Strategies for isoniazid preventive therapy in HIV-positive patients who consume alcohol.

WHO guidance to defer isoniazid preventive therapy (IPT) among those with regular alcohol use because of hepatotoxicity concerns may exclude many people living with HIV (PLWH) at high TB risk in these settings.To evaluate hepatotoxicity during TB preventive therapy (TPT) in PLWH who report alcohol use in Uganda over 10 years.We developed a Markov model of latent TB infection, isoniazid preventive therapy (IPT - a type of TPT), and TB disease using data from the Alcohol Drinkers' Exposure to Preventive Therapy for TB (ADEPTT) study. We modeled several treatment scenarios, including no IPT, IPT with liver enzyme monitoring (AST/ALT) during treatment, and IPT with pre-screening using the tuberculin skin test (TST).The no IPT scenario had 230 TB deaths/100,000 population over 10 years, which is more than that seen in any IPT scenario. IPT, even with no monitoring, was preferred over no IPT when population TB disease incidence was >50 in 100,000.For PLWH who report alcohol use in high TB burden settings, IPT should be offered, ideally with regular AST/ALT monitoring. However, even if regular monitoring is not possible, IPT is still preferable to no IPT in almost every modeled scenario..

Prevalence of, and factors associated with, alcohol use disorder among young adults (aged 15-24 years) living with HIV/AIDS in low-income and middle-income countries: protocol for a systematic review.

INTRODUCTION: Alcohol use is a global driver of HIV infection and disease progression, mediated through risky behaviour and poor antiretroviral adherence. Most studies about the burden of alcohol use among people living with HIV (PLWH)/AIDS have been done in adult populations, but less is known about young people with HIV, especially in low-income and middle-income countries (LMICs), despite the high level of alcohol use in these settings. The aim of this review is to collate evidence on the prevalence of, and factors associated with, alcohol use disorder (AUD) among young adults (aged 15-24 years) living with HIV/AIDS in LMICs. METHODS AND ANALYSIS: Two experienced librarians will conduct an independent article search in PubMed, PsycINFO, Embase and Web of Science databases, using relevant Medical Subject Headings terms and Boolean operators ('AND', 'OR'). We will include English-language articles that were published in peer-reviewed journals from 1 January 2000, to 25 July 2022, that documented the prevalence of AUD among young people (15-24 years) living with HIV in LMICs. We shall exclude systematic review articles and qualitative studies. Two independent reviewers will screen the articles for eligibility and data will be extracted onto a preset Excel spreadsheet. Data analysis will be done using Stata V.14.0. Heterogeneity will be assessed by use of the I2 statistic and data will be pooled in meta-analyses where appropriate. Publication bias will be assessed using the funnel plot. ETHICS AND DISSEMINATION: Ethical approval is not needed as this systematic review will be based on published studies. Findings from this study will be disseminated via submission for publication in a peer-reviewed journal, at conference presentations, and made available to health professionals, scientists and policy makers. Our data set can be made available on request. REGISTRATION DETAILS: PROSPERO, CRD42022308955.

Hepatitis B virus infection and immunization status in a new generation of injection drug users in San Francisco.

Hepatitis B virus (HBV) infection is common among injection drug users (IDU). Younger IDU, however, may be less susceptible to infection due to the implementation of public health interventions, such as universal immunization programs and syringe exchange programs. To investigate the current epidemiology of HBV infection and control among a new generation of drug users in the United States, we conducted interviews and examined HBV serologic markers in a cross-section of street-recruited IDU under age 30 in San Francisco, CA. Of the 831 persons studied, 21% showed serologic evidence of current or past infection; 22% had isolated antibodies to hepatitis B surface antigen consistent with vaccine-mediated immunity; and 56% had no HBV markers. In multivariate analyses, HBV infection was associated with drug use behaviour in heterosexual males; sexual behaviour in males who have sex with males; and both drug use and sexual behaviour in females. Vaccine-mediated immunity was independently associated with female sex and younger age. In conclusion, HBV transmission persists among young IDU in San Francisco. Few young injectors show evidence of successful immunization and the majority remains susceptible to disease. Until the broad effects of universal vaccination are seen, targeted and innovative approaches to immunizing young IDU in the US are needed to prevent a substantial number of new HBV infections.

