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Kholoud Porter - One of the best experts on this subject based on the ideXlab platform.
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CD4 T cell decline following HIV Seroconversion in individuals with and without CXCR4-tropic virus.
The Journal of antimicrobial chemotherapy, 2017Co-Authors: Jade Ghosn, Tatiana Bayan, Karolin Meixenberger, Laurent Tran, Pierre Frange, Antonella D'arminio Monforte, Robert Zangerle, Carmen De Mendoza, Evguenia Krastinova, Kholoud PorterAbstract:Background The natural clinical and immunological courses following HIV Seroconversion with CXCR4-tropic or dual-mixed (X4/DM) viruses are controversial. We compared spontaneous immunological outcome in patients harbouring an X4/DM virus at the time of Seroconversion with those harbouring a CCR5-tropic (R5) virus. Methods Data were included from patients participating in CASCADE, a large cohort collaboration of HIV seroconverters, with ≥2 years of follow-up since Seroconversion. The HIV envelope gene was sequenced from frozen plasma samples collected at enrolment, and HIV tropism was determined using Geno2Pheno (false-positive rate 10%). The spontaneous CD4 T cell evolution was compared by modelling CD4 kinetics using linear mixed-effects models with random intercept and random slope. Results A total of 1387 patients were eligible. Median time between Seroconversion and enrolment was 1 month (range 0-3). At enrolment, 202 of 1387 (15%) harboured an X4/DM-tropic virus. CD4 decrease slopes were not significantly different according to HIV-1 tropism during the first 30 months after Seroconversion. No marked change in these results was found after adjusting for age, year of Seroconversion and baseline HIV viral load. Time to antiretroviral treatment initiation was not statistically different between patients harbouring an R5 (20.76 months) and those harbouring an X4/DM-tropic virus (22.86 months, logrank test P = 0.32). Conclusions: In this large cohort collaboration, 15% of the patients harboured an X4/DM virus close to HIV Seroconversion. Patients harbouring X4/DM-tropic viruses close to Seroconversion did not have an increased risk of disease progression, estimated by the decline in CD4 T cell count or time to combined ART initiation.
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time from human immunodeficiency virus Seroconversion to reaching cd4 cell count thresholds 200 350 and 500 cells mm3 assessment of need following changes in treatment guidelines
Clinical Infectious Diseases, 2011Co-Authors: Sara Lodi, Laurence Meyer, Andrew N. Phillips, Giota Touloumi, Ronald B Geskus, Rodolphe Thiebaut, Nikos Pantazis, Anne M Johnson, A Babiker, Kholoud PorterAbstract:Background. Recent updates of human immunodeficiency virus (HIV) treatment guidelines have raised the CD4+ cell count thresholds for antiretroviral therapy initiation from 350 to 500 cells/mm(3) in the United States and from 200 to 350 cells/mm(3) in mid- and low-income countries. Robust data of time from HIV Seroconversion to CD4+ cell counts of 200, 350, and 500 cells/mm(3) are lacking but are needed to inform health care planners of the likely impact and cost effectiveness of these and possible future changes in CD4+ cell count initiation threshold. Methods. Using Concerted Action on Seroconversion to AIDS and Death in Europe data from individuals with well-estimated dates of HIV Seroconversion, we fitted mixed models on the square root of CD4+ cell counts measured before combined antiretroviral therapy (cART) initiation. Restricting analyses to adults (age >16 years), we predicted time between Seroconversion and CD4+ cell count <200, <350, and <500 cells/mm(3) as well as CD4+ cell count distribution and proportions reaching these thresholds at 1, 2, and 5 years after Seroconversion. Results. Median (interquartile range [IQR]) follow-up for the 18495 eligible individuals from Seroconversion while cART-free was 3.7 years (1.5, 7). Most of the subjects were male (78%), had a median age at Seroconversion of 30 years (IQR, 25-37 years), and were infected through sex between men (55%). Estimated median times (95% confidence interval [CI]) from Seroconversion to CD4+ cell count <500, <350, and <200 cells/mm(3) were 1.19 (95% CI, 1.12-1.26), 4.19 (95% CI, 4.09-4.28), and 7.93 (95% CI, 7.76-8.09) years, respectively. Almost half of infected individuals would require treatment within 1 year of Seroconversion for guidelines recommending its initiation at 500 cells/mm(3), compared with 26% and 9% for guidelines recommending initiation at 350 and 200 cells/mm(3), respectively. Conclusions. These data suggest substantial increases in the number of individuals who require treatment and call for early HIV testing.
