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D Vlahov

Publications and source records attributed to D Vlahov.

At least 181 records · Page 10Linked to original sources

Category of exposure to HIV and age in the progression to AIDS: longitudinal study of 1199 people with known dates of seroconversion. HIV Italian Seroconversion Study Group.

OBJECTIVES: To determine whether rate of development of AIDS is affected by category of exposure to HIV and whether the more rapid development found in older subjects persists for each exposure category. DESIGN: Longitudinal study of people with known date of seroconversion to HIV. SETTING: 16 HIV treatment centres throughout Italy. SUBJECTS: 1199 people infected with HIV through use of injected drugs, homosexual sex, or heterosexual sex. MAIN OUTCOME MEASURES: AIDS as defined by 1987 definition of Centers for Disease Control (including and excluding neoplasms) and by 1993 European definition. RESULTS: 225 subjects (18.8%) progressed to AIDS (Centers for Disease Control 1987 definition) during median follow up of 5.8 years. Univariate analyses showed more rapid progression to AIDS for older subjects compared with younger subjects and for homosexual men compared with other exposure categories. The age effect was of similar size in each exposure category and in men and women. In a bivariate model with age and exposure categories simultaneously included as covariates, differences by exposure category disappeared for use of injected drugs and heterosexual sex compared with homosexual sex (relative hazards 1.02 (95% confidence interval 0.71 to 1.45) and 1.07 (0.70 to 1.64) respectively), while the age effect remained (relative hazard 1.55 (1.32 to 1.83) for 10 year increase in age). Analyses using the other definitions for AIDS did not appreciably change these results. CONCLUSIONS: There was no evidence of differences in rate of development of AIDS by exposure category, while there was a strong tendency for more rapid development in older subjects for all three groups. This supports the view that external cofactors do not play major role in AIDS pathogenesis but that age is of fundamental importance.

Acquired Immunodeficiency Syndrome↗

Evidence for HIV type 1 strains of U.S. intravenous drug users as founders of AIDS epidemic among intravenous drug users in northern Europe.

To establish an epidemiological link between HIV-1 epidemics in U.S. and European homosexual men and intravenous drug users (IVDUs) we analyzed the HIV-1 gp120 V3 sequences in both risk groups. Signature pattern analysis revealed that the V3 sequences of viruses from IVDUs in Northern Europe are distinguishable from those of homosexual men on the basis of one amino acid and two synonymous nucleotide substitutions, which the most conserved was a synonymous nucleotide substitution in the second glycine codon at the tip of the gp120 V3 loop (GGC). This substitution was seen in 17 of 20 (85%) viruses of IVDUs in Northern Europe, in none of 41 homosexual men in either Europe or the United States, and in 5 of 11 (45%) U.S. IVDUs sequences analyzed. Subsequent phylogenetic and multivariate principal coordinate (PCOORD) analyses showed that 16 of 20 (80%) of the Northern European IVDU sequences clustered together with the 5 U.S. IVDU sequences carrying the GGC substitution and away from the sequences of homosexual men from either Europe or the United States. Taken together with the higher level of heterogeneity of U.S. IVDU sequences compared to the Dutch IVDU sequences taken at the same time, these data present suggestive evidence for a U.S. instead of a European origin of the AIDS epidemic among Northern European IVDUs.

Acquired Immunodeficiency Syndrome↗

Effect of Mycobacterium tuberculosis on HIV replication. Role of immune activation.

The prevalence of Mycobacterium tuberculosis (MTB) has increased worldwide, in part due to the HIV epidemic. Epidemiology data have demonstrated that HIV-infected individuals are more susceptible to MTB disease, which may lead to an acceleration in the progression of HIV disease. The purpose of this study was to determine whether MTB modulates HIV infection in vivo and to delineate the mechanisms involved by using in vitro model systems. Plasma viral load was measured in HIV-infected individuals before, during, and after the development of MTB disease; a 5- to 160-fold increase in viral replication was observed during the acute phase of MTB disease. In order to evaluate the mechanisms involved in this MTB-induced HIV replication, we used an in vitro system of primary PBMC and lymph node mononuclear cells isolated from HIV-infected individuals. The data demonstrated that MTB induced HIV replication in CD8+ T cell-depleted lymphocytes from HIV-infected individuals with a history of purified protein derivative (PPD) positivity but not in those who were PPD negative; this induction of HIV replication correlated with the level of cellular activation. In an in vitro acute HIV infection model, MTB increased HIV replication in PBMC from healthy donors with a history of PPD positivity, but not in PBMC from PPD-negative donors and this induction of viral replication also correlated with cellular activation. In conclusion, MTB increased HIV replication in vivo and in an in vitro model. This MTB-mediated viral production likely occurs through Ag-specific activation and infection of responding T cells.

