Impact of human immunodeficiency virus infection on the course of hepatitis C virus infection: A meta-analysis

AIM: To analyze the influence of human immunodeficiency virus (HIV) infection on the course of hepatitis C virus (HCV) infection. METHODS: We performed a meta-analysis to quantify the effect of HIV co-infection on progressive liver disease in patients with HCV infection. Published studies in the English or Chinese-language medical literature involving cohorts of HIV-negative and -positive patients coinfected with HCV were obtained by searching the PUBMED, EMBASE and CBM. Data were extracted independently from relevant studies by 2 investigators and used in a fixed-effect meta analysis to determine the difference in the course of HCV infection in the 2 groups. RESULTS: Twenty-nine trails involving 16 750 patients were identified including the outcome of histological fibrosis or cirrhosis or de-compensated liver disease or hepatocellular carcinoma or death. These studies yielded a combined adjusted odds ratio (OR) of 3.40 [95% confidence interval (CI) = 2.45 and 4.73]. Of note, studies that examined histological fibrosis/ cirrhosis, decompensated liver disease, hepatocellular carcinoma or death had a pooled OR of 1.47 (95% CI = 1.27 and 1.70), 5.45 (95% CI = 2.54 and 11.71), 0.76 (95% CI = 0.50 and 1.14), and 3.60 (95% CI = 3.12 and 4.15), respectively. CONCLUSION: Without highly active antiretroviral therapies (HAART), HIV accelerates HCV diseaseprogression, including death, histological fibrosis/ cirrhosis and decompensated liver disease. However, the rate of hepatocellular carcinoma is similar in persons who had HCV infection and were positive for HIV or negative for HIV.

Safety of lamivudine treatment for chronic hepatitis B in early pregnancy

AIM:To evaluate the safety of lamivudine(LAM) treatment for chronic hepatitis B in early pregnancy.METHODS:A total of 92 pregnant women who received LAM treatment either before pregnancy or in early pregnancy were enrolled in this study.All of the pregnant women volunteered to take lamivudine during pregnancy and were not co-infected with hepatitis C virus,human immunodeficiency virus,cytomegalovirus,or other viruses.All infants received passiveactive immunoprophylaxis with 200 IU hepatitis B immunoglobulin and three doses of 10 μg hepatitis B vaccines(0-1-6 mo) according to the guidelines for the prevention and treatment of chronic hepatitis B.Adverse events were observed throughout the entire pregnancy and perinatal period,and the effectiveness of lamivudine treatment for blocking mother-to-infant transmission of hepatitis B virus(HBV) was evaluated.All adverse events in mothers and infants during pregnancy and the perinatal period and the HBV motherto-infant transmission blocking rate were compared with the literature.RESULTS:Among the 92 pregnant women,spontaneous abortions occurred in 11 cases,while 3 mothers had a second pregnancy after the initial abortion;72 mothers delivered 73 live infants,of whom 68 infants were followed up for no less than 6 mo,and 12 mothers were still pregnant.During pregnancy,the main maternal adverse events were vaginitis(12/72,16.7%),spontaneous abortion(11/95,11.6%),and gestational diabetes(6/72,8.3%);only one case had 1-2 degree elevation of the creatine kinase level(195 U/L).During the perinatal period,the main maternal adverse events were premature rupture of the membranes(8/72,11.1%),preterm delivery(5/72,6.9%),and meconium staining of the amniotic fluid(4/72,5.6%).In addition,2 infants were found to have congenital abnormalities;1 had a scalp hemangioma that did not change in size until 7 mo,and the other had early cerebral palsy,but with rehabilitation training,the infant's motor functions became totally normal at 2 years of age.The incidence of adverse events among the mothers or abnormalities in the infants was not higher than that of normal mothers or HBV-infected mothers who did not receive lamivudine treatment.In only 2 cases,mother-to-infant transmission blocking failed;the blocking rate was 97.1%(66/68),which was higher than has been previously reported.CONCLUSION:Lamivudine treatment is safe for chronic HBV-infected pregnant mothers and their fetuses with a gestational age of less than 12 wk or throughout the entire pregnancy.

