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Biomedical subjects

D Vlahov

Publications and source records attributed to D Vlahov.

At least 19 recordsLinked to original sources

Effect of chronic substance abuse on the neuropsychological performance of intravenous drug users with a high prevalence of HIV-1 seropositivity.

Limited data are available on cognitive performance in populations of intravenous drug users during the early, asymptomatic stages of human immunodeficiency virus type 1 (HIV-1) infection. Between 1988 and 1990, 151 participants from the AIDS Link to Intravenous Experience (ALIVE) Study in Baltimore, Maryland, were evaluated neuropsychologically on a semiannual basis. This analysis focused on whether history of substance abuse influenced neuropsychological test performance. At baseline, 102 participants were HIV-1-seropositives who were free of acquired immunodeficiency syndrome and 49 participants were seronegative. Multivariate analyses, adjusting for correlation of repeated outcome measures, were conducted to determine predictors of neuropsychological functioning. Effects of the frequency of reported past use of marijuana, heroin, cocaine, barbiturates, and alcohol were not statistically associated with performance on the tests. Age and education were the most important predictors of test performance, and a significant practice effect was observed for most measures. After adjustment for age, education, the practice effect, and frequency of drug use, neuropsychological performance over time did not vary by HIV-1 serostatus. Overall, after acutely intoxicated individuals were excluded, neither frequency of drug and alcohol use nor HIV-1 seropositivity significantly influenced neuropsychological test performance over a 1-year period.

Adult

Cancer of the pancreas and drinking water: a population-based case-control study in Washington County, Maryland.

A case-control study was done to assess a potential association between drinking water and pancreatic cancer in Washington County, Maryland. Cases of pancreatic cancer occurring from 1975 through 1989 were identified from the cancer registry. Controls were selected from the private 1975 census of Washington County. There were 101 cases and 206 controls. Chlorinated municipal water was used as a source of drinking water by 79% of cases and 63% of controls, yielding a significant odds ratio of 2.2. Adjustment for age and smoking had almost no effect on the risk, although both age and smoking were independently associated with an increased risk of pancreatic cancer. Although these findings must be interpreted with caution because of limitations in exposure assessment, these results have implications for the prevention of pancreatic cancer because chlorination of water is so widely practiced.

Adult

Changes in T-lymphocyte subsets in intravenous drug users with HIV-1 infection.

OBJECTIVE: To evaluate changes in T-cell subsets in prevalent human immunodeficiency virus type 1 (HIV-1) seronegative and seropositive intravenous drug users (IVDUs) and in HIV-1 seropositive IVDUs with known time of seroconversion. DESIGN: Cohort study with a median 18-month follow-up. SETTING: Community-based clinic established to study the natural history of HIV infection in IVDUs. SUBJECTS: Eight hundred fifty-nine self-referred IVDUs aged 18 through 49 years who injected drugs within the last 10 years and who did not have an AIDS (acquired immunodeficiency syndrome)--defining illness; 152 were seronegative for HIV-1, 621 were seropositive, and 86 seroconverted during the study. OUTCOME MEASURES: Proportions and absolute numbers of lymphocytes and CD3, CD4, and CD8 T cells as determined at 6-month intervals by flow cytometry and complete blood cell counts with automated differential. RESULTS: Median numbers of CD4 lymphocytes at enrollment were 1061/microL (1.06 x 10(9)/L) for seronegative IVDUs, 508/microL for seropositive IVDUs, and 733/microL for those who seroconverted (enrolled a median of 4.5 months after seroconversion); the corresponding figures for CD8 lymphocytes were 628, 894, and 889/microL, respectively. Median rates of decline in absolute numbers and percentages of CD4 lymphocytes per 6 months were 7.6/microL (0.0%) for seropositive IVDUs and 55.1/microL (1.9%) for IVDUs who seroconverted (median follow-up after seroconversion was 12 months). Multivariate regression analysis that incorporated the within-individual correlation of the CD4 lymphocyte counts showed no significant change in these cells over time and no change due to use of drugs. CONCLUSION: Our data suggest that progression of HIV-1 infection in IVDUs, as reflected in decline of CD4 cell counts, is no more rapid than that reported for other risk groups.

