[Current antiretroviral therapy: A review].

The article presents an overview of clinical recommendations for currant antiretroviral therapy. Currently, the current preferred first-line antiretroviral therapy regimens are combinations of 2 or 3 antiretroviral drugs (ARVs) in one tablet with a frequency of administration 1 time per day and, as a rule, include drugs of the 2nd generation (integrase inhibitors or non-nucleoside reverse transcriptase inhibitors). These schemes have high efficiency and a good genetic barrier in the development of HIV resistance mutations. HIV protease inhibitors are used as alternative regimens. Schemes with the least number and spectrum of side effects, no effect on metabolic processes and minimal drug interactions have advantages. Switching patients to injectable therapy regimens with a frequency of administration of drugs once every 2 months can significantly improve the quality of life of patients and, accordingly, adherence to their treatment. The development and introduction of new classes of ARVs into clinical practice ensures the suppression of HIV replication in most patients with HIV strains resistant to drugs of the main groups of ARVs (nucleoside/nucleotide reverse transcriptase.

[Cutaneous and visceral leishmaniasis in patients with HIV infection in Russia. Case report].

The article contains information on the problem of the combined course of HIV infection and leishmaniasis: a number of statistical and overview data in the world. It also presents a brief description of known cases of HIV patients with leishmaniasis in the Russian Federation. In all cases the diagnostics of leishmaniasis was difficult due to the lack of alertness of physicians to this illness, as well as poor knowledge of epidemiological situation of leishmaniasis. All patients with visceral leishmaniasis but one caught it during their stay in Crimea. Cutaneous leishmaniasis was described in HIV infection in the Russian Federation for the second time and is associated with the patient's residence in the Chechen Republic.

[Parameters of the CD4-Cell count and viral load in human immunodeficiency virus type 1 (HIV-1) infected patients].

In this work the specific features of parameters of plasma CD4 T-lymphocytes count and level virus RNA in the HIV-infected patients were studied. 22% correlation between reduction of CD4 cell count and an increase in virus RNA level was observed in persons that did not receive antiretroviral treatment during the third HIV-infection phase. During this phase of infection patients exhibited a growth of the median value of virus load in cases of both rise as decline in CD4 cell count during long observation period. In addition, towards the end of the observation period, the percentage of patients with virus load > 3.3 Ig copies/ml considerably expanded. 43% correlation between CD4 cell count and duration of the HIV-infection was detected during the fourth infection phase in persons that did not receive antiretroviral treatment. Most of the patients in the third and the fourth infection phases had essential CD4 cell count growth during antiretroviral treatment. Best values were observed in patients with the initial value of CD4 > 400 cells/µl belonging to the third HIV-infection phase.

[Impact of etiotropic therapy on the immune status of patients with HIV infection and tuberculosis].

AIM: To evaluate the impact of etiotropic therapy on the immunological efficiency of treatment in patients with HIV infection in relation to the presence of active tuberculosis (TB) and the baseline count of CD4+ lymphocytes. SUBJECTS AND METHODS: A total of 239 HIV-infected patients were examined and divided into 3 groups: 1) 103 HIV-infected patients with TB who received both anti-TB therapy (ATBT) and antiretroviral therapy (ART); 2) 46 HIV-infected patients with TB who did not receive ART during TB treatment; 3) 90 HIV-infected patients without TB who used ART for the first time. CD4+ lymphocyte counts were measured by flow cytofluorometry in all the patients before and 4 and 12 weeks after treatment. RESULTS: Analysis of an increment in CD4+ lymphocyte counts in the HIV-infected patients with tuberculosis showed that those who had very low baseline CD4+ lymphocyte counts (median, 78 cells/µl) were noted to have significant positive changes (median, +146 cells/µl) at 12 weeks of ART. Even without ART, effective ATBT in the patients with a well preserved immune system (> 350 CD4+ cells/µl) in turn resulted in a substantial increase in CD4+ lymphocyte counts (median, +187 cells/µl following 12-week ATBT). At the same time, 10.9% of the patients showed a decrease in the baseline CD4+ lymphocyte counts during progression or delay in the tuberculosis process, which required that ART should be promptly performed. CONCLUSION: The investigation of the time course of changes in the increment of CD4+ lymphocyte counts revealed a swifter response to ART as their rapid increment in patients with coinfection (HIV infection concurrent with TB) than that in those with HIV monoinfection. When the baseline CD4+ lymphocyte counts are over 350 cells/µl, the start of ART should be delayed until TB treatment is completed.