Acute hepatitis C in a chronically HIV-infected patient:Evolution of different viral genomic regions

AIM: To analyze the molecular evolution of different viral genomic regions of HCV in an acute HCV infected patient chronically infected with HIV through a 42-month follow-up.METHODS: Serum samples of a chronically HIV infected patient that seroconverted to anti HCV antibodies were sequenced, from the event of superinfection through a period of 17 months and in a late sample (42nd month). Hypervariable genomic regions of HIV (V3 loop of the gp120) and HCV (HVR-1 on the E2 glycoprotein gene) were studied. In order to analyze genomic regions involved in different biological functions and with the cellular immune response, HCV core and NS5A were also chosen to be sequenced. Amplification of the different regions was done by RT-PCR and directly sequenced. Confirmation of sequences was done on reamplified material. Nucleotide sequences of the different time points were aligned with CLUSTAL W 1.5, and the corresponding amino acid ones were deduced.RESULTS: Hypervariable genomic regions of both viruses (HVR1 and gp120 V3 loop) presented several nonsynonymous changes but, while in the gp120 V3 loop mutations were detected in the sample obtained right after HCV superinfection and maintained throughout, they occurred following a sequential and cumulative pattern in the HVR1. In the NS5A region of HCV, two amino acid changes were detected during the follow-up period, whereas the core region presented several amino acid replacements, once the HCV chronic infection had been established.CONCLUSION: During the HIV-HCV superinfection, each genomic region analyzed shows a different evolutionary pattem.Most of the nucleotide substitutions observed are nonsynonymous and clustered in previously described epitopes,thus suggesting an immune-driven evolutionary process.

Significant increase in HBV, HCV, HIV and syphilis infections among blood donors in West Bengal, Eastern India 2004-2005: Exploratory screening reveals high frequency of occult HBV infection

AIM: To evaluate the prevalence of markers of hepatitis B virus (HBV) and hepatitis C virus (HCV) and human immunodeficiency virus (HIV) among blood donors in Kolkata, Eastern India for two consecutive years and to conduct a pilot study to explore the presence of HBV DNA among hepatitis B surface antigen (HBsAg) negative but anti-HBc positive blood donors. METHODS: Seroprevalence of HBsAg, anti-HCV and anti-HIV was studied among 113 051 and 106 695 voluntary blood donors screened in 2004 and 2005, respectively. Moreover, a pilot study on 1027 HBsAg negative donors was carried out for evaluating the presence of HBV DNA by PCR on HBsAg negative/anti- HBc positive donors. RESULTS: A statistically significant increase in the prevalence of HBV (1448 vs 1768, P < 0.001), HIV (262 vs 374, P < 0.001), HCV (314 vs 372, P = 0.003) and syphilis (772 vs 853, P = 0.001) infections was noted among blood donors of Kolkata West Bengal in 2005 as compared to 2004. Moreover, the exploratory study on 1027 HBsAg negative donors revealed that 188 (18.3%)of them were anti-HBc positive out of which 21% were positive for HBV DNA. CONCLUSION: The findings of this study underscore the significantly increasing endemicity of hepatitis viruses, syphilis and HIV among the voluntary blood donors of our community. The pilot study indicates a high rate of prevalence of HBV DNA among HBsAg negative/anti-HBc positive donors and thus emphasizes the need for a more sensitive and stringent screening algorithm for blood donations.

Indinavir Resistance Evolution in One Human Immunodeficiency Virus Type 1 Infected Patient Revealed by Single-Genome Amplification

Human Immunodeficiency Virus Type 1 exists in vivo as quasispecies, and one of the genome's characteristics is its diversity. During the antiretroviral therapy, drug resistance is the main obstacle to effective viral prevention. Understanding the molecular evolution process is fundamental to analyze the mechanism of drug resistance and develop a strategy to minimize resistance. Objective: The molecular evolution of drug resistance of one patient who had received reverse transcriptase inhibitors for a long time and had treatment which replaced Nevirapine with Indinavir was analyzed, with the aim of observing the drug resistance evolution pathway. Methods: The patient, XLF, was followed-up for six successive times. The viral populations were amplified and sequenced by single-genome amplification. All the sequences were submitted to the Stanford HIV Drug Resistance Database for the analysis of genotypic drug resistance. Results: 149 entire protease and 171 entire reverse transcriptase sequences were obtained from these samples, and all sequences were identified as subtype B. Before the patient received Indinavir, the viral population only had some polymorphisms in the protease sequences. After the patient began Indinavir treatment, the variants carrying polymorphisms declined while variants carrying the secondary mutation G73S gained the advantage. As therapy was prolonged, G73S was combined with M46I/L90M to form a resistance pattern M46I/G73S/L90M, which then became the dominant population. 97.9% of variants had the M46I/G73S/L90M pattern at XLF6. During the emergence of protease inhibitors resistance, reverse transcriptase inhibitors resistance maintained high levels. Conclusion: Indinavirresistance evolution was observed by single-genome amplification. During the course of changing the regimen to incorporate Indinavir, the G73S mutation occurred and was combined with M46I/L90M.