Acquired Immunodeficiency Syndrome↗

Effect of isoniazid chemoprophylaxis on HIV-related mycobacterial disease.

OBJECTIVES: The aims of this study were to (1) identify trends and risk factors for mycobacterial disease and (2) determine the effect of expanded access to isoniazid chemoprophylaxis on tuberculosis incidence. METHODS: A prospective observational cohort study was conducted among community-based injecting drug users (IDUs); 2960 IDUs (942 human immunodeficiency virus [HIV] seropositive) were followed up from January 1988 to June 1994. Directly observed chemoprophylaxis with twice-weekly isoniazid (10 to 15 mg/kg) was offered to purified protein derivative (PPD) tuberculin-positive (> or = 5-mm induration diameter in HIV-seropositive subjects and > or = 10-mm diameter in HIV-seronegative subjects) individuals but not to those with cutaneous anergy. Overall and annual incidence rates of disease due Mycobacterium tuberculosis, Mycobacterium avium complex, and other atypical mycobacteria were estimated using Poisson regression. RESULTS: HIV seropositivity was the strongest risk factor for tuberculosis, M avium complex, and other mycobacterial disease (relative risk [RR], 3.8, 17.2, and 6.9, respectively). Median CD4 lymphocyte cell counts for the three groups of mycobacterial disease were 0.17, 0.03, and 0.02 x 10(9)/L (167/microL, 30/microL, 18/microL) within 6 months of diagnosis (before or after). Overall incidence rates of tuberculosis, M avium complex disease, and other mycobacterial disease were 1.9, 8.8, and 2.7 per 1000 person-years, respectively. Tuberculosis incidence peaked in 1991 at six per 1000 person-years. However, after access to directly observed preventive therapy was expanded for tuberculin-positive subjects, incidence fell to only one case in 1992 and zero cases for 24 months from mid-1992 to mid-1994. During this period the number of PPD-positive patients who completed at least 26 weeks of therapy (or were still receiving isoniazid) more than tripled (from 21 to 70). None of the 12 patients with tuberculosis diagnosed during follow-up had received any preventive therapy. In addition, no tuberculosis developed among participants with cutaneous anergy. Calendar trends in risk for M avium complex and tuberculosis diverged after expanded access to isoniazid prophylaxis. Compared with 1988-1989, risk of M avium complex increased sevenfold. Tuberculosis risk fell 83% from the peak risk in 1990-1991. CONCLUSIONS: Expanded access to directly observed isonazid therapy for tuberculin-positive IDUs with and without HIV infection was associated with an 83% drop in tuberculosis incidence, while in the same period M avium complex incidence significantly increased. These population-based data are consistent with those obtained from clinical trials of isoniazid prophylaxis and were obtained without offering chemoprophylaxis to HIV-infected patients with cutaneous energy.

AIDS-Related Opportunistic Infections↗

Detection of HIV-1 DNA in needle/syringes, paraphernalia, and washes from shooting galleries in Miami: a preliminary laboratory report.

