Kimberly Page

Acute Hepatitis C Virus Infection in Young Adult Injection Drug Users: A Prospective Study of Incident Infection, Resolution, and Reinfection

BACKGROUND Hepatitis C virus (HCV) infection, clearance, and reinfection are best studied in injection drug users (IDUs), who have the highest incidence of HCV and are likely to represent most infections. METHODS A prospective cohort of HCV-negative young IDUs was followed up from January 2000 to September 2007, to identify acute and incident HCV and prospectively study infection outcomes. RESULTS Among 1,191 young IDUs screened, 731 (61.4%) were HCV negative, and 520 (71.1%) of the 731 were enrolled into follow-up. Cumulative HCV incidence was 26.7/100 person-years of observation (95% confidence interval [CI], 21.5-31.6). Of 135 acute/incident HCV infections, 95 (70.4%) were followed; 20 (21.1%) of the 95 infections cleared. Women had a significantly higher incidence of viral clearance than did men (age-adjusted hazard ratio, 2.91 [95% CI, 1.68-5.03]) and also showed a faster rate of early HCV viremia decline (P < .01). The estimated reinfection rate was 24.6/100 person-years of observation (95% CI, 11.7-51.6). Among 7 individuals, multiple episodes of HCV reinfection and reclearance were observed. CONCLUSIONS In this large sample of young IDUs, females show demonstrative differences in their rates of viral clearance and kinetics of early viral decline. Recurring reinfection and reclearance suggest possible protection against persistent infection. These results should inform HCV clinical care and vaccine development.

The effects of female sex, viral genotype, and IL28B genotype on spontaneous clearance of acute hepatitis C virus infection.

Although 20%‐40% of persons with acute hepatitis C virus (HCV) infection demonstrate spontaneous clearance, the time course and factors associated with clearance remain poorly understood. We investigated the time to spontaneous clearance and predictors among participants with acute HCV using Cox proportional hazards analyses. Data for this analysis were drawn from an international collaboration of nine prospective cohorts evaluating outcomes after acute HCV infection. Among 632 participants with acute HCV, 35% were female, 82% were Caucasian, 49% had interleukin‐28 (IL28)B CC genotype (rs12979860), 96% had injected drugs ever, 47% were infected with HCV genotype 1, and 7% had human immunodeficiency virus (HIV) coinfection. Twenty‐eight percent were HCV antibody negative/RNA positive at the time of acute HCV detection (early acute HCV). During follow‐up, spontaneous clearance occurred in 173 of 632, and at 1 year after infection, 25% (95% confidence interval [CI]: 21, 29) had cleared virus. Among those with clearance, the median time to clearance was 16.5 weeks (IQR: 10.5, 33.4), with 34%, 67%, and 83% demonstrating clearance at 3, 6, and 12 months. Adjusting for age, factors independently associated with time to spontaneous clearance included female sex (adjusted hazards ratio [AHR]: 2.16; 95% CI: 1.48, 3.18), IL28B CC genotype (versus CT/TT; AHR, 2.26; 95% CI: 1.52, 3.34), and HCV genotype 1 (versus non‐genotype 1; AHR: 1.56; 95% CI: 1.06, 2.30). The effect of IL28B genotype and HCV genotype on spontaneous clearance was greater among females, compared to males. Conclusions: Female sex, favorable IL28B genotype, and HCV genotype 1 are independent predictors of spontaneous clearance. Further research is required to elucidate the observed sex‐based differences in HCV control. (Hepatology 2014;58:109–120)

HIV infection in homosexual and bisexual men 18 to 29 years of age: the San Francisco Young Men's Health Study.

