Euromedica 2011 E. Ivanova N. Vorobeva efficacy and safety of hematological of phosphazide of highly active antiretroviraltherapy for hiv-infected patients: 48 weeks of treatment"

E. Ivanova N. Vorobeva	EFFICACY AND SAFETY OF HEMATOLOGICAL OF PHOSPHAZIDE OF HIGHLY ACTIVE ANTIRETROVIRAL THERAPY FOR HIV-INFECTED PATIENTS: 48 WEEKS OF TREATMENT
	AIDS & Infectious Diseases Center, Perm, Russia Perm State Academy of Medicine, Russia

Key-words: HIV, antiretroviral therapy, hematological safety, Phosphazide

Background: explore the effectiveness and the hematological safety of the Russian antiretroviral drug Phosphazide (FAZT, Nikavir) - pro drug zidovudine regimens of HIV-infection.

Methods: In 2009 - 2010 of the AIDS & Infectious Diseases Center, Perm, Russia conducted the study on the effectiveness and the hematological safety of Phosphazide in Highly Active Antiretroviral Therapy (HAART) for HIV-infected patients was conducted. The study included 36 patients 19-38 years, 23 women and 13 men with the A2 (2 pers.), B1 (2 pers.), B2 (30 pers.) and B3 (2 pers.) stages of HIV-infection (CDC, USA, 1993). They were divided into two groups: the ﬁrst - 18 patients with mild or moderate severity anemia and received Phosphazide (FAZT)+3TC+EFV; the second group, with no hematological disorders, 18 patients received - CBV(ZDV/3TC)+EFV. In all patients, RNA HIV was > 100.000 copies/ml and CD4+ <350 cells/mm³. Treatment was conducted for 48 weeks according to national protocols of treatment of HIV infected adults. Phosphazide (NIRT class) produced by “AZT FARMA K.B.” ltd. - Phosphorylated derivative of zidovudine, was given per os in the form of tablets of 0.4 g twice a day. 3TC and EFV were used at standard doses. The effectiveness of treatment was evaluated by clinical, immunological and virological criteria. CD4+ blood cells were counted with “FA CS Calibur” BD using ﬂow cytometry and Simultest IMK Plus (“Beston Dickenson”, USA) monoclonal antibodies. Pretreatment and post 4-12-24-36-48 weeks treatment RNA HIV concentration was estimated with real time PCR method and Amplicor HIV-1 Monitor v.1.5; “Khoffman-La Roch” (sensitivity ~ 500 copies/ml). Monitoring the dynamics of changes in clinical blood was performed with hematologic analyser MEK-7222 w.

Results: Phosphazide therapy, resulted in reduction of viral load by 1.5-2 log₁₀, starting from 4 weeks of treatment. This effect was more expressed in group 1 patients. In the next 48 weeks the ﬁgure was ~ 500 copies/ ml, indicating the virological efﬁcacy. Prior to the start of therapy the average level of CD4+ lymphocytes was 155+28x10⁶/l, 4-12 weeks there was a tendency to increase CD4 cell counts to 209+26x10⁶/l, respectively. At 24 weeks the ﬁgure was statistically signiﬁcant 298+34x10⁶/l (p<0.05), indicating the restoration of the immune status of patients. After 48 weeks of therapy cellular restoration rate was higher (by 2.4 times) then in group 2 patients (by 1.6 times). There was no clinical progression of HIV infection.

After 48 weeks of treatment, signiﬁcant reduction in peripheral blood parameters in patients from both groups was found. In contrast, hemoglobin levels in patients from the ﬁrst group of observations have signiﬁcantly increased; starting from 4 weeks of antiretroviral therapy including Phosphazide compared with baseline, and remained stable until the end of the study. There was a tendency to reduce the level of platelets, leukocytes and lymphocytes in groups’ patients at 4-12 weeks from the start of HAART.

Conclusions: therapeutic efﬁcacy of Phosphazide – pro drug zidovudine in antiretroviral therapy, was established most the potential drug. This allows regarding Phosphazide in the treatment of HIV-infection. We can recommend alternative antiretroviral regimens including Phosphazide for patients with anemia of mild to moderate severity.