Durable HIV Suppression Among People Who Inject Drugs From a Community-Based Cohort Study in Baltimore, Maryland, 1997-2017.

People who inject drugs (PWID) face disparities in human immunodeficiency virus (HIV) treatment outcomes and may be less likely to achieve durable viral suppression. We characterized transitions into and out of viral suppression from 1997 to 2017 in a long-standing community-based cohort study of PWID, the AIDS Link to Intravenous Experience (ALIVE) Study, analyzing HIV-positive participants who had made a study visit in or after 1997. We defined the probabilities of transitioning between 4 states: 1) suppressed, 2) detectable, 3) lost to follow-up, and 4) deceased. We used multinomial logistic regression analysis to examine factors associated with transition probabilities, with a focus on transitions from suppression to other states. Among 1,061 participants, the median age was 44 years, 32% were female, 93% were African-American, 59% had recently injected drugs, and 28% were virologically suppressed at baseline. Significant improvements in durable viral suppression were observed over time; however, death rates remained relatively stable. In adjusted analysis, injection drug use and homelessness were associated with increased virological rebound in earlier time periods, while only age and race were associated with virological rebound in 2012-2017. Opioid use was associated with an increased risk of death following suppression in 2012-2017. Despite significant improvements in durable viral suppression, subgroups of PWID may need additional efforts to maintain viral suppression and prevent premature mortality.

Probable transmission of hepatitis E virus (HEV) via transfusion in the United States.

BACKGROUND: Hepatitis E virus (HEV) can inapparently infect blood donors. To assess transfusion transmission of HEV in the United States, which has not been documented, a donor-recipient repository was evaluated. STUDY DESIGN AND METHODS: To identify donations that contained HEV RNA and were linked to patient-recipients with antibody evidence of HEV exposure, we assayed samples from the Retrovirus Epidemiology Donor Study (REDS) Allogeneic Donor and Recipient repository that represents 13,201 linked donations and 3384 transfused patients. Posttransfusion samples, determined to contain IgG anti-HEV by enzyme-linked immunosorbent assay, were reassayed along with corresponding pretransfusion samples for seroconversion (incident exposure) or at least fourfold IgG anti-HEV increase (reexposure). HEV-exposed patients were linked to donations in which HEV RNA was then detected by reverse-transcription quantitative polymerase chain reaction, confirmed by transcription-mediated amplification, and phylogenetically analyzed as subgenomic cDNA sequences. RESULTS: Among all patients, 19 of 1036 (1.8%) who had IgG anti-HEV before transfusion were reexposed; 40 of 2348 (1.7%) without pretransfusion IgG anti-HEV seroconverted. These 59 patients were linked to 257 donations, 1 of which was positive by reverse-transcription quantitative polymerase chain reaction and transcription-mediated amplification. Plasma from this donation contained 5.5 log IU/mL of HEV RNA that grouped with HEV genotype 3, clade 3abchij. The patient-recipient of RBCs from this donation had a greater than eightfold IgG increase; however, clinical data are unavailable. CONCLUSIONS: This is the first report of probable HEV transmission via transfusion in the United States, although it has been frequently observed in Europe and Japan. Additional data on the magnitude of the risk in the United States are needed.

A Ten Year Immunopersistence Study of Hepatitis E Antibodies in Rural Bangladesh.

Hepatitis E virus (HEV) is a major cause of acute, viral hepatitis in Southeast Asia. Several studies have suggested that antibody persistence after HEV infection may be transient, possibly increasing the risk of re-infection and contributing to the frequency of outbreaks in HEV endemic regions. The specific conditions under which antibodies to HEV are lost, or "sero-reversion" occurs, are poorly understood. Here, one hundred participants from population-based studies in rural Bangladesh were revisited in 2015, ten years after a documented HEV infection to examine long-term antibody persistence. Twenty percent (95% confidence interval: 12.0, 28.0) no longer had detectable antibodies at follow-up, suggesting that antibodies generally persist for at least a decade after infection in rural Bangladesh. Those who were seronegative at follow-up were generally younger at infection than those who remained positive (14.4 years versus 33.6 years, P > 0.0001). This age-dependent antibody loss could partially explain cross-sectional sero-prevalence data from South East Asia where children have reportedly low antibody prevalence. The results of this study provide new insight into the immunological persistence of HEV infection in a micronutrient deficient rural population of South Asia, highlighting the importance of age at infection in the ability to produce long-lasting antibodies against HEV.

