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Viral Suppression (viral + suppression)
Selected AbstractsViral suppression of RNA silencing: 2b wins the Golden Fleece by defeating ArgonauteBIOESSAYS, Issue 4 2007Virginia Ruiz-Ferrer In plants, virus-derived double-stranded RNA is processed into small interfering (si)RNAs by RNAse III-type enzymes. siRNAs are believed to guide an RNA-induced silencing complex (RISC) to promote sequence-specific degradation (or ,slicing') of homologous viral transcripts. This process, called RNA silencing, likely involves Argonaute (AGO) proteins that are known components of plant and animal RISCs. Plant viruses commonly counteract the silencing immune response by producing suppressor proteins, but the molecular basis of their action has remained largely unclear. A recent study by Zhang and colleagues1 now shows that the 2b suppressor of Cucumber mosaic virus directly interacts with Arabidopsis AGO1 and inhibits its slicing activity, suggesting that AGO1 might be a component of the elusive plant antiviral RISC. BioEssays 29:319,323, 2007. © 2007 Wiley Periodicals, Inc. [source] Suppression of viral replication with highly active antiretroviral therapy has no impact on the functional profile of HIV-specific CD8+ T cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2008Mariola López Abstract A better control of viral replication in long-term non-progressors has been associated with polyfunctional CD8+ T cell responses. However, low levels of HIV replication could be the cause rather than the consequence of enhanced immune responses in long-term non-progressors. The functional profile and the expansion ability of HIV-Gag- and HIV-Nef-specific CD8 responses were analysed measuring the production of MIP-1,, IL-2, TNF-, and expression of CD107, using polychromatic flow cytometry, in 36,HIV-infected patients at baseline and after 12,months of highly active antiretroviral therapy (HAART) and complete viral suppression. Most patients presented detectable Gag and Nef responses both at baseline and after 1,year of HAART, with a significant decline after achieving viral suppression. At baseline, the majority of CD8+ response was due to cells producing only MIP-1, or simultaneously MIP-1, and CD107. The functional profile did not significantly change after achieving complete viral suppression with HAART. Therefore, control of HIV-1 replication after 1,year of HAART had no significant impact on the quality of HIV-1-specific CD8 response, but the effects of treatment in long-term, or of early HAART are not known. Thus, it is still uncertain whether multifunctional CD8 responses are the cause or consequence of low plasma viremia. [source] Combination therapy with lamivudine and famciclovir for chronic hepatitis B,infected Chinese patients: A viral dynamics studyHEPATOLOGY, Issue 2 2000George Ka Lau M.D. In vitro studies have shown that lamivudine and penciclovir (the active metabolite of famciclovir) act synergistically to inhibit hepatitis B virus (HBV) replication. We compared the effectiveness of HBV viral suppression by lamivudine monotherapy versus lamivudine plus famciclovir combination therapy in Chinese patients with chronic HBV infection. Twenty-one Chinese hepatitis B e antigen (HBeAg)-positive patients, with detectable HBV DNA (Digene Hybrid Capture II), were randomized to receive either lamivudine 150 mg/d orally (group 1, 9 patients) or lamivudine 150 mg/d plus famciclovir 500 mg 3 times a day orally (group 2, 12 patients) for 12 weeks, with a follow-up period of at least 16 weeks. Serial serum HBV-DNA levels were determined and a mathematical model with provision for incomplete inhibition of virus production during therapy was applied to analyze the dynamics of viral clearance. The mean antiviral efficacy was significantly greater in group 2 than in group 1 (0.988 ± 0.012 vs. 0.94 ± 0.03, P = .0012). HBV DNA returned to pretreatment level within 16 weeks after the end of initial treatment in 4 patients (66.7%) in group 1 and none in group 2 (P = .08), who remained HBeAg positive and received no further treatment after week 12. Hence, in Chinese chronic HBeAg-positive patients, combination therapy using lamivudine and famciclovir was superior to lamivudine monotherapy in inhibiting HBV replication. Further studies of longer duration are needed to define whether combination therapy will increase the HBeAg seroconversion