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Biomedical subjects

D Vlahov

Publications and source records attributed to D Vlahov.

At least 127 records · Page 7Linked to original sources
PubMed1998

Patterns of HIV-1 evolution in individuals with differing rates of CD4 T cell decline.

Evolution of HIV-1 env sequences was studied in 15 seroconverting injection drug users selected for differences in the extent of CD4 T cell decline. The rates of increase of either sequence diversity at a given visit or divergence from the first seropositive visit were both higher in progressors than in nonprogressors. Viral evolution in individuals with rapid or moderate disease progression showed selection favoring nonsynonymous mutations, while nonprogressors with low viral loads selected against the nonsynonymous mutations that might have resulted in viruses with higher levels of replication. For 10 of the 15 subjects no single variant predominated over time. Evolution away from a dominant variant was followed frequently at a later time point by return to dominance of strains closely related to that variant. The observed evolutionary pattern is consistent with either selection against only the predominant virus or independent evolution occurring in different environments within the host. Differences in the level to which CD4 T cells fall in a given time period reflect not only quantitative differences in accumulation of mutations, but differences in the types of mutations that provide the best adaptation to the host environment.

Base Sequence↗
PubMed1998

Mycobacterium tuberculosis infection and disease are not associated with protection against subsequent disseminated M. avium complex disease.

OBJECTIVE: To determine the relationship between Mycobacterium tuberculosis infection and disease and subsequent disseminated M. avium complex (MAC) disease in HIV-infected persons. DESIGN: A prospective observational cohort study. SETTING: The AIDS Linked to the Intravenous Experience (ALIVE) cohort of injecting drug users and the Johns Hopkins Hospital Adult HIV Clinic (JHHAHC). PARTICIPANTS: HIV-infected persons aged > 18 years with CD4 lymphocytes < 100 x 10(6)/l were followed between July 1989 and 31 October 1996. There were 182 persons in the ALIVE cohort and 1129 persons in JHHAHC who met these criteria. MAIN OUTCOME MEASURE: The relative risk of disseminated MAC was determined according to a history of prior opportunistic infection, MAC prophylaxis, antiretroviral therapy, M. tuberculosis infection or disease, race, sex, and injecting drug use. RESULTS: Amongst the 30 patients with active tuberculosis, eight developed disseminated MAC, compared with 208 cases of disseminated MAC amongst 1148 patients without prior M. tuberculosis infection or disease [relative risk (RR), 1.5; 95% confidence interval (CI), 0.8-2.7; P=0.2]. Amongst the 10 patients with extrapulmonary tuberculosis, five developed disseminated MAC (RR, 2.8; 95% CI, 1.5-5.2; P=0.02). Injecting drug use was associated with a decreased risk of disseminated MAC (RR, 0.7; 95% CI, 0.6-0.9; P=0.007). In a logistic regression analysis, disseminated MAC was significantly associated with extrapulmonary tuberculosis and other opportunistic disease, whereas antibiotic prophylaxis and injecting drug use were protective. CONCLUSIONS: A history of M. tuberculosis infection or disease was not associated with protection against subsequent disseminated MAC disease in HIV-infected persons. However, persons with extrapulmonary tuberculosis were at increased risk for disseminated MAC, particularly at low CD4 cell levels.

AIDS-Related Opportunistic Infections↗
PubMed1998

Self-reported antiretroviral therapy in injection drug users.

