Viral Resistance

Telbivudine is the latest nucleoside/nucleotide analog approved for the treatment of chronic hepatitis B. It has been extensively studied in Phase I, II and III trials. The Phase III trial (the GLOBE study) recruited more than 1300 chronic hepatitis B patients. It demonstrated that telbivudine was superior to lamivudine with a greater reduction of HBV DNA levels in hepatitis B e antigen (HBeAg)-positive and -negative disease after 1 year of treatment. The resistance rate at year 1 was also lower in patients receiving telbivudine. This antiviral superiority is maintained up to 2 years of treatment. There were no serious adverse effects in patients receiving telbivudine treatment. To further minimize the chance of emergence of drug resistance, careful patient selection according to the baseline HBV DNA levels, alanine aminotransferase levels and HBV DNA levels at week 24 of treatment should be carried out. Continuation of telbivudine monotherapy is associated with a low chance of resi...

BACKGROUND: Drug use evaluation is a performance improvement method that focuses on evaluation and improvement of drug use processes to achieve optimal patient outcomes. The objective of this study was to evaluate the use of cotrimoxazole for prophylaxis among people living with HIV/AIDS in Jimma University Specialized Hospital. METHODS: Drug use evaluation criteria were set along with threshold based on the national guidelines for cotrimoxazole preventive therapy. The study was done by a cohort design with retrospective review of medical records of r sixty people with HIV/AIDS who have been on cotrimoxazole prophylaxis in the hospital from January 19, 2006 to January 18, 2007. A systematic sampling method was used to select records of the study participants. Data were collected from January 19 to February 3, 2007 using structured format and evaluated against the set criteria and thresholds. RESULTS: Fifty one (85.0%) patients were in the age range of 15 to 49 years and 33 (55.0%) were females. In all cases, the indication to start, dose and frequency of administration of cotrimoxazole were according to the national guidelines for Cotrimoxazole Preventive Therapy. Forty-six (76.6%) cases were consistent with guidelines for indications to discontinue the drug; however, CD4 count was done only for 28 (46.7%) of patients during follow-up. Fifty-eight (96.7%) and 59(98.3%) of the cases were in accordance with the guidelines for contraindication and drug interactions, respectively. CONCLUSION: The use of cotrimoxazole for preventive therapy for people living with HIV/AIDS was found to be good in Jimma University Specialized Hospital with regard to initiation and dosage. However, the practice of discontinuation of cotrimoxazole and follow-up for drug adverse effects should be improved by proper implementation of the guideline.

Selection of inhibitor-resistant viral mutants is universal for viruses that display quasi-species dynamics, and hepatitis C virus (HCV) is no exception. Here we review recent results on drug resistance in HCV, with emphasis on resistance to the newly-developed, directly-acting antiviral agents, as they are increasingly employed in the clinic. We put the experimental observations in the context of quasi-species dynamics, in particular what the genetic and phenotypic barriers to resistance mean in terms of exploration of sequence space while HCV replicates in the liver of infected patients or in cell culture. Strategies to diminish the probability of viral breakthrough during treatment are briefly outlined.

Background: In Senegal in 2015, an estimated 4800 children were living with HIV, with 1200 receiving ARV treatment, of whom half had follow-up care in decentralized sites outside Dakar. However, until now no studies have determined the efficacy of pediatric treatment in decentralized settings, even though the emergence of viral resistance, particularly among children in Africa, is a well-known phenomenon. This study aimed to assess the virological status of HIV-infected children in all decentralized facilities to help improve access to quality care. Methods: A cross-sectional epidemiological and virological study was conducted in all of Senegal's regions, except Dakar, between March and June 2015 and sought to include all HIV-infected children and adolescents (0-19 years), treated or not with ARVs. Socio-demographic and clinical data and a blood sample on blotting paper were collected for children from treatment sites. Samples were routed on public transportation, assisted by a network of community health workers. A viral load (VL) assay was performed for each child, followed by genotyping when it exceeded 1000 copies/mL (3 log 10). Results: Of the 851 identified children, 666 (78%) were enrolled in the study. Half of the children were girls, and the average age was 8 years (6 months-19 years). Most of the children (96.7%) were infected with HIV-1, and 90% were treated with ART, primarily with AZT + 3TC + NVP/EFV therapeutic regimen. The median duration of time on ART was 21 months (1-129). VL was measured for 2% of children before this study. Almost two-thirds (64%) of the children are experiencing virological failure. Among them, there was resistance to at least one drug for 86.5% of cases. Also, 25% children presented resistance to one drug and 40% to two out of three. For nearly one-third of the children presenting resistance, none of the three drugs of the treatment was active. Factors associated with virological failure were male sex, follow-up by a generalist rather than a specialist, and treatment interruptions. Conclusions: We observed a high level of virological failure and a high percentage of viral resistance among children receiving health care in decentralized facilities in Senegal.

