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Characterization of Treatment-Naive HIV/HBV Co-Infected Patients Attending ART Clinic of a Tertiary Healthcare Centre in Eastern India  [PDF]
Debraj Saha, Ananya Pal, Avik Biswas, Rajesh Panigrahi, Neelakshi Sarkar, Jayeeta Sarkar, Manisha Pal, Subhasish Kamal Guha, Bibhuti Saha, Sekhar Chakrabarti, Runu Chakravarty
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0073613
Abstract: Objective The study was designed to assess the hepatitis B virus (HBV) and hepatitis C virus (HCV) co-infection scenario among the human immunodeficiency virus (HIV) infected patients attending a tertiary healthcare unit in eastern India. Additionally, clinical and virological characterization of these viruses, prior to antiretroviral therapy (ART) initiation was also done for better understanding of the disease profile. Methods Pool of ART-naive HIV/HBV co-infected and HIV mono-infected patients, participating in two different studies, were included in this study. HBV DNA was detected by nested-PCR amplification followed by HBV genotype determination and HBV reverse transcriptase (RT) region amplification and direct sequencing for detecting drug resistance. Results The prevalence of HBsAg (11.3%) was higher compared to anti-HCV (1.9%) among the HIV infected ART-naive patients. Moreover, majority of the HBeAg positive HIV/HBV co-infected patients (87.7%) had HBV DNA ≥20,000 IU/ml with median HBV DNA significantly higher than that of HBeAg negative subjects (5.7 log10 IU/ml vs. 4.2 log10 IU/ml; p<0.0001). Multivariate analysis also showed that HBeAg-positive status was independently associated with higher HBV DNA level (p = <0.001). Notably, 60.9% of the HBeAg negative co-infected subjects had HBV DNA ≥2,000 IU/ml of which 37.0% had HBV DNA ≥20,000 IU/ml. Genotype HBV/D (68.2%) was the predominant genotype followed by HBV/A (24.3%) and HBV/C (7.5%). Anti-HBV drug resistant mutations were detected in two (3.8%) of the ART-naive patients. Conclusion The prevalence of HIV/HBV co-infection was relatively higher in our study subjects. HBeAg testing might provide clue for early treatment initiation. Furthermore, HBeAg negative patients are also associated with high HBV DNA levels and therefore require appropriate medical attention. Pre-treatment screening for anti-HBV drug resistant mutations is not necessary before ART initiation.
Molecular Characterization of HBV Strains Circulating among the Treatment-Naive HIV/HBV Co-Infected Patients of Eastern India  [PDF]
Debraj Saha, Ananya Pal, Avik Biswas, Rajesh Panigrahi, Neelakshi Sarkar, Dipanwita Das, Jayeeta Sarkar, Subhasish Kamal Guha, Bibhuti Saha, Sekhar Chakrabarti, Runu Chakravarty
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0090432
Abstract: Previously we reported that the exposure to hepatitis B virus (HBV) infection serves as a major threat among the treatment naive HIV infected population of eastern India. Hence, molecular characterization of these strains is of utmost importance in order to identify clinically significant HBV mutations. A total of 85 treatment naive HIV/HBV co-infected participants were included of whom the complete basal core promoter/precore region, the core and the whole envelope gene could be successfully sequenced for 59, 57 and 39 isolates respectively. Following phylogenetic analysis, it was found that HBV/D was the predominant genotype with HBV/D2 (38.5%) being the most prevalent subgenotype followed by HBV/A1. The major mutations affecting HBeAg expression includes the A1762T/G1764A (13.6%), G1896A (22%) and G1862T mutation (33.9%) which was predominantly associated with HBV/A1. Moreover, the prevalence of G1896A was considerably high among the HBeAg negative HIV/HBV co-infected subjects compared to HBV mono-infection. The main amino acid substitutions within the MHC class II restricted T-cell epitope of HBcAg includes the T12S (15.8%) and T67N (12.3%) mutation and the V27I (10.5%) mutation in the MHC class I restricted T-cell epitope. PreS1/S2 deletion was detected in 3 isolates with all harboring the BCP double mutation. Furthermore, the frequently occurring mutations in the major hydrophilic loop of the S gene include the T125M, A128V and M133I/L. Therefore, this study is the first from India to report useful information on the molecular heterogeneity of the HBV strains circulating among the treatment naive HIV/HBV co-infected population and is thus clinically relevant.