CONTEXT: The US Public Health Service and the International AIDS Society-USA recently published recommendations for antiretroviral therapy (ART) for persons infected with human immunodeficiency virus (HIV); however, anecdotal evidence suggests that HIV-infected injection drug users (IDUs) may not be receiving optimal care as defined by the recommendations. OBJECTIVE: To assess ART use in HIV-infected IDUs. DESIGN: A cross-sectional survey of self-reported ART use between July 1996 and June 1997 in IDUs. SETTING: A community-based clinic affiliated with Johns Hopkins University, Baltimore, Md. PARTICIPANTS: A total of 404 HIV-infected IDUs with CD4+ cell counts less than 0.50 x 10(9)/L recruited into a longitudinal study in 1988 and 1989. MAIN OUTCOME MEASURE: Self-reported ART use was assessed: no current therapy, monotherapy, or combination therapy with or without a protease inhibitor. RESULTS: One half (199/404 [49%]) of patients reported no recent ART. A total of 14% (58/404) had monotherapy, 23% (90/404) were receiving combination therapy without a protease inhibitor, and 14% (57/404) had triple-combination therapy with a protease inhibitor. A multivariate analysis of factors associated with ART showed that care continuity and recent HIV-related outpatient visit (odds ratio [OR], 4.30; 95% confidence interval [CI], 2.36-7.81 and OR, 2.84; 95% CI, 1.66-4.88, respectively), CD4+ cell count of less than 0.20 x 10(9) (OR, 2.41; 95% CI, 1.51-3.84), no current drug use and being in drug treatment (OR, 2.16; 95% CI, 1.34-3.47; OR, 2.12; 95% CI, 1.23-3.66, respectively), and unemployment (OR, 2.31; 95% CI, 1.21-4.40) were associated with reporting ART use. In other analysis, less likely to receive protease inhibitors were current drug injectors (OR, 0.5; 95% CI, 0.3-1.0) and those recently incarcerated (OR, 0.2; 95% CI, 0.03-0.9), but patients with acquired immunodeficiency syndrome were more likely to receive protease inhibitors (OR, 2.0; 95% CI, 0.9-4.6). Protease inhibitor use doubled (P<.01) from July and December 1996 to January and June 1997 (7.7% and 14.8%, respectively). CONCLUSIONS: Those IDUs infected with HIV who were not receiving ART tended to be active drug users without clinical disease who have less contact with health care providers. Although we do not have information on clinical judgment regarding treatment decisions or whether persons were prescribed therapy not taken, the proportion of subjects reporting receiving ART suggests that strategies for improving treatment in this population are indicated. Expanding simultaneous treatment services for HIV infection and substance abuse would enhance the response to these related epidemics.

Anti-HIV Agents↗
PubMed1998

Opiates as potential cofactors in progression of HIV-1 infections to AIDS.

Because of the widely documented association of AIDS with opiate abuse, there is considerable interest in knowing whether opiates alter progression of HIV-1 infections to AIDS. The main reason for this interest is that opiates and opiate-abuse have been shown to have broad influence on immune processes as well as in vitro expressions of HIV-1. This article reviews literature defining the connection between opiate use and AIDS. Basic understanding of the effects of opiates on immune process and HIV-1 infection, especially as derived from study of a monkey model of AIDS, are discussed as well as epidemiological data regarding the connection between chronic injected drug abuse and AIDS, in the context of current knowledge about the HIV-1 infectious process and AIDS pathogenesis. Theoretically, there is ample reason to suspect that opiates are involved in progression of HIV-1 infections to AIDS. To date, however, epidemiological approaches have been unable to link decline in CD4 T-cell counts, as a marker of AIDS progression, with opiate use--although other indices of AIDS progression have yet to be thoroughly evaluated in this regard. Also, the impact of opiate use and abuse on opportunistic infections occurring prior to or concurrent with HIV-1 infection has not been closely scrutinized. Interestingly, despite considerable evidence delineating the potential of opiates to exacerbate HIV-1 infections, there is suggestive evidence from both clinical observations and basic studies that homeostatically balancing conditions of chronic, consistent opiate exposure have the potential to protect the host from progression of HIV-1 infections--a situation that may well differ from when opiate-naive subjects first experience exposure to opiates and when opiate dependency is not maintained in a consistent fashion. Taken together, therefore, information from basic studies, including most particularly studies with monkeys, and epidemiological studies, indicates that effects of opiates on progression to AIDS may be conditionally variable. There are many aspects of the drug abuse culture that have potentially offsetting consequences in terms of their potential to up- or down-regulate both HIV-1 expression and host protective responses thereto that could be relevant in this regard. In conclusion, many ambiguities are yet to be considered, and basic and epidemiological studies to be pursued before the opiate-AIDS connection is fully understood.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Genetic restriction of AIDS pathogenesis by an SDF-1 chemokine gene variant. ALIVE Study, Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC)

