Showing papers in "Antiviral Therapy in 2008"
Journal Article•
TL;DR: Silver nanoparticles could inhibit the in vitro production of HBV RNA and extracellular virions and hypothesize that the direct interaction between these nanoparticles and HBV double-stranded DNA or viral particles is responsible for their antiviral mechanism.
Abstract: Background Silver nanoparticles have been shown to exhibit promising cytoprotective activities towards HIV-infected T-cells; however, the effects of these nanoparticles towards other kinds of viruses remain largely unexplored. The aim of the present study was to investigate the effects of silver nanoparticles on hepatitis B virus (HBV). Methods Monodisperse silver nanoparticles with mean particle diameters of approximately 10 nm (Ag10Ns) and approximately 50 nm (Ag50Ns) were prepared from AgNO3 in HEPES buffer. The in vitro anti-HBV activities of these particles were determined using the HepAD38 cell line as infection model. Results Ag10Ns and Ag50Ns were able to reduce the extracellular HBV DNA formation of HepAD38 cells by >50% compared with the vehicle control (that is, HepAD38 cells in the absence of silver nanoparticles). Silver nanoparticles had little effect on the amount of HBV covalently closed circular DNA (cccDNA), but could inhibit the formation of intracellular HBV RNA. Gel mobility shift assays indicated that Ag10Ns bound HBV double-stranded DNA at a DNA:silver molar ratio of 1:50; an absorption titration assay showed that the nanoparticles have good binding affinity for HBV DNA with a binding constant (Kb) of (8.8 +/- 1.0)x10(5) dm(3)mol(-1). As both the viral and Ag10Ns systems are in the nanometer size range, we found that Ag10Ns could directly interact with the HBV viral particles as revealed by transmission electronic microscopy. Conclusions Silver nanoparticles could inhibit the in vitro production of HBV RNA and extracellular virions. We hypothesize that the direct interaction between these nanoparticles and HBV double-stranded DNA or viral particles is responsible for their antiviral mechanism.
514 citations
TL;DR: Reports from resource-limited countries suggest that initial ART programmes are as effective as in resource-rich countries, which should limit HIV drug resistance if programme effectiveness continues during scale-up.
Abstract: Darunavir (TMC114) is a new HIV protease inhibitor that has demonstrated substantial antiretroviral activity against wild-type HIV-1 virus and multidrug-resistant strains Darunavir inhibits and is primarily metabolized by cytochrome P450 3A (CYP3A) isoenzymes and is coadministered with low-dose ritonavir (darunavir/r); ritonavir is an inhibitor of CYP3A isoenzymes and pharmacologically enhances darunavir, resulting in increased plasma concentrations and allowing for a lower daily dose The t1/2 (terminal elimination half-life) of darunavir is 15 h in the presence of ritonavir An extensive darunavir/r drug-drug interaction programme has been undertaken, covering a wide range of therapeutic areas Studies conducted in HIV-negative healthy volunteers and in HIV-infected patients show that the potential for interactions is well characterized and the interactions are manageable For most drugs investigated, no dose adjustments of darunavir/r or the co-administered drug are required This article reviews all the pharmacokinetic and drug-drug interaction studies conducted to date for darunavir/r, providing guidance on how to co-administer darunavir/r with many other antiretroviral or non-antiretroviral medications commonly used in HIV-infected individuals
305 citations
TL;DR: The WHO HIVDR threshold survey method is feasible in resource-limited countries and produces information relevant to ART and drug resistance prevention planning and the main challenges in implementation are acquiring sufficient numbers of eligible specimens and optimizing specimen handling.