[The efficacy and safety of a therapy regimen including raltegravir and a fixed dose combination of lamivudine and abacavir in previously rifabutin-treated patients with tuberculosis and HIV infection].

AIM: To evaluate the efficiency and safety of using raltegravir (RAL) twice daily in conjunction with a once-daily fixed dose combination of abacavir (ABC)/lamivudine (3TC) in patients with HIV infection and active tuberculosis who have not previously received antiretroviral therapy (ART) and have taken rifabutin as antituberculosis therapy (ATT). SUBJECTS AND METHODS: The efficiency of ART was evaluated in 28 patients from a change in HIV RNA levels and from an increase in CD4+ lymphocyte counts during 48-week treatment that had been completed by 15 (53.6%) patients. The main reason for therapy discontinuation was that the patients returned to the use psychoactive agents. RESULTS: After 24 and 48 weeks of ART, the level of HIV RNA reached the undetectable values (less than 50 copies/ml) in 81.25 and 75% of the patients, respectively (according to an analysis including the patients who had completed the study in conformity with the requirements of the protocol). In only 2 patients, the virological therapy proved to be ineffective, which was likely to be associated with noncompliance with drug therapy. Following 24- and 48-week therapy, the increase in median CD4+ lymphocyte counts was 70 and 208.5 per µl, respectively. The concurrent use of ART and ATT caused positive changes in the lung skiagraphic pattern in 92.9% of the patients and complete resolution of lung tissue infiltration in 71.4%. Mixed infection ended in a fatal outcome caused by a progressive tuberculous process in 3 (10.7%) patients, in 2 of them within the first 8 weeks of treatment. The concomitant use of ATT including rifabutin and an ART (RAL + ABC/3TC) regimen was safe since one patient was noted to have a RAL-related adverse event (AE) (an allergic reaction) and caused the patient to discontinue therapy. ATT was not discontinued because of AE in any case. CONCLUSION: The ART regimen containing RAL and a fixed dose combination of ABC/3TC for adult patients with tuberculosis concurrent with HIV infection who are on combined therapy using rifabutin for tuberculosis may be recommended for the treatment of this category of patients.

[The value of changes in CD8+CD28+ and CD4+CD28+ cells in patients with HIV infection concurrent with tuberculosis during treatment].

AIM: To study the proportion of CD8+CD28+ and CD4+CD28+ cells among the CD8+ and CD4+ lymphocytes and the changes in these indicators in patients with HIV infection/tuberculosis (HIV/TB) versus those with HIV infection and those with TB. SUBJECTS AND METHODS: One hundred and six persons were examined and included into 4 study groups: 1) 39 patients with concomitant HIV/TB; 2) 25 patients with HIV monoinfection without TB who had not previously received antiretroviral therapy; 3) 17 patients with TB without HIV infection; 4) 25 healthy individuals (a control group). RESULTS: CD28 expression was found to be much more reduced on the CD8 lymphocytes than that on the CD4 ones. This is likely to be due to earlier CD8 lymphocyte dysfunction in both the patients with HIV infection and those with HIV/TB although the CD4 cell is the basic virus target. CONCLUSION: The study of the proportion of CD8+CD28+ cells among the CD8 lymphocytes is of more informative value than the determination of that of CD4+CD28+ among the CD4 lymphocytes.

[Use of maraviroc, the first CCR5 receptor antagonist, in HIV treatment regimens].

The paper gives the results of international trials of and guidelines for the use of maraviroc, the first CCR5 receptor antagonist, in treatment regimens for HIV-infected patients. The trials have convincingly shown that the maraviroc-containing antiretroviral therapy (ART) regimens are highly effective and safe for R5-tropic HIV-infected patients regardless of previous ART, baseline HIV RNA levels, and CD4+ lymphocyte count. Maraviroc can be recommended for HIV-infected patients who have previously received ART and who have been found to have a R5-tropic virus. The changes in the ART regimen and inclusion of maraviroc may be associated with both an ineffective previous treatment regimen and therapy-induced adverse events. In 2012, Russia's first reagent kit for the determination of HIV tropism was put to tests and registered at the Russian Inspectorate for the Protection of Consumer Rights and Human Welfare.

[Diagnosis of tuberculous pericarditis in patients with HIV-infection].