Shared use of injection equipment (needle/syringes), registering, booting, and backloading are practices among injection drug users (IDUs) that increase the risk for transmission of human immunodeficiency virus type 1 (HIV-1). The sharing of injection paraphernalia (including cookers and cottons) and washwater for rinsing used needle/syringes and dissolving drugs could be potential sources for secondary transmission of HIV-1. Laboratory rinses were made from needle/syringes, cottons, and cookers obtained from shooting galleries, and washwaters were obtained from shooting galleries in Miami. Three rinses were analyzed and antibodies to HIV-1 proteins were detected by using Western blot and HIV-1 DNA was detected by using nested polymerase chain reaction (PCR) specific for the gag and envelope genes of HIV-1. Antibodies to HIV-1 proteins were detected in 12 (52%) of 23 rinses from visibly contaminated needle/syringes, in three (18%) of 17 rinses from cottons, in three (14%) of 21 rinses from cookers, and in one (6%) of 17 washwaters. No antibodies were detected in laboratory rinses from visibly clean needles. Using nested PCR followed by Southern blot confirmation of the amplified targets, HIV-1 gag gene DNA was detected in 16 (84%) of 19 and envelope gene DNA in 17 (85%) of 20 laboratory rinses from visibly contaminated needle/syringes. We detected gag and envelope gene DNA, respectively, in three (27%) and four (36%) of 11 cottons, in six (46%) and seven (54%) of 13 cookers, and in five (38%) of 13 and in 10 (67%) of 15 washwaters from shooting galleries. No HIV-1 DNA was detected in laboratory rinses from visibly clean needles. These results indicate that HIV-1 might be present in contaminated cottons, cookers, and washwaters as well as in contaminated needle/syringes at shooting galleries. Reduction of risks of exposure to HIV-1 among IDUs may require modification of behaviors that are ancillary to the act of injection, such as the use of common cookers, cottons, and washwater.

Blotting, Southern↗

Temporal trends of initial CD4 cell counts following human immunodeficiency virus seroconversion in Italy, 1985-1992. The Human Immunodeficiency Virus Italian Seroconversion Study.

To determine whether initial CD4 cell counts after human immunodeficiency virus (HIV) seroconversion have decreased over calendar time among participants in the Italian Seroconversion Study, HIV seroconverters who between 1985 and 1992 had a documented negative serology followed by a positive serology within 12 months and a first CD4 cell measurement within 24 months of seroconversion (defined as midpoint of negative and positive HIV tests) were cross-tabulated by year of seroconversion. Linear regression methods were used to examine temporal trends in initial CD4 level after adjustment for age, lag time of seroconversion, lag time of CD4 cell measurement, risk group, and clinical center. Between 1985 and 1992, the overall median initial CD4 cell level after seroconversion was 660 microliters with a median lag time of 212 days and 137 days for seroconversion and first CD4 cell measurement, respectively. In univariate and multivariate models, the CD4 cell count increases of 4.3 and 4.2 cells microliters/year, respectively, were not statistically significant. These data do not identify a trend of lower CD4 counts following HIV seroconversion in Italy and suggest indirectly that HIV has probably not become more virulent between 1985 and 1992.

Adolescent↗

Existence and failure of T-cell homeostasis prior to AIDS onset in HIV-infected injection drug users.

Prior studies, based on populations of homosexual men, have shown that during HIV infection, levels of total circulating T-cells (CD3+ lymphocytes) remain constant for long periods of time after seroconversion. This suggested homeostatic phenomenon was observed to break down about 18 months prior to AIDS diagnosis with a quick loss of T-cells. The objective of this study was to determine whether (a) total T-cells are maintained at a constant level for long periods of time among HIV-infected injection drug users (IDUs) and (b) total T-cells decline before AIDS onset in this risk group and, if so, by how long. The design and setting was prospective follow-up, with semiannual clinic visits, of 646 HIV-infected IDUs who participate in the ALIVE study (Baltimore, MD). Among AIDS cases, T-cell levels remained quite stable at about 1500 cells/microl up to approximately 24 months prior to AIDS. However, a steep decline in CD3+ cell levels began approximately 24 months prior to AIDS diagnosis and was -17.5% per 6 months in the last 18 months before AIDS. Among seropositive IDUs without AIDS, a gradual decline of less than -4% per 6 months was observed. These trends remained virtually unchanged after accounting for current injection drug use, smoking, and HIV-related medications. IDUs, like homosexual men, exhibited T-cell homeostasis following HIV infection, as well as failure of this homeostasis about 2 years before AIDS. Although the mechanisms for the maintenance and later failure of the homeostasis of T-lymphocytes are not well understood, the observation has a potentially important prognostic value as well as biological interest.