Association of killer cell immunoglobulin-like receptors with spontaneous clearance of hepatitis C virus in the Chinese population.

BACKGROUND: Natural killer (NK) cells are critical components in innate immune response to viral infection. Killer cell immunoglobulin-like receptors (KIRs) are involved in regulating the balance of activation or inhibitory function of NK cells. However, the association of KIRs with the spontaneous clearance of hepatitis C virus (HCV) remains unclear in the Chinese population. STUDY DESIGN AND METHODS: A total of 407 HCV-seropositive voluntary blood donors were recruited, including 203 with spontaneous viral clearance and 204 with chronic infection. The presence of KIR genes was detected individually by polymerase chain reaction with sequence-specific primers. Data of HLA and interleukin-28B (IL28B) genotypes were extracted from our previous study. RESULTS: Our results showed that KIR2DL2, 2DS2, 2DL2/2DL3, and 2DL5A-/2DL5B+ were more frequent in subjects with HCV clearance than those with chronic infection (odds ratio [OR], 1.640, p = 0.034; OR, 1.664, p = 0.032; OR, 1.636, p = 0.040; and OR, 2.601, p = 0.012, respectively). Multivariate logistic regression analysis showed that KIR2DL5A-/2DL5B+ associated with HCV clearance (OR, 2.448, p = 0.027), independent of sex, IL28B, and other KIRs. In contrast, KIR2DL3/2DL3 (OR, 0.610, p = 0.034) as well as 2DL3/2DL3+HLA-C1 or C1C1 (OR, 0.580, p = 0.017; and OR, 0.639, p = 0.025, respectively) was found associated with chronic HCV infection. The presence of the homozygous KIR2DL3 with or without its HLA ligand increased the OR of developing chronic HCV infection in the context of IL28B. CONCLUSIONS: In this study we identified KIR2DL5A-/2DL5B+ associated with HCV spontaneous clearance, while KIR2DL3/2DL3, 2DL3/2DL3+HLA-C1, or C1C1 associated with chronic infection. Our study highlighted the fact that the roles of KIR and KIR-HLA contributed to the control of HCV infection by innate immune responses.

Addressing gaps in international blood availability and transfusion safety in low- and middle-income countries: a NHLBI workshop.

In April 2017, a workshop sponsored by the National Heart, Lung, and Blood Institute, Division of Blood Diseases and Resources, and the Center for Translation Research and Implementation Science was held to discuss blood availability and transfusion safety in low- and middle-income countries (LMICs). The purpose of the workshop was to identify research opportunities for implementation science (IS) to improve the availability of safe blood and blood components and transfusion practices in LMICs. IS describes the late stages of the translational research spectrum and studies optimal and sustainable strategies to deliver proven-effective interventions. Regional working groups were formed to focus on opportunities and challenges in East Africa, Central/West Africa, Middle East and North Africa, Latin America and the Caribbean, Southeast Asia, Western Pacific Asia, Eastern Europe, and Central Asia. The need for an "adequate supply of safe blood" emerged as the major overriding theme. Among the regional working groups, common cross-cutting themes were evident. The majority of research questions, priorities, and strategies fell into the categories of blood availability, blood transfusion safety, appropriate use of blood, quality systems, health economics and budgeting, and training and education in IS. The workshop also brought into focus inadequate country-level data that can be used as the basis for IS initiatives. A mixed approach of needs assessment and targeted interventions with sufficient evidence base to move toward sustainment is an appropriate next step for blood availability and transfusion safety research in LMICs.

An evaluation of asymptomatic Dengue infections among blood donors during the 2014 Dengue outbreak in Guangzhou, China.