OBJECTIVES Recent studies suggest very high human immunodeficiency virus (HIV) infection rates in some populations of younger homosexual men, but these studies may represent only particularly high-risk populations. The current study obtained population-based data on the HIV epidemic in young homosexual/bisexual men. METHODS A household survey of unmarried men 18 through 29 years of age involved a multistage probability sample of addresses in San Francisco. A follow-up interview and HIV test for men who were HIV negative at baseline were completed; the median follow-up was 8.9 months. RESULTS Sixty-eight of 380 homosexual/bisexual men (17.9%) tested HIV seropositive. Sixty-three percent of men reported one or more receptive anal intercourse partners in the previous 12 months, and 41% of those men did not use condoms consistently. The HIV seroincidence rate among those seronegative at first study was 2.6% per year. CONCLUSIONS HIV infection rates in young homosexual men in San Francisco are lower than those in the early 1980s; however, the rate of infection in these men, most of whom became sexually active after awareness of AIDS had become widespread, threatens to continue the epidemic in the younger generation at a level not far below that of a decade ago.

Hepatitis C virus clearance, reinfection, and persistence, with insights from studies of injecting drug users: towards a vaccine

Hepatitis C virus (HCV) was discovered more than two decades ago, but progress towards a vaccine has been slow. HCV infection will spontaneously clear in about 25% of people. Studies of spontaneous HCV clearance in chimpanzees and human beings have identified host and viral factors that could be important in the control of HCV infection and the design of HCV vaccines. Although data from studies of chimpanzees suggest that protection against reinfection is possible after spontaneous clearance, HCV is a human disease. Results from studies of reinfection risk after spontaneous clearance in injecting drug users are conflicting, but some people seem to have protection against HCV persistence. To guide future vaccine development, we assess data from studies of HCV reinfection after spontaneous clearance, discuss flaws in the methods of previous human studies, and suggest essential components for future investigations of control of HCV infection.

Association of Opioid Agonist Therapy With Lower Incidence of Hepatitis C Virus Infection in Young Adult Injection Drug Users

IMPORTANCE Injection drug use is the primary mode of transmission for hepatitis C virus (HCV) infection. Prior studies suggest opioid agonist therapy may reduce the incidence of HCV infection among injection drug users; however, little is known about the effects of this therapy in younger users. OBJECTIVE To evaluate whether opioid agonist therapy was associated with a lower incidence of HCV infection in a cohort of young adult injection drug users. DESIGN, SETTING, AND PARTICIPANTS Observational cohort study conducted from January 3, 2000, through August 21, 2013, with quarterly interviews and blood sampling. We recruited young adult (younger than 30 years) injection drug users who were negative for anti-HCV antibody and/or HCV RNA. EXPOSURES Substance use treatment within the past 3 months, including non-opioid agonist forms of treatment, opioid agonist (methadone hydrochloride or buprenorphine hydrochloride) detoxification or maintenance therapy, or no treatment. MAIN OUTCOMES AND MEASURES Incident HCV infection documented with a new positive result for HCV RNA and/or HCV antibodies. Cumulative incidence rates (95% CI) of HCV infection were calculated assuming a Poisson distribution. Cox proportional hazards regression models were fit adjusting for age, sex, race, years of injection drug use, homelessness, and incarceration. RESULTS Baseline characteristics of the sample (n = 552) included median age of 23 (interquartile range, 20-26) years; 31.9% female; 73.1% white; 39.7% who did not graduate from high school; and 69.2% who were homeless. During the observation period of 680 person-years, 171 incident cases of HCV infection occurred (incidence rate, 25.1 [95% CI, 21.6-29.2] per 100 person-years). The rate ratio was significantly lower for participants who reported recent maintenance opioid agonist therapy (0.31 [95% CI, 0.14-0.65]; P = .001) but not for those who reported recent non-opioid agonist forms of treatment (0.63 [95% CI, 0.37-1.08]; P = .09) or opioid agonist detoxification (1.45 [95% CI, 0.80-2.69]; P = .23). After adjustment for other covariates, maintenance opioid agonist therapy was associated with lower relative hazards for acquiring HCV infection over time (adjusted hazard ratio, 0.39 [95% CI, 0.18-0.87]; P = .02). CONCLUSIONS AND RELEVANCE In this cohort of young adult injection drug users, recent maintenance opioid agonist therapy was associated with a lower incidence of HCV infection. Maintenance treatment with methadone or buprenorphine for opioid use disorders may be an important strategy to prevent the spread of HCV infection among young injection drug users.