Acquired Immunodeficiency Syndrome↗

The long-term outcome of a personal network-oriented HIV prevention intervention for injection drug users: the SAFE Study.

Social influence processes have been found to affect numerous drug and health-related behaviors. We postulated that by using a network-oriented intervention it may be possible to capitalize on social influence processes to reduce human immunodeficiency virus (HIV) risk behaviors. The present study used an experimental study design for delivering a psychoeducational acquired immunodeficiency syndrome (AIDS) preventive intervention to injection drug sharing networks. Participants were recruited from the ALIVE study, an epidemiological study in Baltimore. In the present paper we examine the self-reported behavioral outcomes of 117 injection drug users 18 months after the baseline interview. HIV seronegative experimental participants reported significantly less frequent needle sharing and less injecting of heroin and cocaine than controls. In multiple logistic regression models of HIV seronegative participants, there was a significant negative association between assignment to the experimental group and the HIV-related behaviors of needle sharing and sharing of cookers in the prior 6 months; controls were 2.8 times more likely than experimentals to report needle sharing and were 2.7 times more likely to report sharing cookers. The results of this 18-month follow-up suggest that among injection drug users network-oriented interventions may be a promising approach to HIV prevention.

Acquired Immunodeficiency Syndrome↗

The relationship between risk networks' patterns of crack cocaine and alcohol consumption and HIV-related sexual behaviors among adult injection drug users: a prospective study.

Social context may be an important determinant of drug and alcohol consumption and HIV-related behaviors. To assess the influence of peers on drug users' risk behaviors this study examined the association between individual level and group level behaviors. This analysis reports on the prospective association between baseline self-reported drug and alcohol use of the network members of injection drug users, and self-reported sexual behaviors and alcohol use at 5-month follow-up. Participants were a nontreatment sample of inner-city injection drug users who volunteered for a network-oriented HIV preventive intervention. They were predominantly unemployed, African American males. Of the 71 index participants who completed both the baseline and follow-up interviews, 227 of their drug network members were enrolled in the study. At baseline indexes' sexual risk behaviors were significantly associated with their drug network members' level of crack cocaine use. At follow-up higher levels of alcohol and crack use among drug network members were associated with indexes' reports of multiple sex partners and increased alcohol consumption. Higher levels of crack use among the drug network members were associated with the indexes' reporting casual sex partners at follow-up. These results highlight the importance of studying the role of peer group influence and the social context of risk behaviors.

Adult↗

Differences in the incidence of hepatitis B and human immunodeficiency virus infections among injecting drug users.

Both hepatitis B virus (HBV) and human immunodeficiency virus (HIV) type 1 seroconversions have been considered as outcome measures to evaluate the effectiveness of needle exchange programs. To assess the relationships between incident HBV and HIV infections among injecting drug users (IDUs), seroconversions were prospectively studied among a cohort of 240 HBV- and HIV- seronegative IDUs. The incidence of HBV seroconversion declined from 24.41/100 person-years in 1988 to 0 seroconversions in 1992. In contrast, HIV seroconversion rates varied little from the overall rate of 3.29/100 person-years. HBV seroconversion predicted subsequent HIV seroconversion among male IDUs (relative incidence [RI]= 4.23) but not among female IDUs (RI=0.86). Because of different transmission dynamics, HBV seroconversion probably has limited utility as a surrogate outcome measure for incident HIV. However, HBV seroconversion itself is an appropriate and important outcome measure for evaluation of prevention programs among IDUs.

Adult↗

The effect of latent Mycobacterium tuberculosis infection on human immunodeficiency virus (HIV) disease progression and HIV RNA load among injecting drug users.