Adult

Prevalence of tuberculin positivity and skin test anergy in HIV-1-seropositive and -seronegative intravenous drug users.

OBJECTIVES: --To identify differences in purified protein derivative (PPD) tuberculin positivity and skin test anergy rates by human immunodeficiency virus (HIV) serostatus, CD4+ lymphocyte count, and other risk factors in intravenous drug users (IVDUs); and to evaluate the appropriateness of the Centers for Disease Control (CDC)--recommended definition for a positive PPD tuberculin skin test result in HIV-1-seropositive patients. DESIGN: --Nested case-control and cross-sectional analyses. SETTING: --Community-based cohort of IVDUs. PATIENTS: --Two hundred sixty HIV-1-seropositive and -seronegative IVDUs, drawn from an unselected cohort, were skin-tested for sensitivity to PPD tuberculin, mumps, and Candida antigens using the Mantoux method. OUTCOME MEASURES: --Positivity to PPD tuberculin, skin test anergy. RESULTS: --Even using the CDC definition of an induration 5 mm or greater in diameter in HIV-1 seropositives, this group was substantially less likely to be PPD tuberculin positive than HIV-1 seronegatives (13.8% vs 25.2%; P = .02). In the HIV-1 seropositives the relative odds of being PPD positive varied depending on whether 10 mm or greater (odds ratio [OR], 0.3; 95% confidence interval [CI], 0.2 to 0.7), 5 mm or greater (OR, 0.5; 95% CI, 0.2 to 0.9), or 2 mm or greater (OR, 0.7; 95% CI, 0.4 to 1.3) was used to define a positive test result. The mean diameter induration in the HIV-1-seropositive group was 2.6 mm vs 5.4 mm in the seronegative group (P = .005). Skin test anergy (to mumps and Candida) appeared to explain the differential. Anergy was substantially higher in the HIV-1 seropositive group and increased as the CD4+ lymphocyte count fell (chi 2 for linear trend, 24.5; P less than .0001). An inverse linear trend for PPD positivity and CD4+ lymphocyte count was also observed (chi 2 for trend, 6.1; P = .01). In multivariate analyses, being 35 years of age or older and being HIV-1 seronegative were significantly associated with PPD positivity, while history of previous police arrest was of borderline significance. Only HIV-1 seropositivity was significantly associated with anergy. CONCLUSIONS: --These findings show that CDC-recommended definition of an induration 5 mm or greater in diameter for PPD tuberculin positivity in HIV-1 seropositives significantly underestimates the "true" infection rate (using the PPD positivity rate in HIV-1 seronegatives as the criterion standard). A definition of 2 mm or greater would appear to be a better cutoff for reducing misclassification in HIV-1 seropositives. This study also confirms that delayed-type hypersensitivity is seriously depressed in HIV-1 seropositive IVDUs and that anergy testing is mandatory to properly assess a negative PPD test result.

Adolescent

Genetic vulnerability to drug abuse. The D2 dopamine receptor Taq I B1 restriction fragment length polymorphism appears more frequently in polysubstance abusers.

Alcoholics are more likely than nonalcoholics to display the Taq I A1 restriction fragment length polymorphism of the D2 dopamine receptor gene, according to four of six studies that examined alcoholics and controls. The current study examines whether the association observed in alcoholism might extend to other addictive substances by examining D2 dopamine receptor Taq I A and B restriction fragment length polymorphisms in polysubstance users and controls free of significant substance use. We hypothesized a stronger association for the B1 restriction fragment length polymorphism since it lies closer to dopamine receptor protein coding and 5' regulatory regions. Heavy polysubstance users and subjects with DSM-III-R psychoactive substance use diagnoses displayed significantly higher Taq I B1 frequencies than control subjects; Taq I A1 results for these comparisons were less robust. These results are consistent with a role for a D2 dopamine receptor gene variant marked by these restriction fragment length polymorphisms in enhanced substance abuse vulnerability.