Pancreatic tuberculosis in a human immunodeficiency virus positive patient:A case report

Despite the increased incidence of tuberculosis related to human immunodeficiency virus (HIV) in recent decades, pancreatic tuberculosis has rarely been described. We report a case of pancreatic tuberculosis in a 39-year- old African man who presented with progressive dysphagia, vomiting, weight loss and productive cough, accompanied by localized epigastric pain and one episode of melena. HIV-1 testing was positive and lymphocyte subset profile showed CD4 count of 9/mm3. Abdominal computed tomography (CT) scan with contrast revealed a cystic mass in the body of the pancreas, significant portal and retroperitoneal cystic adenopathy, and multiple cystic lesions in the spleen and liver. CT guided cyst aspiration and node biopsy detected Mycobacterium tuberculosis. The patient responded well on antituberculosis and antiretroviral therapy. Tuberculosis rarely involves the pancreas, probably due to the presence of pancreatic enzymes which interfere with the seeding of Mycobacterium tuberculosis. Pancreatic tuberculosis is considered to be the result of dissemination of the infection from nearby lymphatic nodes. Endoscopic ultrasound or CT guided fine needle aspiration for cytology is the recommended diagnostic technique. Although the prognosis is good with anti-tuberculosis treatment, it could be fatal without correct diagnosis and treatment. The clinician’s high index of suspicion of pancreatic tuberculosis and application of FNAB to obtain pathological evidence are extremely important to a correct diagnosis, especially in young HIV positive patients.

Characterization of the Receptor-binding Domain of Ebola Glycoprotein in Viral Entry

Ebola virus infection causes severe hemorrhagic fever in human and non-human primates with high mortality. Viral entry/infection is initiated by binding of glycoprotein GP protein on Ebola virion to host cells, followed by fusion of virus-cell membrane also mediated by GP. Using an human immunodeficiency virus (HIV)-based pseudotyping system, the roles of 41 Ebola GP1 residues in the receptor-binding domain in viral entry were studied by alanine scanning substitutions. We identified that four residues appear to be involved in protein folding/structure and four residues are important for viral entry. An improved entry interference assay was developed and used to study the role of these residues that are important for viral entry. It was found that R64 and K95 are involved in receptor binding. In contrast, some residues such as I170 are important for viral entry, but do not play a major role in receptor binding as indicated by entry interference assay and/or protein binding data, suggesting that these residues are involved in post-binding steps of viral entry. Furthermore, our results also suggested that Ebola and Marburg viruses share a common cellular molecule for entry.

Down-regulation of HIV-1 Infection by Inhibition of the MAPK Signaling Pathway

The human immunodeficiency virus type 1 （HIV-1） can interact with and exploit the host cellular machinery to replicate and propagate itself. Numerous studies have shown that the Mitogen-activated protein kinase （MAPK） signal pathway can positively regulate the replication of HIV-1, but exactly how each MAPK pathway affects HIV-1 infection and replication is not understood. In this study, we used the Extracellular signal-regulated kinase （ERK） pathway inhibitor, PD98059, the Jun N-terminal kinase （JNK） pathway inhibitor, SP600125, and the p38 pathway inhibitor, SB203580, to investigate the roles of these pathways in HIV-1 replication. We found that application of PD98059 results in a strong VSV-G pseudotyped HIV-1NL4-3 luciferase reporter virus and HIV-1NL4-3 virus inhibition activity. In addition, SB203580 and SP600125 also elicited marked VSV-G pseudotyped HIV-INL4-3 luciferase reporter virus inhibition activity but no HIV-1NL4-3 virus inhibition activity. We also found that SB203580 and SP600125 can enhance the HIV-1 inhibition activity of PD98059 when cells were treated with all three MAPK pathway inhibitors in combination. Finally, we show that HIV-1 virus inhibition activity of the MAPK pathway inhibitors was the result of the negative regulation of HIV-1 LTR promoter activity.

