Safety and Efficacy of Prolastin®-C (α1Proteinase Inhibitor, α1PI) in Human Immunodeficiency Virus-Infected Subjects

This study protocol is designed to investigate the benefit of a well-tolerated, FDA approved biological product that has been extensively used in a different patient population.

For more than 20 years, α1proteinase inhibitor (α1PI or α1antitrypsin) therapy has been the standard treatment for people with insufficient α1PI blood levels. This disorder, also known as α1antitrypsin deficiency, was previously thought to be caused only as an inherited trait due to the gene PIzz. Recent evidence shows that it can also be an acquired disease. Specifically, individuals with HIV-1 disease have been found to have severely low α1PI blood levels (Bristow et al., 2001; Bristow et al., 2010; Bristow et al., 2012). Many people with the inherited version of α1PI deficiency eventually develop emphysema, and among individuals with HIV-1 disease, 90% have acquired α1PI deficiency. Whether they go on to develop emphysema is still unresolved.

HIV-1 infected individuals are the first patient population identified so far in which severe α1PI deficiency is acquired through infection rather than being inherited.

It was found that a decrease in α1PI blood levels is directly correlated to a decrease in CD4 lymphocytes (Bristow et al., 2001; Bristow et al., 2012): In a pilot study to determine whether α1PI therapy might benefit the CD4 counts in HIV-1 infected patients (Clinicaltrials.gov NCT01370018), HIV-1 patients with infection-related α1PI deficiency received weekly α1PI therapy (120mg/kg) for a period of 8 weeks and results were compared with those of patients having the inherited version of α1PI deficiency who were simultaneously receiving weekly α1PI therapy (60mg/kg). None of the patients in the study had ever previously received α1PI therapy. It was found that CD4 cells rose to normal levels following 2 weeks of intravenous α1PI therapy with no adverse effects observed in the HIV-1 patients (n=3) or the control group of HIV-1 uninfected, α1PI deficiency patients (n=2). The new crop of CD4 cells were functional, capable of fighting infection, and appeared to be generated from bone marrow-derived stem cells (Bristow et al., 2010). As a bonus, it was found in the HIV-1 patients that LDL levels (bad cholesterol) decreased and HDL levels (good cholesterol) increased {Bristow et al., in review).

The information gained from the initial pilot study will be incorporated into this study design to further characterize the mechanism of lymphocyte renewal and to increase the number of patients observed. Only minor modifications to the pilot protocol are proposed including the sample size, addition of volunteers not receiving therapy, and a double-blind design: Ten (10) HIV-1 infected patients will be dosed with PROLASTIN®-C (Grifols Therapeutics Inc.), five (5) will be dosed with placebo, and five (5) uninfected volunteers not receiving therapy will be monitored.