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1.
Kim Tien Ng Lai Yee Ong Sin How Lim Yutaka Takebe Adeeba Kamarulzaman Kok Keng Tee 《PloS one》2013,8(6)
HIV-1 epidemics among men who have sex with men (MSM) continue to expand in developed and developing countries. Although HIV infection in MSM is amongst the highest of the key affected populations in many countries in Southeast Asia, comprehensive molecular epidemiological study of HIV-1 among MSM remains inadequate in the region including in Malaysia. Here, we reported the phylodynamic profiles of HIV-1 genotypes circulating among MSM population in Kuala Lumpur, Malaysia. A total of n = 459 newly-diagnosed treatment-naïve consenting subjects were recruited between March 2006 and August 2012, of whom 87 (18.9%) were self-reported MSM. Transmitted drug resistance mutations were absent in these isolates. Cumulatively, phylogenetic reconstructions of the pro-rt gene (HXB2∶2253–3275) showed that HIV-1 subtype B and CRF01_AE were predominant and contributed to approximately 80% of the total HIV-1 infection among MSM. In addition to numerous unique transmission lineages within these genotypes, twelve monophyletic transmission clusters of different sizes (2–7 MSM sequences, supported by posterior probability value of 1) were identified in Malaysia. Bayesian coalescent analysis estimated that the divergence times for these clusters were mainly dated between 1995 and 2005 with four major transmission clusters radiating at least 12 years ago suggesting that active spread of multiple sub-epidemic clusters occurred during this period. The changes in effective population size of subtype B showed an exponential growth within 5 years between 1988 and 1993, while CRF01_AE lineage exhibited similar expansion between 1993 and 2003. Our study provides the first insight of the phylodynamic profile of HIV-1 subtype B and CRF01_AE circulating among MSM population in Kuala Lumpur, Malaysia, unravelling the importance of understanding transmission behaviours as well as evolutionary history of HIV-1 in assessing the risk of outbreak or epidemic expansion. 相似文献
2.
Xiaoyan Li Yile Xue Hua Cheng Yi Lin Leiming Zhou Zhen Ning Xuqin Wang Xiaolei Yu Wei Zhang Fangwei Shen Xiaohong Zheng Jing Gai Xiaoshan Li Laiyi Kang Phillipe Nyambi Ying Wang Minghua Zhuang Qichao Pan Xun Zhuang Ping Zhong 《PloS one》2015,10(6)
The HIV-1 epidemic among men who have sex with men (MSM) has been spreading throughout China. Shanghai, a central gathering place for MSM, is facing a continuously increasing incidence of HIV-1 infection. In order to better understand the dynamics of HIV-1 diversity and its influence on patient’s immune status at baseline on diagnosis, 1265 newly HIV-1-infected MSM collected from January 2009 to December 2013 in Shanghai were retrospectively analyzed for genetic subtyping, CD4+T cell counts, and viral loads. HIV-1 phylogenetic analysis revealed a broad viral diversity including CRF01_AE (62.13%), CRF07_BC (24.51%), subtype B (8.06%), CRF55_01B (3.24%), CER67_01B (0.95%), CRF68_01B (0.4%), CRF08_BC (0.08%) and CRF59_01B (0.08%). Twenty-four unique recombination forms (URFs) (1.98%) were identified as well. Bayesian inference analysis indicated that the introduction of CRF01_AE strain (1997) was earlier than CRF07_BC strain (2001) into MSM population in Shanghai based on the time of the most recent common ancestor (tMRCA). Three epidemic clusters and five sub-clusters were found in CRF01_AE. Significantly lower CD4+T cell count was found in individuals infected with CRF01_AE than in those infected with CRF07_BC infection (P<0.01), whereas viral load was significantly higher those infected with CRF01_AE than with CRF07_BC (P<0.01). In addition, the patients with >45 years of age were found to have lower CD4+T cell counts and higher viral loads than the patients with <25 years of age (P<0.05). This study reveals the presence of HIV-1 subtype diversity in Shanghai and its remarkable influence on clinical outcome. A real-time surveillance of HIV-1 viral diversity and phylodynamics of epidemic cluster, patient’s baseline CD4+T cell count and viral load would be of great value to monitoring of disease progression, intervention for transmission, improvement of antiretroviral therapy strategy and design of vaccines. 相似文献
3.