In 2014, an outbreak of dengue virus (DENV) infection led to 45 171 clinical cases diagnosed in Guangdong province, Southern China. However, the potential risk of blood donors asymptomatically infected with DENV has not been evaluated . In the current study we detected anti-DENV IgG antibody and RNA in volunteer Chinese blood donors. We found that anti-DENV IgG antibody was positively detected in 3.4% (51/1500) and two donors were detected as being DENV RNA positive out of 3000 blood samples. We concluded that the presence of potential DENV in blood donors might be potential risk for blood safety. Therefore, screening for DENV infection should be considered in blood donations during a period of dengue outbreak in high epidemic area of China.

Acute and Chronic Hepatitis E Virus Infection in Human Immunodeficiency Virus-Infected U.S. Women.

UNLABELLED: Exposure to hepatitis E virus (HEV) is common in the United States, but there are few data on prevalence of HEV/human immunodeficiency virus (HIV) coinfection in U.S. POPULATIONS: We tested 2,919 plasma samples collected from HIV-infected (HIV(+)) women and men enrolled in U.S. cohort studies for HEV viremia using a high-throughput nucleic acid testing (NAT) platform. NAT(+) samples were confirmed by real-time polymerase chain reaction. Samples were selected for testing primarily on the basis of biomarkers of liver disease and immune suppression. Prevalence of HEV viremia was 3 of 2,606 and 0 of 313 in tested plasma samples collected from HIV(+) women and men, respectively. All HEV isolates were genotype 3a. Based on follow-up testing of stored samples, 1 woman had chronic HEV infection for >4 years whereas 2 women had acute HEV detectable at only a single study visit. CONCLUSIONS: To our knowledge, this is the first reported case of chronic HEV infection in an HIV(+) U.S. individual. We also confirm that chronic HEV infection can persist despite a CD4(+) count >200 cells/mm(3). Overall, though, these data suggest that HEV infection is rare in the HIV(+) U.S. population.

The association of elevated alanine aminotransferase levels with hepatitis E virus infections among blood donors in China.

BACKGROUND: Transfusion transmission of hepatitis E virus (HEV) is an emerging health risk, yet blood donors are rarely screened for this pathogen. Many blood centers instituted screening of blood donors for elevated levels of alanine aminotransferase (ALT) levels to prevent hepatitis C virus, which has continued in China. We evaluated whether elevated ALT levels were associated with HEV among blood donors in China. STUDY DESIGN AND METHODS: Blood samples were collected from 9069 qualified volunteer blood donors from four blood centers in China. A total of 5023 had elevated ALT levels, that is, more than 40 IU/L, and 4046 samples had normal ALT. We tested all the 9069 samples for anti-HEV immunoglobulin (Ig)M, anti-HEV IgG, and HEV antigen. Those who were positive for anti-HEV IgM or HEV antigen were tested individually for HEV RNA by polymerase chain reaction. RESULTS: The prevalence of anti-HEV IgG in donors with elevated ALT levels (33.3%) was higher than those with normal ALT (24.9%; p < 0.01). The prevalence of anti-HEV IgM was similar in donations with increased ALT (1.41%) and normal ALT (1.46%). More ALT-elevated donations were HEV antigen positive, 62 of 5023 (1.23%), than were ALT-normal donations, seven of 4046 (0.17%; p < 0.01). Six donors with elevated ALT levels and acute HEV infection markers (anti-HEV IgM or HEV antigen) were HEV RNA positive. CONCLUSION: Markers of active infection including HEV antigen and HEV RNA are significantly more common among donors with elevated ALT levels in China. These data support the fact that ALT testing of donors to HEV antigen or HEV RNA would have greater specificity and exclude fewer acceptable donors.

Hepatitis E: prevention and treatment.

