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СІМЕЙНІ ЛІКАРІ ТА ТЕРАПЕВТИ

НЕВРОЛОГИ, НЕЙРОХІРУРГИ, ЛІКАРІ ЗАГАЛЬНОЇ ПРАКТИКИ, СІМЕЙНІ ЛІКАРІ

КАРДІОЛОГИ, СІМЕЙНІ ЛІКАРІ, РЕВМАТОЛОГИ, НЕВРОЛОГИ, ЕНДОКРИНОЛОГИ

СТОМАТОЛОГИ

ІНФЕКЦІОНІСТИ, СІМЕЙНІ ЛІКАРІ, ПЕДІАТРИ, ГАСТРОЕНТЕРОЛОГИ, ГЕПАТОЛОГИ

ТРАВМАТОЛОГИ

ОНКОЛОГИ, (ОНКО-ГЕМАТОЛОГИ, ХІМІОТЕРАПЕВТИ, МАМОЛОГИ, ОНКО-ХІРУРГИ)

ЕНДОКРИНОЛОГИ, СІМЕЙНІ ЛІКАРІ, ПЕДІАТРИ, КАРДІОЛОГИ ТА ІНШІ СПЕЦІАЛІСТИ

ПЕДІАТРИ ТА СІМЕЙНІ ЛІКАРІ

АНЕСТЕЗІОЛОГИ, ХІРУРГИ

"Actual Infectology" 1 (6) 2015

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Study the causes of virologic failure in the early stages of art of hiv-infected patients

Authors: Liulchuk M.G. - State institution “The L.V.Gromashevsky Institute of Epidemiology and Infectious Disease of NAMS of Ukraine”, Kyiv, Ukraine

Categories: Infectious diseases

Sections: Clinical researches

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Introduction.

One indicator of the effectiveness of antiretroviral therapy (ART) is a viral load (VL) of HIV. At the first time (within the first 4 weeks) the antiretroviral drugs effect on virions of HIV in the blood (α-recession), then ARV drugs act on macrophages and dendrites cells of lymph follicles (β-recession). Beta recession is longer and less pronounced. The maximum antiviral effect is expected after 4-6 months of ART, so the level of VL HIV should be determined after 6 months of ART.

The increase in HIV viral load may be associated with the formation of HIV resistance to ARVs or it may be the case when the patient timely does not take antiretroviral drugs (so-called "low adherence to ART").

Purpose. The reasons of the virological ineffectiveness of antiretroviral therapy for HIV-infected patients in the early period of treatment were examined.

Materials and Methods

HIV genome sequencing was performed on the basis of laboratory leukemia virus SI " D.I.Ivanovskij Research Institute of Virology" (Moscow, Russia) using test kits «ViroSeqTM Genotyping System v.2.1» (Abbott, USA) according to the instructions.

Results and Discussion

Cohort study about determine the frequency of HIV mutations resistance to antiretroviral drugs in HIV-infected patients were organized. Criteria for selection of study participants were: confirmed diagnosis of HIV-infection; lack of experience taking ARVs; presence of indications for use of ART; informed consent to participate in research study. Results of the study groups were involved in 676 HIV-infected patients. These patients in 2009 started receiving ART. The 174 patients of this group discontinued the study. Most (50.6%) patients dropped out of the study because they had low level of adherence to treatment. Of the 174 patients who dropped out, (32,76 ± 3,56%) of people died. Data analysis showed that 42.11% of the patients died from HIV-associated TB.

Patients of the study were examined at the level of HIV VL 6 months after start of the treatment for determines the virological effectiveness of ART.

Established that the vast majority (70,02 ± 1,94%) HIV-infected patients the level of HIV viral load does not exceed 40 RNA copies / ml. However, in 33 (5,92 ± 1,00%) patients after 6 months of therapy the level of HIV in the blood plasma was more than 1000 RNA copies / ml.

21 sample of plasma from HIV-infected patients was analyzed for the presence of mutations of HIV resistance to antiretroviral drugs.

HIV resistance mutations were detected in 4 (from 6) samples of patients Crimean Republican AIDS Center (Table 1).

Table 1 - Results of the sequencing of blood samples of HIV-infected patients Crimean Republican AIDS Center

Patient’s code

sex

transmission of HIV

ART drugs combination

HIV resistance mutations

to PI

to NIRT

tо NNIRT

31АРК

m

IDUs

AZT/3TC/EFV

L10IL

no

no

42АРК

m

sexual

AZT/3TC/EFV

no

no

no

80АРК

m

IDUs

TDF/3TC/EFV

no

A62АV, K65R, М184МV, Т215А

K101HN, Y181C, G190S

84АРК

m

IDUs

TDF/FTC/EFV

no

K65R, D67DG

K101E, Y181CY, G190S

90АРК

m

IDUs

TDF/FTC/EFV

no

L74I, M184V, K219E

L100I, K101E, Y181C, G190S

91АРК

m

sexual

TDF/FTC/EFV

no

K65R, V75L, М184V

K101EK, G190S, M230LM

Most blood samples revealed a mutation M184V resistance. This mutation appears in the reverse transcriptase gene and secured against the backdrop of a lack of virological response to HIV nucleoside reverse transcriptase inhibitors (NRTIs), lamivudine (3TS) and emtricitabine (FTC) (HIV sensitivity to these drugs is reduced by more than 100 times). At the same time, M184V mutation significantly increases the sensitivity of the virus to azidothymidine (AZT), stavudine (d4T), tenofovir (TDF). This makes keeping the HIV strains with mutation M184V in the prevailing levels. So drugs 3TS and FTC are leaving as part of combination ARV drugs.

Another K65R mutation causes resistance to the average ABC, ddI, 3TS, FTC, low to d4T, leading hypersensitivity to AZT. The combination of mutations K65R and M184MV increases resistance virus to ABC and ddI, but greatly increases the sensitivity of HIV to AZT.

Table 1 shows that in all specimens revealed a mutation G190S, which causes resistance to the high level of efavirenz (EFV) and nevirapine (NVP). In this cause therapy drug from NNIRT group should be discontinued because taking this drug will increase the number of HIV resistance mutations to the NNIRT. A similar situation was with resistance mutations K101E / H / N, Y181CY.

The test results of blood samples of HIV-infected patients Nikolaev and Odessa regional AIDS centers showed similar data. In the two centers were tested 10 blood samples (5 of each), resistance mutations were found in only four. In Kyiv City AIDS Center were tested 6 blood samples and was found only 1 sample with HIV resistance mutations to antiretroviral drugs.

In general, mutations of HIV resistance were found only in 8 (38.1%) cases of 21. From remaining 13 (61.9%) patient’s viral load of HIV increased because those patients timely did not take antiretroviral drugs.

Conclusions

1. Integrated research on the detection frequency of mutations of HIV resistance in patients receiving ART, first held in Ukraine.

2.  Virological ineffectiveness of antiretroviral therapy in 5.92% of patients who received ARVs for 6 months was found.

3. On the basis of molecular genetic analysis of the HIV genome was found that among the factors influencing the formation of virological failure in the early stages of treatment, one of the most important are the low level of adherence of patient to therapy.



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