Alcoholism

Characteristics of intravenous drug users by history of arrest and treatment for drug use.

Typically, intravenous drug users are studied by drawing samples from drug treatment programs, from the criminal justice system, or by outreach into the street community via anthropological or ethnographic methods. Among 1405 subjects recruited through extensive community outreach, 46% reported no history of treatment for drug abuse and 16% said they had not been arrested in the preceding 10 years; 130 (9%) reported neither history. A history of arrest was higher among men and those with a history of: treatment for drug abuse, low educational attainment, having received public assistance, and unemployment. A history of drug treatment was higher among women and those of an older age with a history of: arrest, having received public assistance, and a greater duration and intensity of intravenous drug use. Intravenous drug users who had neither a history of arrest since 1977 nor of drug treatment were more likely to be women and more educated, to have not received public assistance, and to inject less than weekly. These data indicate that characteristics of intravenous drug users differ by history of arrest and treatment, substantiating reports of heterogeneity among intravenous drug users.

Black or African American

Correlates of human immunodeficiency virus infection in intravenous drug users: are treatment-program samples misleading?

Using a community-based sample of 1632 intravenous drug users in Baltimore, Maryland, USA, this study evaluated a possible selection bias faced when studying risk factors for human immunodeficiency virus, type 1 (HIV-1) in intravenous drug users drawn solely from treatment programs. Consenting subjects, recruited by extensive distribution of brochures and word-of-mouth, underwent confidential interviews about drug use behaviors in a setting that was independent of community service agencies. Of 1632 subjects, 275 (17%) were currently enrolled in treatment programs. These subjects were similar in many respects to those not currently in treatment, including HIV-1 seroprevalence; however, they differed in that those not in treatment were more likely to be male, younger and black than those currently in treatment, and to have started injecting drugs more recently. However, associations between HIV-1 seropositivity and a series of demographic and drug-using characteristics were mostly similar in direction and magnitude among subjects currently in treatment and those not in treatment. These results suggest that one-time samples of drug users enrolled in treatment programs do not necessarily present a misleading picture of correlates of HIV-1 seropositivity.

Adult

Measurement of HIV risk behaviors among intravenous drug users.

This paper reviews issues related to the measurement of drug use and other behaviors in studies of human immunodeficiency virus (HIV) infection in intravenous drug users. These issues include: (1) choice of variables, (2) study design, (3) time frame of measurement, (4) categories of measurement, (5) interviewer effects, and (6) validity of measurement. Difficulties and approaches for measuring drug use and other intimate behaviors in intravenous drug users are discussed. Attempts to come to terms with these measurement issues in the context of HIV infection in intravenous drug users should lead to the further development of methods for use in the general context of drug abuse research.

HIV Infections

HIV-1 infection and intravenous drug use: longitudinal neuropsychological evaluation of asymptomatic subjects.

A previous baseline cross-sectional comparison of cognitive performance of a group of AIDS-free, HIV-seropositive intravenous drug users with seronegative control intravenous drug users revealed no significant differences attributable to HIV. We now present longitudinal follow-up results from the same cohort of 160 intravenous drug users. There were no differences in performance by serostatus group at either 6- or 12-month follow-up visits, although differences by age and education were observed. Improvement in performance secondary to practice effects was comparable in both serostatus groups. These findings confirm that chronic intravenous drug use may be associated with a wide range of neuropsychological deficits, but there is no evidence that such preexisting deficits interact with HIV infection to produce additional cognitive impairment in otherwise asymptomatic intravenous drug users. Together with results from other high-risk groups such as homosexual/bisexual men and hemophiliacs, these results confirm that neurocognitive abnormalities during the presymptomatic stages of HIV infection are rare, regardless of the route of acquisition of the virus.