Stromal-derived factor (SDF-1) is the principal ligand for CXCR4, a coreceptor with CD4 for T lymphocyte cell line-tropic human immunodeficiency virus-type 1 (HIV-1). A common polymorphism, SDF1-3'A, was identified in an evolutionarily conserved segment of the 3' untranslated region of the SDF-1 structural gene transcript. In the homozygous state, SDF1-3'A/3'A delays the onset of acquired immunodeficiency syndrome (AIDS), according to a genetic association analysis of 2857 patients enrolled in five AIDS cohort studies. The recessive protective effect of SDF1-3'A was increasingly pronounced in individuals infected with HIV-1 for longer periods, was twice as strong as the dominant genetic restriction of AIDS conferred by CCR5 and CCR2 chemokine receptor variants in these populations, and was complementary with these mutations in delaying the onset of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Prognostic indicators for AIDS and infectious disease death in HIV-infected injection drug users: plasma viral load and CD4+ cell count.

CONTEXT: Plasma human immunodeficiency virus type 1 (HIV-1) viral load and CD4+ cell count are used to predict prognosis of persons infected with HIV. However, whether combining these markers improves prognostic accuracy and whether they predict prognosis for injection drug users (IDUs) and nonwhite persons infected with HIV has not been extensively investigated. OBJECTIVE: To evaluate plasma viral load and CD4+ cell count as prognostic indicators for the acquired immunodeficiency syndrome (AIDS) and infectious disease deaths. DESIGN: Cohort study initiated in 1988 and 1989 with follow-up for up to 7.9 years. PARTICIPANTS: Injection drug users infected with HIV recruited from the community in Baltimore, Md. MAIN OUTCOME MEASURES: Plasma HIV-1 RNA and CD4+ cell count measured at baseline compared with time to first clinical AIDS diagnosis and death due to an infectious disease. RESULTS: Of 522 subjects, 96% were African American, 80% were male, 96% injected drugs within the past 6 months, and the median age was 33 years. A total of 146 cases of AIDS and 119 infectious disease deaths were seen during a median follow-up period of 6.4 years. Time-fixed baseline levels of viral load and CD4+ cell count were independent predictors of progression to AIDS and infectious disease deaths, but in proportional hazards models, viral load had better predictive value than CD4+ cell count. Kaplan-Meier analysis of time to AIDS and to infectious disease deaths by viral load (<500, 500-9999, 10000-29 999, > or =30000 copies/mL) at 3 levels of CD4+ cell count (<0.20, 0.20-0.49, and > or =0.50x10(9)/L [<200,200-499, and > or =500/microL]) was reduced to a 5-stage classification scheme using a backward stepwise regression procedure. The 5-year cumulative probabilities for AIDS and infectious disease deaths ranged from 0% and 0%, respectively, for group I (viral load, <500 copies/mL; CD4+ cell count, 0.50x10(9)/L) to 81.2% and 76.1% respectively, for group V (viral load, > or =10000 copies/mL; CD4+ cell count, 0.20x10(9)/L). CONCLUSIONS: In this study, plasma HIV-1 viral load independently and in combination with CD4+ cell count measurements provided powerful prognostic information for progression to AIDS and death caused by infectious disease in a population of predominantly African American IDUs. Combining categories of both markers provided a simple method for prognostically staging HIV disease.

AIDS-Related Opportunistic Infections↗
PubMed1998

Correlates of infection control practices in dentistry.

