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ObjectiveHIV controllers demonstrate high rates of spontaneous clearance of hepatitis C virus (HCV) infection. The objective of this study was to evaluate the role of human leukocyte antigen (HLA) B*57 and other genetic polymorphisms on HCV clearance in HIV controllers.DesignThis is a prospective cohort study.MethodsPatients in the Study of the Consequences of Protease Inhibitor Era (SCOPE) were tested for anti-HCV using enzyme immunoassay (EIA3) and HCV RNA using discriminatory HCV transcription-mediated amplification assay (Norvatis). We compared the proportion of HIV controllers and noncontrollers demonstrating HCV clearance and fitted multivariable Poisson regression models with robust standard errors to estimate adjusted prevalence ratios (APRs) and assessed genetic and immunologic predictors of HCV clearance.ResultsOf 279 HIV/HCV seropositive individuals, 48 were HIV controllers. HIV controllers compared to HIV noncontrollers, were significantly more likely to have HLA B*57 (33 vs. 10%, P

Young injection drug users (IDUs), a highly mobile population, engage in high levels of injecting risk behavior, yet little is understood about how such risk behavior may vary by the characteristics of the cities to which they travel, including the existence of a syringe exchange program (SEP), as well as travel partner characteristics. In 2004-2005, we conducted a 6-month prospective study to investigate the risk behavior of 89 young IDUs as they traveled, with detailed information gathered about 350 city visits. In multivariable analyses, travel to larger urban cities with a population of 500,000-1,000,000 was significantly associated with injecting drugs (adjusted odds ratio (AOR) = 3.71; 95 % confidence interval (CI), 1.56-8.82), ancillary equipment sharing (AES; AOR = 7.05; 95 % CI, 2.25-22.06) and receptive needle sharing (RNS; AOR = 5.73; 95 % CI, 1.11-27.95), as compared with visits to smaller cities with populations below 50,000. Region of the country, and the existence of a SEP within the city visited, were not independently associated with injecting drugs, AES, or RNS during city visits. Traveling with more than one injecting partner was associated with injecting drugs during city visits (AOR = 2.77; 95 % CI, 1.46-5.27), when compared with traveling alone. Additionally, both non-daily and daily/almost daily alcohol use during city visits were associated with AES (AOR = 3.37; 95 % CI, 1.42-7.68; AOR = 3.03; 95 % CI, 1.32-6.97, respectively) as compared with no alcohol consumption. Traveling young IDUs are more likely to inject when traveling with other IDUs and to engage in higher risk injection behavior when they are in large cities. Risk behavior occurring in city visits, including equipment sharing and alcohol consumption, suggests further need for focused interventions to reduce risk for viral infection among this population.

BackgroundDetection of hepatitis C virus (HCV) reinfection and intercalation (ie, intermittent recurrent bouts of viremia with homologous virus interspersed with aviremic periods) requires extensive and frequent evaluation and viral sequencing.MethodsHCV infection outcomes were studied prospectively in active injection drug users with recurrent HCV RNA-positive tests after serial negative results. HCV viremia and viral sequences (Core/E1) were assessed from monthly blood samples.ResultsViral clearance, reinfection, and intercalating infection were all detected. Among 44 participants with apparently resolved HCV (26 incident HCV clearers and 18 enrolled with already resolved infection), 36 (82%) remained persistently HCV RNA negative, but 8 demonstrated intermittent recurrent viremia. Four of these (50%) had confirmed reinfection with a heterologous virus; 3 demonstrated viral intercalation, and 1 was not classifiable as either. Estimated incidence of first reinfection was 5.4 per 100 person-years (95% confidence interval, 2.0-14.5). Six (75%) participants, including 3 of 4 with reinfection, demonstrated sustained viral clearance for a median of 26 months since last HCV RNA test.ConclusionsThese results show that frequent monitoring and viral sequencing are required to correctly assess HCV outcomes and estimate incidence of reinfection (which was previously overestimated). Sustained clearance may take many months and occur after episodes of reinfection and viral intercalation. Three of 4 subjects who had confirmed reinfection showed evidence of long-term clearance. Viral intercalation occurs with significant frequency. Further studies of these events, especially immunological, are needed to inform HCV clinical care and vaccine development.