Min Chen Yanling Ma Yingzhen Su Li Yang Renzhong Zhang Chaojun Yang Huichao Chen Wenyun Yan Yuhua Shi Lijuan Dong Ling Chen Manhong Jia Lin Lu 《PloS one》2014,9(1)
Background
Yunnan has been severely affected by HIV/AIDS in China. Recently, the reported prevalence of HIV-1 among men who have sex with men (MSM) in Yunnan was high in China. To monitor dynamic HIV-1 epidemic among Yunnan MSM, HIV-1 genetic characteristics and transmitted drug resistance (TDR) were investigated.Methods
Blood samples from 131 newly HIV-1 diagnosed MSM were continuously collected at fixed sites from January 2010 to December 2012 in Kunming City, Yunnan Province. Partial gag, pol and env genes were sequenced. Phylogenetic, evolutionary and genotypic drug resistance analyses were performed.Results
Multiple genotypes were identified among MSM in Kunming, including CRF01_AE (64.9%), CRF07_BC (25.2%), unique recombinant forms (URFs, 5.3%), subtype B (3.1%) and CRF08_BC (1.5%). CRF01_AE and CRF07_BC were the predominant strains. The mean of genetic distance within CRF01_AE were larger than that within CRF07_BC. The estimated introducing time of CRF01_AE in Yunnan MSM (1996.9) is earlier than that of CRF07_BC (2002.8). In this study, subtype B was first identified in Yunnan MSM. CRF08_BC seems to be the distinctive strain in Yunnan MSM, which was seldom found among MSM outside Yunnan. The proportion of URFs increased, which further contributed to genetic diversity among MSM. Strikingly, genetic relatedness was found among these strains with MSM isolates from multiple provinces, which suggested that a nationwide transmission network may exist. TDR-associated mutations were identified in 4.6% individuals. The multivariate analysis revealed that non-native MSM and divorced/widowed MSM were independently associated with a higher TDR rate.Conclusion
This work revealed diverse HIV-1 genetics, national transmission networks and a baseline level of TDR in MSM. These findings enhance our understanding of the distribution and evolution of HIV-1 in MSM, and are valuable for developing HIV prevention strategies for MSM. 相似文献4.
Agricola Joachim Charlotta Nilsson Said Aboud Muhammad Bakari Eligius F. Lyamuya Merlin L. Robb Mary A. Marovich Patricia Earl Bernard Moss Christina Ochsenbauer Britta Wahren Fred Mhalu Eric Sandstr?m Gunnel Biberfeld Guido Ferrari Victoria R. Polonis 《PloS one》2015,10(4)
Vaccine-induced HIV antibodies were evaluated in serum samples collected from healthy Tanzanian volunteers participating in a phase I/II placebo-controlled double blind trial using multi-clade, multigene HIV-DNA priming and recombinant modified vaccinia Ankara (HIV-MVA) virus boosting (HIVIS03). The HIV-DNA vaccine contained plasmids expressing HIV-1 gp160 subtypes A, B, C, Rev B, Gag A, B and RTmut B, and the recombinant HIV-MVA boost expressed CRF01_AE HIV-1 Env subtype E and Gag-Pol subtype A. While no neutralizing antibodies were detected using pseudoviruses in the TZM-bl cell assay, this prime-boost vaccination induced neutralizing antibodies in 83% of HIVIS03 vaccinees when a peripheral blood mononuclear cell (PBMC) assay using luciferase reporter-infectious molecular clones (LucR-IMC) was employed. The serum neutralizing activity was significantly (but not completely) reduced upon depletion of natural killer (NK) cells from PBMC (p=0.006), indicating a role for antibody-mediated Fcγ-receptor function. High levels of antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies against CRF01_AE and/or subtype B were subsequently demonstrated in 97% of the sera of vaccinees. The magnitude of ADCC-mediating antibodies against CM235 CRF01_AE IMC-infected cells correlated with neutralizing antibodies against CM235 in the IMC/PBMC assay. In conclusion, HIV-DNA priming, followed by two HIV-MVA boosts elicited potent ADCC responses in a high proportion of Tanzanian vaccinees. Our findings highlight the potential of HIV-DNA prime HIV-MVA boost vaccines for induction of functional antibody responses and suggest this vaccine regimen and ADCC studies as potentially important new avenues in HIV vaccine development.
