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Introduction of the control system for the HIV medicinal resistance to antiretroviral preparations
Musabaev Erkin Isakovich, Research Institute of Virology, doctor of medical sciences, professor Bayjanov Allabergan Kadirovich, Research Institute of Virology, Ph. D. (candidate of Medical Science) E-mail: drbayjanov@mail.ru Mustafaeva Dildora Asadovna, Republican Center of Control of AIDS, Ph. D. (candidate of Medical Science) Mamatkulov Adxam Rustamjonovich, Research Institute of Virology, Researcher Kazakova Evgenia Ivanovna, Research Institute of Virology, Researcher
Introduction of the control system for the HIV medicinal resistance to antiretroviral preparations
Abstract: The development of the surveillance of the primary and acquired drug resistance of the human viral of immune deficit (HIV) to the antiretroviral (ARV) preparations among the people living with HIV (PLH) and introduction of the system of control into the practical health service. The strategy which is used by the system of health service includes the use of standardized and simplified schemes of treatment, which corresponds to the international standards and may be used in relation to the specific of the country [2; 3; 8]. Therefore there has been developed methodic recommendation on monitoring of the development of HIV drug resistance to ARV drugs [1]. Performance of the antiretroviral therapy (ART) without taking into account data about resistance to the used preparations may lead to the development of HIV drug crossed resistance to the majority of essential drugs and risk of the distribution of the HIV resistant strains among the general population, that raises a problem in the choice of effective scheme of treatment [4; 5; 6; 9]. Introduction of the system of identification and monitoring of the development of HIV drug resistance to ARV drugs into the clinical practice allows improvement of the quality of treatment and economic efficacy of the therapy in the patients with HIV-infection. Keywords: HIV, antiretroviral drugs, resistance, genotyping, monitoring.
Materials and methods. In order to study prevalence of the The age of the patients of the second group accounted
HIV strains resistance to ARV preparations among PLH beginning from 21 to 62 years (mean age 33.4 years). Males were 65, wom-ART - ofprimary resistance, the group included adults (> 18 years) en — 77. HIV viral load was from 500 to 56 020 946 copy/ml with HIV-infection, all persons beginning to receive ART for the first (mean 550 014 copies/ml).
time and patients with viral load more than 2000 copies/ml. at the The viral load of HIV RNA was determined with use of poly-
moment ofART beginning. The criteria for exclusion were patients merase chain reaction (PCR). For HIV genotyping with PCR already receiving ART and women receiving previously single dose method and further DNA sequencing the special test-system was of nevirapin during delivery. used. The viral RNA was isolated from plasma and was converted into
For studying of prevalence of the HIV strains resistant to ARV DNA, and some its sites was amplified with use of PCR. The PCR drugs among the PLH, receiving ART during 12 months with ac- underwent to sequencing for determination of the nucleotide se-quired resistance the group was composed of adults (> 18 years) quence which was compared with the nucleotide sequence of the with HIV-infection, all persons having ART during 12 months at the wild type viral genome for identification ofmutations associated with moment of inclusion into the investigation and patients with viral resistance. For interpretation of the results obtained the analysis of load more than 1000 copies/ml. Criteria for exclusion of the patients sequencing was performed with application of specialized program were age under 18 years. The blood plasma of the studied patients being in the free access in the Internet (for example, on the site [12]) was material for testing at identification of the HIV drug resistance for comparison of the spectrum of mutations revealed with dada of to ARV preparations. world computer bases containing information about interrelation-
There were only 375 patients with HIV-infection under our ship of the mutations revealed with clinical resistance [7; 10; 11]. observation. The HIV-infected persons were divided into 2 groups: Results and discussion. The results ofstudy of genotyping with
group 1 consisted of PLH beginning ART for determination of the consequent virus sequence there were received the following changes: HIV drug primary resistance to ARV preparations (n = 234), second among the studied patients from the first group HIV resistance to ARV group was composed of PLH, receiving ART during 12 months for preparations was revealed in 6 patients, that accounted for 2.56 %. determination of the acquired resistance (n = 141). Of 6 patients who had HIV resistance to antiretroviral prepara-
The age of the patients from the first group fluctuated tions in 5 patients there was noted resistance to nucleoside inhibitors from 18 to 65 years (mean age 35.7 years). Males were 119, of the reverse transcriptase, such preparations as nevirapin (NVP), women — 115. The viral load of HIV-infection was from 376 efavirents (EFV) and nelfinavir (NFV/r). Among which in 4 pato 7 451 796 copies/ml (mean 845 248 copies/ml). tients there was found HIV drugs resistant to preparations nevirapin
Section 5. Medical science
(NVR) and efavirentc (EFV). The attenuation of the HIV sensitivity to nevirapin (NVP) in one patient, and to nelfinavir (NFV/r) in the other patients was revealed.