rate and decrease the rate of emergence of lamivudine-resistant variants. [source] Current antiviral therapies for chronic hepatitis BHEPATOLOGY RESEARCH, Issue 6 2008Mari Inada Among current treatment options for chronic hepatitis B, nucleoside/nucleotide analog therapy has better tolerability and most patients respond to the therapy, while interferon (IFN) therapy has rather severe side-effects and a lower response rate. However, nucleoside/nucleotide analog therapies have problems of the emergence of drug resistance and poor sustainability of response after discontinuation. After the first nucleoside/nucleotide analog lamivudine, adefovir and entecavir are now utilized in many countries. Adefovir has efficacy for lamivudine resistant patients and current data suggests that adding adefovir to ongoing lamivudine is better than switching to adefovir in terms of viral suppression and the occurrence of resistance. Entecavir can be the first choice for naïve patients, although cross-resistance has been known for lamivudine resistant patients and mutational screening should take place before using entecavir with such patients. Many other new nucleoside/nucleotide analogs are being developed such as telbivudine, clevudine and tenofovir; the details of each drug will be disclosed in near future. [source] Performance of a World Health Organization first-line regimen (stavudine/lamivudine/nevirapine) in antiretroviral-naïve individuals in a Western settingHIV MEDICINE, Issue 5 2007LWY Tam Objectives In 2003, the World Health Organization (WHO) and Joint United Nations Programme on HIV/AIDS (UNAIDS) introduced the ,3 by 5 Initiative' to treat 3 million individuals by the end of 2005. This study evaluates the time to treatment termination, viral load suppression, and detection of drug resistance among antiretroviral-naïve individuals initiating stavudine/lamivudine/nevirapine (d4T/3TC/NVP) in British Columbia, Canada, to provide a context for future programme planning. Methods Primary outcome was time to treatment termination. Secondary outcome was time to viral suppression. Accumulation of drug resistance mutations was followed systematically in the first 145 individuals over 30 months. Cox proportional hazard regression identified factors associated with termination and suppression. Results 312 antiretroviral-naïve individuals initiated d4T/3TC/NVP between August 1996 and September 2003. Median follow-up time was 26.5 months (interquartile range [IQR] 6.8,46.5). At a median of 12.4 months (IQR 4.3,33.3), 132 (42.3%) patients switched treatment, 53 (17.0%) stopped therapy and 26 (8.3%) died. Of 308 subjects with baseline viral load >500 copies/mL, 223 (72.4%) suppressed to ,500 copies/mL at a median of 2.0 months. Among 145 (46.5%) individuals followed longitudinally, resistance mutations to NNRTI, 3TC, or other NRTI were detected in 11 (7.6%), six (4.1%) and four (2.8%) individuals after 12 months of therapy; and in 23 (15.9%), 17 (12.0%), and six (4.1%) individuals after 30 months. Conclusions The population requiring second-line treatment was 30% at 12 months and 40% at 24 months; 20% had detectable drug resistance mutations by 30 months. While these results are from a Western setting, they illustrate the need to consider second- and third-line approaches as antiretroviral treatment scale-up continues in the developing world. [source] Regulation of adiponectin in adipocytes upon exposure to HIV-1HIV MEDICINE, Issue 4 2006J-LG Sankalé Objectives Adipose dysregulation, dyslipidemia, and insulin resistance are hallmarks of HIV-related lipodystrophy. The precise mechanisms behind these disturbances are unknown. In HIV-infected patients, we previously demonstrated a strong relationship between lipodystrophy and levels of adiponectin, an adipose peptide implicated in regulation of glucose and lipid metabolisms. In this study we investigated the effect of HIV on adipocytes, to determine whether HIV can directly infect adipocytes and/or alter the regulation and secretion of the adipocyte-derived hormone adiponectin. Methods Human subcutaneous preadipocytes and adipocytes were exposed to HIV-1 under various conditions. Adiponectin was measured in supernatants and cell lysates. Results Although adipocytes expressed CD4, the major HIV receptor, they could not be infected in vitro. However, exposure to HIV dramatically increased the secretion of adiponectin from