Adult

Terminology for drug injection practices among intravenous drug users in Baltimore.

Terms for four discrete drug injection practices were obtained by presenting photographs and a brief description of practices to intravenous drug users who enrolled in a longitudinal study of HIV infection in Baltimore. The 2,921 respondents were predominantly male (81%) and Black (90%), the median age was 34 years (range: 18-68 years), and the median duration of intravenous drug use was 13 years (range 0-50 years). Forty-six different terms were used to characterize direct injection into a vein, 51 for the practice of repeatedly withdrawing and reinjecting one's own blood following injection of drug, 39 for subcutaneous injection, and 45 for transferring drug between different syringes. Terms tended to cluster by race and duration of drug use. These data indicate substantial variation in terminology for drug injection practices. Further, they augment prior research showing that photographs may be used as a useful aid in survey research on drug experiences in the population.

Adolescent

Needle-cleaning practices among intravenous drug users who share injection equipment in Baltimore, Maryland.

In Baltimore, Maryland, between 1988 and 1989, 2,921 intravenous drug users were recruited into a study of drug injection practices and human immunodeficiency virus (HIV) infection. Sixty-three percent reported both current use and sharing of needles; almost all these (N = 1,757) reported using injection equipment immediately after it was used by another intravenous drug user. Of the 1,757, 62% said that they "typically" cleaned the used equipment with bleach or alcohol before injecting. These data suggest that information about disinfecting needles has disseminated into this population and identifies several groups to target for interventions.

Adult

Immune serum markers and CD4 cell counts in HIV-infected intravenous drug users.

We examined the association of three serum immune markers with CD4 cell counts in a large cohort of i.v. drug users with and without human immunodeficiency virus (HIV) infection. Levels of beta 2-microglobulin and neopterin were significantly elevated in HIV-infected subjects and increased in association with decline in CD4 cell counts (all p less than 0.001). Serum IgA levels in HIV-seropositive individuals were significantly elevated only when the CD4 cell count was less than 200/microliters (p less than 0.001). After controlling for HIV status and CD4 count, recent history of hepatitis was associated with significantly higher beta 2-microglobulin (p = 0.028) and marginally higher neopterin (p = 0.052) levels. There was no association of race, gender, or drug use patterns with levels of serum immune markers after controlling for HIV status and CD4 count. These data indicate that immune activation is coupled with immunosuppression in HIV-infected i.v. drug users. In addition, beta 2-microglobulin and neopterin levels are elevated in persons with a recent history of hepatitis but not in those with recent non-AIDS-defining bacterial infections. Markers of immune activation do not vary by race, gender, or drug use patterns among i.v. drug users.

Biomarkers

Prognostic indicators for development of AIDS among intravenous drug users.

A cohort of 544 human immunodeficiency virus-1 (HIV-1) seropositive intravenous drug users (IVDUs) was recruited in 1988 and early 1989; data on laboratory markers, clinical symptoms, intravenous drug use, and demographics were collected. Forty-one IVDUs developed AIDS within 2 years of enrollment. Data were analyzed using methods of survival analysis. None of the individuals reported use of antiviral agents or Pneumocystis carinii prophylaxis at baseline. A very strong (p less than 0.001) dose-response relationship was identified between CD4 cell count at baseline and the subsequent development of AIDS. In multivariate analysis, both the presence of more than one clinical HIV-1-related symptom and serum neopterin greater than 12 nmol/L showed significant associations with the relative hazard (95% confidence interval) of AIDS after controlling for CD4 of 2.9 (1.6, 5.6) and 2.0 (1.0, 3.7), respectively. In these IVDUs, serum beta 2-microglobulin did not add predictive power for progression to AIDS. The effect of clinical symptoms was stronger for high CD4 cell counts, indicating the need to monitor HIV seropositive IVDUs with both laboratory studies and clinical evaluation.