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the relationship between hiv Seroconversion illness hiv test interval and time to aids in a seroconverter cohort
Epidemiology and Infection, 2003Co-Authors: F Tyrer, James W Gillett, A. S. Walker, Kholoud PorterAbstract:Seroconversion illness is known to be associated with more rapid HIV disease progression. However, symptoms are often subjective and prone to recall bias. We describe symptoms reported as Seroconversion illness and examine the relationship between illness, HIV test interval (time between antibody-negative and anibody-positive test dates) and the effect of both on time to AIDS from Seroconversion. We used a Cox model, adjusting for age, sex, exposure group and year of estimated Seroconversion. Of 1820 individuals, information on Seroconversion illness was available for 1244 of whom 423 (34%) reported symptomatic Seroconversion. Persons with a short test interval (< or = 2 months) were significantly more likely to report an illness than people with a longer interval (OR 6.76, 95% CI 4.75-9.62). Time to AIDS was significantly faster (P = 0.01) in those with a short test interval. The HIV test interval is a useful replacement for information on Seroconversion illness in studies of HIV disease progression.
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Evaluating the effect of year of Seroconversion on HIV progression in cohort studies
AIDS (London England), 1998Co-Authors: A. Cozzi Lepri, Kholoud Porter, Patrizio Pezzotti, Andrew N. Phillips, Amanda Mocroft, Ca Sabin, G. RezzaAbstract:OBJECTIVES: To show how a spurious association between the calendar year of Seroconversion and HIV progression arises as a result of censoring the follow-up of individuals at their last visit, when the individuals' visits are intermittent. DESIGN: A notional cohort of 1140 seroconverters and a cohort study of 1270 HIV-infected individuals seroconverted between 1985 and 1994, and followed up to December 1995 (the Italian Seroconversion Study cohort). METHODS: Failure times and rate of the patients attending the clinic over the study period were simulated for the notional cohort. Three separate scenarios with different probabilities of making a visit were considered. Standard survival analysis techniques were used to assess the effect of the year of Seroconversion on HIV progression. The progression to a CD4 cell count of 200 x 10(6)/l according to the calendar year of Seroconversion in the Italian Seroconversion Study was assessed using different censoring strategies. RESULTS: A spurious effect of the year of Seroconversion consistently appeared in 100 repeated simulations. When ignoring the visits occurring after the first year of follow-up in the Italian Seroconversion Study cohort, results supported the hypothesis of no effect of the year from Seroconversion. CONCLUSIONS: The choice of the censoring strategy is crucial when assessing the effect of year of Seroconversion using survival analysis in cohort studies with intermittent visit structure. Different censoring strategies should be considered before firmly concluding that more virulent strains or the use of treatment are modifying the natural history of HIV disease from cohort studies of this nature.
Tom Lutalo - One of the best experts on this subject based on the ideXlab platform.