Genetic diversity and drug resistance among newly diagnosed and antiretroviral treatment-naive HIV-infected individuals in western Yunnan: a hot area of viral recombination in China
Chen Min,Ma Yanling,Duan Song,Xing Hui
BMC Infectious Diseases , 2012, DOI: 10.1186/1471-2334-12-382
Abstract: Background The emergence of an HIV-1 epidemic in China was first recognized in Dehong, western Yunnan. Due to its geographic location, Dehong contributed greatly in bridging HIV-1 epidemics in Southeast Asia and China through drug trafficking and injection drug use; and also extensively to the HIV genetic diversity in Yunnan and China. We attempt to monitor HIV-1 in this area by studying the HIV-1 genetic distribution and transmitted drug resistance (TDR) in various at-risk populations. Methods Blood samples from a total of 320 newly HIV-1 diagnosed individuals, who were antiretroviral therapy (ART)-naive, were collected from January 2009 to December 2010 in 2 counties in Dehong. HIV-1 subtypes and pol gene drug resistance (DR) mutations were genotyped. Results Among 299 pol sequences successfully genotyped (93.4%), subtype C accounted for 43.1% (n=129), unique recombinant forms (URFs) for 18.4% (n=55), CRF01_AE for 17.7% (n=54), B for 10.7% (n=32), CRF08_BC for 8.4% (n=25) and CRF07_BC for 1.7% (n=5). Subtype distribution in patients infected by different transmission routes varied. In contract to the previous finding of CRF01_AE predominance in 2002-2006, subtype C predominated in both injecting drug users (IDUs) and heterosexually transmitted populations in this study. Furthermore, we found a high level of BC, CRF01_AE/C and CRF01_AE/B/C recombinants suggesting the presence of active viral recombination in the area. TDR associated mutations were identified in 4.3% (n=13) individuals. A total of 1.3% of DR were related to protease inhibitors (PIs), including I85IV, M46I and L90M; 0.3% to nucleoside reverse transcriptase inhibitors (NRTIs), including M184I; and 2.7% to non-nucleoside reverse transcriptase inhibitors (NNRTIs), including K103N/S, Y181C, K101E and G190A. Conclusion Our work revealed diverse HIV-1 subtype distributions and intersubtype recombinations. We also identified a low but significant TDR mutation rate among ART-naive patients. These findings enhance our understanding of HIV-1 evolution and are valuable for the development and implementation of a comprehensive public health approach to HIV-1 DR prevention and treatment in the region.