Čeprav so rastlinski virusi pomemben del ekosistema, povzročajo izgubo pridelka in škodujejo kmetijskim rastlinam, ki so ključnega pomena za preživetje ljudi in živali. S klasičnimi in novejšimi metodami pridobivamo izboljšane lastnosti rastlin in spoznavamo mehanizme interakcij med gostiteljem in virusom. Z razvojem tehnik genomskega preurejanja kot je CRISPR/Cas sistem, so se odprle možnosti poseganja v genom in še boljšega razumevanja funkcij določenih genov in molekul. Namen dela je povzeti možnosti aplikacij CRISPR/Cas sistema za pridobitev odpornosti na DNA in RNA viruse v kmetijskih rastlinah. Rezultati študij kažejo, da je ta tehnika natančna in uspešna pri pridobitvi odpornosti na viruse kmetijskih rastlin kot so paradižnik, krompir, pšenica, ječmen, manioka, bananovec in pesa. Analize so pokazale, da stopnja odpornosti na viruse korelira s stopnjo izražanja sgRNA molekule in Cas proteina. Optimizacija postopkov je ključna za uspešen vnos CRISPR/Cas sistema in učinkovitost ...

The initiation of ART is best based on CD4 cell count, a marker of immune status, rather than on viral load, a marker of virologic replication. For patients with advanced symptoms, treatment should be started regardless of CD4 count. However, the point during the course of HIV infection at which antiretroviral therapy (ART) is best initiated in asymptomatic patients remains unclear. The objective of this study is to assess ART treatment outcomes verses CD4 count threshold among HIV/AIDS patients in Ras Desta hospital. This was a periodic retrospective cross sectional study of HIV positive patient's ART treatment outcomes in relation to CD4 count threshold in Ras Desta hospital. From all HIV positive patients who had registered for ART from September 2009-February 2011 at Ras Desta hospital, 636 patients had met the criteria of the study and they were selected. Out of the 636 patients chosen for the study, 372 (58.5 %) were females while 264 (41.5 %) were males. For the whole sample under study, the median age was 36 years. Out of 636 patients 504 patients had a CD4 count less than 200 cells /mm 3 , 120 had a CD4 count greater than 200 and less than 350 cells/µl. Lastly, a total of 12 patients had a CD4 count greater than 350 cells /mm 3 at the initiation of ART. Other findings show that for all patients in the study receiving ART, median weight was 53 Kg (range 27 kg to 93 kg). Four hundred eighty (75.5 %) patients were alive, twenty one (3.3 %) patients had transferred out, 67 (10.5 %) were lost to follow-up and 68 (10.7 %) had died during two year period of ART use. A further observations of the deaths revealed that 53 (78 %) were CD4 count less than 200 cells/µl, 14 (20.5 %) patients were CD4 count > 200 and < 350 cells/µl, while only 1 (1.5 %) of the patient were died whose CD4 count > 350 cells/µl. This study show that early initiation of ART at CD4 levels higher than 200 cells/µl reduces mortality, immune-depression and weight loss and also improve outcome of ART treatment in asymptomatic, ART-naive, HIV-infected people. Practitioners and policy-makers may consider initiating ART at levels > 200 cells/ µl.