BACKGROUND: Studies conducted in the first decade of the AIDS epidemic indicated that, in general, dentists had suboptimal levels of compliance with standard infection control practices, including work practices designed to reduce exposure to bloodborne pathogens. This study was designed to assess current rates of compliance with these practices in a population of Maryland dentists and to identify correlates of safe work practices. METHODS: We surveyed 648 Maryland dentists using a confidential, self-administered questionnaire. RESULTS: Three hundred and ninety-two questionnaires were returned (60% response rate). We found that infection control practices were variable as reported by responding dentists. In addition, several potentially modifiable factors were found to be significantly correlated with these practices, including (1) attitudes toward patients infected with HIV and (2) safety program management within the practice. CONCLUSION: These data are encouraging in that recommended infection control practices are being adopted, at least among a sample of Maryland dentists. Strategies for further improvement are identified.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Socially desirable response tendency as a correlate of accuracy of self-reported HIV serostatus for HIV seropositive injection drug users.

AIMS: This study examined the accuracy of self-reported HIV serostatus for injection drug users and the predictive validity of a measure of social desirability to detect inaccurate self-reports. DESIGN: Participants in the ALIVE study were provided testing for HIV antibodies and counseling every 6 months. In the separate SAFE study, the same volunteers were asked their HIV serostatus. PARTICIPANTS: The 348 active injection drug users recruited from the ALIVE study, a longitudinal study of the natural history of HIV among injection drug users, volunteered for an HIV prevention study (SAFE study). MEASUREMENTS: The ALIVE baseline interview included a scale to measure "self-deception", a dimension of socially desirable responding. FINDINGS: Of one hundred and four HIV seropositive participants, 71 (68%) accurately reported their HIV status, 28 (27%) inaccurately reported their HIV serostatus, and five (5%) reported that they did not know or were not sure about their HIV serostatus. Of 242 HIV seronegative participants, 239 (98%) correctly reported their serostatus. Thus the sensitivity of self-report was 72%, specificity 99%, positive predictive value 97%, and the negative predictive value was 90%. For individuals who scored at or below the median on self-deception, the sensitivity of self-reported HIV serostatus was 81%. CONCLUSIONS: The results suggest that high scores on some measures of social desirability may indicate questionable validity of self-reported HIV serostatus.

Female↗
PubMed1998

Diversification of subtype E human immunodeficiency virus type 1 env in heterosexual seroconverters from Northern Thailand.

The C2-V3 region of the human immunodeficiency virus (HIV)-1 env was determined from 15 northern Thailand seroconverters between 1993 and 1995. Similar sequences were also determined from 18 seroconverting injection drug users in Baltimore. All seroconverters from northern Thailand were infected with subtype E HIV-1 on the basis of env sequences. Intersubject viral DNA distances increased from 2.3% in asymptomatic HIV-1-infected subjects characterized between 1990 and 1992 to 7.8% in these more recent seroconverters from Thailand. On the other hand, sequences from 18 seroconverters from Baltimore had a mean intersubject distance of 13.2%. The genetic diversity within HIV-1 subtype E in seroconverters in Thailand has increased significantly but is still less than that observed in HIV-1 from seroconverters in the United States, where the epidemic of HIV-1 infection is more mature. These results suggest that continued monitoring of the molecular epidemiology of HIV-1 infection in Thailand will be important for HIV vaccine development and evaluation.

Amino Acid Sequence↗
PubMed1998

Vitamin A supplementation and human immunodeficiency virus load in injection drug users.

The use of vitamin A therapy during human immunodeficiency virus (HIV) infection is under clinical investigation, and vitamin A could potentially modulate HIV replication because the virus genome contains a retinoic acid response element. A randomized, double-masked, placebo-controlled clinical trial was conducted to determine the impact of single high-dose vitamin A supplementation, 60-mg retinol equivalent (200,000 IU), on HIV load and CD4 lymphocyte count. HIV-infected injection drug users (120) were randomly allocated to receive vitamin A or placebo. Plasma vitamin A level, CD4 lymphocyte count, and HIV load were measured at baseline and 2 and 4 weeks after treatment. Vitamin A supplementation had no significant impact on HIV load or CD4 lymphocyte count at 2 and 4 weeks after treatment. This study suggests that high-dose vitamin A supplementation does not influence HIV load.

Adult↗
PubMed1998

Association of antibody to GB virus C (hepatitis G virus) with viral clearance and protection from reinfection.