It should be especially noted that among the 6 persons living with HIV in 5 patients during study of resistance of HIV to the nucleoside inhibitors of the reverse transcriptase the revealed high resistance to efavirentc (EFV) met only at the background of high resistance to nevirapin (NVP). In one case the HIV high resistance was registered to preparation nevirapin (NVP) in which to efavirentc (EFV) there was revealed HIV resistance of moderate level.
In 4.44 % of cases from the total quantity of the patients of the second group with revealed resistance to ARV preparations there was established HIV high resistance to protease inhibitors: in one case to nelfinavir (NFV/r) and in two cases to fosamprenavir (FPV/r) (Table 1).
Table 1. - Prevalence of the cases of HIV
In one patient from this group the HIV high resistance was revealed to all ARV preparations from the group of protease inhibitors: atazanavir (ATV/r), fosamprenavir (FPV/r), idinavir (IDV/r), lopinavir (LPV/r), nelfinavir (NFV/r), sakvinavir (SQV/r) and tip-ranavir (TPV/r). In the same patient there was found resistance to all ARV preparations of nucleosides and unneucleoside inhibitors of the reverse transcriptase (table 2).
The table 2 shows that the highest prevalence of the cases ofvi-rus resistance equally high revealed to the antiretroviral preparations emtricitabin (FTC) and lamividin (3TC), 46.8 % and 46.8 %, respectively. The lowest degree of HIV drug resistance was registered to azidotimidin (AZT) (7.09 %).
It was also revealed that the HIV drug resistance was revealed mostly frequent to nucleoside inhibitors of the reverse transcriptase (Table 3).
drug resistance to protease inhibitors
Parameter Drug name
ATV/r DRV/r FPV/r IDV/r LPV/r NFV/r SQV/r TPV/r
Number of cases 2 0 3 1 1 2 1 1
at % 1.42 0 2.13 0.71 0.71 1.42 0.71 0.71
Table 2. - Prevalence of the cases of HIV drug resistance to nucleoside inhibitors of the reverse transcriptase
Parameter Drug name
TDF FTC AZT D4T DDI 3TC ABC
Number of cases 24 66 10 13 35 66 36
at % 17.0 46.8 7.09 9.22 24.8 46.8 25.5
Table 3. - Frequency of the cases of HIV drug resistant to nucleoside inhibitors of the reverse transcriptase
Parameter Drug name
RPV EFV ETR NVP
Number of cases 25 78 12 85
at % 17.7 55.3 8.51 60.3
This table shows that in the patients of the second group with high frequency observed there was observed high drug resistance to such nucleoside inhibitors of the reverse transcriptase as azidotimidin (AZT) in 60.3 % cases and efavirence (EFV) in 55.3 % of cases.
It is necessary to note that though the primary resistance among the population accounted for 2.56 %, the acquired resistance with high frequency was revealed to many nucleoside and unnucleo-side inhibitors of the reserve transcriptase that may increase risk of the distribution to ARV resistant HIV drugs among the population.