Role of upper endoscopy in diagnosing opportunistic infections in human immunodeficiency virus-infected patients

Highly active antiretroviral therapy (HAART) has dramatically decreased opportunistic infections (OIs) in human immunodef iciency virus (HIV)-infected patients. However,gastrointestinal disease continues to account for a high proportion of presenting symptoms in these patients. Gastrointestinal symptoms in treated patients who respond to therapy are more likely to the result of drug-induced complications than OI. Endoscopic evaluation of the gastrointestinal tract remains a cornerstone of diagnosis,especially in patients with advanced immunodeficiency,who are at risk for OI. The peripheral blood CD4 lymphocyte count helps to predict the risk of an OI,with the highest risk seen in HIV-infected patients with low CD4 count (< 200 cells/mm3). This review provides an update of the role of endoscopy in diagnosing OI in the upper gastrointestinal tract in HIV-infected patients in the era of HAART.

Primary Pleural Extranodal Non-Hodgkin＇s Lymphoma Presenting As Pleural Thickening-A Case Report

Primary pleural lymphoma is a rare entity that has been described in association with human immunodeficiency virus （HIV） infection or pyothorax. This paper reports on a 27 year old man with no history of HIV infection or pyothorax who presented with progressive dyspnea and heaviness of chest.Chest radiography revealed complete opacification of the left hemithorax, and contrast enhanced computed tomography showed large left pleural effusion and homogeneous, extensive thickening of the parietal pleura. CT guided biopsy of thickened pleura is suggestive of non-Hodgkin＇s lymphoma-T cell lymphoblastic variety. Physicians should be aware of this rare location of primary pleural lymphoma manifested by thickening of the pleura.

Hepatitis B and C infection and liver disease trends among human immunodeficiency virus-infected individuals

AIM:To examine trends in and correlates of liver disease and viral hepatitis in an human immunodeficiency virus (HIV)-infected cohort. METHODS:The multi-site adult/adolescent spectrum of HIV-related diseases (ASD) followed 29 490 HIVinfected individuals receiving medical care in 11 U.S. metropolitan areas for an average of 2.4 years,and a total of 69 487 person-years,between 1998 and 2004. ASD collected data on the presentation,treatment,and outcomes of HIV,including liver disease,hepatitis screening,and hepatitis diagnoses. RESULTS:Incident liver disease,chronic hepatitis B virus (HBV),and hepatitis C virus (HCV) were diagnosed in 0.9,1.8,and 4.7 per 100 person-years. HBV and HCV screening increased from fewer than 20% to over 60% during this period of observation (P < 0.001). Deaths occurred in 57% of those diagnosed with liver disease relative to 15% overall (P < 0.001). Overall 10% of deaths occurred among individuals with a diagnosis of liver disease. Despite care guidelines promoting screening and vaccination for HBV and screening for HCV,screening and vaccination were not universally conducted or,if conducted,not documented. CONCLUSION:Due to high rates of incident liver disease,viral hepatitis screening,vaccination,and treatment among HIV-infected individuals should be a priority.

The Status of Human Immuno-deficiency Virus （HIV） Infection among Youth Aged 15-24 Years in Malawi and Kenya

HIV （Human Immuno-deficiency Virus） prevalence in Malawi is one of the highest in the world, with 10.3% of population living with HIV. Kenya has a prevalence rate of 6% and with 1.6 million people living with HIV infection. The broad objective of the study was to assess the proportion of youth aged 15-24 years affected by HIV in Malawi and Kenya. This was a descriptive study design. Data were mainly collected from reports from government, World Bank, World Health Organization and UN agencies. Graphs, tables and charts have been used to present statistics. Data for specific age cohort were hard to find and hence, data were used for general HIV and AIDS with special attention to the youth where possible. In Kenya, HIV prevalence among young women jumps three folds from 2.8% of 15-17 year olds to 8.3% among 23-24 year olds. In Malawi, around 2,100 young people and adolescents are infected with HIV every day. In 2013, four million young people aged 15-24 were living with HIV, with 29% aged under 19 years. This age group includes school going youths, newly employed, economically productive and sexually active group. HIV prevalence in Malawi has been declining over time among persons aged 15-19 years from 16.4% in 1999 to 11.8 % in 2004 to 10.6% in 2010 and 10.3% in 2016. However, in Kenya, the trend of HIV prevalence reached its peak of 10.55% in 1995-1996 after which it declined to 6.7% in 2003 and has been stable since then.

