 0·48). The stronger factor influencing immune recovery was the CD4 count at ART initiation. First-line integrase-inhibitor-(INSTI)-based regimens were associated with reduced mortality compared to other regimens (aMRR 0·54[0·31-0·93]) and reduced risk of incomplete immune recovery in LP (aOR 0·70[0·52-0·95]). Interpretation: Two-year immune recovery is a good early predictor of long-term mortality in LP after surviving the first high-risk 2 years. Nearly half experienced a favorable immune recovery with a life expectancy similar to non-LP. INSTI-based regimens were associated with higher rates of successful immune recovery and better survival compared to non-INSTI regimens. Funding: Southern-Denmark University, Danish AIDS-foundation, and Region of Southern Denmark.

Originalsprog	Engelsk
Artikelnummer	101600
Tidsskrift	eClinicalMedicine
Vol/bind	52
Antal sider	13
ISSN	2589-5370
DOI	https://doi.org/10.1016/j.eclinm.2022.101600
Status	Udgivet - okt. 2022

Bibliografisk note

Funding Information:
This work was supported by scholarships from the University of Southern Denmark, the Danish AIDS foundation, and Public Regional Funds from the Region of Southern Denmark. The study was investigator-driven and thus independent of any pharmaceutical company. The funding sources were not involved in study design, data collection, analyses, report writing, or decision to submit the paper.

Funding Information:
RMI has received consulting honoraria and/or research grants from GSK, MSD, and Lundbeck, outside the submitted work. RMI has received payment for travel and congress assistance from MSD, outside the present work.

Funding Information:
JMM has received consulting honoraria and/or research grants from AbbVie, Angelini, Contrafect, Cubist, Genentech, Gilead Sciences, Jansen, Lysovant, Medtronic, MSD, Novartis, Pfizer, and ViiV Healthcare, outside the submitted work.

Funding Information:
We also want to thank PADRIS and the Programme for the Prevention, Control and Care for HIV, Sexually Transmitted Diseases and Viral Hepatitis of the Ministry of Health of the Government of Catalonia for their support and the Danish AIDS foundation, the University of Southern Denmark, the Region of Southern Denmark and Odense University Hospital for financial support.

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10.1016/j.eclinm.2022.101600Licens: CC BY

Open Access VersionForlagets udgivne version, 1,77 MBLicens: CC BY

1 Ph.d.-afhandling

Late HIV presentation to care: Earlier HIV diagnosis in Primary Health Care & Long-term survival & Tuberculosis co-infection
Iguacel, R. M., 17. jan. 2023, Syddansk Universitet. Det Sundhedsvidenskabelige Fakultet. 143 s.
Publikation: Afhandling › Ph.d.-afhandling

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Martin-Iguacel, R., Reyes-Urueña, J., Bruguera, A., Aceitón, J., Díaz, Y., Moreno-Fornés, S., Domingo, P., Burgos-Cibrian, J., Tiraboschi, J. M., Johansen, I. S., Álvarez, H., Miró, J. M., Casabona, J., Llibre, J. M., & PISCIS study group (2022). Determinants of long-term survival in late HIV presenters: The prospective PISCIS cohort study. eClinicalMedicine, 52, [101600]. https://doi.org/10.1016/j.eclinm.2022.101600

@article{6e1ae92f3eef47aba9dd7af8ebf29030,

title = "Determinants of long-term survival in late HIV presenters: The prospective PISCIS cohort study",