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use of injectable hormonal contraception and women s risk of herpes simplex virus type 2 acquisition a prospective study of couples in rakai uganda
The Lancet Global Health, 2015Co-Authors: Mary K Grabowski, Ronald H Gray, Fred Makumbi, Joseph Kagaayi, Andrew D Redd, Godfrey Kigozi, Steven J Reynolds, Fred Nalugoda, Tom LutaloAbstract:Summary Background The injectable hormonal contraceptive depo-medroxyprogesterone acetate (DMPA) has been associated with increased risk of HIV acquisition, but findings are inconsistent. Whether DMPA increases the risk of other sexually transmitted viral infections is unknown. We assessed the association between DMPA use and incident herpes simplex virus type 2 (HSV2) infection in women. Methods In this prospective study, we enrolled HIV-negative and HSV2-negative women aged 15–49 years whose HIV-negative male partners were concurrently enrolled in a randomised trial of male circumcision in Rakai, Uganda. We excluded women if either they or their male partners HIV seroconverted. The primary outcome was HSV2 Seroconversion, assessed annually. The male circumcision trial was registered with ClinicalTrials.gov, number NCT00425984. Findings Between Aug 11, 2003, and July 6, 2006, we enrolled 682 women in this study. We noted HSV2 Seroconversions in 70 (10%) women. Incidence was 13·5 per 100 person-years in women consistently using DMPA (nine incident infections per 66·5 person-years), 4·3 per 100 person-years in pregnant women who were not using hormonal contraception (18 incident infections per 423·5 person-years), and 6·6 per 100 person-years in women who were neither pregnant nor using hormonal contraception (35 incident infections per 529·5 person-years). Women consistently using DMPA had an adjusted hazard ratio for HSV2 Seroconversion of 2·26 (95% CI 1·09–4·69; p=0·029) compared with women who were neither pregnant nor using hormonal contraception. Of 132 women with HSV2-seropositive partners, Seroconversion was 36·4 per 100 person-years in consistent DMPA users (four incident infections per 11 person-years) and 10·7 per 100 person-years in women who were neither pregnant nor using hormonal contraception (11 incident infections per 103 person-years; adjusted hazard ratio 6·23, 95% CI 1·49–26·3; p=0·012). Interpretation Consistent DMPA use might increase risk of HSV2 Seroconversion; however, study power was low. These findings should be assessed in larger populations with more frequent follow-up than in this study, and other contraceptive methods should also be assessed. Access to a wide range of highly effective contraceptive methods is needed for women, particularly in sub-Saharan Africa. Funding Bill and Melinda Gates Foundation, Doris Duke Charitable Foundation, US National Institutes of Health, and Fogarty International Center.
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effect of hormonal contraceptive use before hiv Seroconversion on viral load setpoint among women in rakai uganda
Journal of Acquired Immune Deficiency Syndromes, 2011Co-Authors: Chelsea B Polis, Ronald H Gray, Joseph Kagaayi, Godfrey Kigozi, Fred Nalugoda, Tom Lutalo, J B Bwanika, Noah Kiwanuka, David Serwadda, Maria J WawerAbstract:Background—High viral load (VL) setpoint is a marker for rapid HIV progression, but few studies have examined whether use of hormonal contraception (HC) prior to HIV Seroconversion affects VL setpoint. Methods—We determined VL setpoints in 285 HIV seroconverters using blood samples collected six months or more after estimated HIV Seroconversion but before disease progression to CD4≤250 or WHO Stage 3 or 4. We used multivariate linear regression to estimate the effect of HC use prior to HIV Seroconversion on VL setpoint, and multivariate Cox regression to estimate the hazards ratio of death associated with VL setpoint. Results—Of 285 women, 42 (15%) reported using HC prior to HIV Seroconversion. Mean VL setpoint was 4.49 (SD 0.79) log10 copies/mL among women who used HC prior to HIV Seroconversion and 4.47 (SD 0.86) among non-HC users (p=0.88). In multivariate analysis, HC prior to HIV Seroconversion was not associated with VL setpoint (+0.11 log10 copies /mL; p=0.47). Higher socioeconomic status was associated with lower VL setpoint (-0.43 log10 copies/ mL; p=0.04). VL setpoints above the median were associated with faster time to death (adjHR: 2.54, 95% CI: 1.30-4.98, p-value <0.01). Conclusions—Use of HC prior to HIV Seroconversion was not associated with elevated VL setpoint.
Ching-lung Lai - One of the best experts on this subject based on the ideXlab platform.