human adipocytes, in the absence of infection. This was exacerbated with sustained exposure to HIV in a transwell assay. Further, human peripheral mononuclear cells also produced adiponectin, but this was largely dependent upon T-cell activation. Conclusions We propose that the stimulation of adiponectin production by HIV can perturb adiponectin regulation, leading to substantially decreased levels upon viral suppression by antiretroviral therapy. These data suggest a potential molecular mechanism of adiponectin regulation in HIV-infected patients. [source] Successful administration of aggressive chemotherapy concomitant to tuberculostatic and highly active antiretroviral therapy in a patient with AIDS-related Burkitt's lymphomaHIV MEDICINE, Issue 1 2005C Lehmann Treatment of AIDS-related malignant lymphoma (ARL) remains a therapeutic challenge. There are concerns not only about infectious and haematological complications in HIV-infected patients during intensive chemotherapy, but also about potential interactions between chemotherapy and highly active antiretroviral therapy (HAART). Current data on patients treated concomitantly with intensive chemotherapy and HAART are limited, and no data exist on patients with ARL suffering from active opportunistic infections. We report the case of a 38-year-old man with advanced HIV-1 infection, pulmonary tuberculosis and Burkitt's lymphoma. Intensive chemotherapy was administered in parallel with tuberculostatic therapy and HAART. Six months later, the patient achieved not only a complete remission of Burkitt's lymphoma and sustained viral suppression, but also a full recovery from tuberculosis. This case report provides some useful observations on the successful application of intensive chemotherapy in addition to tuberculostatic therapy and HAART in HIV-infected patients. [source] Pre- and post-treatment predictors of the early achievement of HBeAg loss in lamivudine-resistant patients receiving adefovir therapyJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 7 2007Jeong Won Jang Abstract Background and Aim:, This study investigated the clinical variables that predict hepatitis B e antigen (HBeAg) loss in lamivudine-resistant patients receiving adefovir therapy. Methods:, Fifty-six consecutive HBeAg-positive patients treated with adefovir for at least 12 months were enrolled in this study. All had serum alanine aminotransferase (ALT) levels over twice the upper limit of normal (ULN) as a result of lamivudine resistance. Predictors of HBeAg loss after switching from lamivudine to adefovir were examined. Results:, During the follow-up period, 18 (32.1%) of 56 patients showed a loss of HBeAg. The estimated rates of HBeAg loss at 6, 12, and 18 months were 11.5%, 26.8%, and 42.9%, respectively. Univariate analysis revealed that pretreatment ALT levels >10 × ULN (P = 0.029), a viral load at 3 months of therapy (P = 0.017), and viral decline by >3 log10 from baseline at 3 months (P < 0.001) were significantly associated with the loss of HBeAg within 12 months of therapy. With multivariate analysis using the stepwise logistic regression model, pretreatment ALT > 10 × ULN (odds ratio [OR], 4.22; 95% confidence interval [CI], 1.09,19.44; P = 0.044) and viral suppression >3 log10 at 3 months (OR, 10.39; 95% CI, 1.86,58.07; P = 0.008) were identified as the two independent predictors of HBeAg loss. Conclusions:, Pretreatment ALT levels and the initial pattern of post-treatment viral decline are the strongest predictors of the early achievement of HBeAg loss following treatment with adefovir in lamivudine-resistant patients. These results may provide useful information for the optimal timing of adefovir rescue as well as for better monitoring after treatment. [source] Susceptibility of hepatitis B virus to lamivudine restored by resistance to adefovirJOURNAL OF MEDICAL VIROLOGY, Issue 3 2009H.L. Zaaijer Abstract Serial monotherapy and add-on regimes for treatment of chronic hepatitis B virus (HBV) infection may induce the accumulation of viral resistance mutations in patients, reducing the options for ongoing viral suppression. The induction of antiviral resistance by serial application of polymerase inhibitors does not necessarily imply that the subsequent combined use of the drugs will fail. Some HIV strains resistant to one polymerase inhibitor show increased susceptibility to another polymerase inhibitor. After