GB virus C (GBV-C) RNA and envelope antibody were assessed in a median of 4 samples collected over 6.5 years among injection drug users (IDUs). A marker of GBV-C infection was detected in 110 (94.8%) of 116 IDUs. GBV-C RNA was detected at all visits in 32, was never detected in 70, was acquired in 7, and was cleared in 8. The odds of detecting anti-GBV-C were 103-fold higher in participants without detectable RNA (64 of 70) than in IDUs with persistent RNA (3 of 32; P < 10(-7)). Anti-GBV-C was detected in all 8 instances of RNA clearance. GBV-C RNA never reappeared once it was cleared, and there were no new GBV-C infections among 61 anti-GBV-C-positive IDUs observed for 382 person-years, though all had ongoing drug use. Studies using RNA testing alone may significantly underestimate the occurrence of GBV-C infection. Anti-GBV-C is highly associated with viral clearance and protection from reinfection.

Adult↗
PubMed1998

Infection with dual-tropic human immunodeficiency virus type 1 variants associated with rapid total T cell decline and disease progression in injection drug users.

The characteristics of sequential human immunodeficiency virus type 1 (HIV-1) isolates from 12 seroconverters among injection drug users selected for either rapid or slow disease progression were evaluated. All 6 patients who developed AIDS within 5 years were initially infected with syncytium-inducing (SI) variants or showed a transition from non-SI-inducing (NSI) to SI variants. Detection of SI variants was associated with rapid decline of both CD8+ and CD4+ T cells. In contrast, the 6 slow progressors carried only NSI variants and maintained stable or increasing CD8+ T cell levels. The SI variants that were associated with initial infection were dual tropic, with efficient replication in primary macrophages and T cell lines. These results suggest that the ability to replicate in macrophages, rather than the SI or NSI phenotype per se, may be an important determinant of HIV-1 transmission and that dual-tropic viruses, when transmitted, may be associated with rapid progression to AIDS.

Adult↗
PubMed1998

Prevalence and incidence of hepatitis C virus infection among young adult injection drug users.

Through community-based outreach, young adult injection drug users (IDUs) were enrolled in a prospective study of the prevalence, incidence, and risk factors for hepatitis C virus (HCV) infection. Demographics and information on sexual and injecting practices were collected during semiannual interviews, and HCV infection was evaluated using a second-generation antibody assay. Of the 229 participants, 86 (37.6%) were HCV-seropositive at baseline. After adjusting for injecting frequency and duration by logistic regression, HCV seroprevalence was independently associated with reusing syringes at least once in the past 6 months (odds ratio [OR]=3.81, 95% confidence interval [CI] 1.39-11.00), injecting the first time with someone > or =5 years older (OR=2.99; 95% CI, 1.43-6.23) or alone (OR=4.02; 95% CI, 1.12-14.43) versus with someone <5 years older, and injecting cocaine or speedball exclusively (OR=4.29; 95% CI, 1.53-12.01) or with other drugs (OR=5.27; 95% CI, 2.62-10.64) versus injecting no cocaine in the past 6 months. Of the 105 originally HCV-seronegative participants who returned for follow-up, 13 seroconverted (incidence rate=16.0/100 person-years). On bivariate analysis, HCV seroconversion was significantly associated with injecting for <2 years (relative risk [RR]=7.3; 95% CI, 1.6-32.8) and continuing to inject during follow-up (RR=4.4; 95% CI, 1.0-19.9). Young adult IDUs are at high risk for HCV infection. These data support the need for wider legal access to sterile syringes, as well as expanded community outreach education to this population to prevent transmission of HCV.

Adult↗
PubMed1998

Community support for needle exchange programs and pharmacy sale of syringes: a household survey in Baltimore, Maryland.