BackgroundHeavy alcohol consumption has been associated with risk-taking behaviors in intravenous drug users (IDU). However, limited information exists on the relationship between alcohol use and injecting and sexual risk in young adult IDU (

In mammals, the suprachiasmatic nucleus (SCN) is the central pacemaker organizing circadian rhythms of behavior and physiology. At the cellular level, the mammalian clock consists of autoregulatory feedback loops involving a set of "clock genes," including the Cryptochrome (Cry) genes, Cry1 and Cry2. Experimental evidence suggests that Cry1 and Cry2 play distinct roles in circadian clock function. In mice, Cry1 is required for sustained circadian rhythms in dissociated SCN neurons or fibroblasts but not in organotypic SCN slices or at the behavioral level, whereas Cry2 is not required at any of these levels. It has been argued that coupling among SCN cellular oscillators compensates for clock gene defects to preserve oscillatory function. Here we test this hypothesis in Cry1(-/-) mice by first disrupting intercellular coupling in vivo using constant light (resulting in behavioral arrhythmicity) and then examining circadian clock gene expression in SCN slices at the single cell level. In this manner, we were able to test the role of intercellular coupling without drugs and while preserving tissue organization, avoiding the confounding influences of more invasive manipulations. Cry1(-/-) mice (as well as control Cry2(-/-) mice) bearing the PER2::LUC knock-in reporter were transferred from a standard light:dark cycle to constant bright light (~650 lux) to induce arrhythmic locomotor patterns. In SCN slices from these animals, we used bioluminescence imaging to monitor PER2::LUC expression in single cells. We show that SCN slices from rhythmic Cry1(-/-) and Cry2(-/-) mice had similarly high percentages of functional single-cell oscillators. In contrast, SCN slices from arrhythmic Cry1(-/-) mice had significantly fewer rhythmic cells than SCN slices from arrhythmic Cry2(-/-) mice. Thus, constant light in vivo disrupted intercellular SCN coupling to reveal a cell-autonomous circadian defect in Cry1(-/-) cells that is normally compensated by intercellular coupling in vivo.

AbstractBackgroundAlthough cervical cancer is the leading cancer in Cambodia, most women receive no routine screening for cervical cancer and few treatment options exist. Moreover, nothing is known regarding the prevalence of cervical HPV or the genotypes present among women in the country. Young sexually active women, especially those with multiple sex partners are at highest risk of HPV infection. We examine the prevalence and genotypes of cervical HPV, as well as the associated risk factors among young women engaged in sex work in Phnom Penh, Cambodia.MethodsWe conducted a cross-sectional study among 220 young women (15–29 years) engaged in sex work in different venues including brothels or entertainment establishments, and on a freelance basis in streets, parks and private apartments. Cervical specimens were collected using standard cytobrush technique. HPV DNA was tested for by polymerase chain reaction (PCR) and genotyping using type-specific probes for 29 individual HPV types, as well as for a mixture of 10 less common HPV types. All participants were also screened for HIV status using blood samples. Multivariate logistic regression analyses were conducted to assess risk factors for any or multiple HPV infection.ResultsThe prevalence of cervical HPV 41.1%. HPV 51 and 70 were the most common (5.0%), followed by 16 (4.6%), 71 (4.1%) and 81 (3.7%). Thirty-six women (16.4%) were infected with multiple genotypes and 23.3% were infected with at least one oncogenic HPV type. In multivariate analyses, having HIV infection and a higher number of sexual partners were associated with cervical HPV infection. Risk factors for infection with multiple genotypes included working as freelance female sex workers (FSW) or in brothels, recent binge use of drugs, high number of sexual partners, and HIV infection.ConclusionsThis is the first Cambodian study on cervical HPV prevalence and genotypes. We found that HPV infection was common among young FSW, especially among women infected with HIV. These results underscore the urgent need for accessible cervical cancer screening and treatment, as well as for a prophylactic vaccine that covers the HPV subtypes present in Cambodia.