Therefore, monitoring of the HIV drug resistance to antiretroviral therapy is one of the main directions in the prevention of the distribution of the viral resistant forms and in the specific therapy of the patients with HIV-infection.
Thus, there has been studied prevalence of the HIV-drug resistance to the known antiretroviral drugs as in the people, living with HIV not receiving ART so in the patients receiving ART during 12 hours. It was established that the primary resistance was observed in 2,56 % of case among the PLH not receiving ART, the high frequency of HIV drug resistance to many inhibitors of the HIV enzymes should aware about presence of risk of distribution of the
HIV resistant strains among the population. All above-described show necessity of identification of the factors resulting in insufficient ART with development of HIV drug resistance to ART drugs, that, in its turn, increase in efficacy of the antiretroviral therapy performed and results in improvement of the quality and duration of life in the patients with HIV-infection.
Conclusions:
1. Introduction of the surveillance system for the HIV drugs resistance to antiretroviral therapy and into the clinical practice allows determination of the prevalence of the HIV resistant strains both among the people living with HIV, not receiving ART and among he patients being on the background of therapy.
2. The results of the study of HIV drugs resistance to ART drugs show that primary resistance among the people living with HIV not receiving ART accounted only 2.56 %.
3. Analysis of the HIV drug resistance to ARV among the patients receiving ART, show presence of the viral strains resistant to many inhibitors of the viral enzymes that indicates about need in increase of measures for prevention of the distribution of the HIV resistant forms among the population.
References:
1. Atabekov N. S., Bayjanov A. K., Mustafaeva D. A. et al. Surveillance of HIV drug resistance to antiretroviral therapy (methodical rcom-mendations). - Tashkent, 2015. - 55 p.
2. Bobkova M. R. HIV drug resistance. - M.: Human, 2014. - 288 p.
3. Bennett D. E., Bertagnolio S., Sutherland D. and Gilks. C. F. The World Health Organization's global strategy for prevention and assessment of HIV drug resistance//Antivir Ther. - 2008. - 13, Suppl 2: 1-13.
4. Hallack R., Doherty L. E., Wethers J. A. and Parker M. M. Evaluation of dried blood spot specimens for HIV-1 drug-resistance testing using the Trugene HIV-1 genotyping assay//J Clin Virol. - 2008. - 41: 283-287.
Protective efficiency of "Phosphogliv" at high active antiretroviral therapy in patients with HIV-infection...
5. Leober M., Kaderali L., Schnnhuth A., Schräder R. A fractional programming approach to efficient DNA melting temperature calcula-tion//Bioinformatics. - 2005. - 21: 2375-2382.
6. Surveillance of HIV drug resistance in adults receiving ART (acquired HIV drug resistance), July 2014.
7. Surveillance of HIV drug resistance in adults initiating antiretroviral therapy (pre-treatment HIV drug resistance), July 2014.
8. Shafer R. W., Schapiro J. M. Drug resistance and antiretroviral drug development//J. Antimicr. Chemother. - 2005. - Vol. 55. - P. 817-820.
9. World Health Organization. Surveillance of HIV drug resistance in adults initiating antiretroviral therapy (pre-treatment HIV drug resistance)//Concept note. - July 2014.
10. World Health Organization. Surveillance of HIV drug resistance in adults receiving ART (Aquired HIV drug resistance)//Concept note. - July 2014.
11. World Health Organization global strategy for the surveillance and monitoring of HIV drug resistance//An update. - November 2012.