In October 1995, community attitudes toward needle exchange programs were assessed in Baltimore, Maryland. Household interviews were conducted with a random sample of residents living within six contiguous census tracts. Multivariate logistic regression was used to determine which factors were independently associated with acceptance of needle exchange programs. Of 274 eligible respondents contacted, 138 (50%) completed the interview. Respondents were statistically similar to the 1990 census population by income but were more likely to be female, black, between the ages of 35 and 44 years, and to have attended college or be a college graduate. Although 72% of respondents thought needle exchange programs would attract injection drug users to the neighborhood, 65% favored needle exchange, and 47% favored selling needles in a pharmacy without a prescription. Factors independently associated with acceptance of needle exchange programs included the perceptions that needle exchange programs decrease the number of discarded needles on the street, that needle exchange programs do not encourage a person's injection drug use, and that needle exchange programs decrease HIV incidence. Despite concern about attracting injection drug users to the neighborhood, support for needle exchange programs was high.

Adult↗
PubMed1998

Pharmacists' attitudes about pharmacy sale of needles/syringes and needle exchange programs in a city without needle/syringe prescription laws.

We assessed pharmacists' practices for needle and syringe (NS) sales and their attitudes toward a needle exchange program through a telephone survey of 75 randomly selected pharmacies in Baltimore, Maryland, where possession of drug paraphernalia is illegal but where NS can be purchased without a prescription. Pharmacists' (n=46) procedures for NS sales included asking for picture identification (54%), requiring a prescription (34%), or requiring a diabetic identification (DID, 34%) for NS purchase; multiple responses were allowed. The median number of prescription and nonprescription NS sold per month was 950. Most (86.6%) pharmacists reported selling NS without prescriptions at their discretion. Pharmacists sold a median of 16 nonprescription NS per month. Pharmacists who required prescriptions or DID (56.5%) sold nonprescription NS significantly less often than those who did not require prescriptions or DID (p=.007). Most pharmacists (87%) were aware of the needle exchange program, 78.3% supported the program, and 67.4% supported selling nonprescription NS in pharmacies. Although there was no difference in anticipated effects of needle exchange or in support for needle exchange between pharmacists who did or did not require prescriptions, DID, or both, pharmacists who did require these items were significantly less likely to support pharmacy sales of nonprescription NS than pharmacists with less restrictive sales policies (p=.04). Although most pharmacists surveyed supported access to sterile NS by injection drug users through a needle exchange program, there was a diversity of approaches to nonprescription NS sales among pharmacists in a city that does not require prescriptions for access to sterile NS. Most supported nonpharmacy needle exchange programs, and more than one half limited injection drug users' access to NS through restrictive sales practices. To reduce injection drug users' exposure to HIV, pharmacists should be educated about HIV prevention and injection drug use and be included in development of HIV prevention programs, including legal pharmacy NS sales.

Attitude of Health Personnel↗
PubMed1998

Community-based programs for safe disposal of used needles and syringes.

OBJECTIVES: To review issues related to discarded syringes in the community and to describe community-based programs for the safe disposal of used needles and syringes. METHODS: We used the medical literature and chain referral to identify community-based syringe disposal programs other than syringe exchange programs (SEPs). We held a workshop in June 1996 involving staff from disposal programs; manufacturers of syringes, sharps containers, and other disposal devices; solid waste companies; public health staff; and researchers. RESULTS: Fifteen programs for the safe disposal of syringes were identified in the United States, Canada, and Australia. Of these, 12 primarily served persons with diabetes who use insulin, and 3 primarily served injection drug users (IDUs). The programs used three major strategies: puncture-resistant containers discarded in trash, community drop boxes, and sharps containers turned in for biohazard disposal at community sites, hospitals, or pharmacies. Participants in the workshop described key points in developing syringe disposal programs. Programs should involve pharmacists, physicians, waste disposal companies, public health departments, hospitals, diabetes educators, persons with diabetes who use insulin, and IDUs. For IDUs, criminal penalties for possession of syringes are a substantial deterrent to participation in community efforts to safely dispose of used syringes. The multiple and sometimes conflicting local, state, and federal laws and regulations concerning medical waste hinder development of multistate or national approaches to the safe disposal of syringes. More information is needed on community-based syringe disposal programs. CONCLUSION: Communities in the United States, Canada, and Australia have developed different approaches to achieve safe disposal of used syringes.

Australia↗