Trial Registration
Controlled-Trials ISRCTN90053831 The Pan African Clinical Trials Registry ATMR2009040001075080 (currently PACTR2009040001075080) 相似文献5.
Introduction
The HIV epidemic in men who have sex with men (MSM) continues to grow in most countries. However, the phylodynamic and virological differences among HIV-1 strains circulating in MSM and other populations are not well characterized.Methods
Nearly full-length genomes (NFLGs) of the HIV-1 CRF01_AE were obtained from the Los Alamos HIV database. Phylogenetic analyses were conducted using the NFLG, gag, pol and env genes, using the maximum likelihood method. Selection pressure analyses at the codon level were performed for each gene in the phylogenetic clusters using PAML.Results
Sequences isolated from MSM in China clustered in Clusters 1 (92.5%) and 2 (85.71%). The major risk factor for Cluster 3 was heterosexual transmission (62.16%). The ratio of non-synonymous to synonymous substitutions in the env gene (0.7–0.75) was higher than the gag (0.26–0.34) or pol (0.21–0.26) genes. In env gene, Cluster 1 (4.56×10-3subs/site/year) and 2 (6.01×10-3subs/site/year) had higher evolutionary rates than Cluster 3 (1.14×10-3subs/site/year). Positive selection affected 4.2–6.58% of the amino acid sites in the env gene. Two sites (HXB2:136 and 316) evolved similarly in Clusters 1 and 2, but not Cluster 3.Conclusion
The HIV-1 CRF01_AE in MSM is evolving differently than in other populations. 相似文献6.
7.
8.
Ivailo Alexiev Ivanov Danail Beshkov Anupama Shankar Debra L. Hanson Dimitrios Paraskevis Viara Georgieva Lyudmila Karamacheva Hristo Taskov Tonka Varleva Ivaylo Elenkov Mariana Stoicheva Daniela Nikolova William M. Switzer 《PloS one》2013,8(3)
Limited information is available to describe the molecular epidemiology of HIV-1 in Bulgaria. To better understand the genetic diversity and the epidemiologic dynamics of HIV-1 we analyzed 125 new polymerase (pol) sequences from Bulgarians diagnosed through 2009 and 77 pol sequences available from our previous study from persons infected prior to 2007. Epidemiologic and demographic information was obtained from each participant and phylogenetic analysis was used to infer HIV-1 evolutionary histories. 120 (59.5%) persons were infected with one of five different HIV-1 subtypes (A1, B, C, F1 and H) and 63 (31.2%) persons were infected with one of six different circulating recombinant forms (CRFs; 01_AE, 02_AG, 04_cpx, 05_DF, 14_BG, and 36_cpx). We also for the first time identified infection with two different clusters of unique A-like and F-like sub-subtype variants in 12 persons (5.9%) and seven unique recombinant forms (3.5%), including a novel J/C recombinant. While subtype B was the major genotype identified and was more prevalent in MSM and increased between 2000–2005, most non-B subtypes were present in persons ≥45 years old. CRF01_AE was the most common non-B subtype and was higher in women and IDUs relative to other risk groups combined. Our results show that HIV-1 infection in Bulgaria reflects the shifting distribution of genotypes coincident with the changing epidemiology of the HIV-1 epidemic among different risk groups. Our data support increased public health interventions targeting IDUs and MSM. Furthermore, the substantial and increasing HIV-1 genetic heterogeneity, combined with fluctuating infection dynamics, highlights the importance of sustained and expanded surveillance to prevent and control HIV-1 infection in Bulgaria. 相似文献
9.
