CD4+/CD8 + ratio restoration in long-term treated HIV-1-infected individuals

Caby, Fabienne

doi:10.1097/qad.0000000000001533

Cited by 25 publications

(37 citation statements)

References 33 publications

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“…After 12.5 years, women had a mean of 99 to 168 more CD4 + cells/µL than men. We also observed a long‐term difference of +0.31 in the CD4:CD8 ratio between women and men, in accordance with the results of previous studies [34,46‐49]. Such differences in CD4 + T‐cell counts and CD4:CD8 ratio are similar to that reported between the sexes in non‐HIV individuals [50‐52].…”

Section: Discussionsupporting

confidence: 92%

“…The dynamics of CD4 + T‐cell counts, CD4:CD8 ratios and HIV DNA levels were still ongoing at the end of follow‐up. This confirms the benefit of early ART initiation and long‐term ART to sustainably improve immune recovery [33‐36]. The immunological advantage women had over men during AHI strengthened over the first year of ART and was then maintained with sustained ART.…”

Section: Discussionsupporting

confidence: 70%

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Enhanced immunovirological response in women compared to men after antiretroviral therapy initiation during acute and early HIV‐1 infection: results from a longitudinal study in the French ANRS Primo cohort

et al. 2020

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Introduction: Previous studies have reported better immunovirological characteristics in women compared with men after HIV seroconversion. We investigated whether differences persisted under long-term antiretroviral therapy (ART) in individuals treated since acute and early HIV-1 infection (AHI). Methods: Data were obtained for 262 women and 1783 men enrolled between 1996 and 2017 in the French multicentre ANRS PRIMO cohort. We modelled the viral response, long-term immune recovery and HIV DNA decay in the 143 women and 1126 men who initiated ART within the first three months of infection. Results: The participants were mostly white. The mean age was 37 years at AHI diagnosis. Pre-ART viral loads were lower in women than men, 5.2 and 5.6 log 10 copies/mL (p = 0.001). After ART initiation, women more rapidly achieved viral suppression than men (adjusted hazard ratio: 1.33, 95% confidence interval 1.09 to 1.69). They also experienced a faster increase in CD4 + T-cell count and CD4:CD8 ratio during the first months of treatment. Sex-related differences in CD4 + T-cell counts were more pronounced with increasing age. This led to a sustained mean difference of 99 to 168 CD4 + T-cells/µL depending on age between women and men at 150 months of ART. Moreover, CD4:CD8 ratio of women was higher than that of men by 0.31, at 150 months of ART. There was no statistically significant difference between sexes for the levels of HIV DNA over time (mean estimate at the last modelling point: 1.9 log 10 copies/10 6 PBMCs after 70 months of ART for both sexes). Conclusions: The high level of immune recovery and decrease in total HIV DNA levels achieved after ART initiation during AHI reinforce the importance of early diagnosis of HIV infection and immediate ART initiation. The immunological benefit of being female increased throughout prolonged ART duration, which may give women additional protection from adverse clinical events and premature ageing.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 70%

Enhanced immunovirological response in women compared to men after antiretroviral therapy initiation during acute and early HIV‐1 infection: results from a longitudinal study in the French ANRS Primo cohort

et al. 2020

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“…However, reasons for the persistence of elevated CD8 T cells during treatment have not been fully elucidated. Long-term therapy usually determines a significant CD4 recovery, contrasting with, despite a decrease from baseline, persistently elevated CD8 T cell counts [ 23 ]. Previous analyses of cohort data have shown that elevated CD8 T lymphocytes at cART initiation were associated with a poor increase in the CD4 T cell count, even if the studies showed no data on CD8 activation [ 22 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, only individuals with a ratio ≥ 1.5 achieved an apparently normal median CD8 count when compared to healthy HIV-seronegative individuals [ 24 ]. Furthermore, after 8 years of suppressive cART, only one-third of patients of the French Hospital Database on HIV cohort achieved CD4/CD8 restoration [ 23 ]. Encouragingly, Saracino et al have shown that patients with more than 15 years of cART had a progressive increase in the CD4/CD8 ratio which never reached a plateau, but patients included in that analysis were receiving triple therapy [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Switching to dual/monotherapy determines an increase in CD8+ in HIV-infected individuals: an observational cohort study

