98 copies/1000 B-cells (n = 10). Notably, patients who received adjuvant alone “placebo” (i.e. alum) demonstrated an even higher EBV load (median 3.7 copies, n = 16) than those who received rgp160 (also with alum; median 2.1 copies, n = 26; Fig. 1B). In general HIV-infected patients showed a higher EBV-DNA load in their B-lymphocytes than controls. In the control group the median EBV load was 0.049 per 1000 B cells (n = 10, Fig. 1A), while the median value for all the HIV-l infected patients was forty times higher,

2.0 per 1000 B cells (n = 60), a highly significant difference (p < 0.0001). Sex, age, origin of the individuals, and insufficient antiretroviral treatment did not affect the EBV load. One patient had a confirmed diagnosis of lymphoma at the time of blood sampling. This patient's EBV load was 53 copies per 1.000 B cells. The inter-individual variation find more was large between HIV-1-patients, ranging over 10,000-fold (Fig. 1A), from 0.027 to 400 EBV copies per 1000 B cells. Forty percent (24/60) of the HIV-1 positive individuals had the same range of EBV load as the controls. The difference in EBV load between symptomatic and asymptomatic groups of HIV-1 patients was relatively small, however

a tendency to higher load in the asymptomatic group was noted [2.0 copies (n = 45) vs. 1.2 copies per 1000 B cells (n = 15), respectively]. The asymptomatic groups also showed a higher CD4 cell count. This paradoxical finding may be explained by vaccine effects, which will be discussed later. The Compound C clinical trial data from all the patient subgroups are summarised in Table 3. Immunised patients with a history of symptomatic primary HIV-infection (PHI) had a median value of 14 copies

per 1000 B cells (n = 8), while the immunised individuals with no such history had a significantly lower median value of 2.1 copies per 1000 B cells (n = 34, p < 0.05; Fig. 1B). For patients in the vaccine trials with an asymptomatic HIV-1 infection lasting for longer than ten years, EBV load was somewhat lower (median 1.5 copies, n = 8) in comparison to individuals with until an asymptomatic infection lasting for a shorter period of time (median 2.4 copies; n = 34). No statistically significant differences were found. Antibody titers to EBV-antigens were determined in all patients included in the vaccine trials, at the time of sampling for EBV-DNA-load. Nine patients had IgG anti-EA titers >1:80, ten anti-VCA titers >1:640 and three had elevated anti-p107 (EBNA 1)-titers in an ELISA-test. Although this did not correlate to EBV-DNA load, HIV-1 RNA levels or type of vaccine, the five patients with the highest levels of EBV DNA-load also had higher antibody titers. Thirty-three patients were also tested for EBV-DNA in blood plasma. No EBV-DNA was detected in any of these samples.