Zoe Moodie Barbara Metch Linda-Gail Bekker Gavin Churchyard Maphoshane Nchabeleng Koleka Mlisana Fatima Laher Surita Roux Kathryn Mngadi Craig Innes Matsontso Mathebula Mary Allen Carter Bentley Peter B. Gilbert Michael Robertson James Kublin Lawrence Corey Glenda E. Gray 《PloS one》2015,10(9)
Background
The Phase 2b double-blinded, randomized Phambili/HVTN 503 trial evaluated safety and efficacy of the MRK Ad5 gag/pol/nef subtype B HIV-1 preventive vaccine vs placebo in sexually active HIV-1 seronegative participants in South Africa. Enrollment and vaccinations stopped and participants were unblinded but continued follow-up when the Step study evaluating the same vaccine in the Americas, Caribbean, and Australia was unblinded for non-efficacy. Final Phambili analyses found more HIV-1 infections amongst vaccine than placebo recipients, impelling the HVTN 503-S recall study.Methods
HVTN 503-S sought to enroll all 695 HIV-1 uninfected Phambili participants, provide HIV testing, risk reduction counseling, physical examination, risk behavior assessment and treatment assignment recall. After adding HVTN 503-S data, HIV-1 infection hazard ratios (HR vaccine vs. placebo) were estimated by Cox models.Results
Of the 695 eligible, 465 (67%) enrolled with 230 from the vaccine group and 235 from the placebo group. 38% of the 184 Phambili dropouts were enrolled. Enrollment did not differ by treatment group, gender, or baseline HSV-2. With the additional 1286 person years of 503-S follow-up, the estimated HR over Phambili and HVTN 503-S follow-up was 1.52 (95% CI 1.08–2.15, p = 0.02, 82 vaccine/54 placebo infections). The HR was significant for men (HR = 2.75, 95% CI 1.49, 5.06, p = 0.001) but not for women (HR = 1.12, 95% CI 0.73, 1.72, p = 0.62).Conclusion
The additional follow-up from HVTN 503-S supported the Phambili finding of increased HIV-1 acquisition among vaccinated men and strengthened the evidence of lack of vaccine effect among women.Trial Registration
clinicaltrials.gov NCT00413725 SA National Health Research Database DOH-27-0207-1539 相似文献10.
Elena Delgado María Teresa Cuevas Francisco Domínguez Yolanda Vega Marina Cabello Aurora Fernández-García Marcos Pérez-Losada María ángeles Castro Vanessa Montero Mónica Sánchez Ana Mari?o Hortensia álvarez Patricia Ordó?ez Antonio Ocampo Celia Miralles Sonia Pérez-Castro María José López-álvarez Raúl Rodríguez Matilde Trigo Julio Diz-Arén Carmen Hinojosa Pablo Bachiller Silvia Hernáez-Crespo Ramón Cisterna Eugenio Gardu?o Lucía Pérez-álvarez Michael M Thomson 《PloS one》2015,10(11)
11.
Sabina Hirshfield Mary Ann Chiasson Heather Joseph Roberta Scheinmann Wayne D. Johnson Robert H. Remien Francine Shuchat Shaw Reed Emmons Gary Yu Andrew D. Margolis 《PloS one》2012,7(10)
Background
As HIV infection continues unabated, there is a need for effective interventions targeting at-risk men who have sex with men (MSM). Engaging MSM online where they meet sexual partners is critical for HIV prevention efforts.Methods
A randomized controlled trial (RCT) conducted online among U.S. MSM recruited from several gay sexual networking websites assessed the impact of 2 HIV prevention videos and an HIV prevention webpage compared to a control condition for the study outcomes HIV testing, serostatus disclosure, and unprotected anal intercourse (UAI) at 60-day follow-up. Video conditions were pooled due to reduced power from low retention (53%, n = 1,631). No participant incentives were provided.Principal Findings
Follow-up was completed by 1,631 (53%) of 3,092 eligible men. In the 60 days after the intervention, men in the pooled video condition were significantly more likely than men in the control to report full serostatus disclosure (‘asked and told’) with their last sexual partner (OR 1.32, 95% CI 1.01–1.74). Comparing baseline to follow-up, HIV-negative men in the pooled video (OR 0.70, 95% CI 0.54–0.91) and webpage condition (OR 0.43, 95% CI 0.25–0.72) significantly reduced UAI at follow-up. HIV-positive men in the pooled video condition significantly reduced UAI (OR 0.38, 95% CI 0.20–0.67) and serodiscordant UAI (OR 0.53, 95% CI 0.28–0.96) at follow-up.Conclusions/Significance
Findings from this online RCT of MSM recruited from sexual networking websites suggest that a low cost, brief digital media intervention designed to engage critical thinking can increase HIV disclosure to sexual partners and decrease sexual risk. Effective, brief HIV prevention interventions featuring digital media that are made widely available may serve as a complementary part of an overall behavioral and biomedical strategy for reducing sexual risk by addressing the specific needs and circumstances of the target population, and by changing individual knowledge, motivations, and community norms.Trial Registration
ClinicalTrials.gov NCT00649701相似文献12.
