Uninfected Injection Drug Users Research Articles

Socio-demographic and sexual practices associated with HIV infection in Kenyan injection and non-injection drug users

BackgroundSubstance use is increasingly becoming prevalent on the African continent, fueling the spread of HIV infection. Although socio-demographic factors influence substance consumption and risk of HIV infection, the association of these factors with HIV infection is poorly understood among substance users on the African continent. The objective of the study was to assess socio-demographic and sexual practices that are associated with HIV infection among injection drug users (IDUs), non-IDUs, and non-drug users (DUs) at an urban setting of coastal Kenya.MethodsA cross-sectional descriptive study was conducted among 451 adults comprising HIV-infected and -uninfected IDUs (n = 157 and 39); non-IDUs (n = 17 and 48); and non-DUs (n = 55 and 135); respectively at coastal, Kenya. Respondent driven sampling, snowball and makeshift methods were used to enroll IDUs and non-IDUs. Convenience and purposive sampling were used to enroll non-DUs from the hospital’s voluntary HIV testing unit. Participant assisted questionnaire was used in collecting socio-demographic data and sexual practices.ResultsBinary logistic regression analysis indicated that higher likelihood of HIV infection was associated with sex for police protection (OR, 9.526; 95% CI, 1.156-78.528; P = 0.036) and history of sexually transmitted infection (OR, 5.117; 95% CI, 1.924-13.485; P = 0.001) in IDUs; divorced, separated or widowed marital status (OR, 6.315; 95% CI, 1.334-29.898; P = 0.020) in non-IDUs; and unemployment (OR, 2.724; 95% CI, 1.049-7.070; P = 0.040) in non-drug users. However, never married (single) marital status (OR, 0.140; 95% CI, 0.030-0.649; P = 0.012) was associated with lower odds for HIV infection in non-drug users.ConclusionAltogether, these results suggest that socio-demographic and sexual risk factors for HIV transmission differ with drug use status, suggesting targeted preventive measures for drug users.

Frailty, Inflammation, and Mortality Among Persons Aging With HIV Infection and Injection Drug Use.

Serum markers of inflammation increase with age and have been strongly associated with adverse clinical outcomes among both HIV-infected and uninfected adults. Yet, limited data exist on the predictive and clinical utility of aggregate measures of inflammation. This study sought to evaluate the relationship of a recently validated aggregate inflammatory index with frailty and mortality among aging HIV-infected and uninfected injection drug users. Frailty was assessed among HIV-infected and uninfected participants in the AIDS Linked to the IntraVenous Experience (ALIVE) cohort study using the five Fried phenotypic criteria: weight loss, exhaustion, low physical activity, decreased grip strength, and slow gait. The aggregate inflammatory index was constructed from serum measures of interleukin-6 and soluble tumor necrosis factor-α receptor-1. Multinomial logistic regression was used to assess the relationship of frailty with inflammation. Cox proportional hazards models were used to estimate risk for all-cause mortality. Among 1,326 subjects, the median age was 48 years and 29% were HIV-infected. Adjusting for sociodemographics, comorbidity, and HIV status, frailty was significantly associated with each standard deviation increase in log interleukin-6 (odds ratio 1.33; 95% CI, 1.09-1.61), log tumor necrosis factor-α receptor-1 (odds ratio 1.25; 95% CI, 1.04-1.51) and inflammatory index score (odds ratio 1.39; 95% CI, 1.14-1.68). Adjusting for sociodemographics, comorbidity, HIV status, and frailty, the inflammatory index score was independently associated with increased mortality (HR 1.65; 95% CI, 1.44-1.89). A recently validated, simple, biologically informed inflammatory index is independently associated with frailty and mortality risk among aging HIV-infected and uninfected injection drug users.

Serum adiponectin in HIV-1 and hepatitis C virus mono- and co-infected Kenyan injection drug users.

Adiponectin is an important marker of anthropometric profiles of adipose tissue. However, association of adiponectin and adiposity in HIV mono- and co-infected and hepatitis (HCV) injection drug users (IDUs) has not been elucidated. Therefore, the relationship of total adiponectin levels with anthropometric indices of adiposity was examined in HIV mono-infected (anti-retroviral treatment, ART-naive, n=16 and -experienced, n=34); HCV mono-infected, n=36; HIV and HCV co-infected (ART-naive, n=5 and -experienced, n=13); uninfected, n=19 IDUs; and healthy controls, n=16 from coastal Kenya. Anthropometric indices of adiposity were recorded and total circulating adiponectin levels were measured in serum samples using enzyme-linked immunosorbent assay. Adiponectin levels differed significantly amongst the study groups (P<0.0001). Post-hoc analyses revealed decreased levels in HIV mono-infected ART-naive IDUs in comparison to uninfected IDUs (P<0.05) and healthy controls (P<0.05). However, adiponectin levels were elevated in HCV mono-infected IDUs relative to HIV mono-infected ART-naive (P<0.001) and -experienced (P<0.001) as well as HIV and HCV co-infected ART-naive (P<0.05) IDUs. Furthermore, adiponectin correlated with weight (ρ=0.687; P=0.003) and BMI (ρ=0.598; P=0.014) in HIV mono-infected ART-naive IDUs; waist circumference (ρ=−0.626; P<0.0001), hip (ρ=−0.561; P=0.001) circumference, and bust-to-waist ratio (ρ=0.561; P=0.001) in HIV mono-infected ART-experienced IDUs; waist girth (ρ=0.375; P=0.024) in HCV mono-infected IDUs; and waist-to-hip ratio (ρ=−0.872; P=0.048) in HIV and HCV co-infected ART-naive IDUs. Altogether, these results suggest suppression of adiponectin production in treatment-naive HIV mono-infected IDUs and that circulating adiponectin is a useful surrogate marker of altered adiposity in treatment-naive and -experienced HIV and HCV mono- and co-infected IDUs.

