Background. Hepatitis C virus (HCV) readily establishes chronic infection with exhaustion of HCV-specific T cells and escape from neutralizing antibodies. Spontaneous recovery from chronic infection is rare and has never to our knowledge been studied immunologically.

Methods. We prospectively studied, from prior to infection through >2 years of follow-up, cytokines, HCV-specific T cells, and antibodies, as well as viral sequence evolution in a white male who spontaneously cleared HCV genotype 1a after 65 weeks.

Results. Significant alanine aminotransferase and plasma cytokine elevation and broad HCV-specific T-cell responses did not result in HCV clearance in the acute phase. Frequency and effector function of HCV-specific T cells decreased thereafter, and HCV titers stabilized as is typical for the chronic phase. HCV clearance after 65 weeks followed the appearance of neutralizing antibodies at week 48 and was associated with reversal of HCV-specific T-cell exhaustion, as evidenced by reduced programmed death–1 (PD-1) expression and improved T-cell function. Clearance occurred without inflammation or superinfection with hepatitis B virus, human cytomegalovirus virus, influenza, and Epstein-Barr virus.

Conclusions. T-cell exhaustion is reversible at least in the first 2 years of chronic HCV infection, and this reversion in conjunction with neutralizing antibodies may clear HCV. These findings are relevant for immunotherapy of chronic infections.

Among 1369 Urban Health Study participants, we evaluated genetic models for the association of IL28B genotype (rs12979860 and rs8099917) with hepatitis C virus (HCV) clearance. For rs12979860, adjusted odds ratios for spontaneous HCV clearance were as follows: IL28B-CC, 3.88 (P < .001); IL28B-CT, 1.48 (P = .08). On the basis of Akaike information criteria values and χ2 tests, a supra-additive (quadratic) model fit these data best. Models based on rs8099917 provided poorer fit. Evidence that a supra-additive rs12979860-based model best fits the association of IL28B-genotype with HCV clearance may improve clinical prediction models and foster a better understanding of functional mechanisms underlying this association.

Background and Aims

Characterization of inflammatory mediators, such as chemokines, during acute hepatitis C virus (HCV) infection might shed some light on viral clearance mechanisms.

Methods

Plasma levels of CXCR3 (CXCL9-11)- and CCR5 (CCL3-4)-associated chemokines, ALT and HCV RNA were measured in nine injection drug users (median 26 samples/patient) before and during ten acute (eight primary and two secondary) HCV infections. Using functional data analysis, we estimated smooth long-term trends in chemokine expression levels to obtain the magnitude and timing of over-all changes. Residuals were analyzed to characterize short-term fluctuations.

Results

CXCL9-11 induction began 38–53 days and peaked 72–83 days after virus acquisition. Increases in ALT levels followed a similar pattern. Substantial negative autocorrelations of chemokine levels at one week lags suggested substantial week-to-week oscillations. Significant correlations were observed between CXCL10 and HCV RNA as well as ALT and CXCR3-associated chemokines measured in the preceding week, CCL3-4 expression levels did not change appreciably during acute HCV infection.

Conclusions

Elevation of CXCR3-associated chemokines late during acute HCV infection suggests a role for cellular immune responses in chemokine induction. Week-to-week oscillations of HCV RNA, chemokines, and ALT suggest frequent, repeated cycles of gain and loss of immune control during acute hepatitis C.

Injection drug users constitute the largest group of persons infected with the hepatitis C virus (HCV) in the United States, and most new infections occur in drug users. Controlling hepatitis C in the U.S. population, therefore, will require developing, testing, and implementing effective prevention and treatment strategies for persons who inject drugs. Fortunately, a substantial body of research and clinical experience exists on the prevention and management of chronic viral diseases among injection drug users. The need to implement interventions to stop the spread of HCV among drug users is critical. The capacity of substance-use treatment programs need to be expanded to accommodate all who want and need treatment. Physicians and pharmacists should be educated in how to provide access to sterile syringes and to teach safe injection techniques, both of which are lifesaving interventions. The treatment of hepatitis C in drug users requires an interdisciplinary approach that brings together expertise in treating hepatitis and caring for drug users. Treatment decisions should be made individually by patients with their physicians, based on a balanced assessment of risks and benefits and the patient's personal values. Physicians should carefully assess, monitor, and support adherence and mental health in all patients, regardless of whether drug use is known or suspected. Research is needed to better understand how best to prevent and treat hepatitis C in substance users. In the meantime, substantial progress can be made if existing knowledge and resources are brought to bear.