The treatment option for AIDS have drastically changed since 1987 when the first drug of HIV/AIDS Zidovudin (ZDV) was approved, mono therapy has been replaced by the most effective currently is HAART which includes three drugs from one or all the three categories to decrease incidence of viral resistance. From about, 1,387,039 people living with HIV/AIDS in Ethiopia 167,271 people were initiated on ART by October 2009. The aim of this study is to determine comparative effects of ART on CD4 + cell count in Jimma University Specialized Hospital and assess comparative effects of ZDV and d4T based combinations on CD4 + cell count, to assess comparative effects of EFV and NVP based combinations on CD4 + cell count. Cross-sectional retrospective study was employed. Data (from June 2006 to October 1, 2013) was collected from patient records using data collection format to determine comparative effects of ART regimen on CD4 + cell count in Jimma university specialized hospital. One hundred twenty three patients fulfilled the inclusion criteria and were studied. At six month the EFV based regimens CD4 + cell count had increased with mean of 332 cells/mm 3 in the ZDV/3TC/EFV (n = 4) (baseline 139 cells/mm 3 ), a mean of 302.36 cells/mm 3 in the d4T/3TC/EFV (n = 11) (baseline 102.82 cells/mm 3 ) and a mean 283.06 cells/mm 3 in the TDF/3TC/EFV (n = 17) (baseline 110.06 cells/mm 3 ). The mean CD4 + cell count recoveries of EFV and NRTIs were higher than NVP and NRTIs. ZDV/3TC/EFV mean CD4 count was greater than TDF/3TC/EFV.

Both Human Immunodeficiency Virus (HIV) infection and Acquired Immunodeficiency Syndrome (AIDS) remain major public health problems in Ethiopia. Good adherence to antiretroviral therapy is necessary to achieve the best virological response, lower the risk of treatment failure and drug resistance, and reduce morbidity and mortality. There are many alterable factors known to affect the treatment adherence. In this regard, there have been very limited researches particularly in Adama. Therefore, this study was aimed to determine the adherence level and its associated factors among adult people living with HIV and attending their clinical care in Adama Hospital Medical College. A hospital based cross sectional study was conducted from October 1, 2016 - January 30, 2017 G. C in Adama Hospital Medical College among 190 PLWHA on ART. Systematic sampling method was used to select study participants. Data was collected by interviewing the clients and review of their medical records using str...

The initiation of ART is best based on CD4 cell count, a marker of immune status, rather than on viral load, a marker of virologic replication. For patients with advanced symptoms, treatment should be started regardless of CD4 count. However, the point during the course of HIV infection at which antiretroviral therapy (ART) is best initiated in asymptomatic patients remains unclear. The objective of this study is to assess ART treatment outcomes verses CD4 count threshold among HIV/AIDS patients in Ras Desta hospital. This was a periodic retrospective cross sectional study of HIV positive patient's ART treatment outcomes in relation to CD4 count threshold in Ras Desta hospital. From all HIV positive patients who had registered for ART from September 2009-February 2011 at Ras Desta hospital, 636 patients had met the criteria of the study and they were selected. Out of the 636 patients chosen for the study, 372 (58.5 %) were females while 264 (41.5 %) were males. For the whole sample under study, the median age was 36 years. Out of 636 patients 504 patients had a CD4 count less than 200 cells /mm 3 , 120 had a CD4 count greater than 200 and less than 350 cells/µl. Lastly, a total of 12 patients had a CD4 count greater than 350 cells /mm 3 at the initiation of ART. Other findings show that for all patients in the study receiving ART, median weight was 53 Kg (range 27 kg to 93 kg). Four hundred eighty (75.5 %) patients were alive, twenty one (3.3 %) patients had transferred out, 67 (10.5 %) were lost to follow-up and 68 (10.7 %) had died during two year period of ART use. A further observations of the deaths revealed that 53 (78 %) were CD4 count less than 200 cells/µl, 14 (20.5 %) patients were CD4 count > 200 and < 350 cells/µl, while only 1 (1.5 %) of the patient were died whose CD4 count > 350 cells/µl. This study show that early initiation of ART at CD4 levels higher than 200 cells/µl reduces mortality, immune-depression and weight loss and also improve outcome of ART treatment in asymptomatic, ART-naive, HIV-infected people. Practitioners and policy-makers may consider initiating ART at levels > 200 cells/ µl.

Title: Magnitude and causes of first-line antiretroviral therapy regimen changes among HIV patients in Ethiopia: a systematic review and meta-analysis Authors: Zerihun Ataro (zerihunataro@yahoo.com) Birhanu Motbaynor (dovehod@gmail.com) Fitsum Weldegebreal (fwmlab2000@gmail.com) Mekonnen Sisay (mekonnensisay27@gmail.com) Tewodros Tesfa (tewodrost1@gmail.com) Habtamu Mitku (habtemit@gmail.com) Dadi Marami (dmarami4@gamil.com) Zelalem Teklemariam (zelalemtmariam@yahoo.com) Zewdneh Shewamene (zeedshow@gmail.com) Version: 1 Date: 02 Jul 2019 Author’s response to reviews: Date: July 1, 2019

