The prevalence of antibodies against lytic KSHV antigens was 9% (six out of 66) in those with non-Hodgkin’s lymphoma and 6% (four out of 66) in their matched controls (OR=1.5, 95% CI 0.45.3;Table 6). == Table 6. antibodies against KSHV latent (LANA) and lytic (K8.1) antigens and against EBV (VCA) antigens were investigated in relation to subsequent risks of cancer by calculating odds ratios (OR) using conditional logistic regression. Latent antibodies against KSHV were detectable among 38% (72 out of 189) of Kaposi’s sarcoma cases and 12% (23 out of 189) of their controls (OR=4.4, 95% confidence intervals (CI) 2.38.3,P<0.001). The OR for Kaposi's sarcoma increased with increasing antilatent KSHV antibody titre (21for trend=32.2,P<0.001). Lytic antibodies against KSHV were detectable among 33% (61 out of 187) of Kaposi's sarcoma cases and 19% (36 out of 187) of their controls (OR=2.0, 95% CI 1.23.4,P=0.003) and the OR Rabbit Polyclonal to DNA-PK for Kaposi’s sarcoma increased with increasing antilytic KSHV antibody titre (21for trend=6.2,P=0.02). Virtually, all cases and controls had anti-EBV antibodies detected and the OR for non-Hodgkin’s lymphoma associated with a doubling of the anti-EBV antibody titre was estimated to increase by a multiplicative factor of 1 1.3 (95% CI 0.91.7,P=0.1). Kaposi’s sarcoma was not associated with antibody levels against EBV (P=0.4) and non-Hodgkin’s lymphoma was not associated with antibodies against KSHV (latentP=0.3; lyticP=0.5). Adjustment for CD4 count at the time of sample collection made no material difference to any of the results. In conclusion, among human immunodeficiency virus infected people, high levels of antibodies against KSHV latent and lytic antigens are strongly associated with subsequent risk of Kaposi’s sarcoma but not non-Hodgkin’s lymphoma. Antibody titre to EBV does not appear to be strongly associated with subsequent risk of Kaposi’s sarcoma or non-Hodgkin’s lymphoma in HIV infected people. Keywords:Kaposi’s sarcoma, non-Hodgkin’s lymphoma, EpsteinBarr virus, Kaposi’s sarcoma-associated herpesvirus, NH125 human immunodeficiency virus The risk of Kaposi’s sarcoma and non-Hodgkin’s lymphoma is increased in human immunodeficiency virus-1 (HIV) infection (Beral and Newton, 1998). Both of these tumours are also associated with a herpesvirus infection: Kaposi’s sarcoma has been consistently linked with Kaposi’s sarcoma associated herpesvirus (KSHV or human herpesvirus-8 (HHV-8)), while non-Hodgkin’s lymphoma has been linked with another gamma-herpesvirus, the EpsteinBarr virus (EBV) (Boshoff, 1999;Brookset al, 1999). However, there are few data from prospective studies and the role of antibody titres in predicting the subsequent risk of cancer is unclear. The aim of the research described here was to investigate using data collected prospectively, the evolution of antibody responses to KSHV and to EBV in HIV infected individuals, who subsequently NH125 developed Kaposi’s sarcoma or non-Hodgkin’s lymphoma compared to that in HIV infected controls without cancer. == MATERIALS AND METHODS == == Study population == UK participants in the Concorde (1994), Delta (1996) and Alpha (1996) NH125 randomised controlled trials of antiretroviral therapy for HIV infection were followed for the development of AIDS-defining cancers. Cases were all participants who did not have a tumour at trial entry, but who subsequently developed Kaposi’s sarcoma (n=189) or non-Hodgkin’s lymphoma (n=67). The diagnosis of cancer was made at the participating clinical centre according to criteria used in each of the three clinical trials and all data used in these analyses were anonymised. No additional histological confirmation of diagnosis was available for the purposes of this investigation, nor were any details of the specific subtypes of non-Hodgkin’s lymphoma available. Further details of the individual trials can be found elsewhere (Concorde Co-ordinating Committee, 1994;Delta Co-ordinating Committee, 1996;Alpha International Co-ordinating Committee, 1996). For each person with incident cancer, a control was randomly selected from trial participants, who had not developed cancer after the same period of active follow-up (methods of follow-up are described in the individual trial reports), after matching by trial, age group (10 years), sex, HIV transmission group (homosexual, intravenous drug user, haemophiliac, blood transfusion, other blood contact or heterosexual), treatment group used in each trial (zidovudine (AZT) or placebo [Concorde], low-dose or high-dose didanosine NH125 ddI [Alpha], AZT or AZT+ddI or AZT+zalcitabine (ddC) [Delta]), ethnicity (Caucasian, Indian subcontinent, West Indian, African, other or mixed) and length of time from entry into the trial until diagnosis of cancer in cases or the same time interval in controls (3 months). At least one sample of stored serum was available for all cases and their matched controls. In general, these were taken at least 6 months before the date of diagnosis of cancer in cases, or at the same period of follow-up as the cases to whom they were matched for controls referred to as pseudo-diagnosis. Sera were stored centrally at 70C and shipped on dry ice to University College London for antibody analyses. A proportion of cases and controls had.