We followed-up 18 injection drug users for a mean of 33.8 months (range, 4–55 months) after successful treatment for hepatitis C virus (HCV) infection. Fifteen (83%) of the patients remained HCV RNA–negative, 1 patient was not tested, and 2 patients had test results positive for HCV RNA. The estimated rate of reinfection as a result of injection drug use was 0–4.1 cases per 100 person-years (cumulative incidence, 0%–12.6% at 48 months after completion of treatment). Of 50 patients originally treated, 15 (30%) were HCV RNA–negative 3 years later.

Claudin-1 is a recently discovered co-receptor for hepatitis C virus (HCV) that is required for late-stage binding of the virus. Because variants in the gene that encodes claudin-1 (CLDN1) could play a role in HCV infection, we conducted a ‘whole gene association study’ among injection drug users (IDUs) to examine whether CLDN1 genetic variants were associated with the risk of HCV infection or with viral clearance. In a cross sectional study, we examined genotype results for 50 single nucleotide polymorphisms (SNPs) across the CLDN1 gene region, comparing genotypes among participants with chronic HCV (n=658) to those in IDUs who had cleared HCV (n=199) or remained HCV-uninfected (n=68). Analyses were controlled for racial ancestry (African American or European American) by stratification and logistic regression modeling. We found that participants who remained uninfected more often carried CLDN1 promoter region SNPs -15312C [odds ratio (OR), 1.72; 95% confidence interval (CI) 1.00-2.94; p=0.048], -7153A (OR, 2.13; 95% CI, 1.25-3.62; p=0.006) and -5414C (OR, 1.78; 95% CI, 1.06-3.00; p=0.03). HCV-uninfected participants less often carried CLDN1 IVS1-2983C (OR, 0.55; 95% CI, 0.31-0.97; p=0.04), which lies in intron 1. CLDN1 -15312C, -7153A and -5414C formed a haplotype in both the African American and European American participants and a haplotype analysis supported the association of CLDN1 -7153A in the HCV-uninfected participants. The analyses of HCV clearance revealed no associations with any SNP. These results indicate that genetic variants in regulatory regions of CLDN1 may alter susceptibility to HCV infection.

Background/Aims

T-cell responses to HCV antigens have been reported in high-risk HCV seronegative persons, suggesting that an effective cellular immune response might be able to clear infection without the development of antibodies. Such findings, however, could be explained by waning antibody or cross-reactivity to other antigens. To address these issues, we assessed T-cell responses in high-risk, seronegative, young IDUs to multiple peptide mixes spanning the entire HCV genome.

Methods

We evaluated HCV-specific T-cell responses in 26 young (age 18-33 years) aviremic, seronegative IDUs (median duration of injection, 6 years) by interferon-γ ELISpot assay using 429 overlapping HCV peptides pooled in 21 mixes. Seventeen aviremic, seropositive IDUs (spontaneous resolvers) and 15 healthy people were used as positive and negative controls, respectively.

Results

The percentage of patients with HCV-specific cellular immune responses was similar in seronegative and seropositive aviremic IDUs (46% versus 59%, p=0.4), while these responses were not detected in any of the negative controls. Among the seronegative IDUs, 6 (23%) had intermediate to very strong responses to 10-20 peptide mixes and another 6 (23%) had moderately strong responses to 2 to 6 mixes. The 12 seronegative IDUs with HCV-specific T-cell responses had higher demographic and behavioral risk profiles than the 14 IDUs without T-cell responses (estimated risk of HCV infection, 0.47 vs. 0.26, p <0.01).