Can the poor adhere? Incentives for adherence to TB prevention in homeless adults.

SETTING: Community-based population of homeless adults living in San Francisco, California. OBJECTIVE: To compare the effect of cash and non-cash incentives on 1) adherence to treatment for latent tuberculosis infection, and 2) length of time needed to look for participants who missed their dose of medications. DESIGN: Prospective, randomized clinical trial comparing a 5 dollar cash or a 5 dollar non-cash incentive. All participants received directly observed preventive therapy and standardized follow-up per a predetermined protocol. Completion rates and amount of time needed to follow up participants was measured. RESULTS: Of the 119 participants, 102 (86%) completed therapy. There was no difference between the cash and non-cash arms. Completion was significantly higher among males (OR 5.65, 95%CI 1.36-23.40, P = 0.02) and persons in stable housing at study entry (OR 4.86, 95%CI 1.32-17.94, P = 0.02). No substance use or mental health measures were associated with completion. Participants in the cash arm needed significantly less follow-up to complete therapy compared to the non-cash arm (P = 0.03). In multivariate analysis, non-cash incentive, use of crack cocaine, and no prior preventive therapy were associated with more follow-up time. CONCLUSION: Simple, low cost incentives can be used to improve adherence to TB preventive therapy in indigent adults.

Overdosing among young injection drug users in San Francisco.

Heroin overdoses increased sharply in the US in the 1990s, but few studies have addressed overdose risk. We examined overdosing and injection-related risk behavior in young injection drug users (IDUs). We interviewed all consenting injectors under age 30 at needle exchanges and youth outreach sites in San Francisco. Their median age was 22, and their median number of years of injecting was 4. About 48% reported at least one overdose, with a median of two overdoses reported. Overdosing was associated with injecting "speedballs" (i.e. mixtures of heroin and cocaine), with borrowing syringes, and (with P-values of borderline statistical significance) with heroin injection and with gay or bisexual behavior. It was not associated with age, sex, years of injecting, or frequency of injecting. In multivariate analysis, only borrowing syringes and gay or bisexual behavior were independent statistically significant predictors, probably because gay and bisexual subjects were more likely to be heroin or "speedball" injectors. Most subjects (65%) reported that they had not received medical attention at time of last overdose. Risk of overdose in young injectors is acute and closely associated with HIV risk. HIV interventions should include overdose prevention. Emergency response protocols should minimize risk of arrest. Injectors and providers should be trained in overdose prevention, and developing overdose interventions should be a priority among drug educators.

Hepatitis C virus infection and needle exchange use among young injection drug users in San Francisco.

Young injection drug users (IDUs) in San Francisco may be at high risk for hepatitis C virus (HCV) infection despite access to several needle exchange venues. The authors conducted a cross-sectional study from 1997 to 1999 in San Francisco to estimate the prevalence and incidence of antibody to HCV (anti-HCV) among street-recruited IDUs under age 30, and to examine risk behaviors and sources of sterile needles. Among 308 participants, the prevalence of anti-HCV was 45%. Using statistical modeling, incidence of HCV infection was estimated to be 11 per 100 person years. Independent risk factors for anti-HCV included age (odds ratio [OR], 1.17 per year; 95% confidence interval [CI], 1.05-1.30), years injecting (OR, 1.21 per year; 95% CI, 1.10-1.34), years in San Francisco (OR, 1.06 per year; 95% CI, 1.00-1.14), first injected by a sex partner (OR, 4.06; 95% CI, 1.74-9.52), injected daily (OR, 3.85; 95% CI, 2.07-7.17), ever borrowed a needle (OR, 2.56; 95% CI, 1.18-5.53), bleached last time a needle was borrowed (OR, 0.50; 95% CI, 0.24-1.02), snorted or smoked drugs in the prior year (OR, 0.48; 95% CI, 0.26-0.89), and injected by someone else in the prior month (OR, 0.50; 95% CI, 0.25-0.99). In the prior month, 88% used at least 1 of several needle exchange venues, and 32% borrowed a needle. We conclude that anti-HCV prevalence is lower than in previous studies of older IDUs, but 11% incidence implies high risk of HCV infection in a long injecting career. Despite access to sterile needles, borrowing of needles persisted.