PURPOSE OF REVIEW: Infection with the hepatitis E virus (HEV) is very common worldwide. The epidemiology, viral genotypes, and transmission routes differ between low-resource countries and economically developed countries. These differences have resulted in the design of diverse prevention and treatment strategies to combat HEV. RECENT FINDINGS: The population seroprevalence of HEV immunoglobulin G varies between 5 and 50%. However, the diagnosis of acute hepatitis from HEV has not been common in the United States or Western Europe. Chronic progressive HEV infections have been reported among patients who are immunocompromised. Successful treatment of patients with chronic hepatitis from HEV infection with antiviral agents, such as ribavirin or interferon-α, has been reported. Extrahepatic manifestations of HEV infection are common. Large epidemics of hundreds or thousands of cases continue to be reported among populations in Asia and Africa. A subunit peptide HEV vaccine has been found to be highly efficacious in a large clinical trial. However, the vaccine has not been evaluated in populations of pregnant women or other risk groups and is only available in China. SUMMARY: Although HEV infections are increasingly recognized as a global public health problem, there are few methods for prevention and treatment that are widely available.

The natural history of recent hepatitis C virus infection among blood donors and injection drug users in the country of Georgia.

INTRODUCTION: Hepatitis C virus (HCV) infection is a serious health problem in Georgia. METHODS: We conducted a prospective study to identify and characterize the natural history of recent HCV infection since very first days of infection. Recent HCV infection was defined as detectable plasma HCV RNA in the absence of anti-HCV antibodies. RESULTS: A total of 7600 HCV seronegative blood donors and 3600 HCV seronegative drug users were screened for recent HCV infection. Among them 7 (0.09 %) blood donors and 10 (0.28 %) drug users tested positive for HCV RNA and were classified as having recent HCV infection. Of these 17 patients 4 (23.5 %) spontaneously cleared the virus by the end of 24 week follow-up. Five clinical forms of recent HCV infection were identified during the follow-up. Four patients had symptomatic disease, including 3 patients with jaundice and other clinical symptoms (2 of them cleared virus) and 1 patient only had other symptoms without jaundice. All symptomatic patients had ALT elevation. Three distinct variants of asymptomatic disease were identified in 13 patients: 9 patients had ALT elevation and none cleared the virus; 2 patients developed chronic disease without ALT elevation; 2 patients cleared virus without anti-HCV seroconversion and without ALT elevation; this form can be described as transitory HCV viremia. CONCLUSION: Additional studies are needed to define clinical and public health implications of transitory HCV viremia. Our study suggests the need for implementing nucleic acid testing of blood donors and key populations in order to more effectively identify HCV infected persons.

Condom Use During Commercial Sex Among Male Clients of Female Sex Workers in Sichuan China: A Social Cognitive Theory Analysis.

There has been little theory-based research focusing on condom use among male clients of female sex workers (CFSW) in China. The current study applied social cognitive theory to condom use behaviors of CFSW in China. Face-to-face structured interviews were conducted among 584 CFSW recruited through snowball sampling. Bivariate and multivariate logistic regression models were applied to examine factors associated with consistent condom use. A minority (30.65 %) of respondents reported using condoms consistently with FSW, and 7 of 12 social cognitive dimensions/subdimensions were found to be significantly influential. The most significant factors were self-efficacy [adjusted prevalence ratio (APR) = 2.11, 95 %, CI = 1.74-2.43] and personal pleasure reduction (APR = 0.3, 95 % CI = 0.15-0.6). HIV-related knowledge, perceived HIV susceptibility, condom cost, condom efficacy, and embarrassment of carrying condoms were not associated with consistent condom uses with FSW. Findings from the current study suggest future prevention programs should target sex venues, and condom access should ensure both quantity and quality. Peer education should focus on knowledge education and peer norms, and knowledge education should include information on HIV infection severity and how to increase pleasure with condom use.

Host immune status and response to hepatitis E virus infection.