Conclusions

HCV-specific T-cell responses are common among high-risk, seronegative IDUs. The responses are broad and are associated with risk factors for HCV exposure, suggesting that they reflect true exposure to HCV in seronegative persons.

Background

Prior research on adherence to Hepatitis C treatment has documented rates of dose reductions and early treatment discontinuation, but little is known about patients' dose-taking adherence.

Aims

To assess the prevalence of missed doses of pegylated interferon and ribavirin and examine the correlates of dose-taking adherence in clinic settings.

Methods

180 patients on treatment for Hepatitis C (23% co-infected with HIV) completed a cross-sectional survey at the site of their Hepatitis C care.

Results

Seven percent of patients reported missing at least one injection of pegylated interferon in the last four weeks and 21% reported missing at least one dose of ribavirin in the last 7 days. Dose-taking adherence was not associated with HCV viral load.

Conclusions

Self-reported dose nonadherence to Hepatitis C treatment occurs frequently. Further studies of dose nonadherence (assessed by method other than self-report) and its relationship to HCV virologic outcome are warranted.

Background

Injection drug users (IDUs) who successfully clear hepatitis C virus (HCV) have a reduced risk of developing chronic reinfection, despite their continuing exposure to the virus. To identify immunological correlates for this apparent protection, we studied HCV-specific immune responses in long-term IDUs (duration, >10 years).

Methods

HCV-specific T cell responses were assessed in proliferation, enzyme-linked immunospot (ELISPOT), interferon (IFN)–γ secretion, and cytotoxicity assays, whereas HCV-specific antibodies were assessed in enzyme immunoassays (EIAs), chemiluminescent assays, and in vitro neutralization assays.

Results

HCV-specific T cell proliferation and IFN-γ production were more common in nonviremic EIA-positive IDUs (16 [94%] of 17 IDUs) than in viremic EIA-positive IDUs (9 [45%] of 20 IDUs) (P = .003). They were also noted in 16 (62%) of 26 nonviremic EIA-negative IDUs. In contrast, 19 (90%) of 21 viremic IDUs displayed neutralizing antibodies (nAbs), compared with 9 (56%) of 16 nonviremic EIA-positive IDUs (P = .04) and 0 of 24 nonviremic EIA-negative IDUs. Nonviremic IDUs with nAbs were older (P = .0115) than those without nAbs, but these groups did not differ in terms of either injection drug use duration or HCV-specific T cell responses.

Conclusion

The reduced risk of HCV persistence in IDUs previously recovered from HCV infection correlated with T cell responses, and prolonged antigenic stimulation appears to be required to maintain humoral responses.

Fatal heroin overdose has become a leading cause of death among injection drug users (IDUs). Several recent feasibility studies have concluded that naloxone distribution programs for heroin injectors should be implemented to decrease heroin overdose deaths, but there have been no prospective trials of such programs in North America. This pilot study was undertaken to investigate the safety and feasibility of training injection drug using partners to perform cardiopulmonary resuscitation (CPR) and administer naloxone in the event of heroin overdose. During May and June 2001, 24 IDUs (12 pairs of injection partners) were recruited from street settings in San Francisco. Participants took part in 8-hour training in heroin overdose prevention, CPR, and the use of naloxone. Following the intervention, participants were prospectively followed for 6 months to determine the number and outcomes of witnessed heroin overdoses, outcomes of participant interventions, and changes in participants’ knowledge of overdose and drug use behavior. Study participants witnessed 20 heroin overdose events during 6 months follow-up. They performed CPR in 16 (80%) events, administered naloxone in 15 (75%) and did one or the other in 19 (95%). All overdose victims survived. Knowledge about heroin overdose management increased, whereas heroin use decreased. IDUs can be trained to respond to heroin overdose emergencies by performing CPR and administering naloxone. Future research is needed to evaluate the effectiveness of this peer intervention to prevent fatal heroin overdose.