Tuberculosis in the homeless. A prospective study.

We set out to determine tuberculosis incidence and risk factors in the homeless population in San Francisco. We also examined the transmission of tuberculosis by molecular methods. We followed a cohort of 2,774 of the homeless first seen between 1990 and 1994. There were 25 incident cases during the period 1992 to 1996, or 270 per 100,000 per year (350/100,000 in African Americans, 450/100,000 in other nonwhites, 60/100,000 in whites). Ten cases were persons with seropositive HIV. Independent risk factors for tuberculosis were HIV infection, African American or other nonwhite ethnicity, positive tuberculin skin test (TST) results, age, and education; 60% of the cases had clustered patterns of restriction fragment length polymorphism, thought to represent recent transmission of infection with rapid progression to disease. Seventy-seven percent of African-American cases were clustered, and 88% of HIV-seropositive cases. The high rate of tuberculosis in the homeless was due to recent transmission in those HIV-positive and nonwhite. African Americans and other nonwhites may be at high risk for infection or rapid progression. Control measures in the homeless should include directly observed therapy and incentive approaches, treatment of latent tuberculous infection in those HIV-seropositive, and screening in hotels and shelters.

Risk of hepatitis B infection among young injection drug users in San Francisco: opportunities for intervention.

OBJECTIVE: To compare the demographic characteristics and risk behaviors for hepatitis B infection among injection drug users younger than 30 years with those aged 30 or older and to evaluate participants' knowledge, attitudes, and experiences of infection, screening, and vaccination against hepatitis B virus. DESIGN: A systematic sample of injection drug users not currently in a treatment program were recruited and interviewed at needle exchange programs and community sites. PARTICIPANTS: 135 injection drug users younger than 30 years and 96 injection drug users aged 30 or older. RESULTS: Injection drug users younger than 30 were twice as likely as drug users aged 30 or older to report having shared needles in the past 30 days (36/135 [27%] vs 12/96 [13%]). Injection drug users younger than 30 were also twice as likely to report having had more than two sexual partners in the past 6 months (80/135 [59%] vs 29/96 [30%]). Although 88 of 135 (68%) young injection drug users reported having had contact with medical providers within the past 6 months only 13 of 135 (10%) had completed the hepatitis B vaccine series and only 16 of (13%) perceived themselves as being at high risk of becoming infected with the virus. CONCLUSION: Few young injection drug users have been immunized even though they have more frequent contact with medical providers and are at a higher risk for new hepatitis B infection than older drug users. Clinicians caring for young injection drug users and others at high risk of infection should provide education, screening, and vaccination to reduce an important source of hepatitis B infection.

Adherence to isoniazid prophylaxis in the homeless: a randomized controlled trial.

OBJECTIVES: To test 2 interventions to improve adherence to isoniazid preventive therapy for tuberculosis in homeless adults. We compared (1) biweekly directly observed preventive therapy using a $5 monetary incentive and (2) biweekly directly observed preventive therapy using a peer health adviser, with (3) usual care at the tuberculosis clinic. METHODS: Randomized controlled trial in tuberculosis-infected homeless adults. Outcomes were completion of 6 months of isoniazid treatment and number of months of isoniazid dispensed. RESULTS: A total of 118 subjects were randomized to the 3 arms of the study. Completion in the monetary incentive arm was significantly better than in the peer health adviser arm (P = .01) and the usual care arm (P = .04), by log-rank test. Overall, 19 subjects (44%) in the monetary incentive arm completed preventive therapy compared with 7 (19%) in the peer health adviser arm (P = .02) and 10 (26%) in the usual care arm (P = .11). The median number of months of isoniazid dispensed was 5 in the monetary incentive arm vs 2 months in the peer health adviser arm (P = .005) and 2 months in the usual care arm (P = .04). In multivariate analysis, independent predictors of completion were being in the monetary incentive arm (odds ratio, 2.57; 95% CI, 1.11-5.94) and residence in a hotel or other stable housing at entry into the study vs residence on the street or in a shelter at entry (odds ratio, 2.33; 95% CI, 1.00-5.47). CONCLUSIONS: A $5 biweekly cash incentive improved adherence to tuberculosis preventive therapy compared with a peer intervention or usual care. Living in a hotel or apartment at the start of treatment also predicted the completion of therapy.

