Table 3.

Recent literature evaluating immune suppression and risk of non-AIDS-defining malignancies

Author	Design	N	Subjects	Country	Cancer	Exposure	Results
a. Immunosuppression based on AIDS diagnoses
Marin [68**]	Cohort	10,661	HIV(+) with known dates of seroconversion	Australia; Canada; 15 European countries	Any NADM (fatal)	Prior AIDS	HR=2.5 (95% CI=1.2–5.0)
Engels [23**]	Registry match	57,350	HIV(+)	USA	Multiple subtypes	Prior AIDS	Oral/pharynx: RR=3.6 (95% CI=1.6–8.2) Lung: RR=2.3 (95% CI=1.4–3.5) Hodgkin's Lymphoma: RR=3.5 (95% CI=1.7–7.3) Other cancers not statistically significant
Piketty [26**]	Cohort	86,322	HIV(+)	France	Anal	Prior AIDS	HR=2.2 (95% CI=1.5–3.3)
Chaturvedi [27**]	Registry match	397,927	AIDS	USA	Lung	AIDS relative time	Higher rates post vs. pre-AIDS (p<0.001)
b. Immunosuppression based on CD4 T-cell counts
Baker [69*]	RCT	1,397	HIV(+) initiating ART	USA	Any NADM	Current CD4	HR (per 100 cells/ul): 0.82 (p<0.05)
Bruyand [33**]	Cohort	4,194	HIV(+)	France	Any NADM	Duration low CD4	CD4<200: HR (per year)=1.16 (95% CI=1.03–1.30) CD4<500: HR (per year)=1.11 (95% CI=1.01–1.22)
Silverberg [32**]	RCT	5,472	HIV(+)	33 countries representing Asia; Africa; Australia; New Zealand; N. and S. America	Any NADM	CD4 nadir	No significant association (p>0.05)
Marin [68**]	Cohort	10,661	HIV(+) with known dates of seroconversion	Australia; Canada; 15 European countries	Any NADM (fatal)	CD4 nadir	<200 cells/ul: HR=2.7 (95% CI=1.1–6.6) 200–349 cells/ul: HR=3.2 (95% CI=1.4–7.2) ≥350 cells/ul (reference)
Monforte [70*]	Cohort	23,441	HIV(+)	Australia; USA; 21 European countries	Any NADM (fatal)	Current CD4	RR per doubling of CD4=0.61 (95% CI=0.57–0.66)
Bedimo [71**]	Cohort	100,260	HIV(+) / HIV(−) U.S. Veterans	USA	Multiple subtypes	CD4 at study entry	HIV(+) with any NADM, anal, and Hodgkins had lower CD4 vs. HIV(+) without cancer.
Engels [23**]	Registry match	57,350	HIV(+)	USA	Multiple subtypes	CD4 at HIV registration	No significant association (p>0.05) for any individual NADM
Patel [22**]	Cohort	54,780	HIV(+)	USA	Multiple subtypes	low CD4 nadir	Anal: RR=5.8; p=0.017 Colorectal: RR=6.3; p=0.013 Lung: RR=2.4; p=0.017
D'Souza [37**]	Cohort	6,972	HIV(+) and HIV(−) MSM	USA	Anal	CD4 nadir ≤200 cells/ul	HR=2.3 (95% CI=0.80–6.7)
Piketty [26**]	Cohort	86,322	HIV(+)	France	Anal	CD4 nadir	Lower risk with higher nadir CD4 (p>0.05)
Chaturvedi [27**]	Registry match	317,007	AIDS	USA	Lung	CD4 at AIDS registration	No significant association (p>0.05)
Kirk [28**]	Cohort	2,086	HIV(+) and HIV(−) IDU	USA	Lung (fatal)	CD4 nadir	No significant association (p>0.05)
b. Other measures of immune function
Nowicki [72*]	Cohort	1,817	HIV(+) women	USA	Any malignancy	NK, NKT, and CD8 %	Baseline markers not significant (p>0.05) Current NKT: HR (per % higher)=0.7 (95% CI=0.5–0.9)
Grulich [73**]	Meta- analysis	476,149	HIV(+) or AIDS and organ transplant recipients	Australia; Canada; Denmark; England; Finland; Italy; Scotland; Sweden; Switzerland; USA	Multiple subtypes	Elevated SIR in both populations	NADMs elevated in both groups were Hodgkin’s lymphoma, liver, stomach, vulva/vaginal, penis, anal, oral cavity/pharynx, non-melanoma skin, lip, esophagus, larynx, eye, lung, kidney cancers, multiple myeloma, leukemia
Serraino [35*]	Cohort	10,949	HIV(+) and organ transplant recipients	France; Italy	Multiple subtypes	Elevated SIR in both populations	NADMs elevated (p>0.05) in both groups were any NADM and liver cancer
Silverberg [32**]	RCT	5,472	HIV(+)	33 countries representing Asia; Africa; Australia; New Zealand; N. and S. America	Multiple subtypes	CD4 guided ART use vs. continuous ART	No significant association (p>0.05)

ART, antiretroviral therapy; HR, hazard ratio; MSM, men who have sex with men; IDU, injection drug users; NADM, non-AIDS-defining malignancy; RR, risk ratio