A Quantitative Assay for Measuring of Bovine Immunodeficiency Virus Using a Luciferase-based Indicator Cell Line

In order to quantitate the bovine immunodeficiency virus line （BIVL） was established by transfecting baby hamster kidney （BIV） cells infection in vitro, a BIV indicator cell with reporter plasmids containing the firefly luciferase gene driven by a BIV long terminal repeat promoter. The BIV activates promoter activity of the LTR to express luciferase upon infection. BIV infection could therefore by quantified by detection of luciferase activity. Compared to standard assays used to detect BIV infection, the BIVL-based assay is 10 times more sensitive than the the CPE-based assay, and has similar sensitivity with the viral capsid protein Western blot assay BIV indicator cell line could detect BIV infection specifically. Luciferase activity of BIV infected BIVL cells showed a time dependent manner, and 60 h post infection is the optimal time to detect BIV infection. Luciferase activity of BIVL cells correlates with the BIV capsid protein expression. Moreover, a linear relationship was found between MOI and the activated intensity of luciferase expression. In brief, the BIV indicator cell line is an easy, robust and quantitive method for monitoring BIV infection.

DNA-guided hepatitis B treatment:Viral load is insufficient with few exceptions

In DNA-guided hepatitis B treatment, viral load is insufficient, and requires other viral markers for treatment of hepatitis B patients as in patients with acute exacerbation of chronic hepatitis B, end-stage renal disease on dialysis, human immunodeficiency virus co-infected patients. There are exceptions to this rule： a residual level hepatitis B virus （HBV） DNA at 24 wk predicts beneficial outcome and reduced resistance at i year. The genotypic viral resistance to antiviral agents and occult HBV infection can be determined by HBV-DNA levels.

Asymptomatic stage of human immunodeficiency virus infection is the optimal timing for its management with Traditional Chinese Medicine

Acquired immune deficiency syndrome(AIDS) is a worldwide public health problem and an incurable disease.The roles of Traditional Chinese Medicine(TCM) on AIDS had been recognized and accepted by more and more people.Being a relatively long period,to initiate combination antiretroviral therapy(cART) for the asymptomatic human immunodeficiency virus(HIV) infection patient is not consensus.According to TCM theory,not only the imbalance of Yin and Yang but also the disharmony of internal body function and external natural environment had occurred in the body of the patient,the imbalance and the disharmony should be adjusted by the means of the treatment based on the patters identified among the symptoms in terms of TCM.We aimed to analyze the feature of patients with asymptomatic infection,and compare the advantages and disadvantages of the usage of cART for asymptomatic infection,explored the possible mechanism underlying TCM treatment of the asymptomatic infection,by reviewing the TCM treatment progress on asymptomatic HIV infection.

Global properties of a cell mediated immunity in HIV infection model with two classes of target cells and distributed delays

In this paper, we study the global properties of a human immunodeficiency virus （HIV） infection model with cytotoxic T lymphocytes （CTL） immune response. The model is a six-dimensional that describes the interaction of the HIV with two classes of target cells, CD4＋ T cells and macrophages. The infection rate is given by saturation functional response. Two types of distributed time delays are incorporated into the model to describe the time needed for infection of target cell and virus replication. Using the method of Lyapunov functional, we have established that the global stability of the model is determined by two threshold numbers, the basic infection reproduction number R0 and the immune response activation number R0. We have proven that if R0 ≤ 1, then the uninfected steady state is globally asymptotically stable （GAS）, if R0≤ 1 〈 R0, then the infected steady state without CTL immune response is GAS, and if R0〉 1, then the infected steady state with CTL immune response is GAS.

