Introduction The UGT1A1*28 (rs8175347) polymorphism is associated with hyperbilirubinemia. The presence of 6 TA-repeats in the UGT1A1 gene promoter region corresponds to normal UGT1TA1 activity. A detection of 7 TA-repeats in hetero- or homozygous individuals [(TA)6/(TA)7 and (TA)7/(TA)7] is associated with lower UGT1TA1 activity, which may eventually result in the development of Gilbert syndrome and/or modified individual response to drugs metabolized by this enzyme. ATV contributes to the decreased levels of UGT1A1, which may lead to elevations of indirect bilirubin, jaundice and even to therapy discontinuation. We evaluated the prevalence of the UGT1A1*28 among HIV-infected patients and the dependence of the frequency and severity of AE during ATV treatment on individual genetic characteristics.Materials and Methods 47 HIV-infected patients was screen for UGT1A1 genotype and the presence of UGT1A1*28. All patients received ATV in the HAART regimen for 48 weeks. Changes in the total, direct and indirect bilirubin, ALT, AST, GGT and jaundice were evaluated. Statistical analysis was performed using Microsoft Office Excel for Windows XP Professional 2007 and Biostat.Results All patients were followed up in the AIDS Center (males 72.3%, median age 33 years, median CD4+ count-282 cells/µl (19.5%)). HBV/HCV was in 36.2% patients. Ten patients had risk factors that could affect bilirubin turnover (chronic cholecystitis, biliary dyskinesia, etc.). Genotype (TA)6/(TA)6 was found in 42.6% patients, (TA)6/(TA)7-42.6% and (TA)7/(TA)7-14.9%. Overall prevalence of UGT1A1*28 was 57.4%, and homozygous allele frequency was 14.9%. G3/4 of indirect bilirubin were detected in 36.2% patients [(TA)6/(TA)6 in 10–20%, (TA)6/(TA)7-25-40%, (TA)7/(TA)7-72-86%], and significant jaundice in 10.6% [80% with (TA)7/(TA)7]. The OR for hyperbilirubinemia>40 µmol/L in patients with heterozygous UGT1A1*28 was increased 3 times over patients without this allele (OR 3.07, 95% CI 1.54–4.6) and 34 times as compared with homozygotes (OR 33.9, 95% CI 31.45–36.35). The presence of additional risk factors increased the probability of G3/4 hyperbilirubinemia. No significant changes in the ALT, AST, and GGT levels were observed.ConclusionsThe risk of severe hyperbilirubinemia during ATV treatment is minimal for patients without UGT1A1*28 and no more than one additional risk factor and for patients with UGT1A1*28 and no additional risk factors; patients with homozygous genotype UGT1A1*28 are at the highest risk.

The aim of the study was to assess the efficacy and safety of ART regimens that included different doses of the drug 6НР with the reception of QD, in comparison with the scheme of ART, containing, PhAZT, to select the daily dose 6НР in conducting phase III clinical trials.Patients and methods. 125 patients were randomized to 25 people in 4 groups, depending on the daily dose of the drug 6НР (600, 800, 1000, 1200 mg), and in the comparison group (phosphazide). For a daily dose of the drug 6НР the study was blind. All patients, in addition to the studied drugs were receiving 3TC and EFV. The effectiveness of ART regimens was assessed by the proportion of patients with HIV RNA <50 copies/ml and CD4+lymphocyte increase after 24 weeks of therapy.Results. The use of ART scheme, which included 6НР + 3TС + EFV, was highly effective regardless of the daily dose of the drug 6НР, and is comparable to the effectiveness of the comparison mode (PhAZT+3TC+EFV). More than 95.5% of patients receiving 600 mg and 800 mg of the drug 6НР QD, after 24 weeks of therapy, the level of HIV RNA was < 50 copies/ml (in the comparison group – 87.5%). In patients of all groups there was a significant increase in the median CD4+lymphocytes. The maximum result of increasing the median CD4 + lymphocyte count (164 cells/µl) was observed in patients receiving the drug 6НР – 600 mg/day. All the studied modes was safe because of the 24-week study made up 94% of the patients receiving 6НР, and 96% of receiving PhAZT. Only 1 patient (1%) receiving the maximum daily dose 6НР (1200 mg), marked AES possibly related to study medication, and which led to the cancellation of the treatment.Conclusions. The effectiveness and safety of all modes of ART did not depend on the daily dose of the drug 6НР and was comparable to the comparison scheme, which included PhAZT. The maximum virological and immunological response after 24 weeks of therapy was achieved in patients receiving the drug 6НР at a dose of 600 mg QD in the ART scheme. The drug 6HP is recommended for phase III study in a daily dose of 600 mg in the ART.

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Разрабатываемые в США (DHHS) и Евросоюзе (EACS) рекомендации по лечению больных ВИЧ-инфек-цией являются наиболее авторитетными в мире и используются при разработке многих национальных, в том числе российских, рекомендаций. Особенностью рекомендаций Евросоюза и США является стро-гая научная обоснованность и ориентация на применение в странах с высоким уровнем дохода на душу населения. В процессе развития рекомендаций отмечалась тенденция по обновлению рекомендуемых ими препаратов на все более эффективные, безопасные и удобные в приеме, а также расширения по-казаний к назначению АРТ вплоть до рекомендации начинать ее всем больным ВИЧ-инфекцией неза-висимо от клинических проявлений и уровня CD4-лимфоцитов. В статье приводится анализ изменений рекомендаций за последние 6 лет, а также последние их версии. O.G. YURIN, MD, Prof., O.S. EFREMOVA, PhD in Medicine Central Research Institute of Epidemiology under Rospotrebnadzor, Moscow THE EUROPEAN AND AMERICAN GUIDELINES FOR TREATMENT OF HIV INFECTIONThe guidelines for treatment of patients with HIV infection developed in the United States (DHHS) and the European Union (EACS) are the most globally recognised. They are used in the development of many national guidelines, including those in Russia. The guidelines of the European Union and the United States are specific in that they are characterized by high scientific validity and target countries with high income per capita. In the process of the guidelines evolution, they tended to update the recommended drugs with more efficient, safe and easy to use medications; they expanded the list of indications for antiretroviral therapy to the extent that it was recommended to all HIV patients regardless of clinical manifestations and the level of CD4 cells. The article also analyzes the changes that the guidelines underwent over the past 6 years. There are recent versions of the guidelines.