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. 2022 Aug 3:52:101600.
doi: 10.1016/j.eclinm.2022.101600. eCollection 2022 Oct.

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

Raquel Martin-Iguacel  1   2 , Juliana Reyes-Urueña  1 , Andreu Bruguera  1 , Jordi Aceitón  1 , Yesika Díaz  1 , Sergio Moreno-Fornés  1 , Pere Domingo  3 , Joaquín Burgos-Cibrian  4 , Juan Manuel Tiraboschi  5 , Isik Somuncu Johansen  2 , Hortensia Álvarez  6 , Josep M Miró  7   8 , Jordi Casabona  1   9   10   11 , Josep M Llibre  12 ; PISCIS study group
Affiliations

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

Raquel Martin-Iguacel et al. EClinicalMedicine. .

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.

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Conflict of interest statement

All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. 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. 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. JML has received payments or honoraria for lectures, presentations or speaker's bureaus from Janssen-Cilag, Gilead Sciences, and ViiV Healthcare, outside of the present work.

Figures

Figure 1
Figure 1
Flowchart of cohort construction.
Figure 2
Figure 2
Mortality rates upon immune recovery 2 years after initiation of antiretroviral therapy stratified by nadir CD4 cell count at ART initiation.
Figure 3
Figure 3
Kaplan-Meier curves for overall survival by immune recovery 2 years after antiretroviral therapy (ART) initiation (non-late presenter with CD4 counts >500 cells/µL versus late presenters with CD4 counts >500 cells/µL, late presenters with CD4 counts >350-500 cells/µL, late presenters with CD4 counts 200-350 cells/µL and late presenters with CD4 counts <200 cells/µL at 2 years after ART initiation.
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