Project description:Injection drug use is increasingly an important route of HIV transmission in Romania (from 1.5% of the newly diagnosed cases prior to 2010 to 31% in 2013). In this study we investigated the viral characteristics and relationships in newly HIV infected persons who inject drugs in Bucharest, Romania.ResultsHIV-1 pol sequencing, followed by phylogenetic and clustering analysis was performed on blood from 37 injecting drug users (IDUs) newly diagnosed with HIV infection. While HIV subtype F1, the dominant strain in Romania since 1990, remains prevalent, new subtypes were found including G, B, B/G and B/F recombinants. Overall, 27 of the available sequences (72.9%) clustered with at least one other. Network and phylogenetic analysis revealed tight monophyletic clusters for both subtypes F and G, with short genetic distances between sequences, suggesting recent numerous acute to acute transmissions or single burst-type episodes. No transmitted drug-resistance mutations were identified. Greater immunosuppression was present in subjects forming the subtype G cluster, possibly indicating a faster rate of progression associated with this subtype.ConclusionsThe recent increasing numbers of IDU related HIV transmissions in Bucharest, has resulted in closely-knit transmission networks that maychange the genetic profile of the local HIV epidemic.
Project description:Human immunodeficiency virus type 1 (HIV-1) circulating recombinant form (CRF) 07_BC has caused serious HIV-1 epidemics among injecting drug users (IDUs) in East Asia. Little is known about the characteristics of the virus and its impact on disease progression among the infected individuals. In this study, we compared immunological progression between 423 IDUs infected with CRF07_BC and 194 men who have sex with men (MSM) with primary subtype B infection, and a representative full-length CRF07_BC molecular clone, pCRF07_BC, was constructed to characterize the virus. We found that IDUs infected with CRF07_BC had significantly slower immunological progression in the Cox proportional hazards model (hazard ratio: 0.30; 95% confidence interval: 0.13-0.69; P=0.004). The constructed recombinant CRF07_BC viruses had a reduced processing of the Gag/Gag-Pol polyproteins, a decreased incorporation of Vpr in the virus particle, tethering of virus particles on the plasma membrane and decreased virus growth kinetics. These phenotypes are related to the unique 7-amino acid deletion in the p6 of CRF07_BC, since complementation of the 7-amino acid in pCRF07_BC could improve the defective phenotypes. In summary, compared with MSM infected with HIV-1 subtype B, IDUs infected with CRF07_BC had slower immunological progression, which is likely correlated with interference of virus particle maturation by the 7-amino acid deletion in p6.
Project description:BackgroundInvasive pneumococcal disease (IPD) isolates forming genomic clusters can reflect rapid disease transmission between vulnerable individuals.MethodsWe performed whole genome sequencing of 2820 IPD isolates recovered during 2019 through Centers for Disease Control and Prevention's Active Bacterial Core surveillance to provide strain information (serotypes, resistance, genotypes), and 2778 of these genomes were analyzed to detect highly related genomic clusters.ResultsIsolates from persons experiencing homelessness (PEH) were more often within genomic clusters than those from persons not experiencing homelessness (PNEH) (105/198 [53.0%] vs 592/2551 [23.2%]; P < .001). The 4 western sites accounted for 33.4% (929/2778) of isolates subjected to cluster analysis yet accounted for 48.7% (343/705) of clustering isolates (P < .001) and 75.8% (150/198) of isolates recovered from PEH (P < .001). Serotypes most frequent among PEH were (in rank order) 12F, 4, 3, 9N, 8, 20, and 22F, all of which were among the 10 serotypes exhibiting the highest proportions of clustering isolates among all cases. These serotypes accounted for 44.9% (1265/2820) of all IPD cases and are included within available vaccines.ConclusionsWe identified serotype-specific and geographic differences in IPD transmission. We show the vulnerability of PEH within different regions to rapidly spreading IPD transmission networks representing several pneumococcal serotypes included in available vaccines.