Abstract: Background: The World Health Organization (WHO) HIV drug resistance (HIVDR) threshold survey method was developed for surveillance of transmitted HIVDR in resource-limited countries. The method is being implemented with minimal resources as a routine public health activity to produce comparable results in multiple countries and areas within countries. Transmitted drug resistant HIV strains will be seen first in cities or health districts where antiretroviral treatment (ART) has been widely available for years. WHO recommends countries begin surveillance in these areas. Methods: Each survey requires ≤47 specimens from individuals consecutively diagnosed with HIV to categorize resistance to each relevant drug class as 15%. Use of routinely collected information and remnant specimens is recommended to minimize costs. Site and individual eligibility criteria are designed to minimize inclusion of ARV-experienced individuals and individuals infected before ART was available. Results: Surveys have been implemented in 21 countries. In this supplement, seven countries report results of <5% transmitted HIVDR in areas where ART has been available for the longest time period. The main challenges in implementation are acquiring sufficient numbers of eligible specimens and optimizing specimen handling. Conclusion: The WHO HIVDR threshold survey method is feasible in resource-limited countries and produces information relevant to ART and drug resistance prevention planning.
275 citations
TL;DR: The World Health Organization (WHO) recommends a minimum-resource strategy for prevention and assessment of HIVDR in resource-limited countries, which should limit HIV drug resistance if programme effectiveness continues during scale-up.
Abstract: Antiretroviral treatment (ART) for HIV is being scaled up rapidly in resource-limited countries. Treatment options are simplified and standardized, generally with one potent first-line regimen and one potent alternate first-line regimen recommended. Widespread HIV drug resistance (HIVDR) was initially feared, but reports from resource-limited countries suggest that initial ART programmes are as effective as in resource-rich countries, which should limit HIV drug resistance if programme effectiveness continues during scale-up. ART interruptions must be minimized to maintain viral suppression on the first-line regimen for as long as possible. Lack of availability of appropriate second-line drugs is a concern, as is the additional accumulation of resistance mutations in the absence of viral load testing to determine failure. The World Health Organization (WHO) recommends a minimum-resource strategy for prevention and assessment of HIVDR in resource-limited countries. The WHO's Global Network HIVResNet provides standardized tools, training, technical assistance, laboratory quality assurance, analysis of results and recommendations for guidelines and public health action. National strategies focus on assessments to guide immediate public health action to improve ART programme effectiveness in minimizing HIVDR and to guide regimen selection. Globally, WHO HIVResNet collects and analyses data to support evidence-based international policies and guidelines. Financial support is provided by major international organizations and technical support from HIVDR experts worldwide. As of December 2007, 25 countries were planning or implementing the strategy; seven countries report results in this supplement.
243 citations
TL;DR: There was no clear evidence to suggest that ART interruption per se or a higher HIV viral load were associated with an increased CVD risk in the DC group, and Lipid changes were less favourable among DC compared with VS patients, which could offer a partial explanation.
Abstract: BackgroundThe SMART trial found a raised risk of cardiovascular disease (CVD) events in patients undergoing CD4+ T cell-count guided intermittent antiretroviral therapy (ART) compared with patients
237 citations
TL;DR: The WHO has developed a population-based HIVDR assessment and prevention strategy, which includes standardized HIVDR monitoring surveys in populations receiving first-line ART at sentinel sites, which will inform evidence-based decision making regarding national and global ART regimen selection and minimize the emergence of HIVDR at a population level.
Abstract: The World Health Organization (WHO) estimates that >2 million people will have started antiretroviral therapy (ART) by the end of 2006. As the development of some HIV drug resistance (HIVDR) is inevitable in populations taking ART, the emergence of HIVDR must be balanced against the benefits of providing ART, including improved health outcomes and decreased HIV/AIDS-associated morbidity and mortality. ART programmes should operate to minimize the emergence of HIVDR in populations receiving therapy and HIVDR itself must be monitored to ensure ongoing regimen efficacy. ART regimens in resource-limited settings are usually selected at the national level following a public health approach: generally only one first-line regimen with alternate regimen(s) incorporating within-class drug substitutions are available in the public sector. The WHO has developed a population-based HIVDR assessment and prevention strategy, which includes standardized HIVDR monitoring surveys in populations receiving first-line ART at sentinel sites. The WHO surveys monitor HIVDR prevention in sentinel sites by utilizing a standardized, minimum-resource prospective survey methodology to assess the success of adult and paediatric ART sites in preventing HIVDR emergence during the first year of ART. The surveys also identify associated factors that can be addressed at the level of the ART site or programme. WHO HIVDR monitoring surveys are designed to be integrated easily into a country's ongoing, routine HIV-related evaluation activities. Performed regularly at representative sites, the data generated will inform evidence-based decision making regarding national and global ART regimen selection and minimize the emergence of HIVDR at a population level.