Mussini

Lorenzini

Cozzi‐Lepri

et al. 2018

BMC Med

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BackgroundThe CD4/CD8 ratio has been associated with the risk of AIDS and non-AIDS events. We describe trends in immunological parameters in people who underwent a switch to monotherapy or dual therapy, compared to a control group remaining on triple antiretroviral therapy (ART).MethodsWe included patients in Icona who started a three-drug combination ART regimen from an ART-naïve status and achieved a viral load ≤ 50 copies/mL; they were subsequently switched to another triple or to a mono or double regimen. Standard linear regression at fixed points in time (12-24 months after the switch) and linear mixed model analysis with random intercepts and slopes were used to compare CD4 and CD8 counts and their ratio over time according to regimen types (triple vs. dual and vs. mono).ResultsA total of 1241 patients were included; 1073 switched to triple regimens, 104 to dual (72 with 1 nucleoside reverse transcriptase inhibitor (NRTI), 32 NRTI-sparing), and 64 to monotherapy. At 12 months after the switch, for the multivariable linear regression the mean change in the log10 CD4/CD8 ratio for patients on dual therapy was −0.03 (95% confidence interval (CI) –0.05, –0.0002), and the mean change in CD8 count was +99 (95% CI +12.1, +186.3), taking those on triple therapy as reference. In contrast, there was no evidence for a difference in CD4 count change. When using all counts, there was evidence for a significant difference in the slope of the ratio and CD8 count between people who were switched to triple (points/year change ratio = +0.056, CD8 = −25.7) and those to dual regimen (ratio = −0.029, CD8 = +110.4).ConclusionsWe found an increase in CD8 lymphocytes in people who were switched to dual regimens compared to those who were switched to triple. Patients on monotherapy did not show significant differences. The long-term implications of this difference should be ascertained.Electronic supplementary materialThe online version of this article (10.1186/s12916-018-1046-2) contains supplementary material, which is available to authorized users.

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“…The benefits of ART for recovery of CD4 + cell counts are well documented [ 14 – 16 ]. However, few studies have investigated long-term trends in CD8 + cell counts [ 17 – 21 ] and in CD4 + : CD8 + ratio [ 17 – 24 ] after starting ART, with almost all based on small (<150) or moderate (<2000) sample sizes. Given the potential health implications of elevated CD8 + cell counts and CD4 + : CD8 + ratios below 1 [ 19 , 20 , 25 ], more information is needed about their long-term trends in treated patients.…”

Section: Introductionmentioning

confidence: 99%

Long terms trends in CD4+ cell counts, CD8+ cell counts, and the CD4+

Hughes

May

Tilling

et al. 2018

Aids

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CD4+/CD8 + ratio restoration in long-term treated HIV-1-infected individuals

Abstract: At 8 years, only one-third of individuals achieved CD4/CD8 ratio restoration with sustained virological control. Treatment at the earliest stage, and starting cART in recent years appeared to be key determinants.

Cited by 25 publications

References 33 publications

Enhanced immunovirological response in women compared to men after antiretroviral therapy initiation during acute and early HIV‐1 infection: results from a longitudinal study in the French ANRS Primo cohort

Enhanced immunovirological response in women compared to men after antiretroviral therapy initiation during acute and early HIV‐1 infection: results from a longitudinal study in the French ANRS Primo cohort

Switching to dual/monotherapy determines an increase in CD8+ in HIV-infected individuals: an observational cohort study

Long terms trends in CD4+ cell counts, CD8+ cell counts, and the CD4+

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