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Title
CD4/CD8 ratio and risk of Kaposi sarcoma and non-Hodgkin lymphoma in people living with HIV achieving suppressed viraemia on antiretroviral therapy
Presenter
Sophie Grabar
Authors
F. Caby1,2, S. Grabar1,3, on behalf of the CD4/CD8 Ratio and Cancer Working Group of the COHERE in EuroCoord
Institutions
1Sorbonne Université, INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique, UMR_S 1136, Paris, France, 2Centre Hospitalier VIctor Dupouy, Infectious diseases, Argenteuil, France, 3AP-HP, Groupe Hospitalier Cochin-Hôtel Dieu, Université Paris Descartes, Unite de Biostatistique et Epidémiologie, Paris, France

Background: A persistently abnormal CD4/CD8 ratio despite combination antiretroviral therapy (cART) reflects ongoing immune dysfunction and has been inversely correlated with the risk of non-AIDS defining cancer in people living with HIV (PLHIV). However the predictive value of the CD4/CD8 ratio has never been studied for AIDS-defining cancers such as Kaposi sarcoma (KS) and non-Hodgkin lymphoma (NHL) which remain the most frequent cancers in PLHIV receiving cART. Here, we evaluated the impact of CD4/CD8 ratio restoration (≥1) on KS and NHL risks in PLHIV achieving suppressed viraemia on cART.
Methods: PLHIV from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) were included if they achieved virological control (viral load≤500 copies/mL) within 9 months following cART initiated between 2000 and 2014. Baseline was the time of the first CD4/CD8 measurement after virological control, with persistent suppressed viraemia. Patients with KS or NHL before baseline were excluded. Cox models were used to identify factors associated with KS and NHL risks.
Results: A total of 58308 patients (76% men, median[IQR] age 38 [32-45] years) were followed-up during 59[30-96] months. At baseline, CD4 count, CD8 count and CD4/CD8 ratio were 412[292-550]/mm3, 937[668-1306]/mm3 and 0.43[0.28-0.64] respectively. Overall, 221 KS and 187 NHL were diagnosed, 9[2-37] and 18[7-42] months after baseline respectively. At 2 years, CD4/CD8 ratio was restored (≥1) in 28% (95%CI:27-28). CD4/CD8 ratio restoration, in addition to CD4 restoration, tended to decrease KS risk (see table). High baseline CD8 count was associated with higher NHL risk. Both KS and NHL risks were strongly increased in case of virological failure.
Conclusions: In this population of patients who had achieved suppressed viraemia, restoration of the CD4/CD8 ratio may confer an additional benefit to CD4 restoration with regard to KS risk. For NHL risk, the main immunological associated factor was baseline CD8 count. Furthermore, avoiding virological failure appeared to be key to minimize KS and NHL risks. A closer clinical monitoring should be proposed in patients with high CD8 count despite virological control and/or low persistent CD4/CD8 ratio.


   Kaposi sarcomaNon-Hodgkin lymphoma
   Adjusted* HR (CI95%)pAdjusted* HR (CI95%)p
After baseline:
CD4< 350/mm3
CD4>=350/mm3and CD4/CD8<1
CD4>= 350/mm3and CD4/CD8>=1
1.76(1.25-2.48)
1
0.68(0.44-1.06)		0.0006




1.66(1.11-2.49)
1
0.79(0.52-1.20)
0.0075



BaselineCD8count (/mm3)
< 1000
[1000-2000[
>= 2000

1
1.02(0.77-1.36)
1.10(0.65-1.88)		0.9387




1
1.00(0.72-1.37)
1.92(1.20-3.08)		0.0156



Virological failure after baseline
(viral load >500 copies/mL)		2.71(1.79-4.11)

< 0.0001

2.34(1.56-3.51)

< 0.0001

*Models were adjusted for baseline characteristics (age, sex, geographical origin, HIV transmission group, calendar period of cART introduction, CDC stage) and for time-dependent covariables measured after baseline: virological failure (>500 copies/mL) and a composite 3-level variable (CD4<350/mm3, CD4≥350/mm3 and CD4/CD8<1, CD4≥350/mm3 and CD4/CD8≥1).
[Immuno-virological factors associated with KS and NHL risks: multivariable analyses]