failure of sequential lamivudine and adefovir monotherapy, two patients with hepatitis B changed to treatment with lamivudine plus adefovir and had renewed suppression of HBV. To study the mutational history of resistant HBV subpopulations in the two patients, a part of the HBV polymerase gene was amplified, cloned, sequenced, and analyzed for the presence of mutations, in sequential plasma samples. In both patients serial monotherapy caused the replacement in all HBV clones of wild-type virus by classical lamivudine resistant mutants (L180M and M204V/I), which were replaced subsequently by adefovir resistant mutants (A181V and N236T). When finally lamivudine was added to adefovir, the A181V adefovir mutation persisted in all clones and lamivudine-related mutations did not reappear. During 18 months of combination therapy, HBV-DNA levels decreased 10,000, respectively, 1,000-fold, despite the earlier resistance to lamivudine and adefovir. Although clinically insufficient, this effect indicates that HBV polymerase resistance mutations may be antagonistic, which is relevant if chronic HBV infection is to be treated by a combination of polymerase inhibitors. J. Med. Virol. 81:413,416, 2009. © 2009 Wiley-Liss, Inc. [source] Favorable outcome of ex-vivo purging of monocytes after the reintroduction of treatment after interruption in patients infected with multidrug resistant HIV-1,JOURNAL OF MEDICAL VIROLOGY, Issue 11 2007Hamid Hasson Abstract In multidrug resistant patients treatment interruptions allow the selection of archived wild-type drug-susceptible viruses that compete for the less fit drug-resistant strains. However, the selection of viruses with increased replicative capacity is often followed by a loss of CD4+ T cells. In addition, drug resistant variants later re-emerge limiting the overall clinical benefit of treatment interruption. Blood monocytes are a key component of the HIV reservoir and can be partially removed by a system for purging of myeloid cells (MYP). This study tested the safety and efficacy of MYP on multidrug resistant patients who underwent treatment interruption. Twelve patients were randomized to receive or not six cycles of MYP during treatment interruption. An optimized antiretroviral regimen was reintroduced after the reappearance of a drug susceptible genotype. Following therapy reintroduction, a long lasting increase in CD4+ T cell counts was observed only in the treatment interruption,+,MYP patients but not in the control patients. Five/six treatment interruption,+,MYP patients never experienced virological rebound during a median follow up period of 98 weeks. In contrast, 4/6 patients who did not receive MYP never reached complete viral suppression and had a virological rebound after a median of 16.5 weeks after treatment reintroduction. The difference between the two groups in the time to virological rebound was statistically significant (P,=,0.021). A consistent decrease of HIV DNA load in CD14+ purified cells was observed only in treatment interruption,+,MYP patients. These data suggest that MYP can improve the immunological and virological response to treatment interruption. J. Med. Virol. 79:1640,1649, 2007. © 2007 Wiley-Liss, Inc. [source] Significant link between sCD30 changes and HIV viremia in patients treated with HAART,JOURNAL OF MEDICAL VIROLOGY, Issue 12 2006Priscilla Biswas Abstract Elevated sCD30 levels were generally associated with poor prognosis in chronic HIV infection prior to the era of highly active antiretroviral therapy (HAART). Little information is available on sCD30 and HIV-1 viremia. In this study, the association between sCD30 and HIV-1 viremia was investigated in HIV-infected patients who underwent HAART. sCD30 was measured in 276 patients prior (T0) and 6 months after HAART (T6). Standard survival analyses were used to evaluate the prognostic value of sCD30 and sCD30 change from baseline to predict the virological response to HAART. Higher levels (>30 U/ml) of sCD30 prior to HAART were associated with relatively higher viremia (P,=,0.0001) and tended to be associated with a lower chance of achieving virological success (P,=,0.13). The median T6 sCD30 level in patients who concomitantly had viremia >500 copies/ml was higher than the median sCD30 level of those with viremia ,500 copies/ml (P,=,0.002). Conversely, within the patients who achieved viral suppression on HAART, those who had concomitantly a larger reduction in sCD30 subsequently experienced a higher rate of virological failure (P,=,0.04). A strong, but complex, link exists between sCD30 levels and HIV viremia in the era of HAART. The change in sCD30 levels from pre-therapy to the date of first viral suppression could be used to identify patients who are more likely to experience later virological rebound among those who achieve initially virological success. J. Med. Virol. 