A molecular epidemiologic analysis of tuberculosis trends in San Francisco, 1991-1997.

BACKGROUND: To decrease tuberculosis case rates and cases due to recent infection (clustered cases) in San Francisco, California, tuberculosis control measures were intensified beginning in 1991 by focusing on prevention of Mycobacterium tuberculosis transmission and on the use of preventive therapy. OBJECTIVE: To describe trends in rates of tuberculosis cases and clustered cases in San Francisco from 1991 through 1997. DESIGN: Population-based study. SETTING: San Francisco, California. PATIENTS: Persons with tuberculosis diagnosed between 1 January 1991 and 31 December 1997. MEASUREMENTS: DNA fingerprinting was performed. During sequential 1-year intervals, changes in annual case rates per 100,000 persons for all cases, clustered cases (cases with M. tuberculosis isolates having identical fingerprint patterns), and cases in specific subgroups with high rates of clustering (persons born in the United States and HIV-infected persons) were examined. RESULTS: Annual tuberculosis case rates peaked at 51.2 cases per 100,000 persons in 1992 and decreased significantly thereafter to 29.8 cases per 100,000 persons in 1997 (P < 0.001). The rate of clustered cases decreased significantly over time in the entire study sample (from 10.4 cases per 100,000 persons in 1991 to 3.8 cases per 100,000 persons in 1997 [P < 0.001]), in persons born in the United States (P < 0.001), and in HIV-infected persons (P = 0.003). CONCLUSIONS: The rates of tuberculosis cases and clustered tuberculosis cases decreased both overall and among persons in high-risk groups. This occurred in a period during which tuberculosis control measures were intensified.

Incidence and clinical implications of isolation of Mycobacterium kansasii: results of a 5-year, population-based study.

BACKGROUND: Mycobacterium kansasii, an unusual pathogen in the pre-AIDS era, is increasingly reported to cause infection among patients with HIV infection. Little is known about the epidemiology and clinical implications of M. kansasii infection in the AIDS era. OBJECTIVE: To compare the incidence, demographic characteristics, and clinical features of M. kansasii infection in HIV-positive and HIV-negative persons. DESIGN: Population-based laboratory surveillance. SETTING: Three counties in northern California. PATIENTS: All persons who had a positive culture for M. kansasii between 1 January 1992 and 31 December 1996. MEASUREMENTS: Cumulative incidence rates were calculated for each year by dividing the number of adult patients by the annual estimated adult population. Demographic and socioeconomic data for a single county were obtained by linkage with the 1990 U.S. Census report. RESULTS: 270 patients (69.3% of whom were HIV positive) were identified, for an incidence of 2.4 cases per 100,000 adults per year (95% CI, 2.1 to 2.7), 115 cases per 100,000 HIV-positive persons per year (CI, 99 to 133), and 647 cases per 100,000 persons with AIDS per year (CI, 554 to 751). Indicators of lower socioeconomic status were common among patients: Median incomes were $32,317 in census tracts in which cases were identified and $38,048 in census tracts without cases (P = 0.001), and 35.7% of patients had unstable housing situations. Ninety-four percent of cases were from respiratory isolates, and 87.5% of patients had evidence of infection. Persons with HIV infection differed from those without HIV infection with respect to mycobacteremia (9.6% compared with 0%; P = 0.001), need for hospitalization (77.4% compared with 51.9%; P < 0.001), and smear positivity (41.7% compared with 20.7%; P = 0.005). Chronic diseases were common among HIV-negative persons; however, 40.3% had no predisposing medical condition. CONCLUSIONS: Mycobacterium kansasii isolation is more common in HIV-positive persons, but most patients with M. kansasii infection have clinical and radiologic evidence of infection regardless of HIV status. Persons infected with HIV and M. kansasii have a higher rate of hospitalization and a greater burden of organisms. A possible association with poverty suggests mechanisms of transmission and requires further study.