Identification of Germinal Center B Cells in Blood from HIV-infected Drug-naive Individuals in Central Africa  [PDF]
Lydie Béniguel,Evelyne Bégaud,Fabrice Cognasse,Philippe Gabrié,Christophe D. Mbolidi,Odile Sabido,Mary A. Marovich,Christiane deFontaine,Anne Frésard,Frédéric Lucht,Christian Genin,Olivier Garraud
Clinical and Developmental Immunology , 2004, DOI: 10.1080/10446670410001670454
Abstract: To better understand the pathophysiology of B cell populations—the precursors of antibody secreting cells—during chronic human immunodeficiency virus (HIV) infection, we examined the phenotype of circulating B cells in newly diagnosed Africans. We found that all African individuals displayed low levels of naive B cells and of memory-type CD27
Seroprevalence and Risk Factors of Syphilis Infection among Antiretroviral Therapy Naive HIV Patients at the Cape Coast Teaching Hospital, Ghana  [PDF]
Prince Asare-Bediako, Kwabena Dankwa, Daniel E. Azumah, Samuel V. Nuvor
World Journal of AIDS (WJA) , 2018, DOI: 10.4236/wja.2018.83007
Abstract: Diagnosis of sexually transmitted infections is very important considering the spread of HIV and the extensive use of highly active antiretroviral therapy worldwide. This will assist in planning of treatment schedule in controlling these infections. The study therefore aimed at determining the prevalence of syphilis in HIV positive antiretroviral therapy naive patients in Cape Coast and the associated risk factors involved in infection. A cross-sectional study was carried out using initial HIV rapid and confirmation tests, and then Venereal Disease Research Laboratory test with the Ultra Rapid Test Kits for syphilis. Demographic data, risky sexual behaviours capable of co-transmission of both HIV and Syphilis, were also collected through the use of questionnaires. In all, 150 HIV positive antiretroviral naive subjects were studied and 15 (10%) were positive for VDRL test, with females (6.00%) and males (4.00%), who were mainly within the age group of 20 - 39 years. A significant number of males (p = 0.019) and females (p = 0.015) participants were not smoking with a fewer number of the females (p = 0.002) having multiple sexual partners. Also a smaller number of those who were infected with the bacteria (p = 0.004) did not support the control of sexually transmitted infection (p = 0.022). The result showed that co-infection of Syphilis in HIV positive antiretroviral therapy naive patients persists in the Cape Coast Metropolis, which is an indication of prominence of STIs that require further study on a larger scale to ascertain the extent of co-infection and to formulate policy for treatment to help minimize the rate of infection.
Genetic Analysis of HIV-1 Integrase Sequences from Treatment Naive Individuals in Northeastern South Africa  [PDF]
Pascal Obong Bessong,Julius Nwobegahay
International Journal of Molecular Sciences , 2013, DOI: 10.3390/ijms14035013
Abstract: Raltegravir, an integrase inhibitor, is not a component of the current South African antiretroviral treatment guidelines, but it could be introduced in the near future as cases of virological failures from current treatment regimens begin to occur. The aim of this study was to analyze the complete HIV integrase gene obtained from individuals at two treatment sites in northeastern South Africa for the presence of Raltegravir associated drug resistant mutations and viral subtypes based on the integrase gene. Examination for mutations against other integrase inhibitors, such as Elvitegravir and Dolutegravir, was also done. Viruses from 127 treatment naive individuals were analyzed. Genetic drug resistance mutations were determined using the Stanford HIV Drug Resistance Interpretation program and the International AIDS society-USA guidelines. Viral subtyping was done by phylogenetic analysis, and recombinants were determined using the REGA, jpHMM and RIP tools. No major resistance mutations were detected. However, 7% of the sequences had minor mutations and polymorphisms. The majority (99%) of the viruses were HIV-1 C. Recombination analysis showed that the polymerase gene of one virus was likely composed of HIV-1 subtype A1 and C sequences. The present study indicates that Raltegravir, Elvitegravir and Dolutegravir resistant mutations may be absent in the study communities and further indicates the presence of recombinant viruses in northeastern South Africa.
Differences between naive and memory T cell phenotype in Malawian and UK adolescents: a role for Cytomegalovirus?