Geneviève A. F. S. van Liere Martijn S. van Rooijen Christian J. P. A. Hoebe Titia Heijman Henry J. C. de Vries Nicole H. T. M. Dukers-Muijrers 《PloS one》2015,10(10)
Background
Both anorectal Chlamydia trachomatis (CT) and Neisseria gonorrhoea (NG) can occur as a rectal-only infection or concurrently with simultaneous urogenital infection with the same pathogen. Characterising the target groups in which rectal-only infections occur may improve the efficacy of screening practices.Methods
We analysed data from two Dutch outpatient sexually transmitted infection (STI) clinics between 2011 and 2012. We included all men who have sex with men (MSM) (n = 9549) and women (n = 11113), ≥18 years, who had been tested for anorectal and urogenital CT and/or NG (either as a result of reporting anal sex/symptoms or via routine universal testing). Factors associated with rectal-only CT and NG infections were assessed using univariable and multivariable logistic regression.Results
In MSM, anorectal CT prevalence was 9.8% (693/7094), anorectal NG prevalence was 4.2% (397/9534). In women this was 9.5% overall (439/4597) and 0.9% (96/10972) respectively. Anorectal CT prevalence among women who were routinely universally tested was 10.4% (20/192), for selective testing this was 9.5% (419/4405) (p = 0.68). Anorectal NG infections were not detected among women who were routinely universally tested (p = 0.19). Among CT or NG positive MSM, rectal-only CT infections were found in 85.9% (595/693), for NG this was 85.6% (340/397) respectively. In positive women these figures were 22.1% (97/439)for CT and 20.8% (20/96) for NG, respectively. In MSM, independent factors associated with rectal-only CT were: being a sex worker (OR0.4,CI0.2–1.0), exclusively having sex with men (OR3.4,CI1.7–6.8), and absence of urogenital symptoms (OR0.2,CI0.2–0.4). In women, these factors were: older age (OR2.3, CI1.3–4.0) and non-Western nationality (OR1.8, CI1.0–3.5). Factors associated with rectal-only NG in MSM were: having been warned for STIs by an (ex) partner (OR2.9,CI1.1–7.5), oropharyngeal NG infection (OR2.4,CI1.0–5.3), and absence of urogenital symptoms (OR0.02,CI0.01–0.04), while in women no significant factors were identified.Conclusions
The prevalence of anorectal CT and NG was substantial in MSM and prevalence of anorectal CT was also substantial in women. Anorectal infections occurred mostly as rectal-only infections in MSM and mostly concurrent with other infections in women. Given the lack of useful indicators for rectal-only infections, selective screening based on a priori patient characteristics will have low discriminatory power both in relation to MSM and women. 相似文献13.
Nicolas Bertholet John A. Cunningham Mohamed Faouzi Jacques Gaume Gerhard Gmel Bernard Burnand Jean-Bernard Daeppen 《PloS one》2015,10(12)
Introduction
Alcohol use is one of the leading modifiable morbidity and mortality risk factors among young adults.Study Design
2 parallel-group randomized controlled trial with follow-up at 1 and 6 months.Setting/Participants
Internet based study in a general population sample of young men with low-risk drinking, recruited between June 2012 and February 2013.Intervention: Internet-based brief alcohol primary prevention intervention (IBI). The IBI aims at preventing an increase in alcohol use: it consists of normative feedback, feedback on consequences, calorific value alcohol, computed blood alcohol concentration, indication that the reported alcohol use is associated with no or limited risks for health. Intervention group participants received the IBI. Control group (CG) participants completed only an assessment.Main Outcome Measures
Alcohol use (number of drinks per week), binge drinking prevalence. Analyses were conducted in 2014–2015.Results
Of 4365 men invited to participate, 1633 did so; 896 reported low-risk drinking and were randomized (IBI: n = 451; CG: n = 445). At baseline, 1 and 6 months, the mean (SD) number of drinks/week was 2.4(2.2), 2.3(2.6), 2.5(3.0) for IBI, and 2.4(2.3), 2.8(3.7), 2.7(3.9) for CG. Binge drinking, absent at baseline, was reported by 14.4% (IBI) and 19.0% (CG) at 1 month and by 13.3% (IBI) and 13.0% (CG) at 6 months. At 1 month, beneficial intervention effects were observed on the number of drinks/week (p = 0.05). No significant differences were observed at 6 months.Conclusion
We found protective short term effects of a primary prevention IBI.Trial Registration
Controlled-Trials.com ISRCTN55991918 相似文献14.