AIM: To study specific features of the incidence, course and diagnosis of tuberculosis pericarditis (TP) in patients with HIV-infection. MATERIAL AND METHODS: We analysed results of diagnosis of 304 primary patients with organ tuberculosis in combination with HIV infection treated in Moscow tuberculosis hospital N 7 in 2006-2010. CD4 lymphocyte count median in tuberculosis onset was 140 in 1 mcl, 63.2% patients had a baseline level of CD4 lymphocytes under 200 in 1 mcl. RESULTS: TP incidence in primary patients with tuberculosis and HIV-infection was 6.3% while in patients with tuberculosis of multiple locations--13.7%. Cardiac tamponade symptoms were registered only in one case. Pericardial effusion was classified as moderate and large in 68.4% patients. Patients with large effusion (more than 20 mm in isolation of pericardial leaves) have undergone diagnostic pericardiocentesis and, in some cases, microdrainage. Sensitivity of exudate test for M. tuberculosis DNA with use of polymerase chain reaction was 100%. CONCLUSION: Active surgical policy in massive effusion tuberculosis pericarditis in line with adequate antituberculosis and antiretrovirus therapy in HIV-infected patients results in rapid resorption of the effusion.

[Current course of pneumocystic pneumonia in HIV-infected patients].

AIM: To describe clinical and laboratory characteristics of pneumocystic pneumonia (PP) in patients with HIV-infection for improvement of diagnosis quality. MATERIAL AND METHODS: Detailed examination was performed in 111 HIV-infected patients with suggested diagnosis of PP. The following investigations were made: clinical, x-ray examinations, total count and biochemical blood tests, enzyme immunoassay, indirect immunofluorescence reaction (II-FR) for Pneumocystis jiroveci antigens in bronchoalveolar lavage fluid (BALF) or induced sputum. For diagnosis of other secondary diseases PCR was used for investigation of BALF and bronchial biopsy to detect DNA of Mycobacterium tuberculosis complex, Candida albicans, Cytomegalovirus, Toxoplasma gondii, Mycoplasma spa., Herpes simplex I, II. DNA of cytomegalovirus in blood was detected with PCR. Microscopic tests of the sputum were conducted for detection of acid-resistant mycobacteria. RESULTS: PP was associated with other secondary diseases in 59% patients (pulmonary tuberculosis ---16%, CMV pneumonia--31%, combination of all the lesions--5%). PP diagnosis was cancelled and pulmonary tuberculosis was diagnosed in 12 patients. In combination of PP with other pathology dominant were symptoms observed in PP monoinfection and only effective anti-pneumocystic treatment revealed signs of comorbid pathology. Tuberculosis patients had weaker signs of respiratory failure, symmetric bilateral interstitial or small-focal alterations were detected less frequently. CONCLUSION: Current PP course characteristics in HIV infection are identified. In clinical diagnosis of PP special attention should be paid to data complex especially to increasing respiratory failure, high ESR, elevated lactate dehydrogenase, low blood pO2, fast response to ex juvantibus therapy. The most effective method of the diagnosis verification--BALF IIFR.

[Analysis of lethal outcomes in patients with newly-diagnosed tuberculosis of the respiratory organs in combination with HIV-infection].

AIM: To analyse lethal outcomes in patients with newly-diagnosed respiratory tuberculosis comorbid with HIV-infection depending on initial count of CD4+ lymphocytes. MATERIAL AND METHODS: Of 304 HIV patients with newly-diagnosed tuberculosis treated in Moscow Tubercusis Hospital N 7 in 2006-2010, 40 (13.2%) patients died. Tuberculosis diagnosis was made after detection of M. tuberculosis (MT) by different tests, MT DNA in different biological material, histological verification or by effectiveness of specific antituberculous therapy. Postmortem examinations were made according to the protocol. RESULTS: Significant differences were detected in patients with initial count of CD4+ lymphocytes less than 50 in 1 mcl. Specific CNS affection was found in patients with initial lymphocyte count CD4+ less than 100 in 1 mcl. Most of autopsy examinations registered generalized acutely progressive tuberculosis with multiple lesions of internal organs and lymph nodes (LN). Microscopy revealed obscure morphological picture of specific inflammation with prevalence of alternative-exudative tissue reactions in the absence of a productive inflammation component. Cases with submiliary dissemination which was invisible in macroscopic examination due to a bright picture of exudative tissue reaction (rare plethora of the lungs, alveolar and interstitial edema, perifocal inflammatory reaction of nonspecific reactive nature) and small size of the lesions. The comparison of clinical and autopsy diagnoses revealed that involvement of intrathoracic LN and miliary dissemination, according to autopsy, occurred much more frequently than shown by antemortem standard x-ray examination of the chest. CONCLUSION: It is strongly recommended to perform computed tomography of the chest in all HIV-infected patients with long-term fever but without visible alterations on chest x-ray.