Anne Ben-Smith, Patricia Gorak-Stolinska, Sian Floyd, Rosemary E Weir, Maeve K Lalor, Hazzie Mvula, Amelia C Crampin, Diana Wallace, Peter CL Beverley, Paul EM Fine, Hazel M Dockrell
BMC Infectious Diseases , 2008, DOI: 10.1186/1471-2334-8-139
Abstract: Venous blood from HIV-negative adolescents and blood from the umbilical cords of babies, born to HIV-negative women, post-delivery was collected and analysed using flow cytometry. T cell phenotype was determined from peripheral blood lymphocytes and cytomegalovirus (CMV) seropositivity was assessed by ELISA in adolescents.HIV-negative Malawian adolescents were shown to have a lower percentage of na?ve T cells (CD45RO-CD62Lhi CD11alo), a higher proportion of memory T cells and a higher percentage of CD28- memory (CD28-CD45RO+) T cells compared to age-matched UK adolescents. Malawian adolescents also had a lower percentage of central memory (CD45RA-CCR7+) T cells and a higher percentage of stable memory (CD45RA+CCR7-) T cells than UK adolescents. All of the adolescents tested in Malawi were seropositive for CMV (59/59), compared to 21/58 (36%) of UK adolescents. CMV seropositivity in the UK was associated with a reduced percentage of na?ve T cells and an increased percentage of CD28- memory T cells in the periphery. No differences in the proportions of na?ve and memory T cell populations were observed in cord blood samples from the two sites.It is likely that these differences between Malawian and UK adolescents reflect a greater natural exposure to various infections, including CMV, in the African environment and may imply differences in the ability of these populations to induce and maintain immunological memory to vaccines and natural infections.The immune system maintains both na?ve and memory T cells, so that individuals can mount an immune response to a variety of new antigens while keeping appropriate levels of memory T cells that recognise previously encountered pathogens. Na?ve and memory T cells can most simply be characterised by the reciprocal expression of the CD45RA or CD45RO isoforms [1,2]. In general, na?ve (CD45RA+/CD45RO-) T cells represent the most homogeneous pool of T cells as they lack most effector functions. These cells migrate through secondar
Hepatitis E Virus Infection in HIV Positive ART Naive and Experienced Individuals in Nigeria  [PDF]
Georgina N. Odaibo, David O. Olaleye
World Journal of AIDS (WJA) , 2013, DOI: 10.4236/wja.2013.33029
Abstract:

Background: Studies have shown Hepatitis E Virus to be a causative agent of acute and chronic hepatitis in severely immunocompromised patients such as organ transplant recipients and person with HIV infection. This study was designed to determine the burden of HEV infection among HIV positive individuals in Nigeria and the effect of HIV treatment on the burden of HEV infection among this group of patients. Methods: Aliquot of plasma samples collected for laboratory investigations such as CD4 enumeration, blood chemistry (AST, ALT, Creatine, Urea) were used to determine the presence of HEV IgG and IgM antibodies using commercially available ELISA. Samples analysed in the study were collected from 180 HIV positive individuals (90 ART naive and 90 ART experienced) attending the ART clinic at the University College Hospital, Ibadan, Nigeria. Results: Twenty two of the 180 (12.2%) samples were positive for either HEV IgG (20/180) or IgM (2/180). The rate of HEV IgG was higher among ART naive individuals and the two IgM positive persons were ART naive. There was no significant difference in the mean CD4 count and mean ALT between HEV seronegative and seropositive individuals (P = 0.8 and 0.2 respectively). Conclusions: The results of this study suggest the need to test for HEV infection in HIV positive individuals for the early diagnosis and proper management since HEV is known to be fulminant in the presence of underlying liver disease that is common among HIV infected persons. In addition, the use of ART may reduce the incidence of HEV infection in HIV positive persons.