Young Women Engaged in Sex Work in Phnom Penh, Cambodia, Have High Incidence of HIV and Sexually Transmitted Infections, and Amphetamine-Type Stimulant Use: New Challenges to HIV Prevention and Risk

Objectives: To estimate prevalence and incidence of HIV and sexually transmitted infections (STI) and associated risk factors among young women working as sex workers (SWs) in Phnom Penh, Cambodia. Methods: A prospective study of young (<29 years) women working as SWs in brothels, entertainment establishments, and freelance. Sociodemographics, sexual risk, and use of amphetamine-type stimulants (ATS) (“yama” and “crystal”) were assessed by self-report. HIV and STI (Chlamydia trachomatis and Neisseria gonorrhoeae) testing were conducted on blood and urine specimens, respectively. Results: Baseline prevalences of HIV, C. trachomatis, and N. gonorrhoeae were 23%, 11.5%, and 7.8%, respectively. HIV incidence was 3.6 per 100 person-years (95% confidence interval [CI], 1.2%–11.1%); STI incidence was 21.2 per 100 person-years (95% CI, 12.6%–35.8%). At baseline, 26.5% reported recent ATS use. HIV infection was associated with freelance SW (adjusted odds ratio, 5.85; 95% CI, 1.59–21.58) and younger age of first sex (≤15 years; adjusted odds ratio, 3.06; 95% CI, 1.01–8.46). Incident STI was associated with duration (per year) of SW (adjusted hazard ratio, 1.1; 95% CI, 1.1–1.2) and recent yama use (adjusted hazard ratio, 3.9; 95% CI, 1.5–10.3). Conclusions: HIV and STI infection rates were high among SWs working in various settings; freelancers had highest risk. ATS use was associated with incident STI. Venue of sex work and drug prevention should be considered in prevention programs.

Policing Drug Users in Russia: Risk, Fear, and Structural Violence

We undertook qualitative interviews with 209 injecting drug users (IDUs) (primarily heroin) in three Russian cities: Moscow, Barnaul, and Volgograd. We explored IDUs accounts of HIV and health risk. Policing practices and how these violate health and self, emerged as a primary theme. Findings show that policing practices violate health and rights directly, but also indirectly, through the reproduction of social suffering. Extrajudicial policing practices produce fear and terror in the day-to-day lives of drug injectors, and ranged from the mundane (arrest without legal justification; the planting of evidence to expedite arrest or detainment; and the extortion of money or drugs for police gain) to the extreme (physical violence as a means of facilitating “confession” and as an act of “moral” punishment without legal cause or rationale; the use of methods of “torture”; and rape). We identify the concept of police bespredel—living with the sense that there are “no limits” to police power—as a key to perpetuating fear and terror, internalized stigma, and a sense of fatalist risk acceptance. Police besprediel is analyzed as a form of structural violence, contributing to “oppression illness.” Yet, we also identify cases of resistance to such oppression, characterized by strategies to preserve dignity and hope. We identify hope for change as a resource of risk reduction as well as escape, if only temporarily, from the pervasiveness of social suffering. Future drug use(r)-related policies, and the state responses they sponsor, should set out to promote public health while protecting human rights, hope, and dignity.

Patterns of hepatitis C virus RNA levels during acute infection: the InC3 study.