Community characteristics have been associated with racial and ethnic health disparities for a wide range of ailments and conditions. Previous research has found that rates of AIDS cases among injection drug users (IDUs) vary by community characteristics. However, few studies have examined whether community characteristics are associated with HIV risk behaviors among IDUs. To address this gap in the literature, we examined the associations between census-tract-level community characteristics and injection-related and sex-related HIV risk behaviors among IDUs in the San Francisco Bay Area. Individual HIV risk behaviors were collected from 4,956 IDUs between 1998 and 2002. Using 2000 US census data, we constructed four census-level community measures: percent African American, percent male unemployment, percent of households that receive public assistance, and median household income. All community variables were measured continuously. Multilevel modeling was used to determine if community characteristics were associated with recent (in the last 6 months) receptive and distributive syringe sharing, multiple sex partners, and unprotected sex risk while controlling for potential individual-level confounders. In bivariate analysis, most of the census-tract-level community characteristics were significantly associated with injection-related HIV risk, while no community characteristics were associated with sex-related risk. However, results from multivariate multilevel models indicate that only percent African American in a census tract was associated with receptive [adjusted odds ratio (AOR) = 0.93; 95% confidence interval (CI) = 0.89, 0.99] and distributive syringe sharing (AOR = 0.94; 95% CI = 0.92, 0.99), net of individual-level characteristics. Accounting for individual-level factors in the multivariate model in the sex-related risk models revealed a significant inverse relationship between percent African American and propensity to engage in unprotected sex (AOR = 0.95; 95% CI = 0.92, 0.99); community-level characteristics remained unassociated with multiple sex partners. In this exploratory analysis, percent African American in a census tract was inversely associated with injection-related risk. The census-tract-level community characteristics we examined seem to exert little influence on individual risk among long-term chronic IDUs. More research is needed examining the influence of other community characteristics that were unmeasured in this paper but might be related to sex and drug risk among IDUs such as shooting galleries, crack houses, drug markets, and availability of preventive HIV services.

Surveillance for hepatitis C virus (HCV) is limited by the challenge of differentiating between acute and chronic infections. In this study, we evaluate a cross-sectional testing strategy that identifies individuals with acute HCV infection and we estimate HCV incidence. Anti-HCV-negative persons from four populations with various risks, i.e., blood donors, Veterans Administration (VA) patients, young injection drug users (IDU), and older IDU, were screened for HCV RNA by minipool or individual sample nucleic acid testing (NAT). The number of detected viremic seronegative infections was combined with the duration of the preseroconversion NAT-positive window period (derived from analysis of frequent serial samples from plasma donors followed from NAT detection to seroconversion) to estimate annual HCV incidence rates. Projected incidence rates were compared to observed incidence rates. Projected HCV incidence rates per 100 person-years were 0.0042 (95% confidence interval [95% CI], 0.0025 to 0.007) for blood donors, 0.86 (95% CI, 0.02 to 0.71) for VA patients, 39.8 (95% CI, 25.9 to 53.7) for young IDU, and 53.7 (95% CI, 23.4 to 108.8) for older IDU. Projected rates were most similar to observed incidence rates for young IDU (33.4; 95% CI, 28.0 to 39.9). This study demonstrates the value of applying a cross-sectional screening strategy to detect acute HCV infections and to estimate HCV incidence.

Background

Genetic variations in MBL2 that reduce circulating levels and alter functional properties of the mannose binding lectin (MBL) have been associated with many autoimmune and infectious diseases. We examined whether MBL2 variants influence the outcome of hepatitis C virus (HCV) infection.

Methods

Participants were enrolled in the Urban Health Study of San Francisco Bay area injection drug users (IDU) during 1998 through 2000. Study subjects who had a positive test for HCV antibody were eligible for the current study. Participants who were positive for HCV RNA were frequency matched to those who were negative for HCV RNA on the basis of ethnicity and duration of IDU. Genotyping was performed for 15 single nucleotide polymorphisms in MBL2. Statistical analyses of European American and African American participants were conducted separately.