Acquired Immunodeficiency Syndrome

HIV-1 infection in the correctional setting.

The correctional setting provides an opportunity to serve IV drug users who might otherwise be difficult to access. Interventions--including education, counseling, treatment for HIV-1 infection, and treatment for drug abuse--conducted in the correctional setting could have benefits for individual inmates and the surrounding community.

HIV Infections

Antibody responses to Haemophilus influenzae type B vaccines in men with human immunodeficiency virus infection.

BACKGROUND: Persons with human immunodeficiency virus (HIV) infection are at increased risk for serious infections caused by Haemophilus influenzae, yet there are few data on their antibody responses to the H. influenzae type b vaccines. METHODS: We evaluated antibody responses in 248 men who were randomly assigned to receive a single dose of either the H. influenzae type b polysaccharide (PRP) vaccine or the polysaccharide-mutant diphtheria toxoid conjugate vaccine (PRP-CRM). The subjects were stratified into four groups: seronegative men (67 subjects), men with asymptomatic HIV infection (79), men with symptomatic HIV infection (47), and men with the acquired immunodeficiency syndrome (AIDS) (55). RESULTS: Before immunization, the subjects with AIDS had the lowest PRP-antibody titers; 40 percent had titers below the putative protective level (less than 0.15 micrograms per milliliter). In the seronegative subjects, those with asymptomatic HIV infection, and those with symptomatic HIV infection, the PRP-CRM vaccine led to a threefold greater increase in geometric mean antibody titers than did the PRP vaccine (P less than 0.01). However, the subjects with AIDS had a greater antibody response to the PRP vaccine. The antibody response of HIV-seropositive men to the PRP-CRM vaccine correlated significantly with the number of CD4 lymphocytes (r = 0.47, P less than 0.0001, as compared with r = -0.01 for the PRP vaccine). In these HIV-infected men, both vaccines elicited the dominant anti-PRP idiotype described previously in populations not infected with HIV. CONCLUSIONS: Immunization with the PRP-CRM conjugate vaccine early in the course of HIV infection is likely to confer protection against disease caused by H. influenzae type b.

AIDS Vaccines

New evidence on intravenous cocaine use and the risk of infection with human immunodeficiency virus type 1.

To examine whether recent intravenous use of cocaine might be associated with increased risk of human immunodeficiency virus type 1 (HIV) infection, the authors studied 2,597 active intravenous drug users: 2,399 with recent cocaine injection and 198 with recent injection of heroin or other drugs but not cocaine. These subjects were adult residents of Baltimore City and the surrounding Maryland counties, recruited via outreach into the community between February 1988 and March 1989. In contrast to the first report on the cocaine-HIV association, the present study sample was not recruited solely from drug treatment programs. In the present study, estimated HIV seroprevalence was 26.4% for recent cocaine injectors as compared with 10.6% among all other recent intravenous drug users; the relative odds estimate was 3.03. In the untreated segment of the sample, HIV seroprevalence was 26.0% for recent cocaine injectors as compared with 8.9% among others (relative odds (RO) = 3.61). The estimated degree of association did not change appreciably when multiple logistic regression was used to hold constant potentially confounding and/or mediating variables such as receptive anal intercourse, number of sex partners, and use of injection equipment obtained at shooting galleries (RO = 2.64). Augmenting these cross-sectional data, preliminary prospective data showed excess risk of HIV seroconversion among recent cocaine injectors (estimated relative risk = 2.11). While other research has examined the cocaine-HIV association, the present study differs in that it has allowed a test for whether the association was a spurious artifact of studying drug users recruited solely from drug treatment programs, a broad array of alternative determinants of HIV infection have been held constant, and the association has been examined with seroconversion data. The results lend support to the abiding concern about the risk of HIV infection among cocaine users.

Adolescent