Background Understanding the patterns of HCV RNA levels during acute hepatitis C virus (HCV) infection provides insights into immunopathogenesis and is important for vaccine design. This study evaluated patterns of HCV RNA levels and associated factors among individuals with acute infection. Methods Data were from an international collaboration of nine prospective cohorts of acute HCV (InC3 Study). Participants with well-characterized acute HCV infection (detected within three months post-infection and interval between the peak and subsequent HCV RNA levels≤120 days) were categorised by a priori-defined patterns of HCV RNA levels: i) spontaneous clearance, ii) partial viral control with persistence (≥1 log IU/mL decline in HCV RNA levels following peak) and iii) viral plateau with persistence (increase or <1 log IU/mL decline in HCV RNA levels following peak). Factors associated with HCV RNA patterns were assessed using multinomial logistic regression. Results Among 643 individuals with acute HCV, 162 with well-characterized acute HCV were identified: spontaneous clearance (32%), partial viral control with persistence (27%), and viral plateau with persistence (41%). HCV RNA levels reached a high viraemic phase within two months following infection, with higher levels in the spontaneous clearance and partial viral control groups, compared to the viral plateau group (median: 6.0, 6.2, 5.3 log IU/mL, respectively; P=0.018). In the two groups with persistence, Interferon lambda 3 (IFNL3) CC genotype was independently associated with partial viral control compared to viral plateau (adjusted odds ratio [AOR]: 2.75; 95%CI: 1.08, 7.02). In the two groups with viral control, female sex was independently associated with spontaneous clearance compared to partial viral control (AOR: 2.86; 95%CI: 1.04, 7.83). Conclusions Among individuals with acute HCV, a spectrum of HCV RNA patterns is evident. IFNL3 CC genotype is associated with initial viral control, while female sex is associated with ultimate spontaneous clearance.

Predictors of injection drug use cessation and relapse in a prospective cohort of young injection drug users in San Francisco, CA (UFO Study)

BACKGROUND Studies of injection drug use cessation have largely sampled adults in drug treatment settings. Little is known about injection cessation and relapse among young injection drug users (IDU) in the community. METHODS A total of 365 HCV-negative IDU under age 30 years were recruited by street outreach and interviewed quarterly for a prospective cohort between January 2000 and February 2008. Participants were followed for a total of 638 person-years and 1996 visits. We used survival analysis techniques to identify correlates of injection cessation (> or =3 months) and relapse to injection. RESULTS 67% of subjects were male, median age was 22 years (interquartile range (IQR) 20-26) and median years injecting was 3.6 (IQR 1.3-6.5). 28.8% ceased injecting during the follow-up period. Among those that ceased injecting, nearly one-half resumed drug injection on subsequent visits, one-quarter maintained injecting cessation, and one-quarter were lost to follow-up. Participating in a drug treatment program in the last 3 months and injecting less than 30 times per month were associated with injection cessation. Injecting heroin or heroin mixed with other drugs, injecting the residue from previously used drug preparation equipment, drinking alcohol, and using benzodiazepines were negatively associated with cessation. Younger age was associated with relapse to injection. CONCLUSION These results suggest that factors associated with stopping injecting involve multiple areas of intervention, including access to drug treatment and behavioral approaches to reduce injection and sustain cessation. The higher incidence of relapse in the younger subjects in this cohort underscores the need for earlier detection and treatment programs targeted to adolescents and transition-age youth.

Rare Birds in North America: Acute Hepatitis C Cohorts

In this issue, the Comment from the Editor highlights 8 cohorts of acute hepatitis C patients and the dedicated investigators who are tracking these rarely identified patients in variety of unusual settings— collectively identifying 643 patients since 1996. The identification, enrollment, prospective monitoring and treatment of patients with acute HCV infections require enormous collaborative efforts and networking among individuals and institutions in addition to multiple sources of research funding. Acute hepatitis C provides a critical window of opportunity to understand the early and dynamic host-virus interactions that define the outcome of HCV infection, an opportunity that is lost once HCV persistence or resolution is firmly established. These cohorts continue to provide valuable insights about the natural history, outcome, therapy and immune pathogenesis of acute hepatitis C in various populations while offering important collaborative opportunities.