Project description:BackgroundThere is currently no systematic screening for hepatitis C (HCV) reinfection in people who inject drugs (PWID) after treatment in Belgium. However, in a recent meta-analysis, the overall HCV reinfection rate was 5.9/100 person-years (PY) among PWID. Accordingly, this study was undertaken to investigate the reinfection rate in former and active PWID who achieved the end of treatment response after direct-acting antiviral (DAA) treatment in Belgium.MethodsThis observational cross-sectional study recruited individuals with a history of injecting drug use who had achieved the end of treatment response to any DAA treatment between 2015 and 2020. Participants were offered a post-treatment HCV RNA test.ResultsEighty-five potential participants were eligible to participate and contacted, of whom 60 participants were enrolled in the study with a median age of 51.0 (IQR 44.3-56.0) years; it was reported that 23.3% continued to inject drugs intravenously after DAA treatment. Liver cirrhosis was present in 12.9%. The majority had genotype 1a (51.7%) or genotype 3 (15.0%) infection. We detected no reinfections in this study population. The total time patients were followed up for reinfection in the study was 78.5 PY (median 1.0 years IQR 0.4-2.0).ConclusionReinfection after successful treatment with DAA initially appears to be very low in Belgian PWID. Therefore, efforts should be made to screen individuals with persistent risk behaviors for reinfection systematically. In addition, a national HCV registry should be established to accurately define the burden of HCV infection and reinfection in Belgium and support the elimination of viral hepatitis C in Europe. Trial registration clinicaltrials.gov NCT04251572, Registered 5 Feb 2020-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04251572 .
Project description:Patients with acute hepatitis C virus (HCV) infection who receive treatment achieve high rates of sustained virologic response (SVR), but few studies have examined outcomes among injecting drug users (IDUs). We evaluated the efficacy of treatment of recent HCV infection in IDUs with acute and early chronic HCV.We analyzed data from the Australian Trial in Acute Hepatitis C-a prospective study of the natural history and treatment outcomes of patients with recent HCV infection. Participants eligible for the study had their first anti-HCV antibody-positive test result within the past 6 months and either acute clinical HCV within the past 12 months or documented anti-HCV seroconversion within 24 months. Participants with HCV received pegylated interferon-alfa-2a (180 microg/wk, n = 74); those with HCV/human immunodeficiency virus (HIV) co-infection received pegylated interferon-alfa-2a (180 microg/wk) with ribavirin (n = 35) for 24 weeks.From June 2004 to February 2008, 167 participants were enrolled in the Australian Trial in Acute Hepatitis C; 79% had injected drugs in the previous 6 months. Among 74 with only HCV, the SVRs were 55% and 72% by intention-to-treat and per-protocol analysis, respectively. In multivariate analyses, baseline factors independently associated with lower SVR included decreased social functioning and current opiate pharmacotherapy. Adherent participants had higher SVR rates (63% vs 29%; P = .025). Of the 35 participants with HCV/HIV co-infection, the SVRs were 74% and 75% by intention-to-treat and per-protocol analysis, respectively.Treatment of recent HCV infection among IDUs, including those with HIV co-infection, is effective. Strategies to engage socially marginalized individuals and increase adherence should improve treatment outcomes in this population.
Project description:BackgroundHepatitis B virus (HBV) infection is a major health problem worldwide.ObjectivesThe aim of this study was to investigate the frequency of occult hepatitis B infection (OBI) and its associated risk factors, together with the molecular characterization of the virus in injecting drug users of Tehran.Patients and methodsThe study consisted of 229 injecting drug users. Serum samples were collected and tested for the presence of hepatitis B core antibody (HBcAb) and hepatitis B surface antigen (HBsAg) by an enzyme-linked immunosorbent assay (ELISA). HBV B virus DNA was extracted from the serum samples, and a fragment of the S gene was amplified using the nested polymerase chain reaction. The genotype, subgenotypes, subtype, and S gene mutation of HBV were determined by direct sequencing. A phylogenetic tree was constructed using the neighbor-joining method.ResultsSixty-four (28%) participants were HBcAb positive, 59 cases were HBcAb positive and HBsAg negative, and 5 cases were HBsAg positive. Hepatitis B DNA was found in three HBsAg-positive cases. Thirteen of 59 (22%) individuals were hepatitis B DNA positive. The phylogenetic tree of hepatitis B DNA showed the existence of genotype D. The only significant correlation was between sharing a syringe and OBI.ConclusionsIn comparison with the rate of HBcAb positivity reported in other Iranian studies, the rate was higher in the present study. There were a few variations, genotypes, and subtypes among the infected injecting drug users. Further investigations are needed to unravel the molecular characterization of OBI.