HIV-1 integrase resistance among antiretroviral treatment naive and experienced patients from Northwestern Poland  [cached]
Parczewski Mi?osz,Bander Dorota,Urbańska Anna,Boroń-Kaczmarska Anna
BMC Infectious Diseases , 2012, DOI: 10.1186/1471-2334-12-368
Abstract: Background HIV integrase inhibitor use is limited by low genetic barrier to resistance and possible cross-resistance among representatives of this class of antiretrovirals. The aim of this study was to analyse integrase sequence variability among antiretroviral treatment naive and experienced patients with no prior integrase inhibitor (InI) exposure and investigate development of the InI drug resistance mutations following the virologic failure of the raltegravir containing regimen. Methods Sequencing of HIV-1 integrase region from plasma samples of 80 integrase treatment naive patients and serial samples from 12 patients with observed virologic failure on raltegravir containing treatment whenever plasma vireamia exceeded >50 copies/ml was performed. Drug resistance mutations were called with Stanford DB database and grouped into major and minor variants. For subtyping bootstrapped phylogenetic analysis was used; Bayesian Monte Carlo Marcov Chain (MCMC) model was implemented to infer on the phylogenetic relationships between the serial sequences from patients failing on raltegravir. Results Majority of the integrase region sequences were classified as subtype B; the remaining ones being subtype D, C, G, as well as CRF01_AE , CRF02_AG and CRF13_cpx recombinants. No major integrase drug resistance mutations have been observed in InI-treatment naive patients. In 30 (38.5%) cases polymorphic variation with predominance of the E157Q mutation was observed. This mutation was more common among subtype B (26 cases, 54.2%) than non-B sequences (5 cases, 16.7%), p=0.00099, OR: 5.91 (95% CI:1.77-22.63)]. Other variants included L68V, L74IL, T97A, E138D, V151I, R263K. Among 12 (26.1%) raltegravir treated patients treatment failure was observed; major InI drug resistance mutations (G140S, Q148H and N155H, V151I, E92EQ, V151I, G163R) were noted in four of these cases (8.3% of the total InI-treated patients). Time to the development of drug resistance ranged from 2.6 to 16.3 months with mean increase of HIV viral load of 4.34 (95% CI:1.86-6.84) log HIV-RNA copies/ml at the time of emergence of the major mutations. Baseline polymorphisms, including E157Q were not associated with the virologic failure on raltegravir. Conclusions In InI treatment naive patients polymorphic integrase sequence variation was common, with no major resistance mutants. In the treatment failing patients selection of drug resistance occurred rapidly and followed the typical drug resistance pathways. Preexisting integrase polymorphisms were not associated with the treatment failure.
Population-based survey of HIV sero-status and vertical transmission among naive pregnant women in Sokoto, Nigeria  [PDF]
Fiekumo Igbida Buseri, Charity Ngozi Okonkwo
Asian Journal of Medical Sciences , 2015, DOI: 10.3126/ajms.v6i3.11530
Abstract: Background: This study aims at investigating the seroprevalence of HIV infection among status naive pregnant women and probable vertical transmission in Sokoto, Nigeria. Materials and Methods : This cross-sectional study examined 13,026 apparently healthy pregnant women aged between 14 and 45 years and 312 mother-baby pairs in 4 different hospital settings in Sokoto State, North West, Nigeria between March, 2011 and February, 2013. The babies were aged between 8 and 16 months. HIV screening was performed using qualitative rapid tests and ELISA and HIV-DNA polymerase chain reaction (PCR) techniques. Measurement of CD4+ T-lymphocytes was carried out by the BD FACScount System. All seropositive pregnant women were immediately placed on triple antiretroviral therapy (ART) throughout the duration of the pregnancy and beyond. Results: An overall 2.4% prevalence of HIV-1 infection among the pregnant women and 20.5% incident of mother-to-child transmission were found. Of the seropositive pregnant women, 75.0% were full-time house wives, 13.8% and 11.2% were traders and civil servants respectively; of which, 70.2% were within the ages of 14 and 27 years (youthful predominance). Pearson’s χ 2 analysis did not show any statistically significant difference in the Mean values in the 4 health facilities (χ 2 =2.084, df=3, P-value=0.555). Similarly, no significant difference in HIV seropositivity in the demographic data of the pregnant women were observed (P>0.05). Infection was recorded in all age groups but there was no statistical significance between age groups and infection (P = 0.833). Of the 64 seropositive babies, 62 (92.5%) contracted HIV from antiretroviral therapy non-adherence mothers (χ 2 =271.457, df=1, P<0.01), OR=1506.6 (95%CI=285.5-7950.4). Conclusion: This study found high prevalence of vertical transmission due to ART non-adherence. Intervention initiatives should, therefore, focus seriously on ART non-adherence. DOI: http://dx.doi.org/10.3126/ajms.v6i3.11530 Asian Journal of Medical Sciences Vol.6(3) 2015 49-57 ? ?
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