abstract = "Background: Late HIV diagnosis (i.e CD4≤350 cells/µL) is associated with poorer outcomes. However, determinants of long-term mortality and factors influencing immune recovery within the first years after antiretroviral treatment (ART) initiation are poorly defined. Methods: From PISCIS cohort, we included all HIV-positive adults, two-year survivors after initiating ART between 2005–2019. The primary outcome was all-cause mortality according to the two-year CD4 count. We used Poisson regression. The secondary outcome was incomplete immune recovery (i.e., two-year CD4<500 cells/µL). We used logistic regression and propensity score matching. Findings: We included 2,719 participants (16593·1 person-years): 1441 (53%) late presenters (LP) and 1278 non-LP (1145 non-LP with two-year CD4 count >500 cells/µL, reference population). Overall, 113 patients (4·2%) died. Mortality was higher among LP with two-year CD4 count 200–500 cells/µL (aMRR 1·95[95%CI:1·06-3·61]) or <200 cells/µL (aMRR 4·59[2·25-9·37]). Conversely, no differences were observed in participants with two-year CD4 counts >500 cells/µL, regardless of being initially LP or non-LP (aMRR 1·05[0·50-2·21]). Mortality rates within each two-year CD4 strata were not affected by the initial CD4 count at ART initiation (test-interaction, p = 0·48). The stronger factor influencing immune recovery was the CD4 count at ART initiation. First-line integrase-inhibitor-(INSTI)-based regimens were associated with reduced mortality compared to other regimens (aMRR 0·54[0·31-0·93]) and reduced risk of incomplete immune recovery in LP (aOR 0·70[0·52-0·95]). Interpretation: Two-year immune recovery is a good early predictor of long-term mortality in LP after surviving the first high-risk 2 years. Nearly half experienced a favorable immune recovery with a life expectancy similar to non-LP. INSTI-based regimens were associated with higher rates of successful immune recovery and better survival compared to non-INSTI regimens. Funding: Southern-Denmark University, Danish AIDS-foundation, and Region of Southern Denmark.",

keywords = "Delayed HIV diagnosis, HIV, Immune recovery, Immune response, Integrase inhibitors, Late presenters, Mortality",

author = "Raquel Martin-Iguacel and Juliana Reyes-Urue{\~n}a and Andreu Bruguera and Jordi Aceit{\'o}n and Yesika D{\'i}az and Sergio Moreno-Forn{\'e}s and Pere Domingo and Joaqu{\'i}n Burgos-Cibrian and Tiraboschi, {Juan Manuel} and Johansen, {Isik Somuncu} and Hortensia {\'A}lvarez and Mir{\'o}, {Josep M.} and Jordi Casabona and Llibre, {Josep M.} and {PISCIS study group}",

note = "Publisher Copyright: {\textcopyright} 2022 The Authors",

year = "2022",

month = oct,

doi = "10.1016/j.eclinm.2022.101600",

language = "English",

volume = "52",

journal = "eClinicalMedicine",

issn = "2589-5370",

publisher = "Elsevier",

}

Martin-Iguacel, R, Reyes-Urueña, J, Bruguera, A, Aceitón, J, Díaz, Y, Moreno-Fornés, S, Domingo, P, Burgos-Cibrian, J, Tiraboschi, JM, Johansen, IS, Álvarez, H, Miró, JM, Casabona, J, Llibre, JM & PISCIS study group 2022, 'Determinants of long-term survival in late HIV presenters: The prospective PISCIS cohort study', eClinicalMedicine, bind 52, 101600. https://doi.org/10.1016/j.eclinm.2022.101600

TY - JOUR

T1 - Determinants of long-term survival in late HIV presenters

T2 - The prospective PISCIS cohort study

AU - Martin-Iguacel, Raquel

AU - Reyes-Urueña, Juliana

AU - Bruguera, Andreu

AU - Aceitón, Jordi

AU - Díaz, Yesika

AU - Moreno-Fornés, Sergio

AU - Domingo, Pere

AU - Burgos-Cibrian, Joaquín

AU - Tiraboschi, Juan Manuel

AU - Johansen, Isik Somuncu

AU - Álvarez, Hortensia

AU - Miró, Josep M.

AU - Casabona, Jordi

AU - Llibre, Josep M.

