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Efficacy and safety of highly active antiretroviral therapy comprising tenofovir in patients with HIV infection
Among the associated diseases chronic virus hepatitis B was diagnosed in 18 (17.3%), chronic virus hepatitis C — in 35 (33.6%), B+D — in 8 (7.70%) and B+C+D — in 6 (5.80%) patients.
Therefore, the HIV-infection in patients under natural course of the disease is characterized by pathological process progressive course with progress of the generalized forms of tuberculosis and cytomegalovirus infection, systemic candidiasis, pneumocystic pneumonia, herpes simplex with frequent recurrence, which frequently result in severe consequences.
Conclusions:
1. The opportunistic diseases under the HIV-infection were often manifested by tuberculosis with process generalization, candidiasis with esophageal affection, cytomegalovirus infection with chorioretinitis complications and the risk of detachment of the retina, and herpes simplex with frequent recurrence;
2. Severe forms of the opportunistic diseases were mainly observed in the HIV-infected patients under the 4th clinical stage of the disease and under CD4-lymphocites count less than 200 cells/mcl;
3. Among the associated pathologies, the HIV-infection was frequently accompanied by chronic virus hepatitis C.
References:
1. Buchacz K. AIDS-defining opportunistic illnesses in US patients, - 1994-2007: A cohort study. AIDS - 2010. Jun 19; 24:1549.
2. Bushman F. D., Nabel G. J., Swanstrom R. HIV: From biology to prevention and treatment. - Cold Spring Harbor, New York, USA: Cold Spring Harbor Laboratory Press, - 2012. - P. 321-343.
3. Clark P. M., Karagoz T., Apikogly-Rabus S., Izzettin F. V. Effect of pharmacist-led patient education on adherence to tuberculosis treat-ment//Amer. J. Health-System Pharmacy. - 2007. - Vol. 64, N 5. - P. 497-505.
4. Duerst R. Innate immunity to herpes simplex virus type 2//Viral immunology - 2003 - Vol. 16, № 4 - P. 475-490.
5. Friedrich B. M., Dziuba N., Li G. et. Host factors mediating HIV-1 replication. Virus Res. - 2011 Nov; 161 (2): 101-14.
6. Hall J. C., Hall B. J., Cockerell C. J. HIV/AIDS in the post-HAART era: Manifestations, treatment, and epidemiology. - Shelton, CT, USA: People's Medical Publishing House - USA, - 2011. - P. 389-403.
7. Joshi D., O'Grady J., Dieterich D. et al. Increasing burden of liver disease in patients with HIV infection. Lancet, - 2011; - 377: 11981209.
8. Lever A. M., Jeang K. T. Insights into cellular factors that requlate HIV-1 replication in human cells. Biochemistry. - 2011 Feb - 15; 50(6): 920-31.
9. Saag M. S., Chambers H. F., Eliopoulos G. M., Gilbert D. N., Moellering R. C. The Sanford guide to HIV/AIDS therapy - 2012. - Sper-ryville, VA, USA: Antimicrobial Therapy Inc., - 2012. - P. 214.
DOI: http://dx.doi.org/10.20534/ESR-16-9.10-79-81
Bayjanov Allabergan Kadirovich, Research Institute of Virology, Ph.D. (candidate of Medical Science) E-mail: [email protected]
Efficacy and safety of highly active antiretroviral therapy comprising tenofovir in patients with HIV infection
Abstract: The objective of the study was to evaluate the effectiveness and safety of highly active antiretroviral therapy regimens containing tenofovir — TDF in HIV patients. Three classes of antiretroviral agents today are commonly used for the specific treatment of patients with HIV: nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors (1, 5, 7). The other drugs of the same class — nucleoside reverse transcriptase inhibitors — were developed in the following years (3, 4). One of the current nucleoside reverse transcriptase inhibitor is Tenofovir (2). Inclusion of Tenofovir drug into antiretroviral therapies leads to suppression of the replicative capacity of human immunodeficiency virus. The nucleoside inhibitors bind stronger to reverse transcriptase than to host cell DNA polymerases. This provides them with a relatively selective effect on the virus. The drug Tenofovir (TDF) in 2001 was approved for use as part of antiretroviral therapy (ART) for the treatment of patients with HIV infection (6).
Key words: antiretroviral therapy, tenofovir, viral load, nucleotide and non-nucleoside reverse transcriptase inhibitor.
Materials and methods. In accordance with the objectives of this study we totally examined 101 patients with HIV infection admitted to the hospital of the Research Institute of Virology.
Among 101 HIV-infected patients forty-five were men and 56 were women (44,5% and 55,5%), respectively. Patients' age ranged from 21 to 61 years. The average age of the examined patients was 42,5 years. The diagnosis of HIV infection among the patients examined was established based on generally accepted clinical and epidemiological data, and further confirmed in the Republican AIDS Center by laboratory detection of specific antibodies to
the human immunodeficiency virus and its proteins using ELISA and immunoblotting. All patients were on antiretroviral therapy containing tenofovir.