Loss of Rb expression in an ACTH-secreting pituitary carcinoma.

Little is known about the molecular mechanisms of tumor progression in the pituitary. However, animal studies suggest that the Rb gene may be involved in the development of pituitary carcinoma. Pathologic examination of a pituitary tumor that included both benign and malignant components provided insight into this mechanism. Both benign and malignant tumors were immunoreactive for ACTH. The benign adenoma showed strong nuclear immunoreactivity for Rb, however, both the adjacent sellar carcinoma and its metastases were Rb-negative. This study suggests that loss of Rb may in some cases be important in the progression of pituitary adenoma to carcinoma.

Stability of Mycobacterium tuberculosis DNA genotypes.

To assess genotype stability in Mycobacterium tuberculosis, DNA genotypes were compared in sequential isolates from 49 patients who had sputum cultures separated by at least 90 days that grew M. tuberculosis. By use of IS6110 and the polymorphic GC-rich sequence (PGRS) as markers, it was found that paired isolates from 14 (29%) of 49 patients showed changes in their DNA genotypes between isolates (12 in IS6110 genotypes and 2 in PGRS genotypes). Changed IS6110 genotypes were confined to strains with 8-14 bands and were not related to the bacterial drug susceptibility, the patients' human immunodeficiency virus serostatus, or adherence to therapy. Although this rate of change complicates the interpretation of molecular epidemiologic studies, it can be exploited to gain additional insight into disease transmission. Furthermore, IS6110-related mutations may be a major source of genetic plasticity in M. tuberculosis and provide insights into the organism's evolution and virulence.

Incidence of tuberculosis in injection drug users in San Francisco: impact of anergy.

Between 1990 and 1994, we conducted a prospective study in five methadone maintenance clinics in San Francisco to determine the rate of tuberculosis (TB) in injection drug users, including those who were anergic. Of the 1,745 persons seen in the clinics, 1,109 completed an evaluation that included skin testing with tuberculin and at least two other antigens (mumps, tetanus, and/or Candida), as well as HIV testing. All persons with a positive tuberculin skin test (TST) and anergic individuals who had radiographic evidence of tuberculous infection (i.e., calcified granulomas) were offered isoniazid (INH) preventive therapy. The median follow-up was 22.0 mo. There were 338 (30.5%) human immunodeficiency virus (HIV)-seropositive patients and 771 (69.5%) HIV-seronegative patients; 96 (28.0%) and 336 (44.0%), respectively, had positive TSTs. Of the HIV-seropositive subjects, 108 (31.9%) had no reaction to any of the three antigens, and were therefore classified as anergic. The rate of TB among the HIV-seropositive, TST-positive patients who did not take INH preventive therapy was 5.0 per 100 person-yr, compared with 0.4 per 100 person-yr among the HIV-seronegative, TST-positive patients (p = 0.007). There were no cases of TB among the anergic subjects. These data indicate that INH preventive therapy is not routinely indicated in anergic, HIV-seropostive patients.

Who uses needle exchange? A study of injection drug users in treatment in San Francisco, 1989-1990.

