CD4/CD8 Ratio and the Risk of Kaposi Sarcoma or Non-Hodgkin Lymphoma in the Context of Efficiently Treated Human Immunodeficiency Virus (HIV) Infection: A Collaborative Analysis of 20 European Cohort Studies
Authors: Caby Fabienne , Guiguet Marguerite , Weiss Laurence , Winston Alan , Miro Jose M , Konopnicki Deborah , Le Moing Vincent , Bonnet Fabrice , Reiss Peter , Mussini Cristina , Poizot-Martin Isabelle , Taylor Ninon , Skoutelis Athanasios , Meyer Laurence , Goujard Cécile , Bartmeyer Barbara , Boesecke Christoph , Antinori Andrea , Quiros-Roldan Eugenia , Wittkop Linda , Frederiksen Casper , Castagna Antonella , Thurnheer Maria Christine , Svedhem Veronica , Jose Sophie , Costagliola Dominique , Mary-Krause Murielle , Grabar Sophie ,   (CD4/CD8 ratio and cancer risk) project Working Group for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in EuroCoord, Judd Ali , Zangerle Robert , Touloumi Giota , Warszawski Josiane , Meyer Laurence , Dabis François , Krause Murielle Mary , Ghosn Jade , Leport Catherine , Wittkop Linda , Reiss Peter , Wit Ferdinand , Prins Maria , Bucher Heiner , Gibb Diana , Fätkenheuer Gerd , Del Amo Julia , Obel Niels , Thorne Claire , Mocroft Amanda , Kirk Ole , Stephan Christoph , Pérez-Hoyos, Santiago , Hamouda Osamah , Bartmeyer Barbara , Chkhartishvili Nikoloz , Noguera-Julian Antoni , Antinori Andrea , Monforte Antonella d’Arminio , Brockmeyer Norbert , Prieto Luis , Conejo Pablo Rojo , Soriano-Arandes Antoni , Battegay Manuel , Kouyos Roger , Mussini Cristina , Casabona Jordi , Miró Jose M , Castagna Antonella , Konopnick Deborah , Goetghebuer Tessa , Sönnerborg Anders , Torti Carlo , Sabin Caroline , Teira Ramon , Garrido Myriam , Haerry David 
Published: August 2020

Background

A persistently low CD4/CD8 ratio has been reported to inversely correlate with the risk of non-AIDS defining cancer in people living with human immunodeficiency virus (HIV; PLWH) efficiently treated by combination antiretroviral therapy (cART). We evaluated the impact of the CD4/CD8 ratio on the risk of Kaposi sarcoma (KS) or non-Hodgkin lymphoma (NHL), still among the most frequent cancers in treated PLWH.

Methods

PLWH 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 and without previous KS/LNH diagnosis. Cox models were used to identify factors associated with KS or NHL risk, in all participants and those with CD4 ≥ 500/mm3 at virological control. We analyzed the CD4/CD8 ratio, CD4 count and CD8 count as time-dependent variables, using spline transformations.

Results

We included 56 708 PLWH, enrolled between 2000 and 2014. At virological control, the median (interquartile range [IQR]) CD4 count, CD8 count, and CD4/CD8 ratio were 414 (296–552)/mm3, 936 (670–1304)/mm3, and 0.43 (0.28–0.65), respectively. Overall, 221 KS and 187 NHL were diagnosed 9 (2–37) and 18 (7–42) months after virological control. Low CD4/CD8 ratios were associated with KS risk (hazard ratio [HR] = 2.02 [95% confidence interval {CI } = 1.23–3.31]) when comparing CD4/CD8 = 0.3 to CD4/CD8 = 1) but not with NHL risk. High CD8 counts were associated with higher NHL risk (HR = 3.14 [95% CI = 1.58–6.22]) when comparing CD8 = 3000/mm3 to CD8 = 1000/mm3). Similar results with increased associations were found in PLWH with CD4 ≥ 500/mm3 at virological control (HR = 3.27 [95% CI = 1.60–6.56] for KS; HR = 5.28 [95% CI = 2.17–12.83] for NHL).

Conclusions

Low CD4/CD8 ratios and high CD8 counts despite effective cART were associated with increased KS/NHL risks respectively, especially when CD4 ≥ 500/mm3.