193 citations
TL;DR: If no contraindications are present, interferon may be considered as first-line therapy in all genotype A patients and in individuals with genotype B who are HBeAg positive, because this analysis is explorative and hypothesis generating only.
Abstract: ObjectiveStandard treatment for hepatitis B is either based on interferon or on nucleos(t)ide analogues. Available evidence on treatment outcome by hepatitis B virus genotype was summarized and ana...
118 citations
TL;DR: It is confirmed that concomitant rifampicin substantially decreases concentration of both efavirenz and nevirapine; however, for efvirenz this effect was more than counterbalanced by the effect of ethnicity and increased efAVirenz dose.
Abstract: BackgroundThe aim of this study was to examine factors influencing plasma concentration of efavirenz and nevirapine.MethodsData from the Liverpool Therapeutic Drug Monitoring (TDM) registry were li...
110 citations
TL;DR: Using the threshold survey, resistance prevalence overall and for each drug class in 2002 and 2004 was <5% for the Gauteng province of South Africa, suggesting that surveillance should be conducted annually among untreated populations to determine if this increases with time.
Abstract: Background: Surveillance for transmitted HIV-1 drug resistance was conducted among drug-naive HIV-1-infected pregnant women in South Africa, where single-dose nevirapine has been in use since 2001 and a national antiretroviral treatment programme started in 2004. Methods: All subjects were from the Gauteng Province and were part of the 2002 and 2004 annual antenatal HIV seroprevalence survey conducted by the South African National Department of Health. All subjects met the inclusion criteria as set out by the World Health Organisation guidelines for HIV-1 transmitted drug resistance surveillance (women <22 years of age and in first pregnancy). Genotyping was performed on viral RNA by sequencing the protease and reverse transcriptase genes. Samples were also tested for the K103N mutation using a highly sensitive allele-specific real-time PCR assay (AS-PCR). Results: Of 128 eligible participants from 2002, 65 (51%) samples were successfully amplified. None of them had evidence of resistance mutations by genotyping or by AS-PCR. Of 117 eligible participants from 2004, 48 (41%) samples were successfully amplified. Of these, one had T69D and one had the K70R resistance mutation, to give a total of 2/48 (4.2%) participants with evidence of resistance mutations by genotyping. One sample that was wild-type by genotyping was positive for K103N by AS-PCR. All samples clustered phylogenetically with HIV-1 subtype C, the predominant subtype circulating in South Africa. Conclusions: Using the threshold survey, resistance prevalence overall and for each drug class in 2002 and 2004 was <5% for the Gauteng province of South Africa. The detection of a low frequency of resistance mutations in the 2004 survey suggests that surveillance should be conducted annually among untreated populations to determine if this increases with time.
109 citations
TL;DR: Mitochondrial changes and oxidative damage could partly explain the premature senescence of fibroblasts and adipose cells induced by stavudine and zidovudine in HIV-infected patients taking antiretroviral drugs.
Abstract: ObjectivesTreatment of HIV-infected patients is associated with early onset of aging-related comorbidities. Some of the adverse effects of antiretroviral therapy have been attributed to the mitocho...
109 citations
TL;DR: An IP-10 cutoff level of 400 pg/ml might serve as a useful predictive marker for anti- HCV therapy in HIV-HCV-coinfected patients because it could discriminate patients with expected NR or HCV relapse after therapy from patients with an SVR before starting antiviral treatment.
Abstract: BackgroundInterferon (IFN)-γ inducible protein 10 (IP-10) is increased in hepatitis C virus (HCV) monoinfection, correlates with hepatic inflammation and predicts non-response (NR) to antiviral the...