Olivier Richel Henry J. C. De Vries Marcel G. W. Dijkgraaf Carel J. M. Van Noesel Jan M. Prins 《PloS one》2013,8(12)
Objective
Anal Intraepithelial Neoplasia (AIN) is present in the majority of HIV+ men who have sex with men (MSM) and routine AIN-screening is subject of discussion. In this study we analysed a wide range of potential risk factors for AIN in order to target screening programs.Methods
We screened 311 HIV+ MSM by high resolution anoscopy, with biopsies of suspect lesions. HIV-parameters, previous sexual transmitted infections (STI’s), anal pathology, sexual practices and substance use were analysed in relation to AIN by uni- and multivariable logistic regression.Results
AIN (any grade) was found in 175/311 MSM (56%), high grade (HG)AIN in 30%. In the univariable analysis, years since HIV diagnosis, years of antiretroviral therapy (cART) and anal XTC use decreased AIN risk, while a history of anogenital warts and use of GHB (γ-hydroxybutyric acid) increased this risk. In the multivariable analysis three parameters remained significant: years of cART (OR=0.92 per year, p=0.003), anal XTC use (OR=0.10, p=0.002) and GHB use (OR=2.60, p=0.003). No parameters were significantly associated with HGAIN, but there was a trend towards increased risk with anal enema use prior to sex (>50 times ever; p=0.07) and with a history of AIN (p=0.06). CD4 count, STI’s, anal pathology, smoking, number of sex partners and anal fisting were not associated with (HG)AIN.Conclusion
GHB use increases the risk for AIN, while duration of cART and anal XTC use are negatively correlated with AIN. Given the high prevalence of AIN in HIV+ MSM, these associations are not helpful to guide a screening program. 相似文献15.
16.
Subtype-Specific Differences in the Human Immunodeficiency Virus Type 1 Reverse Transcriptase Connection Subdomain of CRF01_AE Are Associated with Higher Levels of Resistance to 3′-Azido-3′-Deoxythymidine
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Krista A. Delviks-Frankenberry Galina N. Nikolenko Frank Maldarelli Saiki Hase Yutaka Takebe Vinay K. Pathak 《Journal of virology》2009,83(17):8502-8513
17.
Kok Keng Tee Shigeru Kusagawa Xiao-Jie Li Narumi Onogi Maya Isogai Saiki Hase Rie Uenishi Huanan Liao Adeeba Kamarulzaman Yutaka Takebe 《PloS one》2009,4(8)
A growing number of emerging HIV-1 recombinants classified as circulating recombinant forms (CRFs) have been identified in Southeast Asia in recent years, establishing a molecular diversity of increasing complexity in the region. Here, we constructed a replication-competent HIV-1 clone for CRF33_01B (designated p05MYKL045.1), a newly identified recombinant comprised of CRF01_AE and subtype B. p05MYKL045.1 was reconstituted by cloning of the near full-length HIV-1 sequence from a newly-diagnosed individual presumably infected heterosexually in Kuala Lumpur, Malaysia. The chimeric clone, which contains the 5′ LTR (long terminal repeat) region of p93JP-NH1 (a previously isolated CRF01_AE infectious clone), showed robust viral replication in the human peripheral blood mononuclear cells. This clone demonstrated robust viral propagation and profound syncytium formation in CD4+, CXCR4-expressing human glioma NP-2 cells, indicating that p05MYKL045.1 is a CXCR4-using virus. Viral propagation, however, was not detected in various human T cell lines including MT-2, M8166, Sup-T1, H9, Jurkat, Molt-4 and PM1. p05MYKL045.1 appears to proliferate only in restricted host range, suggesting that unknown viral and/or cellular host factors may play a role in viral infectivity and replication in human T cell lines. Availability of a CRF33_01B molecular clone will be useful in facilitating the development of vaccine candidates that match the HIV-1 strains circulating in Southeast Asia. 相似文献
18.