[Raltegravir is the first HIV integrase inhibitor as part of antiretroviral treatment regimens].

The paper gives the results of the largest international studies demonstrating the efficacy and safety of Raltegravir as part of antiretroviral treatment (ARVT) regimens in both patients starting therapy (STARTMRK study) and those pretreated with antiretroviral drugs (BENCHMRK study). The advantage of Raltegravir over Efavirens is the lower incidence of adverse central nervous system reactions. Based on the results of published investigations, specialists from the USA and European Union have incorporated the first HIV integrase inhibitor Raltegravir into a first-line ARTV regimen. Raltegravir is the drug of choice and should be used in special categories of patients, such as those with chronic hepatitis C or fat metabolic disturbances.

[The course and treatment of chronic hepatitis B in HIV-infected patients].

The paper reviews the data available in the literature on patients with mixed hepatitis B virus (HBV) and HIV infection, its course and outcomes. The unity of the mechanisms of contamination with HBV and HIV increases the likelihood of these infections in patients. About 70% of HIV-infected patients are carriers of the markers, the presence of which is indicative of current or previous HBV infection. An average of 7.6% of HIV-infected patients were diagnosed as having chronic hepatitis B (CHB) in West Europe and North America. The notification rate of CHB in adult HIV-infected patients was 5-7% in the Russian Federation. Most specialists report that HIV-infected patients have a severer course of HBV. Mixed HBV and HIV infection, and low CD4+ lymphocyte count in particular, increase the risk for death from hepatic diseases and there is evident hepatotoxicity during antiretroviral therapy. The management of patients with mixed HBV and HIV infection is determined by indications for therapy for both HIV infection and CHV infection, by the availability of double-action antiviral drugs (that suppress either HIV or HBV replication), by the development of their resistance in one or both viruses. Indications and preferable variants of using various treatment regimens are given.

[Treatment of infection caused by human immunodeficiency virus in the Russian Federation].

AIM: To study efficacy and safety of highly active antiretrovirus treatment (HAAT) used in the Russian Federation for development of recommendations for HIV infection treatment. MATERIAL AND METHODS: A total of 285 patients with chronic HIV infection and 42 patients with acute HIV infection participated in investigation of efficacy and safety of different HAAT schemes in 1997-2008. Efficacy of the treatment was assessed by percentage of the patients who had HIV RNA undetectable by the test system (< 400 copy/ml) after 24-48 treatment weeks, by a mean reduction of HIV RNA in blood plasma and an increase in the number of CD4-lymphocytes in 1 mcl of blood. RESULTS: A 12-year experience in antiretrovirus therapy administration for management of HIV infection is reviewed. Efficacy and safety of Russian antiretrovirus drug Phosphaside in HAAT schemes are shown in patients with both chronic and acute HIV infection. The model of HIV patients consulting before the treatment, psychological support during the treatment, methods of individual and group consulting, conception of the school for patients on HAAT are presented. Recommendations are proposed for administration of antiretroviral therapy and a model of calculation of the number of HIV-infected patients in need of antiretroviral therapy in Russia. Basing on the results of investigations on efficacy and safety of HAAT schemes, the physicians of the National Anti-AIDS Center have developed clinical recommendations, guidelines on the treatment of HIV infection, standards of medical care for HIV-infected patients.

[Use of nanocolonies for detection of minimal residual disease in patients with leukemia t(8;21)].

A complete diagnostic procedure was developed that allows single molecules of mRNA AML1-ETO to be detected in samples of whole blood and bone marrow of the leukemia t(8;21)(q22;q22) patients. The procedure includes: a method for preservation of biological samples ensuring the RNA integrity; an improved method for isolation of RNA from the unfractionated whole blood and bone marrow; an optimized reverse transcription; and the use of nanocolonies for detection and enumeration of RNA target molecules. The developed procedure is the first one that provides for determination of the absolute titer of an RNA target without reference to a control (housekeeping) gene, and significantly increases sensitivity, precision and reliability of detection of the minimal residual disease at a leukemia associated with known chromosomal translocation.

