Protease inhibitors in the homeless.
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Biomedical subjects
Publications and source records attributed to A R Moss.
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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.
To characterize the associations of age, immunosuppression, and AIDS outcomes, we evaluated serial measures of CD4+ lymphocytes from 376 homosexual men with documented dates of HIV-1 seroconversion registered in the Tricontinental Seroconverter Study. Using regression models and adjusting for variation within individuals, we found no association between age and the number of CD4+ lymphocytes at seroconversion or with CD4+ lymphocyte decline after seroconversion. Men who developed opportunistic infections had fewer CD4+ lymphocytes at the time of diagnosis compared with men who developed AIDS-defining Kaposi's sarcoma. Older age was significantly associated with higher numbers of CD4+ lymphocytes in individuals diagnosed with AIDS-defining Kaposi's sarcoma but was not significant for individuals with opportunistic infections. Because older age shortens the latency period of Kaposi's sarcoma and does not affect the CD4+ lymphocyte loss, it results in higher CD4+ lymphocytes at the time of diagnosis. These findings suggest distinct biologic mechanisms for various AIDS manifestations, which is important for clinical decision making and health care planning.
The purpose of this study was to describe the perceived health of the homeless, and to measure the effect of time homeless on perceived health status, after controlling for sociodemographic characteristics and health conditions. The design was cross-sectional; the population was a representative sample of homeless in San Francisco, interviewed on health issues. Analysis of predictors of poor or fair health status was by logistic regression. In this sample of 2780 persons, 37.4% reported that their health status was poor or fair as compared to good or excellent. Reporting poor or fair health status was significantly associated with time homeless, after controlling for sociodemographic variables and health problems including results from screening for HIV and TB (OR = 1.49, 95% CI 1.24-1.79). Comparisons with data from the National Health Interview Survey (NHIS) showed poorer health status among the homeless persons in this study. Standardized morbidity ratios were highest for asthma; there was twice the number of homeless persons reporting asthma, in younger as well as older adults, as would be expected using NHIS rates. There was also an excess of arthritis, high blood pressure and diabetes in those age 18-44 as compared to adults in the Health Interview Survey. The time spent homeless remains associated with self-reported health status, after known contributors to poor health are controlled. Persons who have been homeless for longer periods of time may be the persons to whom health care interventions should be aimed.
SETTING: Incident patients with active tuberculosis (TB) resistant to two or more drugs in New York City hospitals in 1992. OBJECTIVE: To examine the New York-wide distribution of Public Health Research Institute (PHRI) strain W of Mycobacterium tuberculosis, an extremely drug-resistant strain identified by a 17-band Southern hybridization pattern using IS6110, during the peak tuberculosis year of 1992. We also compared strain W with other strains frequently observed in New York. DESIGN: Blinded retrospective study of stored M. tuberculosis cultures by restriction fragment length polymorphism (RFLP) DNA fingerprinting, and chart review. RESULTS: We found 112 cultures with the strain W fingerprint and 8 variants in 21 hospitals among incident patients hospitalized in 1992. Almost all isolates were resistant to four first-line drugs and kanamycin. This single strain made up at least 22% of New York City multiple-drug-resistant (MDR) TB in 1992, far more than any other strain. Almost all W-strain cases were acquired immune deficiency syndrome (AIDS) patients. The cluster is the most drug-resistant cluster identified in New York and the largest IS6110 fingerprint cluster identified anywhere to date. CONCLUSION: Because recommended four-drug therapy will not sterilise this very resistant strain, there was a city-wide nosocomial outbreak of W-strain TB in the early 1990s among New York AIDS patients. Other frequently seen strains were either also very resistant, or, surprisingly, pansusceptible. Individual MDR strains can be spread widely in situations where AIDS and TB are both common.
SETTING: San Francisco, California. OBJECTIVE: To determine the relative contributions of infection acquired in San Francisco and reactivation of tuberculous infection acquired elsewhere in Mexican-born persons who developed tuberculosis in San Francisco, and to determine the frequency of transmission leading to secondary cases of tuberculosis in other persons. DESIGN: The study population consisted of all Mexican-born tuberculosis patients reported in San Francisco from 1991 through June 1995. All patients had positive cultures for Mycobacterium tuberculosis and DNA fingerprinting of isolates using IS6110 with more than two bands. Patients were classified as infected in San Francisco or infected elsewhere based on pre-defined criteria that included a second DNA fingerprinting technique (polymorphic guanine-cytosine-rich sequence), chart reviews, and selected patient interviews. RESULTS: Of the 43 Mexican-born patients studied, nine (21%) met the definition of infection acquired in San Francisco and 34 (79%) met the definition of reactivation of infection acquired elsewhere. Only one of the 43 cases resulted in two secondary cases in US-born persons. CONCLUSION: One-fifth of the Mexican-born patients who developed tuberculosis in San Francisco acquired their tuberculous infection in San Francisco; transmission from Mexican-born persons leading to tuberculosis in other persons is uncommon.