Results

The analysis included 198 study subjects who were positive for HCV antibody, but negative for HCV RNA, and 654 IDUs who were positive for both antibody and virus. There was no significant association between any of the genetic variants that cause MBL deficiency and the presence of HCV RNA. Unexpectedly, the MBL2 -289X promoter genotype, which causes MBL deficiency, was over-represented among European Americans who were HCV RNA negative (OR = 1.65, 95% CI 1.05–2.58), although not among the African Americans.

Conclusion

This study found no association between genetic variants that cause MBL deficiency and the presence of HCV RNA. The observation that MBL2 -289X was associated with the absence of HCV RNA in European Americans requires validation.

Injection drug use accounts for most of the incident infections with hepatitis C virus (HCV) in the United States and other developed countries. HCV infection is a complex and challenging medical condition in injection drug users (IDUs). Elements of care for hepatitis C in illicit drug users include prevention counseling and education; screening for transmission risk behavior; testing for HCV and human immunodeficiency virus infection; vaccination against hepatitis A and B viruses; evaluation for comorbidities; coordination of substance-abuse treatment services, psychiatric care, and social support; evaluation of liver disease; and interferon-based treatment for HCV infection. Caring for patients who use illicit drugs presents challenges to the health-care team that require patience, experience, and an understanding of the dynamics of substance use and addiction. Nonetheless, programs are successfully integrating hepatitis C care for IDUs into health-care settings, including primary care, methadone treatment and other substance-abuse treatment programs, infectious disease clinics, and clinics in correctional facilities.

Community characteristics have been associated with racial and ethnic health disparities for a wide range of ailments and conditions. Previous research has found that rates of AIDS cases among injection drug users (IDUs) vary by community characteristics. However, few studies have examined whether community characteristics are associated with HIV risk behaviors among IDUs. To address this gap in the literature, we examined the associations between census-tract-level community characteristics and injection-related and sex-related HIV risk behaviors among IDUs in the San Francisco Bay Area. Individual HIV risk behaviors were collected from 4,956 IDUs between 1998 and 2002. Using 2000 US census data, we constructed four census-level community measures: percent African American, percent male unemployment, percent of households that receive public assistance, and median household income. All community variables were measured continuously. Multilevel modeling was used to determine if community characteristics were associated with recent (in the last 6 months) receptive and distributive syringe sharing, multiple sex partners, and unprotected sex risk while controlling for potential individual-level confounders. In bivariate analysis, most of the census-tract-level community characteristics were significantly associated with injection-related HIV risk, while no community characteristics were associated with sex-related risk. However, results from multivariate multilevel models indicate that only percent African American in a census tract was associated with receptive [adjusted odds ratio (AOR)=0.93; 95% confidence interval (CI)=0.89, 0.99] and distributive syringe sharing (AOR=0.94; 95% CI=0.92, 0.99), net of individual-level characteristics. Accounting for individual-level factors in the multivariate model in the sex-related risk models revealed a significant inverse relationship between percent African American and propensity to engage in unprotected sex (AOR=0.95; 95% CI=0.92, 0.99); community-level characteristics remained unassociated with multiple sex partners. In this exploratory analysis, percent African American in a census tract was inversely associated with injection-related risk. The census-tract-level community characteristics we examined seem to exert little influence on individual risk among long-term chronic IDUs. More research is needed examining the influence of other community characteristics that were unmeasured in this paper but might be related to sex and drug risk among IDUs such as shooting galleries, crack houses, drug markets, and availability of preventive HIV services.