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The role of interleukin-27 in predicting spontaneous HBeAg Seroconversion in chronic hepatitis B infection
Liver international : official journal of the International Association for the Study of the Liver, 2017Co-Authors: Lung-yi Mak, Danny Ka-ho Wong, James Fung, Wai-kay Seto, Ching-lung Lai, Man-fung YuenAbstract:Background and Aims Hepatitis B e Seroconversion, associated with preceding hepatic inflammation, marks the transition from immune active to residual phase in the natural disease history of chronic hepatitis B. Recently, interleukin-27 has been reported to be associated with hepatic inflammation in hepatitis B infection. We aimed to evaluate the role of interleukin-27 in predicting spontaneous e Seroconversion in chronic hepatitis B. Methods 142 treatment-naive hepatitis B patients with positive e antigen were recruited. Interleukin-27, hepatitis B viral DNA levels and liver function parameters, were measured on presentation. Patients who had spontaneous e Seroconversion within 3 years of follow-up were compared with those without e Seroconversion within the same period of time. Factors predictive of spontaneous e Seroconversion were identified. Results Of the 142 patients (M:F= 80:62, median age: 31), 44 (31%) had spontaneous e Seroconversion within 3 years of follow-up. Multivariate analyses revealed that younger age, lower viral DNA and lower interleukin-27 levels on presentation independently predicted spontaneous e Seroconversion: the rate was significantly higher in patients aged
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a large population study of spontaneous hbeag Seroconversion and acute exacerbation of chronic hepatitis b infection implications for antiviral therapy
Gut, 2003Co-Authors: Man-fung Yuen, Danny Ka-ho Wong, H J Yuan, C K Hui, W M Wong, Aoo Chan, Bcy Wong, Ching-lung LaiAbstract:Background and aim: Clinical data on spontaneous hepatitis B e antigen (HBeAg) Seroconversion and acute exacerbation of chronic hepatitis B (CHB) virus infection from large population studies are lacking. In the present study we examined the clinical features and significance of HBeAg Seroconversion and acute exacerbation in 3063 Chinese CHB patients. Methods: Clinical assessment, liver biochemistry, hepatitis B virus (HBV) serology and HBV DNA, time of HBeAg Seroconversion, and acute exacerbation were monitored. Results: Median age at HBeAg Seroconversion was 34.5 years. The cumulative HBeAg Seroconversion rate significantly increased with alanine aminotransferase (ALT) levels on presentation (p re version and mortality occurred in 2.7% and 0.7% of acute exacerbations, respectively. Conclusion: In the present study we have provided information on HBeAg Seroconversion and acute exacerbation, which are important in decision making for CHB treatment and in designing clinical trials.
Yunfan Liaw - One of the best experts on this subject based on the ideXlab platform.
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age specific prognosis following spontaneous hepatitis b e antigen Seroconversion in chronic hepatitis b
Hepatology, 2010Co-Authors: Yicheng Chen, Chiaming Chu, Yunfan LiawAbstract:Hepatitis B e antigen (HBeAg) Seroconversion in chronic hepatitis B virus infection confers a favorable prognosis, but untoward outcomes may develop in some patients. The impact of the age of HBeAg Seroconversion on prognosis is not clearly known. HBeAg-positive patients with biopsy-proven chronic hepatitis B were followed up long-term. Follow-up studies included liver biochemistry, alpha-fetoprotein, and ultrasonography every 3 to 6 months or more frequently if clinically indicated. Of the patients who underwent spontaneous HBeAg Seroconversion, the incidences of HBeAg-negative hepatitis, cirrhosis, hepatocellular carcinoma (HCC), and hepatitis B surface antigen seroclearance were compared between patient groups with different ages at the time of HBeAg Seroconversion using Kaplan–Meier survival analysis and Poisson regression model. Spontaneous HBeAg Seroconversion was documented in 508 patients. Of the 483 patients who had no evidence of cirrhosis or HCC at the time of HBeAg Seroconversion, HBeAg Seroconversion occurred before age 30 in 218 patients (group A), between age 31 and 40 in 199 patients (group B), and after age 40 in 66 patients (group C). The 15-year cumulative incidences of HBeAg-negative hepatitis, cirrhosis, and HCC increased with increasing age of HBeAg Seroconversion, the lowest being in group A (31.2%, 3.7%, and 2.1%, respectively) and highest being in group C (66.7% [P < 0.0001], 42.9% [P <0.0001], and 7.7% [P = 0.29], respectively). The hazard ratio of HBeAg-negative hepatitis, cirrhosis, and HCC was 2.95, 17.6, and 5.22, respectively, in group C compared with group A. Conclusion: Patients with HBeAg Seroconversion before age 30 have excellent prognosis, whereas patients with delayed HBeAg Seroconversion after age 40 have significantly higher incidences of HBeAg-negative hepatitis, cirrhosis, and HCC. (HEPATOLOGY 2010.)