Traditional Chinese Medicine etiology and pathogenesis of acquired immune deficiency syndrome in simian immunodeficiency virus-infected Chinese rhesus macaques

OBJECTIVE： To investigate the traditional Chinese Medicine （TCM） etiology and pathogenesis of ac- quired immune deficiency syndrome （AIDS） by 18-month observation of Chinese rhesus macaques infected with simian immunodeficiency virus （SIV） mac239. METHODS： Thirty-five healthy Chinese rhesus ma- caques were divided into a model group （n=30） and a control group （n=5）. The model was estab- lished by inoculating monkeys intravenously with SIVmac239. Changes in TCM symptoms after SIV in- fection within 18 months were then observed and recorded. Routine blood tests, SIV viral load, T-lym-phocyte subsets, plasma triiodothyronine （T3）, tet- raiodothyronine （14）, adrenocorticotropic hormone （ACTH） and cortisol （Cor） were tested periodically during the experiment. RESULTS： During the acute infection period of SIV, model monkeys temporarily showed clinical symp- toms such as diarrhea, dysphoria and slight weight loss. Decrease percentages of CD4~ T-lymphocytes were observed but levels of T3, 14, Cot, and ACTH were relatively unchanged. Monkeys in the model group during the early and middle periods of infec- tion showed no obvious symptoms, except few monkeys exhibited transient diarrhea and reduced food intake. All variables at this stage showed nor- mal fluctuations. In the middle period model group monkeys showed chronic and persistent diarrhea, weight loss, reduced food intake and low levels of 13 and Cot. In the late period, symptoms including emaciation, weight loss, listlessness, crouching in corners and low levels of T3appeared. CONCLUSION： The results suggest that the rhesus monkey SIWSAIDS model can be applied to re- search on TCM etiology and pathogenesis of AIDS. According to this model, the etiology of disease is the SIV virus. The pathogenesis manifests as the in- vasion of SIV virus, incubation of the virus, balance between virus and healthy ＂Qi＂, damage to spleen and kidney as the disease progressed, exhaustion of vitality and finally the failure of five zang and six fu organs.

Survival of people living with HIV after treatment with Traditional Chinese Medicine in Henan province of China: a retrospective cohortstudy

OBJECTIVE: To provide survival estimates of people living with human immunodeficiency virus(PLHIV) after treatment with Traditional Chinese Medicine(TCM) in rural China, to identify the prognostic factors at enrollment, and to explore the effectiveness of TCM intreating PLHIV.METHODS: PLHIV who enrolled in national TCM HIV treatment trial program in October 2004 were analyzed in this study and followed up to October 2010. Survival time was estimated by the Kaplan-Meier curve and hazard ratios, and identifying prognostic factors were computed through Cox proportional hazard models.RESULTS:A total of 1666 PLHIV were included with 102 591 person-months of follow-up. Overall, 312(18.7%) patients died. The total mortality rate over the study period was 3.6 per 100 person-years,which was lower than the worldwide rate. The cumulative survival rate was 95.9% at 1 year[95% confidence interval(CI)(94.8-96.8)] and 80.4% at 6years [95% CI(78.4-82.3)]. Elevated death risks emerged among males, older individuals, and thosewithlowerCD4+T-cellcounts.CONCLUSION: TCM could increase survival and lengthen the life span of PLHIV in Henan province of China, as shown by our retrospective cohort study. Factors such as sex, age, education, and CD4+ T-cell counts correlated to survival. However,retrospective cohorts bias the data, so more prospective studies should be performed to confirm our primary results.

SATURATION EFFECTS FOR CTL MEDIATED CONTROL OF HIV-1 INFECTION： A MATHEMATICAL STUDY

The relations between the Human Immunodeficiency Virus-1 （HIV-1） and the human immune system are astonishingly multifaceted, where the critical role for cytotoxic T lymphocytes （CTLs） in the suppression of viral replication in HIV-1 infected individuals cannot be ignored. In this research paper, we have proposed a mathematical model incorporating half saturation constant through the CTL mediated killing process and also in that sense, it has been infiltrated in the generation process of CTL through infected cells. To make the model more realistic, a time lag is introduced in the generation term of CTL population. Also an optimal control theory paradigm is used in our mathematical model to suppress the viral production. From our entire analysis, we have found threshold condition of half saturation constant and treatment schedule so that we can handle the situation of Acquired Immunodeficiency Syndrome （AIDS） patients in a better way. Our analysis reveals that, if the half saturation constant is around 47 mm^-3 in the saturation process and the drug therapy is to be used around 76 days, then we can get adequate results for better treatment of a HIV-1 patient. Based on numerical results, we observed that in a highly unstable situation, administration of chemotherapy at a high dose can stabilize the system.