Antiretroviral treatment regimens and immune parameters in the prevention of systemic AIDS-related non-Hodgkin's lymphoma.
OBJECTIVE
Immunosuppression induced by HIV-1 increases the risk of developing non-Hodgkin's lymphoma (NHL). We measured the influence of immunologic factors and highly active antiretroviral therapy (HAART) on this risk. As there are no data demonstrating that specific antiretroviral regimens are effective at protecting from NHL, we compared different HAART regimens.


METHODS
The protective effect of HAART regimens, containing protease inhibitors (PI) and/or non-nucleoside reverse transcriptase inhibitors (NNRTIs) on the development of NHL was examined in a prospectively recorded cohort of 9,621 HIV-infected individuals. Lymphocyte and natural killer subset data were also entered in univariate and multivariate analyses to establish and stratify the risk of NHL.


RESULTS
From this cohort of 9,621 patients, 102 have been diagnosed with systemic AIDS-related NHL since 1996, when HAART became freely available here. By univariate analysis, increased age, higher nadir CD4 and CD8 T-cell counts, CD19 B-cell count, CD16/56 natural killer count and exposure to NNRTI or PI containing HAART conferred significant protection against NHL (P <.05). In a multivariate analysis, age, nadir CD4 and CD8 T-cell counts, and exposure to HAART were independent predictors of risk of NHL (P <.02). NNRTI-based HAART (adjusted rate ratio, 0.4; 95% CI, 0.3 to 0.5) was as protective as PI-based HAART, and these were significantly more protective than nucleoside analogues alone (rate ratio, 0.5; 95% CI, 0.4 to 0.7) or no antiretrovirals (P <.001).


CONCLUSIONS
Effective HAART-induced maintenance of CD4 and CD8 counts protects from systemic AIDS-related NHL.
Stebbing
Justin
J
Department of Oncology, The Chelsea and Westminster Hospital, 369 Fulham Rd, London SW10 9NH, United Kingdom.
Gazzard
Brian
B
Mandalia
Sundhiya
S
Teague
Alastair
A
Waterston
Ashita
A
Marvin
Vanessa
V
Nelson
Mark
M
Bower
Mark
M
D000328:Adult; D018941:Antigens, CD19 / Q000097:blood; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D005260:Female; D015497:HIV-1; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism; D016014:Linear Models; D016131:Lymphocyte Subsets; D016483:Lymphoma, AIDS-Related / Q000276:immunology* / Q000517:prevention & control*; D008297:Male; D015999:Multivariate Analysis; D011446:Prospective Studies; D012306:Risk
D018941:Antigens, CD19