Hepatitis E virus (HEV), identified over 30 years ago, remains a serious threat to life, health, and productivity in developing countries where access to clean water is limited. Recognition that HEV also circulates as a zoonotic and food-borne pathogen in developed countries is more recent. Even without treatment, most cases of HEV-related acute viral hepatitis (with or without jaundice) resolve within 1 to 2 months. However, HEV sometimes leads to acute liver failure, chronic infection, or extrahepatic symptoms. The mechanisms of pathogenesis appear to be substantially immune mediated. This review covers the epidemiology of HEV infection worldwide, the humoral and cellular immune responses to HEV, and the persistence and protection of antibodies produced in response to both natural infection and vaccines. We focus on the contributions of altered immune states (associated with pregnancy, human immunodeficiency virus [HIV], and immunosuppressive agents used in cancer and transplant medicine) to the elevated risks of chronic infection (in immunosuppressed/immunocompromised patients) and acute liver failure and mortality (among pregnant women). We conclude by discussing outstanding questions about the immune response to HEV and interactions with hormones and comorbid conditions. These questions take on heightened importance now that a vaccine is available.

Breastfeeding while taking lamivudine or tenofovir disoproxil fumarate: a review of the evidence.

Lamivudine and tenofovir disoproxil fumarate (TDF) are both active against hepatitis B virus (HBV). Due to its potency, high genetic barrier to resistance, and safety during pregnancy, TDF may be useful to prevent HBV transmission from mother to child, which is the leading cause of transmission globally. Despite the safety record of lamivudine and TDF in pregnancy, the labels for both of these drugs recommend against their use during breastfeeding. In this review, we discuss the data regarding lamivudine and TDF use during pregnancy and breastfeeding and find that the exposure to the drug is lower from breastfeeding than from in utero exposure. Thus, the data do not support the contraindication to their use during breastfeeding.

High frequency of active HCV infection among seropositive cases in west Africa and evidence for multiple transmission pathways.

BACKGROUND: Sub-Saharan Africa (SSA) has one of the highest global hepatitis C virus (HCV) prevalence estimates. However, reports that suggest high rates of serologic false positives and low levels of viremia have led to uncertainty regarding the burden of active infection in this region. Additionally, little is known about the predominant transmission risk factors in SSA. METHODS: We prospectively recalled 363 past blood donors (180 who were rapid screen assay [RSA] positive and 183 who were RSA negative at time of donation) to identify the level of active infection and risk factors for infection at a teaching hospital in Kumasi, Ghana. Participants had repeat blood testing and were administered a questionnaire on risk factors. RESULTS: The frequency of HCV active infection ranged from 74.4% to 88% depending on the criteria used to define serologically positive cases. Individuals with active disease had biochemical evidence of liver inflammation and median viral loads of 5.7 log copies/mL. Individuals from the northern and upper regions of Ghana had greater risks of infection compared with participants from other areas. Additional risk factors included traditional circumcision, home birth, tribal scarring, and hepatitis B virus coinfection. CONCLUSIONS: Viremic infection was common among serologically confirmed cases. Attention to testing algorithms is needed in order to define the true HCV burden in SSA. These data also suggest that several transmission modes are likely contributing to the current HCV epidemic in Ghana and that the distribution of these practices may result in substantial regional variation in prevalence.

Seroprevalence for Hepatitis E and Other Viral Hepatitides among Diverse Populations, Malawi.

Data on prevalence of hepatitis E virus (HEV) in Malawi is limited. We tested blood samples from HIV-uninfected and -infected populations of women and men enrolled in research studies in Malawi during 1989-2008 to determine the seroprevalence of HEV, hepatitis A virus (HAV), hepatitis B virus (HBV), and hepatitis C virus (HCV). Samples were tested for IgG against HEV, total antibodies against HAV and HCV, and presence of HBV surface antigens. Of 800 samples tested, 16.5% were positive for HEV IgG, 99.6% were positive for HAV antibodies, 7.5% were positive for HBV surface antigen, and 7.1% were positive for HCV antibodies. No clear trends over time were observed in the seroprevalence of HEV, and HIV status was not associated with hepatitis seroprevalence. These preliminary data suggest that the seroprevalence of HEV is high in Malawi; the clinical effects may be unrecognized or routinely misclassified.

HLA-B alleles B*15:01 and B*15:02: opposite association with hepatitis C virus infection in Chinese voluntary blood donors.