TL;DR: The use of abacavir might interfere with the anti-HCV activity of PEG-IFN plus RBV as both antivirals are guanosine analogues, which might explain this observation, which is more prominent in patients with lower RBV exposure.
Abstract: BackgroundThere is little information about the influence of antiretroviral drugs on the antiviral activity of pegylated interferon (PEG-IFN) plus ribavirin (RBV) against hepatitis C virus (HCV).Me...
TL;DR: Prevalence of transmitted HIVDR among recently infected pregnant women in Dar es Salaam is low and should be repeated during the next HIV sentinel survey and extended to other regions where ART is being scaled up.
Abstract: Background: In resource-limited settings where antiretroviral treatment (ART) access is being scaled-up, the World Health Organization (WHO) recommends surveillance of transmitted HIV drug resistance (HIVDR). We used the WHO HIVDR threshold survey method to assess transmitted HIVDR in Dar es Salaam where ART was introduced in 1995 and where ~11,000 people are currently on ART. Methods: From November 2005 to February 2006, dried blood spot (DBS) specimens were made from remnant specimens collected during the national HIV serosurvey from 60 primagravidas <25 years old attending six antenatal clinics for routine syphilis testing. Genotyping was performed at the Centers for Disease Control and Prevention, Atlanta, Georgia, USA. Protease and reverse transcriptase drug resistance mutations were identified using the Stanford University HIV drug resistance database. We used the National Institutes of Health genotyping tool for HIV-1 subtyping. HIVDR prevalence categorization was based on the WHO threshold survey binomial sequential sampling method. Results: Among the 60 eligible specimens collected, 50 DBS were successfully amplified using RT-PCR. Sequencing was performed on the first 39 specimens: 13 (33.3%) were subtype A1, 13 (33.3%) subtype C, and 4 (10.3%) subtype D, the remainder differed in the closest subtype based on protease versus reverse transcriptase. No resistance mutations were seen; HIVDR to all drug classes was categorized as <5%. Conclusions: Our survey indicates that prevalence of transmitted HIVDR among recently infected pregnant women in Dar es Salaam is low (<5%). The survey should be repeated during the next HIV sentinel survey in Dar es Salaam and extended to other regions where ART is being scaled up.
TL;DR: Patients on first-line HAART who maintain consistent VL undetectability for 1 year have a low risk of subsequent virological failure, including women and patients on Pl/r-based HAART.
Abstract: BackgroundWe aimed to investigate the long-term virological outcomes of a cohort initially showing good responses to first-line highly active antiretroviral therapy (HAART) with no evidence of viro
TL;DR: In this paper, a detailed understanding of the hepatitis B virus-specific T-cell responses may potentially lead to a better understanding of how the immune response to hepatitis B viruses (HBV) works.
Abstract: BackgroundThe immune response to hepatitis B virus (HBV) is important for both viral control and disease pathogenesis. A detailed understanding of the HBV-specific T-cell responses may potentially ...
TL;DR: In this article, severe unexplained liver disease in HIV-infected individuals have been reported and are often associated with exposure to didanosine (ddI) and nodular regenerative hyper...
Abstract: BackgroundCases of severe unexplained liver disease in HIV-infected individuals have recently been reported and are often associated with exposure to didanosine (ddI) and nodular regenerative hyper...
TL;DR: Patients undergoing successful anti-HBV therapy with potent nucleos(t)ide analogues seem to indirectly benefit from suppression of HDV replication, albeit not very efficiently.
Abstract: BackgroundHepatitis delta virus (HDV) has a unique replication process that requires coinfection with hepatitis B virus (HBV). Treatment is currently limited to interferon therapy. The role of pote...
TL;DR: Baseline anaemia continued to predict mortality (and to a lesser extent progression to AIDS) in patients with normal haemoglobin or mild anaemia at 6 months, including in patients whose haenoglobin levels improved or normalized during the first 6 months of HAART.