The observation of the patients in the course of treatment included the collection of epidemiological history, medical history, clinical examination, evaluation of the severity of the principal disease and the severity of clinical symptoms, and the presence of opportunistic infections and comorbidities. Patients' clinical, immunological and virological indicators were studied at the 6th months after antiretroviral therapy. Monitoring the effectiveness
Sectiom 6. Medical science
of antiretroviral therapy was performed using clinical and laboratory criteria.
Results and discussion. The study results showed that patients with the most commonly found diseases such as persistent fever of unknown origin, recurrent aphthous stomatitis, herpes infection, oral candidiasis, Kaposi's sarcoma, Pneumocystis pneumonia, HIV
encephalopathy, oropharyngeal candidiasis, weight loss of more than 10% body weight. Among the surveyed HIV-infected patients 5 (4,95%) had peripheral neuropathy. 25 (24,7%) patients revealed the history of injecting drug use.
Distribution by the route of transmission is represented in Figure № 1 (parenteral, sexual, unknown):
parenteral sexual
Figure 1. Distribution
The observed patients have been administered the following HAART regimens, containing tenofovir: TDF/FTC+EFV — 26 (25.7%), TDF/FTC+LPV/r — 13 (12.9%), TDF/FTC+NVP — 1 (0,99%), TDF+3TC+EFV — 44 (43,6%), TDF+3TC+LPV/r — 11 (10,9%), TDF+3TC+NVP — 6 (5,94%).
Evaluation of effectiveness of tenofovir containing HAART have shown virologie and immunologic efficacy: in 90,1% of patients at 6 months after the start of treatment, the mean HIV viral
5,00%-4,50%-4,00%-3,50%-3,00%-2,50%-2,00%-1,50%-1,00%-0,50%-0,00%-
by route of transmission
load in the blood was <1000 copies/ml and the average content of T-lymphocytes (CD4 cells) — 345,0 cells/ml.
Virologic failure was detected in 10 (9,90%) patients, who received the following regimens: TDF/FTC+LPV/r - 2 (1,98%) patients, TDF/FTC+EFV - 1 (0,99%) patient, TDF+3TC+EFV -4 (3,96%) patients, TDF+3TC+NVP - 1 (0,99%) and TDF+3TC + +LPV/r — 2 (1,98%) patients (fig. 1).
TDF/FTC+LPV/r TDF/FTC+EFV TDF+3TC+EFV TDF+3TC+NVP TDF+3TC+LPV/r
Figure 2. Virological failure of highly active antiretroviral
4 patients (3,96%) showed impaired liver function as elevated liver enzymes — increased content of alanine aminotransferase (ALT) (from 42,5 mmol/l to 154,3 mmol/l, with an average of 74,7 mmol/l). In 6 (5,94%) patients urine protein — proteinuria was found (from protein traces up to a level of 0,169 g/l), 6 (5,94%) patients had elevated levels of serum creatinine (from 169,9 mmol/l to 191,9 mmol/l, with the average level of 179,7 mmol/l), which indicate a potential kidney disease with damaged filtration function (possibly due to nephrotoxic effect of tenofovir included in the therapy regimens).
The blood test of the patients showed a slight decrease in hemoglobin content (mean 97,9 g/l), RBC (mean 3.26x10 12/l) WBC (mean 4,45x10 12/l) and a slight increase in erythrocyte sedimentation rate (ESR) (mean 19,3 mm/h).
The viral load of human immunodeficiency virus in the blood was determined from 500 copies/ml and 82,625 copies/ml (mean
therapy containing tenofovir in patients with HIV infection
3620,1 copies/ml). The content of T-lymphocytes (CD4 cells) in the blood was between 4 cells/ml to 1328 cells/ml (average was 257,1 cells/ml).
During clinical observation in the course of the disease among the examined patients the most frequently present clinical symptoms were nausea in 53 (52,5%) patients, vomiting (sometimes recurrent) in 19 (18,8%) patients, dizziness in 67 (66,3%) patients and bloating — flatulence in 58 (57,4%) patients.
Thus, analyzing the data, we can say that highly active antiret-roviral therapy containing the drug — tenofovir in HIV-infected patients is effective. Despite the effectiveness of therapy, some patients observed in the course of treatment demonstrated some some clinical and laboratory findings pertaining renal and hepatic functional damage, which is important to consider in when administering tenofovir containing ART regimens.
Indirect influence of hormonal status on the development of ischemic insult and its gender peculiarities
Conclusions:
1. Clinical and laboratory efficiency was identified in administration of highly active antiretroviral regimens containing the drug — tenofovir.
2. Adverse effects of highly active antiretroviral therapy regimens containing tenofovir, manifested in nausea, vomiting, bloating and dizziness.