To examine the relationship between latent Mycobacterium tuberculosis infection and human immunodeficiency virus (HIV) disease progression, two studies were done among a cohort of HIV-infected injecting drug users. First, the decline in CD4 cell count after baseline tuberculin skin testing was prospectively compared for 37 tuberculin-positive (induration > or = 5 mm) and 284 tuberculin-negative (induration < or = 2 mm) persons. After adjustment for baseline immune function, the mean 6-month CD4 cell decline was not significantly different (34.5 vs. 45.6 cells, respectively, P = .14). Second, the plasma HIV burden at baseline skin testing was compared for 33 tuberculin-positive cases and 33 matched tuberculin-negative controls. HIV RNA was detected in 8 cases and 10 controls (odds ratio = 0.67, 95% confidence interval = 0.19-2.36). Among the 14 pairs with HIV detected in > or = 1 member, the HIV concentration was higher for the case in 4 and for the control in 10 (P = .18). These findings suggest that unlike active tuberculosis, latent M. tuberculosis infection does not hasten HIV progression.

Adult↗

An international collaborative study of the effects of coinfection with human T-lymphotropic virus type II on human immunodeficiency virus type 1 disease progression in injection drug users.

To determine whether human T-lymphotropic virus (HTLV) type II coinfection affects progression of human immunodeficiency virus type 1 (HIV) infection, longitudinal data on 370 HIV-infected injection drug users (IDUs) with known HIV seroconversion dates from four cohort studies were pooled. HTLV infection was determined by EIA and confirmed and typed by Western blot. Proportional hazards models were used to determine whether HTLV-II infection was associated with AIDS or AIDS-related mortality. Regression analyses were used to compare declines in CD4 cell percents in singly and dually infected persons. Of 370 IDUs, 61 (16%) were HTLV-II-coinfected. During follow-up, 43 (12%) developed and 24 (6%) died of AIDS. HTLV-II coinfection was not associated with progression to AIDS (relative hazard [RH], .82; 95% confidence interval [CI], 0.34-1.94]) or AIDS mortality (RH, 1.69; 95% CI, 0.62-4.60). Rates of decline in CD4 cell percent were similar in singly and dually infected IDUs. These results suggest that HTLV-II does not affect the progression of HIV infection.

Acquired Immunodeficiency Syndrome↗

Effect of human immunodeficiency virus on hepatitis C virus infection among injecting drug users.

To assess the effect of human immunodeficiency virus (HIV) immunosuppression on ongoing hepatitis C virus (HCV) infection, CD4 lymphocyte counts and serum concentrations of HCV RNA, HIV RNA, and alanine aminotransferase (ALT) were evaluated among members of a cohort of injecting drug users (IDUs). With 100 participants randomly selected at various stages of HIV-related immunosuppression, serum HCV RNA concentrations increased with age (P = .007) and were higher in HIV-positive IDUs with 201-500 (P = .026) and 51-200 (P = .004) CD4 cells/mL than in HIV-negative participants. Among 27 HCV-infected IDUs who acquired HIV infection, serum HCV RNA concentrations varied between semiannual visits by a mean of 0.45 logs, increasing by 0.60 logs after HIV seroconversion (P < .0001), by 0.12 logs each subsequent year (P = .006), and by 0.36 logs per log increase in CD4 cells (P = .01). Serum ALT levels were similar between HIV-positive (40.1 IU/mL) and HIV-negative (45.4 IU/mL) patients (P > .10). While HIV infection and possibly HIV progression are associated with increased HCV RNA levels, other factors appear to affect biochemical and virologic markers of HCV infection in some dually infected persons.

Adolescent↗

Human immunodeficiency virus infection and infective endocarditis among injecting drug users.

Human immunodeficiency virus (HIV) infection and infective endocarditis are serious complications of injection drug use. To determine whether HIV infection may increase the risk of endocarditis beyond that associated with drug injection, we performed a nested case-control study among injecting drug users taking part in an ongoing cohort. We identified 26 participants with infective endocarditis between cohort enrollment (in 1988-1989) and June 1992, through reviews of medical records and death certificates. We matched each endocarditis case with up to five controls (N = 120) on enrollment date, race/ethnicity, and follow-up time. Data were taken from baseline and from the one follow-up visit: the last visit before the endocarditis occurred for cases and the closest visit (+/- 3 months) for controls. We used conditional logistic regression to quantify the association between HIV serostatus at follow-up and subsequent endocarditis, after adjusting for a history of endocarditis or sepsis before enrollment, injection duration, current injection frequency, and a recent history of abscess at injection sites. Among current injectors at follow-up, the adjusted odds ratio (OR) of developing endocarditis for HIV-seropositive subjects with > or = 350 CD4 cells per microliter, compared with HIV-seronegative subjects, was 2.31 [95% confidence interval (CI) = 0.61-8.78]; the corresponding OR for HIV-seropositive subjects with < 350 CD4 cells per microliter was 8.31 (95% CI = 1.23-56.37). These data indicate that HIV-related immunodeficiency may independently increase the risk of infective endocarditis among injecting drug users.