Fatal heroin overdose has become a leading cause of death among injection drug users (IDUs). Several recent feasibility studies have concluded that naloxone distribution programs for heroin injectors should be implemented to decrease heroin overdose deaths, but there have been no prospective trials of such programs in North America. This pilot study was undertaken to investigate the safety and feasibility of training injection drug using partners to perform cardiopulmonary resuscitation (CPR) and administer naloxone in the event of heroin overdose. During May and June 2001, 24 IDUs (12 pairs of injection partners) were recruited from street settings in San Francisco. Participants took part in 8-hour training in heroin overdose prevention, CPR, and the use of naloxone. Following the intervention, participants were prospectively followed for 6 months to determine the number and outcomes of witnessed heroin overdoses, outcomes of participant interventions, and changes in participants’ knowledge of overdose and drug use behavior. Study participants witnessed 20 heroin overdose events during 6 months follow-up. They performed CPR in 16 (80%) events, administered naloxone in 15 (75%) and did one or the other in 19 (95%). All overdose victims survived. Knowledge about heroin overdose management increased, whereas heroin use decreased. IDUs can be trained to respond to heroin overdose emergencies by performing CPR and administering naloxone. Future research is needed to evaluate the effectiveness of this peer intervention to prevent fatal heroin overdose.

The dual risks of male-to-male sex and drug injection have put men who have sex with men and inject drugs (MSM-IDU) at the forefront of the HIV epidemic, with the highest rates of infection among any risk group in the United States. This study analyzes data collected from 357 MSM-IDU in San Francisco between 1998 and 2002 to examine how risk behaviors differ by HIV serostatus and self-identified sexual orientation and to assess medical and social service utilization among HIV-positive MSM-IDU. Twenty-eight percent of the sample tested HIV antibody positive. There was little difference in risk behaviors between HIV-negative and HIV-positive MSM-IDU. Thirty percent of HIV-positive MSM-IDU reported distributive syringe sharing, compared to 40% of HIV negatives. Among MSM-IDU who reported anal intercourse in past 6 months, 70% of positives and 66% of HIV negatives reported unprotected anal intercourse. HIV status varied greatly by self-identified sexual orientation: 46% among gay, 24% among bisexual, and 14% among heterosexual MSM-IDU. Heterosexual MSM-IDU were more likely than other MSM-IDU to be homeless and to trade sex for money or drugs. Gay MSM-IDU were more likely to have anal intercourse. Bisexual MSM-IDU were as likely as heterosexual MSM-IDU to have sex with women and as likely as gay-identified MSM-IDU to have anal intercourse. Among MSM-IDU who were HIV positive, 15% were currently on antiretroviral therapy and 18% were currently in drug treatment, and 87% reported using a syringe exchange program in the past 6 months. These findings have implications for the development of HIV interventions that target the diverse MSM-IDU population.

Syringe-exchange programs (SEPs) have proven to prevent the spread of bloodborne pathogens, primarily human immunodeficiency virus (HIV), among injection drug users (IDUs). In the United States, only about 7% of IDUs have access to and use SEPs. Some IDUs engage in secondary syringe exchange (SSE), meaning that one IDU (a “provider”) obtains syringes at an SEP to distribute to other IDUs (“recipients”). This formative qualitative research was conducted to understand why and how IDUs engage in SSE to aid in the development of a large-scale peer HIV prevention intervention. Interviews with 47 IDUs in Oakland and Richmond, California, indicated that SSE was embedded in existing social networks, which provided natural opportunities for peer education. SSE providers reported a desire to help other IDUs as their primary motivation, while recipients reported convenience as their primary reason for using SSE. Building SSE into SEP structures can facilitate an effective provision of risk reduction supplies and information to IDUs who do not access SEPs directly.