3. Laboratory changes appeared in mild anemia, elevated en-symes (increased levels of alanine aminotransferase) and increased creatinine in the blood, which should be taken into considered when administering the antiretroviral therapy to the HIV patients with kidney and/or liver diseases.
4. Administration of antiretroviral regimens containing tenofovir, considering efficacy and safety allows to enhance the quality of highly active antiretroviral therapy for HIV infection.
References:
1. Bushman F. D., Nabel G. J., Swanstrom R. HIV: From biology to prevention and treatment. - Cold Spring Harbor, New York, USA: Cold Spring Harbor Laboratory Press, - 2012. - P. 321-343.
2. Daar E., Tierney C., Fischl M. et al. ACTG 5202: final results ofABC/3TC or TDF/FTC with either EFV or ATV/r in treatment-naive HIV-infected patients. Program and abstracts of the 17th Conference on Retroviruses and Opportunistic Infections. February, 16-19. 2010. San Francisco, California. Abstract, - 59 LB.
3. Hall J. C., Hall B. J., Cockerell C. J. HIV/AIDS in the post-HAART era: Manifestations, treatment, and epidemiology. - Shelton, CT, USA: People's Medical Publishing House - USA, 2011. - P. 389-403.
4. McComsey G., Kitch D., Daar E. et al. Bone and limb fat outcomes of ACTG A5224s, a substudy of ACTG A5202: a prospective, randomized, partially blinded phase III trial of ABC/3TC or TDF/FTC with EFV or ATV/r for initial treatment of HIV-1 infection. Program and abstracts of the 17th Conference on Retroviruses and Opportunistic Infections. February, - 16-19. - 2010. San Francisco. Abstract 106 LB.
5. Saag M. S., Chambers H. F., Eliopoulos G. M., Gilbert D. N., Moellering R. C. The Sanford guide to HIV/AIDS therapy 2012. - Sper-ryville, VA, USA: Antimicrobial Therapy Inc., - 2012. - P. 214.
6. Shafer R. W., Schapiro J. M. Drug resistance and antiretroviral drug development in patients with HIV infection//J. Antimicrob. Chemother. - 2005. - Vol. 55. - P. 817-820.
7. Volberding P. A., Greene W. C., Lange J. M. A., Gallant J. E., Sewankambo N. Sande's HIV/AIDS medicine: Medical management of AIDS - 2013. - Elsevier. - P. 133-191.
DOI: http://dx.doi.org/10.20534/ESR-16-9.10-81-83
VakhabovaNargiza Maksudovna, senior scientific assistant, Neurology department applicant,
Tashkent Medical Academy E-mail: [email protected]
Indirect influence of hormonal status on the development of ischemic insult and its gender peculiarities
Abstract: Hypercortisolemia immediately participated in pathogenetic mechanisms of ischemia deteriorating clinical progress of the disease in patients with ischemic insult. We revealed negative impact of low concentrations of oestradiolum and testosterone on the development and severity of ischemic insult progressing. Keywords: ischemic insult, hormonal status, gender peculiarities.
Ischemic insult (II) is one of the causes of high rate mortality and invalidation of people of workable age; and that conditions the necessity of the study of the factors effecting the progress and outcome of cerebral vascular process.
It is known, that acute stress developing in II causes activation of hypothalamus-petuitary-adrenal system (HPAS) with further increase of glucocorticoids (GC) in blood [1; 4; 5]. In several researches negative effects of hyper cortisolemia, observed in the conditions of excessive or long-lasting stress, were studied, and the interrelation of high concentrations of GC and hyperglycemia (HG) (rr) in acute period of insult was underlined [6]. The existing contradictions in the assessment of the parameters of stress reaction in patients with II, and define the importance of the further study of cortisol metabolism in that category of patients [7; 11].
Significant attention in references is paid to the study of the impact of sexual hormones such as oestradiolum and testosterone on the pathogenesis of brain infarction. It is known and doubtless fact
that, men suffer cardiac diseases more often; though scientists offered the explanation of that phenomenon for the first time. According to the results of the study performed in Lester University, Great Britain, it happens due to sexual hormones [2].
Estrogen hormones play a part of protective factors in ischemic insult. Some experimental studies illustrate that status, in details showing molecular mechanisms and conditions of protective function of that group of hormones. It was determined that, in the conditions of increased physiological level of estradiol (proestrus) CA1 neurons of hippocampus were less injured by the common cerebral-vascular ischemia [10].
Clinical study of the amount of thyroxin, triiodothyronine, thyrotropin, ACTH (etc.), in patients with acute ischemic insult revealed "low triiodothyronine syndrome" and increase of thyrotropin, ACTH, and rennin concentration on the 2nd day of insult; amount of thyroxin was increased on the 7th day of the disease [3; 4].