Title: Magnitude and causes of first-line antiretroviral therapy regimen changes among HIV patients in Ethiopia: a systematic review and meta-analysis Authors: Zerihun Ataro (zerihunataro@yahoo.com) Birhanu Motbaynor (dovehod@gmail.com) Fitsum Weldegebreal (fwmlab2000@gmail.com) Mekonnen Sisay (mekonnensisay27@gmail.com) Tewodros Tesfa (tewodrost1@gmail.com) Habtamu Mitku (habtemit@gmail.com) Dadi Marami (dmarami4@gamil.com) Zelalem Teklemariam (zelalemtmariam@yahoo.com) Zewdneh Shewamene (zeedshow@gmail.com) Version: 1 Date: 02 Jul 2019 Author’s response to reviews: Date: July 1, 2019

Tenofovir (TDF) based regimen is one of the first line agents that has been utilized routinely since 2013 in Ethiopia. Unfortunately, there is limited information regarding the Clinical outcomes and associated risk factors in this setting, where patients generally present late, have high rates of TB and other infectious conditions. A two year retrospective cohort study was conducted from February 10/2015 to March 10/2015 at Jimma University Specialized Hospital. A total of 280 records were reviewed by including data from September 3, 2012 to July 31, 2014. Records were selected using a simple random sampling technique. Data was collected on socio-demographic, clinical and drug related variables. Data was analyzed using STATA 13.1. Kaplan-Meier and Cox regression were used to compare survival experience and identify independent predictors. Propensity score matching analysis was conducted to elucidate the average treatment effects of each regimen over opportunistic infections. Of 280 ...

Background: Tenofovir (TDF) based regimen was reported to have better immunological outcomes. Unfortunately, there is limited information regarding the immunologic outcome associated with this regimen in Ethiopia, as its routine utilization in this setting begun since 2013.

Background: Hematological abnormalities are common in HIV positive patients. Of these, thrombocytopenia is a known complication which has been associated with a variety of bleeding disorders. However, its magnitude and related factors have not been well-characterized in the era of highly active antiretroviral therapy (HAART) in Ethiopia. Therefore, this study aimed to assess the prevalence of thrombocytopenia before and after initiation of HAART among HIV positive patients attending Black

Human immunodeficiency virus (HIV) infection and its treatment cause a range of hematological abnormalities. Anemia is one of the commonly observed hematologic manifestations in HIV positive persons and it has multifactorial origin. We aimed to determine the prevalence and risk factors of anemia in highly active antiretroviral therapy (HAART) naïve and HAART experienced HIV positive persons. A facility-based comparative cross sectional study was conducted in Jimma University Specialized Hospital from February 1 to March 30, 2012. A total of 234 HIV positive persons, 117 HAART naïve and 117 HAART experienced, were enrolled in this study. Blood and stool specimens were collected from each participant. Blood specimens were examined for complete blood count, CD4 count and blood film for malaria hemoparasite; whereas stool specimens were checked for ova of intestinal parasites. Socio-demographic characteristics and clinical data of the participants were collected using pre-tested questio...