12. [Electronic resource]. - Available from: http://hivdb6.stanford.edu
Bayjanov Allabergan Kadirovich, Research Institute of Virology, Ph. D. (candidate of Medical Science) E-mail: drbayjanov@mail.ru
Protective efficiency of "Phosphogliv" at high active antiretroviral therapy in patients with HIV-infection, associated with chronic viral hepatitis C
Abstract: Purpose of research was assessment of the hepatoprotector efficacy in high active antiretroviral therapy (HAART) in the patients with HIV-infection associated with chronic viral hepatitis C. There has been studied efficacy of the drug hepatoprotector "Phosphogliv" in the complex of specific HAART in the patients with HIV-infection associated with chronic viral hepatitis C, and it has been established that the positive dynamics has been noted as in relation to clinical symptoms (attenuation and/or elimination of clinical expressions of disorders in the hepatobiliary system), so as in the biochemical characteristics, which has been expressed by reduction in the contents of total bilirubin, activity of transaminases, thymol test, AP and GGTP, insignificant reduction of the contents of cholesterol and glucose in the blood.
Keywords: HIV-infection, phosphogliv, high active antiretroviral therapy, chronic viral hepatitis C, treatment.
Antiretroviral drugs are hepatotoxic [1; 3; 6; 10]. There was chosen drug "Phosphogliv" with purpose of reduction of hepa-totoxicity of antiretroviral drugs in treatment of the patients with HIV-infection associated with chronic viral hepatitis C [5; 9]. Phosphogliv is a hepatoprotector. Phospholipids have ability to effect on the state of the cellular membranes as their integral components and have strong hepatoprotective effect on the liver. This drug prevents atrophy of the cellular structures in the liver, normalizes activity of the alaninaminotransferase (ALT) and aspartataminotransfer-ase (AST). Phosphogliv is used in dose 2 capsule 3 times a day during 3 months in hepatitis of various etiology. Taking into account that one of the unfavourable effect of HAART is hepatotoxicity, the study of efficacy of Phosphogliv with purpose of reduction of hepatotoxicity of HAART in the patients with HIV-infection associated with chronic viral hepatitis C seems to be rational.
Material and methods. Our surveillance covered only 65 patients with HIV-infection associated with chronic viral hepatitis C at the age of16 to 58 years. The patients were divided into 2 groups: studied group consisted of patients with HIV-infection associated with chronic viral hepatitis C, who were prescribed phosphogliv additionally to HAART ( n = 36), control group was composed of patients with HIV-infection associated with chronic viral hepatitis C who received HAART without phosphogliv (n = 29).
The patients were comparable in relation to sex, age, health state, clinical stages of HIV-infection, presence of accompanied and opportunistic infections. In the both groups the general health state was evaluated as of moderate severity.
The diagnosis of "chronic viral hepatitis C" in the studied patients was verified on the basis of epidemiological, clinical and
laboratory data (by method of immunoenzymatic analysis there were revealed antiHCV in blood, with method ofpolymerase chain reaction the quantitative and qualitative determination ofviral hepatitis C RNA — HCV RNA was performed).
HAART was prescribed for the patients in the both groups according to the recommendations of the World Health Organization (WHO). The patients of the both groups received schemes HAART without hepatotoxic drug nevirapin. The patients in the both groups did not receive specific antiviral preparations against viral hepatitis C.
According to a number of authors hepatic toxicity of the antiretroviral preparations is often observed in the first 4 weeks (to 3 months after prescription of HAART) [2; 4; 7; 8].
So, the patients were examined before onset and one month after HAART prescription.
The complex clinical-biochemical examination included assessment of the treatment efficacy by dynamics of the clinical symptoms of the hepatobiliary system impairment and biochemical blood parameters.
The determination of the total protein in the blood serum was performed with use of biuretic method, and albumin concentration in the blood serum was measured by unified colorimetric method. There were used reagents of the Manufacture OOO "Olvex Diagnosticum" (Russia).
Activity ofAlT, AsT, y-glutamiltranspeptidasa (GGTP) and alkaline phosphatase (AP) in the blood serum was determined with kinetic US method (IFCC) with kits of reagents of firm "Herbos Diagnostika" (Croatia).
The level of bilirubin total and its fractions in the blood serum was determined with method of Endrassic-Grof.