Naloxone, an injectable opiate antagonist, can immediately reverse an opiate overdose and prevent overdose death. We sought to determine injection drug users’ (IDUs) attitudes about being prescribed take-home naloxone. During November 1999 to February 2000, we surveyed 82 street-recruited IDUs from the San Francisco Bay Area of California who had experienced one or more heroin overdose events. We used a questiomaire that included structured and open-ended questions. Most respondents (89%) had witnessed an overdose, and 90% reported initially attempting lay remedies in an effort to help companions survive. Only 51% reported soliciting emergency assistance (calling 911) for the last witnessed overdose, with most hesitating due to fear of police involvement. Of IDUs surveyed, 87% were strongly in favor of participating in an overdose management training program to receive take-home naloxone and training in resuscitation techniques. Nevertheless, respontdents expressed a variety of concerning attitudes. If provided naloxone, 35% predicted that they might feel comfortable using greater amounts of heroin, 62% might be less inclined to call 911 for an overdose, 30% might leave an overdose victim after naloxone resuscitation, and 46% might not be able to dissuade the victim from using heroin again to alleviate with drawal symptoms induced by naloxone. Prescribing take-home naloxone to IDUs with training in its use and in resuscitation techniques may represent a life-saving, peer-based adjunct to accessing emergency services. Nevertheless, strategies for overcoming potential risks associated with the use of take-home naloxone would need to be emphasized in an overdose management training program.

Heroin-related overdose is the single largest cause of accidental death in San Francisco. We examined demographic, location, nontoxicological, and toxicological characteristics of opiate overdose deaths in San Francisco, California. Medical examiner’s case files for every opioid-positive death from July 1, 1997, to June 30, 2000, were reviewed and classified as overdose deaths or other. Demographic variables were compared to two street-based studies of heroin users and to census data. From 1997 to 2000, of all heroin-related overdoses in San Francisco 47% occurred in low-income residential hotels; 36% occurred in one small central area of the city. In 68% of deaths, the victim was reportedly alone. When others were present between last ingestion of heroin and death, appropriate responses were rare. In three cases, police arrested the person who called emergency services or others present on the scene. We recommend the development of overdose response training targeted at heroin users and those close to them, including the staff of residential hotels.

Evidence for human immunodeficiency virus type 1 (HIV-1) superinfection was sought among 37 HIV-1-positive street-recruited active injection drug users (IDUs) from the San Francisco Bay area. HIV-1 sequences from pairs of samples collected 1 to 12 years apart, spanning a total of 215 years of exposure, were generated at p17 gag, the V3-V5 region of env, and/or the first exon of tat and phylogenetically analyzed. No evidence of HIV-1 superinfection was detected in which a highly divergent HIV-1 variant emerged at a frequency >20% of the serum viral quasispecies. Based on the reported risk behavior of the IDUs and the HIV-1 incidence in uninfected subjects in the same cohort, a total of 3.4 new infections would have been expected if existing infection conferred no protection from superinfection. Adjusted for risk behaviors, the estimated relative risk of superinfection compared with initial infection was therefore 0.0 (95% confidence interval, 0.00, 0.79; P = 0.02), indicating that existing infection conferred a statistically significant level of protection against superinfection with an HIV-1 strain of the same subtype, which was between 21 and 100%.

Setting

A community-based directly observed preventive therapy (DOPT) program for treatment of latent tuberculosis infection among injection drug users (IDUs) in an innercity neighborhood.

Objective

To test adherence to a 6-month course of DOPT using cash incentives and an easily accessible neighborhood location.

Design

Street-recruited IDUs (N=205) were screened forMycobacterium tuberculosis (TB) infection using the Mantoux test and two controls. Subjects who had a purified protein derivative (PPD) reaction of ≥5 mm, were anergic, or had a history of a positive PPD received clinical evaluation at a community field site, provided in collaboration with the San Francisco Department of Public Health Tuberculosis Clinic. Twenty-eight subjects were considered appropriate candidates for prophylaxis with isoniazid, and 27 enrolled in the pilot study. Participants received twice-weekly DOPT at a community satellite office, with a $10 cash incentive at each visit.

Results

The 6-month (26-week) regimen was completed by 24/27 (89%) participants. The median time to treatment completion was 27 weeks (range 26 to 34 weeks). The median proportion of dosing days attended in 6 months was 96%.

Conclusion

Community-based DOPT using cash incentives resulted in high levels of adherence and treatment completion among drug users.