ABSTRACT
Virus infections still cause serious losses of the potato crop. Potato virus X- (PVX) and potato leafroll virus (PLRV) are the most widespread and serious viruses of potato in Eastern Europe. The research aimed at identifying host factors involved in either viral resistance or viral pathogenicity is encouraged by the use of the model system of relatively isogenic clones of potato, which are contrast on the resistance to PVX and/ or PLRV. The database on the protein markers of the state of resistance of potato to PVX and/ or PLRV was created. Previous results testify the role of a number of proteins in the formation of the reactions of resistance or susceptibility to named viruses. Created model of nearly isogenic clones allows to isolate genes, specifically involved in the realization of the resistance/susceptibility states and estimate the effect of the expression of these genes. RT-PCR of the clones, contrast by the resistance/susceptibility to PVX and /or PLRV revealed the different expression of the several genome regions. Fragment 500 bp was quantitatively more expressed at resistant to PLRV in comparison with resistant to PVX clone of Loshitski cv. and was not determined at susceptible to PLRV and both viruses clones. Random primers allowed to mark the resistance to PLRV: fragment ~800 bp was detected at cDNA amplification with a mix of OPV-08 and OPK-08 primers only at X + L- clones with genotypes of Loshitski and Javar cv. Further cloning of revealed fragments on the basis of preliminary protein data base will allow to determine the sequence and structure of putative genes and proteins, which are equipped in the reactions of resistance and susceptibility to this viruses. GenBank Submissions: GH626173.1 [GI:221090249]. 181/2-02/01 Polymorphic cDNAs of nearly isogenic clones of cultivar Loshitsky, differed by resistance to PVX and PLRV Solanum tuberosum cDNA clone 181/2-02 5-, mRNA sequence. 638 bp linear mRNA// 2009, BLAST database, NCBI. GH626172.1 [GI:221090248]. 181/2-01/01 Polymorphic cDNAs of nearly isogenic clones of cultivar Loshitsky, differed by resistance to PVX and PLRV Solanum tuberosum cDNA clone 181/2-01 5-, mRNA sequence. 1,388 bp linear mRNA// 2009, BLAST database, NCBI.
N. B. Vlasava, A. N. Palilova and E. V. Spiridovich. Expression and identification of the protein and cDNA markers of resistance or susceptibility of Solanum tuberosum to potato virus X- and potato leafroll virus on the basis of the experimental model of nearly isogenic potato clones (2005). The FEBS Journal, Volume 272. -P. 519.

The object of present research are related clones of Solanum tuberosum contrast on resistance to X- and L- viruses of a potato (PVX, PLRV), subject peculiarities of protein spectra component structure of various protein fractions depending on the resistance of clones to the given viruses. The purpose of the current study: definition of chains of protein metabolism at related clones of Solanum tuberosum, which are most sensitive to the attack of X- and L- virus infection and revealing of the protein components responsible for realization of conditions of resistance/susceptibility to these viruses. This study employed methods of fractionating of various proteins, electrophoretic division of proteins in polyacrilamidic gel in denaturing conditions, immunoidentification of proteins by Western-blotting, enzyme-linked immunosorbent assay and virology methods. On the model system of related clones of S. tuberosum it was shown, that they demonstrate polymorphism of proteins of various fractions depending on the degree of clones' resistance to PV and PLRV. The protein fractions most actively answering to pathogen attack are revealed. The original data on participation of proteins of chloroplasts in processes of pathogenesis and in reactions of virus resistance are received. For the first time on the available model system of related clones at a protein level it is confirmed synergistic pathogenic influence of X-and L-viruses on a protein metabolism of the host plant, including those confirming role of PV as a helper to phloem-limited L- virus. Also for the first time protein markers of conditions of resistance and susceptibility of a potato to X-and L-viruses have been proposed, and also protein components of a resistance/ susceptibility to each virus separately are found out. Received data promotes to the deepening of knowledge on the mechanisms of interference of the host plant and its virus pathogen, and also allows using revealed protein markers for carrying out selection aimed at seeking of new resources of potato resistance genes to viruses.

The treatment option for AIDS have drastically changed since 1987 when the first drug of HIV/AIDS Zidovudin (ZDV) was approved, mono therapy has been replaced by the most effective currently is HAART which includes three drugs from one or all the three categories to decrease incidence of viral resistance. From about, 1,387,039 people living with HIV/AIDS in Ethiopia 167,271 people were initiated on ART by October 2009. The aim of this study is to determine comparative effects of ART on CD4 + cell count in Jimma University Specialized Hospital and assess comparative effects of ZDV and d4T based combinations on CD4 + cell count, to assess comparative effects of EFV and NVP based combinations on CD4 + cell count. Cross-sectional retrospective study was employed. Data (from June 2006 to October 1, 2013) was collected from patient records using data collection format to determine comparative effects of ART regimen on CD4 + cell count in Jimma university specialized hospital. One hundred twenty three patients fulfilled the inclusion criteria and were studied. At six month the EFV based regimens CD4 + cell count had increased with mean of 332 cells/mm 3 in the ZDV/3TC/EFV (n = 4) (baseline 139 cells/mm 3), a mean of 302.36 cells/mm 3 in the d4T/3TC/EFV (n = 11) (baseline 102.82 cells/mm 3) and a mean 283.06 cells/mm 3 in the TDF/3TC/EFV (n = 17) (baseline 110.06 cells/mm 3). The mean CD4 + cell count recoveries of EFV and NRTIs were higher than NVP and NRTIs. ZDV/3TC/EFV mean CD4 count was greater than TDF/3TC/EFV.