We examined use of the San Francisco needle exchange program (NEP) by 1093 injection drug users (IDUs) recruited in methadone maintenance and out-patient detoxification programs in the first 2 years after the opening of the NEP in 1988. Thirty-one percent of IDUs had ever used the NEP. IDUs who were frequent injectors, homeless, and aware of their serostatus were more likely to use the NEP. To assess self-selection of IDUs at risk for seroconversion for using needle exchange, we calculated pre-needle exchange seroconversion rates. Among 385 IDUs seen twice, the HIV seroconversion rate was 0.38% per person year among subjects who never used needle exchange, but it was 9.34% per person year among those who later used needle exchange (p = 0.003). NEP attracted a subset of IDUs at very high risk for HIV infection. Among injectors who were interviewed before and after the opening of the needle exchanges in San Francisco, the number of sharing partners did not change among IDUs who attended or among IDUs who never attended the NEP. The NEP attracted a very-high-risk subgroup of IDUs, as measured by risk behavior and pre-needle exchange HIV-seroconversion rate. NEPs should be considered prime sites for behavior-change interventions.

Prophylaxis in liver transplant recipients using a fixed dosing schedule of hepatitis B immunoglobulin.

Prophylactic hepatitis B immunoglobulin (HBIg) reduces the risk of reinfection in hepatitis B surface antigen (HBsAg)-positive liver transplant recipients. In the medical center of this study, high-dose HBIg immunoprophylaxis is administered at a fixed dose of 10,000 IU monthly, and in this study, the long-term efficacy of this treatment regimen was examined. Of 52 HBsAg-positive liver transplant recipients, 24 were administered HBIg immunoprophylaxis, and 28 were administered no specific therapy; the 2-year recurrence rates (defined by the reappearance of HBsAg) were 19% and 76%, respectively. Fifty-four percent of the HBIg-treated patients were positive for HBeAg or hepatitis B virus (HBV) DNA (by hybridization assay) pretransplantation. In patients administered monthly HBIg, intrapatient and interpatient variability in trough antibody to HBsAg (anti-HBs) titer was significant, highlighting the potential difficulties of using anti-HBs titer to guide therapy. Trough anti-HBs titers were less in patients who became HBsAg positive than in patients who remained HBsAg-negative (490 vs. 1290 mIU/mL) (P = .0001), reflecting either the cause or effect of HBV reinfection. Of 9 patients who remained HBsAg-negative and who were administered monthly HBIg for at least 1 year, HBV DNA by polymerase chain reaction amplification was detectable in the sera of 67%, the lymphocytes of 50%, and the liver of 57%. In conclusion, a fixed monthly dose of HBIg reduces the recurrence of HBs antigenemia, even in patients with indices of active viral replication pretransplantation. The presence of residual virus in the majority of patients administered HBIg suggests that long-term HBIg administration may be necessary.

Severity of liver disease in liver transplantation recipients with hepatitis C virus infection: relationship to genotype and level of viremia.

Infection with hepatitis C virus (HCV) genotype 1b has been reported to be associated with more severe posttransplantation liver disease than infection with non-1b genotypes. To address this issue, we evaluated the outcome in 124 patients who underwent liver transplantation for chronic HCV infection. The HCV genotype and/or serotype responsible for infection was determined by four different methods. HCV RNA was detected in serum samples by polymerase chain reaction (PCR) amplification, and quantified by branched DNA assay. Disease severity was expressed as a histological score (which included grading of portal inflammation, lobular activity, fibrosis, and cytopathic changes). Median duration of histological follow-up was 25 months (range 1-75 months). Genotype was assignable in 112 (92.5%) patients. Genotypes responsible for infection were as follows: 1a = 32.2%, 1b = 27.3%, 2a = 7.4%, 2b = 8.3%, 3a = 14%, and mixed infection (more than one subtype) = 3.3%. Level of viremia, alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, and total histological score were not significantly different in patients infected with type 1b compared with patients infected with other genotypes. While duration of histological follow-up was greater in patients infected with type lb versus other types (P = .02), by univariate and multivariate analysis neither HCV genotype (lb versus others), level of viremia nor duration of histological follow-up were associated with disease severity. Moreover, there was no significant difference in the actuarial graft survival in patients infected with type lb compared with that of patients infected with non-lb types (82% and 87% at 3 years, respectively). Reanalysis using HCV genotype 1 showed no association with disease severity, graft survival, and patient survival. We conclude that HCV genotype 1 and subtype 1b are not associated with disease severity or graft survival in liver transplantation recipients.