[Express hybridization of molecular colonies with fluorescent probes].

DNA colonies formed during PCR in a polyacrylamide gel and RNA colonies grown in an agarose gel containing Qbeta replicase can be identified using the procedure of transfer of molecular colonies onto a nylon membrane followed by membrane hybridization with fluorescent oligonucleotide probes. The suggested improvements significantly simplify and accelerate the procedure. By the example of a chimeric AML1-ETO sequence, a marker of frequently occurring leukemia, the express hybridization method was shown to allow the rapid identification of single molecules and the determination of titers of DNA and RNA targets. Hybridization with a mixture of two oligonucleotide probes labeled with different fluorophores complementary to components of the chimeric molecule ensures the identification of molecular colonies containing both parts of the chimeric sequence and improves the specificity of diagnostics.

[Pulmonary diseases in patients with HIV infection].

AIM: To characterize the spectrum, incidence rate and features of pulmonary pathology in HIV-infected inpatients with reference to a fall in the count of CD4-lymphocytes. MATERIAL AND METHODS: A total of 2370 patients with HIV infection admitted to Moscow infectious hospital N 2 were examined. The protocol of examination included: standard diagnostic tests, bronchoscopy with examination of bronchoalveolar lavage and bronchial biopsies for genetic markers of basic pulmonary disease pathogens, assessment of external respiration function by spirometry. By the count of CD4-lymphocytes in the blood (> 500 cells/mcl; 500-200 cells/mcl and < 200 cells/mcl) the patients with pulmonary pathology were divided into groups 1, 2 and 3. RESULTS: Affection of the lower respiratory tract (LRT) was detected in 1209 (51%) patients. Incidence, etiological spectrum and severity of LRT lesions increased significantly with aggravation of immunological disorders. The patients of group 1 were affected more frequently with bacterial bronchitis, pneumonia (88.2%), group 2 patients - with bacterial pneumonia (67.1%) and pulmonary tuberculosis (28.1%), group 3 - with tuberculosis including generalized forms (53.9%), cytomegalovirus infection (11.2%), pneumocystosis (7.2%). Combined pulmonary pathology was diagnosed in 25% cases. CONCLUSION: Changes in external respiration function were most evident in pneumocystosis and tuberculosis, but they were most persistent in cytomegaloviral lesion of the lungs. Some tuberculosis and CMV infection patients exhibited ventilatory disorders prior to clinical and x-ray symptoms, this suggests prognostic significance of spirometry.

[Chronic hepatitis C treatment with pegilated interferon alpha2a and ribavirin in patients with HIV-infection].

AIM: To study efficacy and safety of combined therapy of chronic hepatitis C (CHC) with pegilated interferon-alpha2a in combination with ribavirin at early stages of CHC and HIV-infection untreated with highly active antiretroviral therapy (HAART). MATERIAL AND METHODS: An open, nonrandomized, retrospective and prospective trial included 50 patients with subclinical HIV infection (stage 3; n = 47) and the stage of secondary diseases 4A at a remission phase untreated with HAART. The patients were given pegilated interferon-alpha2a and ribavirin for 48 weeks. RESULTS: The above combined treatment was highly effective, comparable to the results achieved in CHC patients without HIV infection. Tolerance was satisfactory. Most frequent side effects were thrombocytopenia, leukopenia and neutropenia. These were not the cause of the patients withdrawal (n = 9; 18%). The treatment was discontinued because of depression and long-term fever. A significant reduction of CD4+ lymphocytes count was observed but clinical manifestations of HIV-infection progress were not reported. CONCLUSION: CHC treatment in HIV-infected patients should be started as early as possible after diagnosis of chronic hepatitis, before symptoms of cirrhosis. In this case probability of achievement of a stable virusological response in CHC patients with HIV-infection is similar to that in CHC patients without HIV infection.

[Retention of nucleic acid integrity in guanidine thiocyanate lysates of whole blood].

High-molecular-mass RNA and DNA have been shown to retain their integrity for three days at room temperature, no less than two weeks at +4 degrees C, and more than a year at -20 degrees C when whole blood samples are stored as lysates containing 4 M guanidine thiocyanate. Storage time at room temperature can be prolonged at least up to 14 days if nucleic acids were precipitated by two volumes of isopropanol. This preservation technique allows storage and transportation of samples at ambient temperature and is completely compatible with the procedure of subsequent isolation of nucleic acids.