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BACKGROUND: Adherence to tuberculosis evaluation is poor in a high-risk population such as the homeless. OBJECTIVE: To test two interventions aimed at improving adherence to tuberculosis evaluation and to identify predictors of adherence. METHODS: We conducted a randomized clinical trial in shelters and food lines in the inner city of San Francisco, Calif. We randomized 244 eligible subjects infected with tuberculosis to (1) peer health adviser (assistance by a peer [n = 83]), (2) monetary incentive ($5 payment [n = 82]), or (3) usual care (referral slips and bus tokens only [n = 79]). The primary outcome of the study was adherence to a first follow-up appointment at the tuberculosis clinic, where subjects were evaluated for active tuberculosis and the need for isoniazid prophylaxis. RESULTS: Of the subjects assigned to a monetary incentive, 69 (84%) completed their first follow-up appointment, compared with 62 subjects (75%) assigned to a peer health adviser and 42 subjects (53%) assigned to usual care. Adherence was higher in the monetary incentive and peer health adviser groups than in the usual care group (P < .001 and P = .004, respectively). Patients not using intravenous drugs and patients 50 years of age or older were more likely to adhere to a first follow-up appointment (odds ratios [95% confidence intervals], 2.5 [1.3 to 5.0] and 3.3 [1.2 to 8.8], respectively). Among the 173 tuberculosis-infected subjects who completed their appointment, isoniazid therapy was started for 72 individuals, and three cases of active tuberculosis were identified. CONCLUSION: A monetary incentive or a peer health adviser is effective in improving adherence to a first follow-up appointment in homeless individuals infected with tuberculosis. A monetary incentive appears to be superior. Intravenous drug users and young individuals are at high risk for poor adherence to referral.
OBJECTIVE: To identify appropriate criteria for characterizing HIV-infected nonprogressors. DESIGN: Five definitions were compared as follows: (1) last CD4 count > 500 x 10(6)/l; (2) two most recent CD4 counts > 500 x 10(6)/l; (3) calculated CD4 count based on linear regression > 500 x 10(6)/l; (4) CD4 slope > or = 0 with no antiretroviral use; (5) all CD4 counts > 500 x 10(6)/l, decline in CD4 slope < 5 cells per year, no antiretroviral use. PARTICIPANTS: Five prospective cohorts of homosexual men with documented dates of HIV-1 seroconversion. MAIN OUTCOME MEASURES: Proportions of nonprogressors were calculated 7, 8, 9 and 10 years following seroconversion (n = 285). Definitions were evaluated with respect to consistency over time and across sites. Subjects lacking CD4 counts within 3 years preceding end of follow-up were excluded. RESULTS: Across sites, proportions of nonprogressors ranged from 1% (definition 5) to 17.5% (definition 1) 10 years after seroconversion. Definitions based on absolute CD4 counts (definitions 1-3) had higher proportions and were less consistent than those based on stable slopes (definitions 4 and 5). For each definition, proportions decreased as follow-up increased, but were most stable for definition 4 (3%). Site differences decreased as follow-up increased, but remained nearly threefold for definitions 1-3. None of the definitions classified the same subjects as nonprogressors at any timepoint. CONCLUSIONS: Observations regarding nonprogression are highly dependent on the definition and the duration of follow-up. Our findings highlight methodological challenges which will need to be overcome in natural history studies of nonprogression.
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In developed countries the major tuberculosis epidemics declined long before the disease became curable in the 1940s. We present a theoretical framework for assessing the intrinsic transmission dynamics of tuberculosis. We demonstrate that it takes one to several hundred years for a tuberculosis epidemic to rise, fall and reach a stable endemic level. Our results suggest that some of the decline of tuberculosis is simply due to the natural behaviour of an epidemic. Although other factors must also have contributed to the decline, these causal factors were constrained to operate within the slow response time dictated by the intrinsic dynamics.