Abstract: BACKGROUND: In HIV type-1-infected patients starting highly active antiretroviral therapy (HAART), the prognostic value of haemoglobin when starting HAART, and of changes in haemoglobin levels, are not well defined METHODS: We combined data from 10 prospective studies of 12,100 previously untreated individuals (25% women) A total of 4,222 patients (35%) were anaemic: 131 patients (11%) had severe (<80 g/dl), 1,120 (9%) had moderate (male 80-<110 g/dl and female 80- < 100 g/dl) and 2,971 (25%) had mild (male 110- < 130 g/ dl and female 100- < 120 g/dl) anaemia We separately analysed progression to AIDS or death from baseline and from 6 months using Weibull models, adjusting for CD4+ T-cell count, age, sex and other variables RESULTS: During 48,420 person-years of follow-up 1,448 patients developed at least one AIDS event and 857 patients died Anaemia at baseline was independently associated with higher mortality: the adjusted hazard ratio (95% confidence interval) for mild anaemia was 142 (117-173), for moderate anaemia 256 (207-318) and for severe anaemia 526 (355-781) Corresponding figures for progression to AIDS were 160 (137-186), 200 (166-240) and 224 (146-342) At 6 months the prevalence of anaemia declined to 26% Baseline anaemia continued to predict mortality (and to a lesser extent progression to AIDS) in patients with normal haemoglobin or mild anaemia at 6 months CONCLUSIONS: Anaemia at the start of HAART is an important factor for short- and long-term prognosis, including in patients whose haemoglobin levels improved or normalized during the first 6 months of HAART
Journal Article•
TL;DR: A novel sequential sampling method for the surveillance of transmitted HIV drug resistance by cross-sectional survey that provides useful sample size savings and operational simplicity and could provide the basis for a rapid and reliable survey method for classifying the prevalence of transmittedAIDS drug resistance in circumstances where resources do not allow fullscale surveillance to be established.
Abstract: This article describes the development of a novel sequential sampling method for the surveillance of transmitted HIV drug resistance by cross-sectional survey. Two commonly used sequential sampling methods are described and their applicability to the problem of classifying the prevalence of transmitted HIV drug resistance investigated. Both methods are rejected due to insufficient savings in sample size and operational complexity. A novel method is proposed and this is tested using computer-based simulation. This method provides useful sample size savings and operational simplicity and could provide the basis for a rapid and reliable survey method for classifying the prevalence of transmitted HIV drug resistance in circumstances where monitoring HIV drug resistance is an important issue, but resources do not allow fullscale surveillance to be established. The method is currently being used in several such settings.
TL;DR: In HBeAg-negative CHB, combination PEG-IFN-alpha2a plus ADV for 48 weeks is safe and resulted in greater on-treatment efficacy than PEG/ifN- alpha2a monotherapy.
Abstract: BackgroundPegylated interferon (PEG-IFN)-α monotherapy is the current standard of care for short-term antiviral treatment of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB). We aim...
Journal Article•
TL;DR: A simple self-report adherence questionnaire repeatedly administered provides a sensitive measure of non-adherence that predicts viral rebound.
Abstract: BACKGROUND: The aim of this study was to explore the predictive value of longitudinal self-reported adherence data on viral rebound. METHODS: Individuals in the Swiss HIV Cohort Study on combined antiretroviral therapy (cART) with RNA 2) in the previous 28 days. Viral rebound was defined as RNA >500 copies/ml. Cox regression models with time-independent and -dependent covariates were used to evaluate time to viral rebound. RESULTS: A total of 2,664 individuals and 15,530 visits were included. Across all visits, missing doses were reported as follows: 1 dose 14.7%, 2 doses 5.1%, >2 doses 3.8% taking or =2 consecutive doses 3.2%. In total, 308 (11.6%) patients experienced viral rebound. After controlling for confounding variables, self-reported non-adherence remained significantly associated with the rate of occurrence of viral rebound (compared with zero missed doses: 1 dose, hazard ratio [HR] 1.03, 95% confidence interval [CI] 0.72-1.48; 2 doses, HR 2.17, 95% CI 1.46-3.25; >2 doses, HR 3.66, 95% CI 2.50-5.34). Several variables significantly associated with an increased risk of viral rebound irrespective of adherence were identified: being on a protease inhibitor or triple nucleoside regimen (compared with a non-nucleoside reverse transcriptase inhibitor), >5 previous cART regimens, seeing a less-experienced physician, taking co-medication, and a shorter time virally suppressed. CONCLUSIONS: A simple self-report adherence questionnaire repeatedly administered provides a sensitive measure of non-adherence that predicts viral rebound.