AU - PISCIS study group

PY - 2022/10

Y1 - 2022/10

N2 - Background: Late HIV diagnosis (i.e CD4≤350 cells/µL) is associated with poorer outcomes. However, determinants of long-term mortality and factors influencing immune recovery within the first years after antiretroviral treatment (ART) initiation are poorly defined. Methods: From PISCIS cohort, we included all HIV-positive adults, two-year survivors after initiating ART between 2005–2019. The primary outcome was all-cause mortality according to the two-year CD4 count. We used Poisson regression. The secondary outcome was incomplete immune recovery (i.e., two-year CD4<500 cells/µL). We used logistic regression and propensity score matching. Findings: We included 2,719 participants (16593·1 person-years): 1441 (53%) late presenters (LP) and 1278 non-LP (1145 non-LP with two-year CD4 count >500 cells/µL, reference population). Overall, 113 patients (4·2%) died. Mortality was higher among LP with two-year CD4 count 200–500 cells/µL (aMRR 1·95[95%CI:1·06-3·61]) or <200 cells/µL (aMRR 4·59[2·25-9·37]). Conversely, no differences were observed in participants with two-year CD4 counts >500 cells/µL, regardless of being initially LP or non-LP (aMRR 1·05[0·50-2·21]). Mortality rates within each two-year CD4 strata were not affected by the initial CD4 count at ART initiation (test-interaction, p = 0·48). The stronger factor influencing immune recovery was the CD4 count at ART initiation. First-line integrase-inhibitor-(INSTI)-based regimens were associated with reduced mortality compared to other regimens (aMRR 0·54[0·31-0·93]) and reduced risk of incomplete immune recovery in LP (aOR 0·70[0·52-0·95]). Interpretation: Two-year immune recovery is a good early predictor of long-term mortality in LP after surviving the first high-risk 2 years. Nearly half experienced a favorable immune recovery with a life expectancy similar to non-LP. INSTI-based regimens were associated with higher rates of successful immune recovery and better survival compared to non-INSTI regimens. Funding: Southern-Denmark University, Danish AIDS-foundation, and Region of Southern Denmark.

AB - Background: Late HIV diagnosis (i.e CD4≤350 cells/µL) is associated with poorer outcomes. However, determinants of long-term mortality and factors influencing immune recovery within the first years after antiretroviral treatment (ART) initiation are poorly defined. Methods: From PISCIS cohort, we included all HIV-positive adults, two-year survivors after initiating ART between 2005–2019. The primary outcome was all-cause mortality according to the two-year CD4 count. We used Poisson regression. The secondary outcome was incomplete immune recovery (i.e., two-year CD4<500 cells/µL). We used logistic regression and propensity score matching. Findings: We included 2,719 participants (16593·1 person-years): 1441 (53%) late presenters (LP) and 1278 non-LP (1145 non-LP with two-year CD4 count >500 cells/µL, reference population). Overall, 113 patients (4·2%) died. Mortality was higher among LP with two-year CD4 count 200–500 cells/µL (aMRR 1·95[95%CI:1·06-3·61]) or <200 cells/µL (aMRR 4·59[2·25-9·37]). Conversely, no differences were observed in participants with two-year CD4 counts >500 cells/µL, regardless of being initially LP or non-LP (aMRR 1·05[0·50-2·21]). Mortality rates within each two-year CD4 strata were not affected by the initial CD4 count at ART initiation (test-interaction, p = 0·48). The stronger factor influencing immune recovery was the CD4 count at ART initiation. First-line integrase-inhibitor-(INSTI)-based regimens were associated with reduced mortality compared to other regimens (aMRR 0·54[0·31-0·93]) and reduced risk of incomplete immune recovery in LP (aOR 0·70[0·52-0·95]). Interpretation: Two-year immune recovery is a good early predictor of long-term mortality in LP after surviving the first high-risk 2 years. Nearly half experienced a favorable immune recovery with a life expectancy similar to non-LP. INSTI-based regimens were associated with higher rates of successful immune recovery and better survival compared to non-INSTI regimens. Funding: Southern-Denmark University, Danish AIDS-foundation, and Region of Southern Denmark.

KW - Delayed HIV diagnosis

KW - HIV

KW - Immune recovery

KW - Immune response

KW - Integrase inhibitors

KW - Late presenters

KW - Mortality

U2 - 10.1016/j.eclinm.2022.101600

DO - 10.1016/j.eclinm.2022.101600

M3 - Journal article

C2 - 35958520

AN - SCOPUS:85135405825

SN - 2589-5370

VL - 52

JO - eClinicalMedicine

JF - eClinicalMedicine

M1 - 101600

ER -

Determinants of long-term survival in late HIV presenters: The prospective PISCIS cohort study

Abstract

Bibliografisk note

Dokumenter og links

Fingeraftryk

Relaterede publikationer

Late HIV presentation to care: Earlier HIV diagnosis in Primary Health Care & Long-term survival & Tuberculosis co-infection

Citationsformater