Adult↗

Alcohol use and T-lymphocyte subsets among injection drug users with HIV-1 infection: a prospective analysis.

OBJECTIVES: Alcohol use is known to alter immune function and has immunosuppressive effects that may modify T-lymphocyte subpopulations. However, there is no clear evidence regarding the relationship of alcohol use with the progression of immunodeficiency in human immunodeficiency virus-type 1 (HIV-1)-seropositive individuals, particularly injection drug users (IDUs). METHODS: Using prospective data from a cohort of IDUs in a study of the natural history of HIV infection, we examined the relationship of alcohol use and changes in T-lymphocyte subsets. Among the 2921 IDUs followed semiannually in outpatient clinics, 188 were documented HIV-1 seroconverters with known time of seroconversion. At each visit, all study participants were interviewed, underwent physical examinations, and had blood drawn for laboratory studies. Alcohol use was measured by reported frequency and quantity of alcoholic beverages. Longitudinal analyses included data for up to 5 years postseroconversion. To formally test the association of alcohol use with change in levels of CD4+ and CD8+ cells subsequent to HIV seroconversion, regression models incorporating autocorrelation structure were applied. RESULTS: Alcohol use was not appreciably related to age, gender, marital status, income, education, or the duration of intravenous drug use. CD4% decreased for all IDUs within the first 5 years after seroconversion, with no significant differences between alcohol categories. CD8% increased for all IDUs, with no significant differences by alcohol category within the first 2 years after seroconversion. However, between 2 to 5 years postseroconversion, there was a statistically significant increase among the heaviest drinkers: CD8% increased 6.9%/year [95% confidence interval (CI): 4.7, 8.0] for the IDUs who reported > 21 drinks/week, 2.4%/year (95% CI: 0.8, 4.0) for IDUs who drank 21 drinks/week or less, and 0.4% (95% CI: -2.1, 2.9) for abstainers. Similar results were obtained for CD4 and CD8 absolute counts. CONCLUSIONS: In this study population of IDUs, CD8% (but not CD4%) is associated with alcohol consumption early after HIV seroconversion. This is the first prospective study to date to assess the relationship of alcohol use with HIV progression from the time of HIV seroconversion among a cohort of IDUs. If confirmed in future investigations, the findings may have significant implications for prevention and early intervention programs aimed at inhibiting disease progression among HIV-positive IDUs.

Adult↗

Selective transmission of human immunodeficiency virus type 1 variants to SCID mice reconstituted with human peripheral blood monoclonal cells.

The relative infectiousness of laboratory and primary human immunodeficiency virus type 1 (HIV-1) variants was evaluated in in vitro cell cultures of peripheral blood mononuclear cells or MT-2 cells and in Hu-PBL-SCID mice. HIV(MN) and syncytium-inducing primary isolates were preferentially transmitted to cells in tissue culture. HIV(Ba-L) and non-syncytium-inducing (NSI) primary isolates were more infectious in Hu-PBL-SCID mice. Phylogenetic analysis of env sequences derived from the primary isolates, from the cell cultures, and from five Hu-PBL-SCID mice was performed by using methods designed for resolving differences among closely related sequence pairs. This analysis demonstrated preferential transmission of an evolutionarily related subset of NSI variants to Hu-PBL-SCID mice. The pattern of selective transmission of a restricted range of NSI variants that is observed in the clinical setting is maintained in Hu-PBL-SCID mice and not in tissue culture systems. The Hu-PBL-SCID mouse model system, when used with appropriate phylogenetic analysis methodologies, will be useful for identifying and characterizing the more infectious HIV-1 variants that should be targeted for vaccine development.

Amino Acid Sequence↗