TL;DR: Pioglitazone 30 mg once daily for 48 weeks improved limb fat atrophy in antiretroviral-treated HIV-1-infected patients, although clinical benefits were not perceived by the patients.
Abstract: BackgroundAlthough thiazolidinediones have been shown to increase subcutaneous fat in congenital lipodystrophy, rosiglitazone did not show convincing results in HIV lipoatrophy. We assess a potenti...
Journal Article•
TL;DR: It is suggested that transmission of HIV-1 can occur despite undetectable pVL, and should be added to the discussion of prevention strategies, which should not advise the abandonment of safer-sex practices without referring to the relatively low but not impossible risk of virus transmission in this context.
Abstract: Several studies have shown that HIV-1 transmission in serodiscordant couples is significantly reduced when the plasma viral load (pVL) in the infected partner is low or undetectable However, residual infectivity in the seminal compartment despite undetectable pVL has also been shown Here we report HIV-1 transmission in a serodiscordant couple despite successful antiretroviral therapy of the HIV-infected partner The newly infected partner had a negative HIV-1 screening ELISA when his HIV-1-positive partner was already on antiretroviral treatment with undetectable pVL, which remained undetectable beyond the time of seroconversion in the initially negative partner Frozen blood samples were analyzed phylogenetically from the HIV-1-positive patient and the newly infected partner before treatment and shortly after seroconversion, respectively; they showed a true relationship On the basis of these data, the present report suggests that transmission of HIV-1 can occur despite undetectable pVL This should be added to the discussion of prevention strategies, which should not advise the abandonment of safer-sex practices without referring to the relatively low but not impossible risk of HIV-1 transmission in this context
TL;DR: Concerns are raised that TDF use could result in osteomalacia with a loss in bone mineral density at least in a subset of patients and this potentially severe long-term toxicity should be addressed in future studies.
Abstract: BACKGROUND: Tenofovir (TDF) use has been associated with proximal renal tubulopathy, reduced calculated glomerular filtration rates (cGFR) and losses in bone mineral density. Bone resorption could result in a compensatory osteoblast activation indicated by an increase in serum alkaline phosphatase (sAP). A few small studies have reported a positive correlation between renal phosphate losses, increased bone turnover and sAP. METHODS: We analysed sAP dynamics in patients initiating (n = 657), reinitiating (n = 361) and discontinuing (n = 73) combined antiretroviral therapy with and without TDF and assessed correlations with clinical and epidemiological parameters. RESULTS: TDF use was associated with a significant increase of sAP from a median of 74 U/I (interquartile range 60-98) to a plateau of 99 U/I (82-123) after 6 months (P < 0.0001), with a prompt return to baseline upon TDF discontinuation. No change occurred in TDF-sparing regimes. Univariable and multivariable linear regression analyses revealed a positive correlation between sAP and TDF use (P < or = 0.003), but no correlation with baseline cGFR, TDF-related cGFR reduction, changes in serum alanine aminotransferase (sALT) or active hepatitis C. CONCLUSIONS: We document a highly significant association between TDF use and increased sAP in a large observational cohort. The lack of correlation between TDF use and sALT suggests that the increase in sAP is because of the bone isoenzyme and indicates stimulated bone turnover. This finding, together with published data on TDF-related renal phosphate losses, this finding raises concerns that TDF use could result in osteomalacia with a loss in bone mineral density at least in a subset of patients. This potentially severe long-term toxicity should be addressed in future studies.