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HBeAg Seroconversion as an important end point in the treatment of chronic hepatitis B
Hepatology International, 2009Co-Authors: Yunfan LiawAbstract:During the natural history of chronic hepatitis B virus (HBV) infection, the loss of serum hepatitis B e antigen (HBeAg) and the development of anti-HBe antibodies (HBeAg Seroconversion) mark a transition from the immune-active phase of disease to the inactive carrier state. This review examines the evidence from natural history and cohort studies on the relationship between HBeAg Seroconversion and disease progression. The role of HBeAg Seroconversion as an important milestone in the management of HBeAg-positive patients with chronic hepatitis B (CHB), as well as the advantages and disadvantages of administering a finite course of therapy for HBeAg-positive CHB, is also discussed. The evidence from natural history and cohort studies indicates that spontaneous or treatment-induced HBeAg Seroconversion is associated with lower rates of disease progression to cirrhosis and hepatocellular carcinoma, a potential of hepatitis B surface antigen Seroconversion, and improved survival rates. Updated guidelines developed by major liver associations recommend stopping oral therapy for HBeAg-positive patients who achieve sustained HBeAg Seroconversion with polymerase chain reaction-undetectable HBV-DNA on two separate occasions for 6 or more months apart, taking into consideration the individual’s clinical and virologic response to therapy, as well as the severity of liver disease. Thus, early induction of HBeAg Seroconversion with interferon-based therapy or oral nucleos(t)ide analogues has important clinical and socioeconomic implications for the management of CHB.
Jia Wei - One of the best experts on this subject based on the ideXlab platform.
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Systematic review and meta-analysis: Development of hepatocellular carcinoma in chronic hepatitis B patients with hepatitis e antigen Seroconversion.
Journal of Viral Hepatitis, 2018Co-Authors: Tai-cheng Zhou, Xin Lai, M.‐h. Feng, Yang Tang, Liang Zhang, Jia WeiAbstract:Hepatitis B e antigen (HBeAg) Seroconversion is considered to have significantly favourable clinical outcomes for patients with chronic hepatitis B (CHB). However, inconsistent study results suggest that hepatocellular carcinoma (HCC) still occurs in patients with HBeAg Seroconversion. We performed a systematic review and meta-analysis to determine the incidence of HCC in patients with CHB after HBeAg Seroconversion. Web of Science, PubMed and Embase databases were searched through January 2017. The incidence of HCC in CHB patients after HBeAg Seroconversion was pooled using a random-effects model or fix-effects model. Sixteen studies were finally included, involving 4910 patients with HBeAg Seroconversion. The overall pooled proportion suggested that 3.33% (95% confidence interval (CI): 2.28%-4.58%) of patients with CHB develop HCC despite HBeAg Seroconversion. In patients with HBeAg Seroconversion without cirrhosis, the pooled proportion of HCC development was 0.94% (95% CI: 0.15%-2.4%). Moreover, patients with cirrhosis, active hepatitis, or aged greater than 40 years at the time of HBeAg Seroconversion were at significantly higher risk for HCC development. HBeAg Seroconversion was significantly associated with a reduced risk of HCC compared with persistently positive HBeAg (RR = 0.58, 95% CI: 0.35-0.97, P = .04). Despite the reduced risk with HBeAg Seroconversion, HCC can still occur in a proportion of patients with CHB after HBeAg Seroconversion. Long-term monitoring is needed for patients with established cirrhosis, active hepatitis or those older than 40 years at the time of HBeAg Seroconversion.