78:1513,1519, 2006. © 2006 Wiley-Liss, Inc. [source] Joint Inference on HIV Viral Dynamics and Immune Suppression in Presence of Measurement ErrorsBIOMETRICS, Issue 2 2010L. Wu Summary:, In an attempt to provide a tool to assess antiretroviral therapy and to monitor disease progression, this article studies association of human immunodeficiency virus (HIV) viral suppression and immune restoration. The data from a recent acquired immune deficiency syndrome (AIDS) study are used for illustration. We jointly model HIV viral dynamics and time to decrease in CD4/CD8 ratio in the presence of CD4 process with measurement errors, and estimate the model parameters simultaneously via a method based on a Laplace approximation and the commonly used Monte Carlo EM algorithm. The approaches and many of the points presented apply generally. [source] Peripheral CD4 loss of regulatory T cells is associated with persistent viraemia in chronic HIV infectionCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2007C. A. R. Baker Summary Chronic HIV infection is associated with T cell abnormalities and altered effector function. Regulatory T cells (Treg) are CD4+ T cells that play a critical role in regulating the immune system. The impact of regulatory T cells on HIV infection and disease progression may be highly significant. We hypothesize that chronic antigenic stimulation from a persistent, high viraemic state may promote a population of Treg that contributes to HIV-associated immune dysfunction. We evaluated the pattern of Treg in chronically infected, HIV-positive individuals over a course of 6 months. Treg are depleted at a distinct rate from that of absolute CD4 cells and loss of Treg is slower in the presence of viral suppression. In vitro depletion of CD25+ CD4+ cells resulted in increased Gag-specific CD4 and CD8 responses. A significant correlation between ex vivo measurement of Treg and Gag-specific CD4 T cell responses was observed (r = ,0·41, P = 0·018) with a trend observed with Gag-specific CD8 T cell responses (P = 0·07). The impact of HIV infection on the Treg population directly complicates the measured effect of Treg on the immune dysfunction although our data support the important role of Treg on modulating the effector T cell response in chronic infection. [source] Analysis of the influence of therapy and viral suppression on high-risk sexual behaviour and sexually transmitted infections among patients infected with human immunodeficiency virus in TaiwanCLINICAL MICROBIOLOGY AND INFECTION, Issue 7 2006S.-C. Chen Abstract This study examined the effects of certain characteristics of human immunodeficiency virus (HIV)-infected patients related to the risks of practising unprotected sex (UPS) among 919 HIV-infected patients who attended the sexually transmitted disease (STD) clinic of the Taipei City STD Control Center, Taiwan, during the period January,July 2004. After learning that they were HIV-positive, 517 (56%) subjects had practised UPS, 476 (52%) had a new STD diagnosis, and 106 (12%) had used some form of injected drug. UPS was reported by 76% of homosexual/bisexual males, 19% of heterosexual males and 5% of females, and was reported more often by those individuals with casual sexual partners (p < 0.001). According to multivariate logistic regression analyses, UPS was associated with male-to-male sexual intercourse (OR 2.46; 95% CI 1.26,4.86, p < 0.001), with casual sexual partners (OR 2.82; 95% CI 1.62,4.88, p < 0.001), and with an individual's knowledge of his/her HIV status for >,11 years (OR 2.06; 95% CI 1.02,4.18, p < 0.05). Although using anti-retroviral therapy to prevent sexual transmission of HIV is rational, the avoidance of at-risk sexual behaviour should also be a priority among HIV-seropositive individuals. Ongoing risk-reduction counselling related to HIV transmission is needed to reduce certain sexual behaviours associated with HIV transmission. [source] | |||||||||||||||||||||||||