TL;DR: The data that must be considered to determine which of the many HIV-1 drug resistance mutations are likely to be both sensitive and specific indicators of transmitted drug resistance are reviewed.
Abstract: Programmes that monitor local, national and regional levels of transmitted HIV-1 drug resistance inform treatment guidelines and provide feedback on the success of HIV-1 treatment and prevention programmes. The World Health Organization (WHO) has established a global programme for genotypic surveillance of HIV-1 drug resistance and has recommended the adoption of a consensus definition of genotypic drug resistance. Such a definition is necessary to accurately compare transmitted drug resistance rates across geographical regions and time periods. HIV-1 diversity and the large number of mutations associated with antiretroviral drug resistance complicate the development of a consensus definition for genotypic drug resistance. This paper reviews the data that must be considered to determine which of the many HIV-1 drug resistance mutations are likely to be both sensitive and specific indicators of transmitted drug resistance. The process used to create a previously published list of drug resistance mutations for HIV-1 surveillance is reviewed and alternative approaches to this process are discussed.
TL;DR: The data indicate that an HBV polymerase rtA181T/surface truncation mutant could emerge spontaneously without previous antiviral treatment, and warrants careful re-evaluation of the current strategy of prolonged antiviral therapy.
Abstract: BackgroundPreviously, a less prevalent lamivudine-resistant mutant (rtA181T) was discovered in Taiwanese patients, in which a stop codon in the surface gene concomitantly occurred, leading to impai...
TL;DR: Pyrosequencing is ideally suited for early identification of emerging antiviral resistance in human and avian influenza infection and is a useful tool for laboratory surveillance and pandemic preparedness.
Abstract: BackgroundEmerging resistance of influenza viruses to neuraminidase inhibitors is a concern, both in surveillance of global circulating strains and in treatment of individual patients. Current meth...
Journal Article•
TL;DR: Malawi HIVDR transmission can be classified as <5% for all relevant drugs and drug classes in this population and an expanded HIVDR surveillance system will be implemented to inform the ART program as it continues to scale-up.
Abstract: Background: Malawi started rapid scale-up of antiretroviral therapy (ART) in 2004 and by December 2006 had initiated 81,821 patients on treatment in the public sector. Owing to capacity constraints, standard patient care, treatment initiation and follow up are based on World Health Organization (WHO) clinical staging and do not provide laboratory monitoring to assess treatment failure. Methods: To monitor possible transmission of HIV drug resistance (HIVDR) an HIVDR threshold surveillance based on the WHO guidelines was implemented in Malawi. Anonymous dried blood specimens were collected from routine blood samples of HIV-positive women attending primagravida antenatal care and aged <25 years. Results: Of 59 samples tested, 54 were successfully amplified indicating good specimen quality and processing. The WHO protocol algorithm to classify the prevalence of transmitted drug resistance in the site sample only required the genotyping of 34 of the samples. None of the major drug resistance mutations on the WHO surveillance list were found in these 34 specimens. Conclusions: Malawi HIVDR transmission can be classified as <5% for all relevant drugs and drug classes in this population. On the basis of the very positive experience of this survey, an expanded HIVDR surveillance system will be implemented to inform the ART program as it continues to scale-up.
TL;DR: Quantitative HBsAg and HBeAg cannot substitute for HBV DNA quantification during the assessment of antiviral therapy; however, the decline ofHBsAg does predict eventual HBs Ag clearance.
Abstract: BackgroundThe elimination of hepatitis B virus surface antigen (HBsAg) is the final goal of hepatitis B treatment, but is rarely achieved. As quantitative assays for HBsAg recently became available...
TL;DR: These results, which remain to be confirmed in large clinical trials, highlight the potential relevance of ribavirin plasma level monitoring at an early stage of treatment and could be of help in guiding antiviral therapy by offering dose adjustment in patients with ribaviral plasma level below the 2 mg/l threshold.
Abstract: BackgroundPegylated interferon/ribavirin combination is currently the standard treatment for chronic hepatitis C virus (HCV) infection. Body weight adjustment of ribavirin is crucial for response. ...