BACKGROUND: Although human leukocyte antigens (HLA) have been shown in association with the outcomes of hepatitis C virus (HCV) infection among different ethnic groups, such studies remain absent in China, where the HCV prevalence is higher than the global average. METHODS: In this study, 426 HCV-infected and 709 uninfected blood donors were analyzed, among whom the HLA alleles were sequenced using a high-resolution genotyping method. RESULTS: At the 2-digit level, none of the alleles showed a statistical difference between the HCV-infected and uninfected groups. However, at the 4-digit level, the HLA-B alleles B*15:01 and B*15:02 showed an opposite association with HCV infection, i.e. B*15:01 was significantly higher in the HCV-infected group (odds ratio, OR = 1.561, p = 0.010), while B*15:02 was significantly higher in the uninfected group (OR = 0.778, p = 0.016). We also identified a higher frequency of B*13:02 in the HCV-infected group (OR = 1.515, p = 0.009) and a higher frequency of B*07:05 in the uninfected group (OR = 0.299, p = 0.001). CONCLUSIONS: The frequencies of four HLA alleles, B*07:05, B*13:02, B*15:01, and B*15:02, were found to be significantly different between the HCV-infected and uninfected blood donors in China, revealing an inverse relation of B*15:01 and B*15:02 with HCV infection. This finding suggests that the ethnic genetic variations of HLA may greatly affect the host immune responses against HCV.

Occupational ionising radiation and risk of basal cell carcinoma in US radiologic technologists (1983-2005).

OBJECTIVE: To determine risk for incident basal cell carcinoma from cumulative low-dose ionising radiation in the US radiologic technologist cohort. METHODS: We analysed 65,719 Caucasian technologists who were cancer-free at baseline (1983-1989 or 1994-1998) and answered a follow-up questionnaire (2003-2005). Absorbed radiation dose to the skin in mGy for estimated cumulative occupational radiation exposure was reconstructed for each technologist based on badge dose measurements, questionnaire-derived work history and protection practices, and literature information. Radiation-associated risk was assessed using Poisson regression and included adjustment for several demographic, lifestyle, host and sun exposure factors. RESULTS: Cumulative mean absorbed skin dose (to head/neck/arms) was 55.8 mGy (range 0-1735 mGy). For lifetime cumulative dose, we did not observe an excess radiation-related risk (excess relative risk/Gy=-0.01 (95% CI -0.43 to 0.52). However, we observed that basal cell carcinoma risk was increased for radiation dose received before age 30 (excess relative risk/Gy=0.59, 95% CI -0.11 to 1.42) and before 1960 (excess relative risk/Gy=2.92, 95% CI 1.39 to 4.45). CONCLUSIONS: Basal cell carcinoma risk was unrelated to low-dose radiation exposure among radiologic technologists. Because of uncertainties in dosimetry and sensitivity to model specifications, both our null results and our findings of excess risk for dose received before age 30 and exposure before 1960 should be interpreted with caution.

Arsenic exposure and hepatitis E virus infection during pregnancy.

BACKGROUND: Arsenic has immunomodulatory properties and may have the potential to alter susceptibility to infection in humans. OBJECTIVES: We aimed to assess the relation of arsenic exposure during pregnancy with immune function and hepatitis E virus (HEV) infection, defined as seroconversion during pregnancy and postpartum. METHODS: We assessed IgG seroconversion to HEV between 1st and 3rd trimester (TM) and 3 months postpartum (PP) among 1100 pregnancies in a multiple micronutrient supplementation trial in rural Bangladesh. Forty women seroconverted to HEV and were matched with 40 non-seroconverting women (controls) by age, parity and intervention. We assessed urinary inorganic arsenic plus methylated species (∑As) (µg/L) at 1st and 3rd TM and plasma cytokines (pg/mL) at 1st and 3rd TM and 3 months PP. RESULTS: HEV seroconverters' urinary ∑As was elevated throughout pregnancy. Non-seroconverters' urinary ∑As was similar to HEV seroconverters at 1st TM but declined at 3rd TM. The adjusted odds ratio (95% confidence interval) of HEV seroconversion was 2.17 (1.07, 4.39) per interquartile range (IQR) increase in average-pregnancy urinary ∑As. Increased urinary ∑As was associated with increased concentrations of IL-2 during the 1st and 3rd TM and 3 months PP among HEV seroconverters but not non-seroconverters. CONCLUSIONS: The relation of urinary arsenic during pregnancy with incident HEV seroconversion and with IL-2 levels among HEV-seroconverting pregnant women suggests arsenic exposure during pregnancy may enhance susceptibility to HEV infection.