A decline in the proportion of Kaposi's sarcoma among AIDS cases since the 1980s has been attributed to changes in sexual behavior among homosexual men and a decreasing exposure to a hypothesized Kaposi's sarcoma cofactor. Recent studies have shown that the incidence rate of Kaposi's sarcoma has remained relatively stable, which seems to argue against the hypothesis of a declining exposure to the putative cofactor. To examine this paradox, we evaluated the incidence of Kaposi's sarcoma, using Cox proportional hazard analyses, and performed a simulation to compare incidences of different AIDS outcomes among 407 homosexual men with documented dates of seroconversion. Our data show that men who seroconverted early in the epidemic did not progress faster to Kaposi's sarcoma than men who seroconverted more recently. A lower incidence rate of Kaposi's sarcoma would be expected among the latter group if exposure to the hypothesized cofactor is decreasing over time. The percentage of Kaposi's sarcoma among incident AIDS cases decreased over the years following seroconversion, but not over calendar time. This study demonstrates that the decline in the proportion of Kaposi's sarcoma among AIDS cases should not be interpreted as a decline in the incidence of Kaposi's sarcoma and that there is no evidence that a hypothesized Kaposi's sarcoma cofactor is declining over calendar time.
We followed 93 subjects from the San Francisco General Hospital Cohort for one year after notifying them of their HIV-1 antibody test results in order to examine self-disclosure, reactions, and concerns regarding disclosure. By one year post-notification, 92% of gay friends, 82% of primary sexual partners, 56% of new sexual partners, 46% of co-workers, 71% of physicians, 37% of dentists, 57% of psychotherapists, and 37% of family members had been told. Subjects were twice as likely to tell primary sexual partners, and more likely to self-disclose to all categories of persons (except physicians and dentists) than anticipated prior to notification. Least favorable reactions to seropositivity were from male family members and primary sexual partners, while seronegative subjects experienced unfavorable reactions only from some family members. Subjects were most concerned about health insurance (71%) and stigmatization (61%), but the latter declined (to 36%) at 12 months. Although encouraging, these findings suggest that self-disclosure should be discussed in both pre- and post-test counseling sessions.
Data on 403 homosexual/bisexual men with documented dates of human immunodeficiency virus (HIV) seroconversion were merged. All subjects originated from cohort studies that started between 1982 and 1984 in Amsterdam, The Netherlands; San Francisco, California; Sydney, Australia; and Vancouver, British Columbia, Canada. With respect to the four geographic locations, no statistically significant differences in progression time from HIV seroconversion to acquired immunodeficiency syndrome (AIDS) and death as well as in AIDS diagnoses patterns could be demonstrated. The median time from HIV seroconversion to AIDS was 8.3 years, that from HIV seroconversion to death was 8.9 years, and that from AIDS to death was 17 months. The authors evaluated HIV disease progression with respect to demographic, clinical, and behavioral cofactors. Younger age and use of prophylaxis against Pneumocystis carinii pneumonia were significantly related to slower progression from seroconversion to death. In addition, an association between slower progression and earlier dates of seroconversion was found. No relation of sexual behavior; history of sexually transmitted diseases; or use of alcohol, tobacco, and recreational drugs with rates of disease progression could be demonstrated.
OBJECTIVE: To determine the prevalence and risk factors for human immunodeficiency virus (HIV) and tuberculosis (TB) infection and investigate the relationship between these two infections in homeless adults. DESIGN: Cross-sectional study. SETTING: Inner-city shelters and free meal programs. PARTICIPANTS: A representative sample of 1226 adults (> or = 18 years) were enrolled from community sites. MAIN OUTCOME MEASURES: Serum HIV-1 antibody status and tuberculin skin test reactivity. RESULTS: Human immunodeficiency virus seroprevalence was 8.5% (95% confidence interval [CI], 7.0% to 10.1%) and the prevalence of TB infection was 32% (95% CI, 30% to 37%). Nineteen percent of the HIV-seropositive subjects had positive tuberculin skin tests. Independent risk factors for HIV infection included younger age, black race, male homosexual contact, injection drug use, use of injection drugs in shooting galleries, and selling sex. Tuberculosis infection was associated with the duration of homelessness and living in crowded shelters or single-room-occupancy hotels. Injection drug use, a risk factor for HIV, was also a risk factor for TB, with a particularly strong association in women. No evidence of an association between TB and HIV infection was found, even after accounting for anergy. CONCLUSIONS: The homeless population in the United States should be considered a group at high risk for HIV infection and TB. Given the constellation of risk factors present, the high prevalence of infection, and lack of access to medical services, we anticipate that these communicable diseases in this population will represent a growing public health problem.
