The effect of monoclonal or ion‐exchange purified factor VIII concentrate on HIV disease progression: a prospective cohort comparison

Abstract

The CD4 count has been reported to decline less rapidly in HIV-infected haemophiliacs treated with monoclonally purified factor VIII concentrates than in those using intermediate-purity concentrates. No survival advantage has been demonstrated for this effect, and it is unclear whether this effect occurs with all high-purity concentrates. Two cohorts of patients with severe haemophilia A and HIV treated with either ion-exchange-purified or monoclonally-purified concentrates were compared. The CD4 count, survival, AIDS-defining illnesses, CDC category and anti-retroviral therapy were recorded at 6-monthly intervals for 3 years following the change from intermediate to high-purity factor VIII. 116 patients were recruited, 37 of whom were treated with an ion-exchange purified factor VIII concentrate at three centres, mean (SD) age 31.1 (12.2) years, and 79 were treated with monoclonally purified factor VIII concentrate at two centres, mean (SD) age 29.8 (11.2) years. At the start of the study the median CD4 count was (monoclonal v ion-exchange) 0.30 v 0.16 x 10(9)/l. The CD4 count declined in both arms to a median of (monoclonal v ion-exchange) 0.16 v 0.08 x 10(9)/l at the final visit. Analysis of the (CD4 count)(1/2) over time, using a random coefficients model, found that the mean (SE) rates of decline were not statistically significantly different in the two treatment groups (monoclonal v ion exchange: -0.050 (0.008) v -0.034 (0.011) (CD4 count)(1/2) per year, P = 0.24). No statistically significant difference in survival (log-rank test: P = 0.33) was found. There was no difference in the proportion of individuals experiencing one or more AIDS-defining illnesses (P = 0.32) or in the proportion progressing to CDC category IV (P = 0.28) during the study. The CD4 count declined during the study at a rate similar to that previously reported in patients treated with intermediate-purity factor VIII concentrate, and there was no evidence of any difference between the two treatment groups.

TGF‐β is not the principal immunosuppressive component in coagulation factor concentrates

“…The cause of the immune changes in haemophiliacs remains uncertain ( Goedert et al , 1989 ; De Biasi et al , 1991 ; Hay et al , 1998 ). Some of these may have arisen as a direct effect of non‐factor VIII or IX components of therapeutic concentrates on the patient's lymphocyte subsets and their function.…”

“…These immune disturbances may be caused by the massive protein load, specific impurities, or the effects of viruses in the therapeutic concentrates ( Schulman, 1991; Wadhwa et al , 1994 ; Evans et al , 1995 ; Pasi et al , 1995 ). Whether the observed changes in the immune system are of clinical importance remains controversial ( Goedert et al , 1989 ; De Biasi et al , 1991 ; Hay et al , 1998 ).…”

Guidelines on the selection and use of therapeutic products to treat haemophilia and other hereditary bleeding disorders

“…There is anecdotal evidence for reduction in allergic reactions associated with the use of high‐purity materials. Several studies suggest benefit in HIV disease progression with high‐purity products produced using immunoaffinity chromatography [27,28] but these findings were not confirmed in a further study [29] and changes in CD4 counts were not associated with reduction in progression to AIDS or death [30]. Furthermore, any such effects of high‐purity concentrates are insignificant compared to the immune reconstitution produced by highly active antiretroviral therapy (HAART).…”