Changes in HIV incidence among people who inject drugs in Taiwan following introduction of a harm reduction program: a study of two cohorts.

BACKGROUND: Harm reduction strategies for combating HIV epidemics among people who inject drugs (PWID) have been implemented in several countries. However, large-scale studies using sensitive measurements of HIV incidence and intervention exposures in defined cohorts are rare. The aim of this study was to determine the association between harm reduction programs and HIV incidence among PWID. METHODS AND FINDINGS: The study included two populations. For 3,851 PWID who entered prison between 2004 and 2010 and tested HIV positive upon incarceration, we tested their sera using a BED HIV-1 capture enzyme immunoassay to estimate HIV incidence. Also, we enrolled in a prospective study a cohort of 4,357 individuals who were released from prison via an amnesty on July 16, 2007. We followed them with interviews at intervals of 6-12 mo and by linking several databases. A total of 2,473 participants who were HIV negative in January 2006 had interviews between then and 2010 to evaluate the association between use of harm reduction programs and HIV incidence. We used survival methods with attendance at methadone clinics as a time-varying covariate to measure the association with HIV incidence. We used a Poisson regression model and calculated the HIV incidence rate to evaluate the association between needle/syringe program use and HIV incidence. Among the population of PWID who were imprisoned, the implementation of comprehensive harm reduction programs and a lower mean community HIV viral load were associated with a reduced HIV incidence among PWID. The HIV incidence in this population of PWID decreased from 18.2% in 2005 to 0.3% in 2010. In an individual-level analysis of the amnesty cohort, attendance at methadone clinics was associated with a significantly lower HIV incidence (adjusted hazard ratio: 0.20, 95% CI: 0.06-0.67), and frequent users of needle/syringe program services had lower HIV incidence (0% in high NSP users, 0.5% in non NSP users). In addition, no HIV seroconversions were detected among prison inmates. CONCLUSIONS: Although our data are affected by participation bias, they strongly suggest that comprehensive harm- reduction services and free treatment were associated with reversal of a rapidly emerging epidemic of HIV among PWID. Please see later in the article for the Editors' Summary.

Hepatitis C virus genotypes circulating in patients with chronic hepatitis C in Thailand and their responses to combined PEG-IFN and RBV therapy.

Different genotypes of hepatitis C virus (HCV) are circulating in different areas of the world. In Thailand, distribution of HCV genotypes has been investigated mostly in the central area while the information in other regions is limited. This study aimed to determine the HCV genotypes circulating in chronic hepatitis C patients in Chiang Mai, Thailand and to investigate the response of different HCV genotypes to pegylated interferon (PEG-IFN) and ribavirin (RBV) treatment. Patients infected chronically with HCV were treated with PEG-IFN/RBV based on the standard regimens for each HCV genotype and followed up the patients until the end of treatment and 6 months afterward. Out of 158 patients, three major HCV genotypes and eight subtypes were identified. Genotype 3 was the most predominant at 54.5%, followed by genotypes 1 (31%) and 6 (14.5%). Among subtypes, 3a was the most prevalent subtype (45%), followed by 1b (18.4%), 1a and 6f (each at 12.6%), 3b (9.5%), and 6a, 6i, 6n (each at 0.63%). Patients with genotype 3 showed higher rate of responding to the treatment at 80.2% compared to genotypes 1 (73.5%) and 6f (65%). Additionally, patients with genotype 6f showed higher rate of relapsing (25%) compared to genotypes 1 and 3 (14.3% and 16.3%, respectively). In conclusion, this study reported multiple HCV genotypes circulated in Thai patients and the response of different HCV genotypes to PEG-IFN/RBV treatment.