BACKGROUND: The incidence of tuberculosis and drug resistance is increasing in the United States, but it is not clear how much of the increase is due to reactivation of latent infection and how much to recent transmission. METHODS: We performed DNA fingerprinting using restriction-fragment-length polymorphism (RFLP) analysis of at least one isolate from every patient with confirmed tuberculosis at a major hospital in the Bronx, New York, from December 1, 1989, through December 31, 1992. Medical records and census-tract data were reviewed for relevant clinical, social, and demographic data. RESULTS: Of 130 patients with tuberculosis, 104 adults (80 percent) had complete medical records and isolates whose DNA fingerprints could be evaluated. Isolates from 65 patients (62.5 percent) had unique RFLP patterns, whereas isolates from 39 patients (37.5 percent) had RFLP patterns that were identical to those of an isolate from at least 1 other study patient; the isolates in the latter group were classified into 12 clusters. Patients whose isolates were included in one of the clusters were inferred to have recently transmitted disease. Independent risk factors for having a clustered isolate included seropositivity for the human immunodeficiency virus (HIV) (odds ratio for Hispanic patients, 4.31; P = 0.02; for non-Hispanic patients, 3.12; P = 0.07), Hispanic ethnicity combined with HIV seronegativity (odds ratio, 5.13; P = 0.05), infection with drug-resistant tuberculosis (odds ratio, 4.52; P = 0.005), and younger age (odds ratio, 1.59; P = 0.02). Residence in sections of the Bronx with a median household income below $20,000 was also associated with having a clustered isolate (odds ratio, 3.22; P = 0.04). CONCLUSIONS: In the inner-city community we studied, recently transmitted tuberculosis accounts for approximately 40 percent of the incident cases and almost two thirds of drug-resistant cases. Recent transmission of tuberculosis, and not only reactivation of latent disease, contributes substantially to the increase in tuberculosis.
The relationship between progressive immunodeficiency related to infection with human immunodeficiency virus (HIV) and waning immunity to measles was investigated in this retrospective cohort study. Titers of serum antibodies to measles virus were measured by enzyme immunoassay of stored sera from a cohort of homosexual men who were studied at San Francisco General Hospital. Subjects underwent a baseline and follow-up measure of measles antibodies. High levels of antibodies to measles virus were maintained in the HIV-positive and negative groups. One (2%) of the 50 HIV-negative controls was seronegative for the measles virus, and no controls evidenced seroreversal (decline in antibody to a level at which protection is not provided) during the study. Two (1.4%) of the 145 HIV-positive subjects were measles-seronegative, and two others evidenced seroreversal. Analysis with Spearman's rank correlation revealed no relationship between changes in the CD4 cell count and measles antibody level. Thus we conclude that waning measles immunity is not greatly accelerated in HIV-infected adults despite progressive HIV-related immunodeficiency.
OBJECTIVE: To examine the HIV seroconversion rate, risk factors for seroconversion, and changes in risk behavior over time in intravenous drug users (IVDU) in San Francisco, 1985-1990. DESIGN: Observational study. SETTING: All methadone maintenance and 21-day methadone detoxification programs in San Francisco. PARTICIPANTS: A total of 2351 heterosexual IVDU, of whom 681 were seronegative at first visit and seen at least twice ('repeaters'). MAIN OUTCOME MEASURES: HIV seroconversion rates, risk factors for seroconversion, and changes in behavior. RESULTS: The HIV seroconversion rate in repeaters was 1.9% per person-year (ppy) of follow-up [2.1% in women versus 1.7% in men (not significant); 4% in African Americans versus 1% in whites (P = 0.006); 3.9% ppy in the first third of the study, 1.2% in the second (P = 0.007), and 1.9% in the last (not significant)]. Risk factors for seroconversion were five or more sexual partners per year [hazard ratio (HR) = 2.6; P = 0.02], use of shooting gallery ever (HR = 2.9; P = 0.02), and less than 1 year (lifetime) in methadone maintenance (HR = 2.7; P = 0.02). Self-reported intravenous cocaine use fell from 33 to 15% over 5 years, shooting gallery use fell from 19 to 6%, and the proportion with five or more sexual partners fell from 25 to 10%. Bleach use rose to 75% of needle-sharers. CONCLUSIONS: The 1985-1990 HIV seroconversion rate in IVDU (1.9% ppy) was comparable to that in San Francisco cohorts of homosexual men (1.4% ppy). A decline in HIV seroconversion coincided with changes in risk behavior. Stable attendance of methadone maintenance was highly protective: the seroconversion rate in subjects with 1 year or more in methadone was 12% ppy.