Abstract Objective To assess concordance between self-reported amphetamine-type stimulant (ATS) use and toxicology results among young female sex workers (FSW) in Phnom Penh, Cambodia. Methods Cross-sectional data from the Young Women’s Health Study-2 (YWHS-2), a prospective study of HIV and ATS use among young (15 to 29 years) FSW in Phnom Penh, Cambodia, was analyzed. The YWHS-2 assessed sociodemographic characteristics, HIV serology, HIV risk, and ATS use by self-report and urine toxicology testing at each quarterly visit, the second of which provided data for this assessment. Outcomes include sensitivity, specificity, positive- and negative predictive values (overall and stratified by age), sex-work setting, and HIV status. Results Among 200 women, prevalence of positive toxicology screening for ATS use was 14% (95% confidence interval [CI], 9.2, 18.9%) and concurrent prevalence of self-reported ATS was 15.5% (95% CI, 10.4, 20.6%). The sensitivity and specificity of self-reported ATS use compared to positive toxicology test results was 89.3% (25/28), and 96.5% (166/172), respectively. The positive predictive value of self-reported ATS use was 80.6% (25/31); the negative predictive value was 98.2% (166/169). Some differences in concordance between self-report and urine toxicology results were noted in analyses stratified by age group and sex-work setting but not by HIV status. Conclusion Results indicate a high prevalence of ATS use among FSW in Phnom Penh, Cambodia, and high concordance between self-reported and toxicology-test confirmed ATS use.

Abstract Background The risk environment framework provides a valuable but under-utilised heuristic for understanding environmental vulnerability to HIV and other sexually transmitted infections among female sex workers. Brothels have been shown to be safer than street-based sex work, with higher rates of consistent condom use and lower HIV prevalence. While entertainment venues are also assumed to be safer than street-based sex work, few studies have examined environmental influences on vulnerability to HIV in this context. Methods As part of the Young Women's Health Study, a prospective observational study of young women (15-29 years) engaged in sex work in Phnom Penh, we conducted in-depth interviews (n = 33) to explore vulnerability to HIV/STI and related harms. Interviews were conducted in Khmer by trained interviewers, transcribed and translated into English and analysed for thematic content. Results The intensification of anti-prostitution and anti-trafficking efforts in Cambodia has increased the number of women working in entertainment venues and on the street. Our results confirm that street-based sex work places women at risk of HIV/STI infection and identify significant environmental risks related to entertainment-based sex work, including limited access to condoms and alcohol-related intoxication. Our data also indicate that exposure to violence and interactions with the police are mediated by the settings in which sex is sold. In particular, transacting sex in environments such as guest houses where there is little or no oversight in the form of peer or managerial support or protection, may increase vulnerability to HIV/STI. Conclusions Entertainment venues may also provide a high risk environment for sex work. Our results indicate that strategies designed to address HIV prevention among brothel-based FSWs in Cambodia have not translated well to street and entertainment-based sex work venues in which increasing numbers of women are working. There is an urgent need for targeted interventions, supported by legal and policy reforms, designed to reduce the environmental risks of sex work in these settings. Future research should seek to investigate sex work venues as risk environments, explore the role of different business models in mediating these environments, and identify and quantify exposure to risk in different occupational settings.

Abstract Background Hepatitis C virus (HCV) genotype (GT) has become an important measure in the diagnosis and monitoring of HCV infection treatment. In the United States (U.S.) HCV GT 1 is reported as the most common infecting GT among chronically infected patients. In Europe, however, recent studies have suggested that the epidemiology of HCV GTs is changing. Methods We assessed HCV GT distribution in 460 patients from three HCV-infected high risk populations in San Francisco, and examined patterns by birth cohort to assess temporal trends. Multiple logistic regression was used to assess factors independently associated with GT 1 infection compared to other GTs (2, 3, and 4). Results Overall, GT 1 was predominant (72.4%), however younger injection drug users (IDU) had a lower proportion of GT 1 infections (54.7%) compared to older IDU and HIV-infected patients (80.5% and 76.6%, respectively). Analysis by birth cohort showed increasing proportions of non-GT 1 infections associated with year of birth: birth before 1970 was independently associated with higher adjusted odds of GT 1: AOR 2.03 (95% CI: 1.23, 3.34). African-Americans as compared to whites also had higher adjusted odds of GT 1 infection (AOR: 3.37; 95% CI: 1.89, 5.99). Conclusions Although, HCV GT 1 remains the most prevalent GT, especially among older groups, changes in GT distribution could have significant implications for how HCV might be controlled on a population level and treated on an individual level.