Claudia Spies Alawi Luetz Gunnar Lachmann Markus Renius Clarissa von Haefen Klaus-Dieter Wernecke Marcus Bahra Alexander Schiemann Marco Paupers Christian Meisel 《PloS one》2015,10(12)
Purpose
Surgical patients are at high risk for developing infectious complications and postoperative delirium. Prolonged infections and delirium result in worse outcome. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and influenza vaccination are known to increase HLA-DR on monocytes and improve immune reactivity. This study aimed to investigate whether GM-CSF or vaccination reverses monocyte deactivation. Secondary aims were whether it decreases infection and delirium days after esophageal or pancreatic resection over time.Methods
In this prospective, randomized, placebo-controlled, double-blind, double dummy trial setting on an interdisciplinary ICU of a university hospital 61 patients with immunosuppression (monocytic HLA-DR [mHLA-DR] <10,000 monoclonal antibodies [mAb] per cell) on the first day after esophageal or pancreatic resection were treated with either GM-CSF (250 μg/m2/d), influenza vaccination (Mutagrip 0.5 ml/d) or placebo for a maximum of 3 consecutive days if mHLA-DR remained below 10,000 mAb per cell. HLA-DR on monocytes was measured daily until day 5 after surgery. Infections and delirium were followed up for 9 days after surgery. Primary outcome was HLA-DR on monocytes, and secondary outcomes were duration of infection and delirium.Results
mHLA-DR was significantly increased compared to placebo (p < 0.001) and influenza vaccination (p < 0.001) on the second postoperative day. Compared with placebo, GM-CSF-treated patients revealed shorter duration of infection (p < 0.001); the duration of delirium was increased after vaccination (p = 0.003).Conclusion
Treatment with GM-CSF in patients with postoperative immune suppression was safe and effective in restoring monocytic immune competence. Furthermore, therapy with GM-CSF reduced duration of infection in immune compromised patients. However, influenza vaccination increased duration of delirium after major surgery.Trial Registration
www.controlled-trials.com ISRCTN27114642 相似文献19.
Objective
Men who have sex with men (MSM) practice role segregation – insertive or receptive only sex positions instead of a versatile role - in several international settings where candidate biomedical HIV prevention interventions (e.g., circumcision, anal microbicide) will be tested. The effects of these position-specific interventions on HIV incidence are modeled.Materials and Methods
We developed a deterministic compartmental model to predict HIV incidence among Indian MSM using data from 2003–2010. The model’s sex mixing matrix was derived from network data of Indian MSM (n = 4604). Our model captures changing distribution of sex roles over time. We modeled microbicide and circumcision efficacy on trials with heterosexuals.Results
Increasing numbers of versatile MSM resulted in little change in HIV incidence over 20 years. Anal microbicides and circumcision would decrease the HIV prevalence at 10 years from 15.6% to 12.9% and 12.7% respectively. Anal microbicides would provide similar protection to circumcision at the population level despite lower modeled efficacy (54% and 60% risk reduction, respectively). Combination of the interventions were additive: in 5 years, the reduction in HIV prevalence of the combination (−3.2%) is almost the sum of their individual reductions in HIV prevalence (−1.8% and −1.7%).Conclusions
MSM sex role segregation and mixing, unlike changes in the sex role distribution, may be important for evaluating HIV prevention interventions in international settings. Synergies between some position-specific prevention interventions such as circumcision and anal microbicides warrant further study. 相似文献20.
Xingguang Li Xihui Zang Chuanyi Ning Yi Feng Cunxin Xie Xiang He Yutaka Takebe Liuyan Sun Qi Guo Hui Xing Marcia L. Kalish Yiming Shao 《PloS one》2014,9(10)