Project description:We systematically reviewed reports about determinants of HIV infection in injecting drug users from 2000 to 2009, classifying findings by type of environmental influence. We then modelled changes in risk environments in regions with severe HIV epidemics associated with injecting drug use. Of 94 studies identified, 25 intentionally examined risk environments. Modelling of HIV epidemics showed substantial heterogeneity in the number of HIV infections that are attributed to injecting drug use and unprotected sex. We estimate that, during 2010-15, HIV prevalence could be reduced by 41% in Odessa (Ukraine), 43% in Karachi (Pakistan), and 30% in Nairobi (Kenya) through a 60% reduction of the unmet need of programmes for opioid substitution, needle exchange, and antiretroviral therapy. Mitigation of patient transition to injecting drugs from non-injecting forms could avert a 98% increase in HIV infections in Karachi; whereas elimination of laws prohibiting opioid substitution with concomitant scale-up could prevent 14% of HIV infections in Nairobi. Optimisation of effectiveness and coverage of interventions is crucial for regions with rapidly growing epidemics. Delineation of environmental risk factors provides a crucial insight into HIV prevention. Evidence-informed, rights-based, combination interventions protecting IDUs' access to HIV prevention and treatment could substantially curtail HIV epidemics.
Project description:ObjectiveTo explore HIV virological failure and drug resistance among injecting drug users (IDUs) receiving first-line antiretroviral treatment (ART) in China.DesignA series of cross-sectional surveys from 2003 to 2012 from the Chinese National HIV Drug Resistance (HIVDR) Surveillance and Monitoring Network.SettingChina.ParticipantsData were analysed by the Chinese National (HIVDR) Surveillance and Monitoring Network from 2003 to 2012. Demographic, ART and laboratory data (CD4+ cell count, viral load and drug resistance) were included. Factors associated with virological failure were identified by logistic regression analysis.Results929 of the 8556 individuals in the Chinese HIVDR database were IDUs receiving first-line ART. For these 929 IDUs, the median duration of treatment was 14 months (IQR 6.0-17.8). 193 of the 929 IDUs (20.8%) experienced virological failure (HIV viral load ≥1000 copies/mL). The prevalence of HIVDR among patients with virological failure was 38.9% (68/175). The proportion of patients with drug resistance to non-nucleoside reverse transcriptase inhibitor (NNRTIs), nucleoside reverse transcriptase inhibitor (NRTIs) and protease inhibitors (PIs) was 52.9%, 76.5% and 4.4%, respectively. Factors independently associated with virological failure include: ethnic minorities, junior high school education or less, farmers, self-reported missing doses in the past month, CD4 cell count at survey from 200 to 349 cells/mm(3) or from 0 to 199 cells/mm(3), and residence of Guangxi and Yunnan provinces.ConclusionsThe proportion of virological failure was high among IDUs receiving first-line ART in China. However, better treatment outcomes were observed in Guangxi and Yunnan, which indicates the importance of ART education and adherence to intervention, especially for patients who are farmers, minorities or have a poor educational background.
Project description:Global HIV-1 surveillance has led to the detection of its new recombinant forms. This study was carried out for the first time to elucidate the genetic characterization and evolutionary relationship of HIV-1 strains among injecting drug users of Nagaland, northeastern India. A total of 156 injecting drug users participated in this study voluntarily. Among them 18 were seropositive for HIV-1 (11.5%).The Heteroduplex Mobility Assay (HMA) of HIV-1 based on p24-p7 region of gag gene and C2-V3 region of env gene revealed 11 samples to be subtype C (gag/env), 1 sample as subtype B (gag/env) and 6 samples to be recombinants between subtype C and B. Also, the sequencing and phylogenetic analysis of gag (p24-p7) and env (C2-V3) genes from eighteen samples of Nagaland IDUs with different global HIV-1 strains showed the presence of Indian, African, Thai and their recombinant forms. However, more recombinant strains based on different genomic regions of HIV-1 were detected using Multiregional Hybridization Assay (MHA) where 8 out of 18 samples were found to be recombinants between subtype C and B. Thus, multiregional hybridization assay along with heteroduplex mobility assay can serve as an efficient tool in the characterization of recombination pattern among the newly emerging HIV-1 recombinants.
Project description:Young people aged 15-24 years account for fifty percent of all new AIDS cases worldwide. Moreover, half of all new HIV infections are associated with injection drug use. The average age for initiation into injecting drug use is 20 years of age. This paper investigates whether HIV prevention programs have reduced risk behaviours in young people.