Behavioural, Mucosal and Systemic Immune Parameters in HIV-infected and Uninfected Injection Drug Users.

ObjectiveInjection drug use (IDU) remains a major risk factor for HIV-1 acquisition. The complex interplay between drug use, non-sterile injection, and Hepatitis C remains poorly understood. We conducted a pilot study to determine the effect of IDU on immune parameters among HIV-uninfected and -infected individuals. We hypothesized that IDU could further augment immunological changes associated with HIV-1 infection, which could in turn affect HIV pathogenesisMethodsHIV-uninfected and -infected subjects with IDU, and non-IDU controls were recruited to obtain socio-demographic and drug-related behaviours. Blood (PBMC) and mucosal (MMC) mononuclear cells were analysed for cellular markers of immune activation (CD38 and Ki67). Serum ELISA was performed to determine levels of soluble CD14, a marker of immune activation.ResultsNo significant quantitative differences in CD4+ and CD8+ T cell levels were observed between IDU and non-IDU subjects when accounting for the presence of HIV-1 infection. However, increased levels of cellular and soluble markers of immune activation were documented in cells and plasma of HIV-uninfected IDU subjects compared to non-injectors. Additionally, sharing of injection paraphernalia was related to immune activation among HIV-uninfected IDU subjects.ConclusionIDU, with or without HIV-1 infection, results in a significant increase in immune activation in both the peripheral blood and the GI tract. This may have significant impact on HIV transmission, pathogenesis, and immunologic responses to combination antiviral therapy. This study provides compelling preliminary results which in turn support larger studies to better define the relationship between IDU, infection with HIV-1, co-infection with Hepatitis C and immunity.

Protection against hepatitis C infection via NK cells in highly-exposed uninfected injecting drug users

HCV seroprevalence surveys in longstanding injecting drug users (IDUs) reveal a small minority who remain seronegative, with some exhibiting HCV-specific cellular immunity. This study aimed to characterise this immunity, assess associations with risk behaviours and protection against infection. A nested case-control series from a prospective cohort of seronegative IDUs was selected with incident cases (IN; n = 28) matched by demographics and risk behaviour to exposed uninfected (EU) subjects (n = 28). Samples were assayed for natural killer (NK) cell phenotypes and function, HCV-specific IFNγ in ELISpot, and HCV-specific CD4 T effector responses. IL28B and HLA-C/KIR2DL3 genotypes were tested. Numbers of activated (CD69(+)) NK cells in the mature CD56(dim)CD16(+) subset, and cytotoxic (NKp30(+)) cells in the CD56(bright)CD16(+) subset were higher in the EU subjects (p = 0.040, p = 0.038 respectively). EU subjects had higher frequencies of interferon gamma (IFNγ) producing NK cells, and lower frequencies of CD107a expression (p = 0.003, p = 0.015 respectively). By contrast, the frequency, magnitude, and breadth of HCV-specific CD4 and CD8 T cell responses did not differ, nor did IL28B, HLA-C, or KIR2DL3 allele frequencies. Sustained NK cell activation contributes to protection against HCV infection. HCV-specific cellular immunity is prevalent in EU subjects but does not appear to be protective.

Risk factors for vitamin D deficiency among HIV-infected and uninfected injection drug users.

IntroductionVitamin D deficiency is highly prevalent and is associated with bone disease, cardiovascular disease, metabolic syndrome and malignancy. Injection drug users (IDUs), with or without HIV infection, are at risk for these conditions; however, limited data on vitamin D deficiency exist in this population. We determined the prevalence and correlates of vitamin D deficiency among urban IDUs in the AIDS Linked to the IntraVenous Experience (ALIVE) Study cohort.MethodsFor this cross-sectional sub-study, vitamin D deficiency was defined as a serum 25(OH)-vitamin D level <20 ng/mL. Multivariable logistic regression was used to identify factors independently associated with vitamin D deficiency.ResultsOf 950 individuals analyzed, 29% were HIV-infected. The median age was 49 years; 65% were male, and 91% were black. The median vitamin D level was 13.5 ng/mL (IQR, 9.0–20.3); 74% were deficient (68% in HIV-infected vs. 76% in HIV-uninfected, p = 0.01). Non-black race, fall/winter season, multivitamin intake, higher serum albumin, HCV seropositivity and HIV-infection were associated with significantly lower odds of vitamin D deficiency.ConclusionsVitamin D deficiency is prevalent among IDUs. Notably, HIV-infected IDUs were less likely to be vitamin D deficient. Higher vitamin D levels were associated with multivitamin intake and with higher albumin levels, suggesting that nutritional status contributes substantially to deficiency. The association between HCV serostatus and vitamin D level remains unclear. Further investigation is needed to define the clinical implications of the heavy burden of vitamin D deficiency in this high-risk, aging population with significant co-morbidities.

Effectiveness and Cost Effectiveness of Oral Pre-Exposure Prophylaxis in a Portfolio of Prevention Programs for Injection Drug Users in Mixed HIV Epidemics

BackgroundPre-exposure prophylaxis with oral antiretroviral treatment (oral PrEP) for HIV-uninfected injection drug users (IDUs) is potentially useful in controlling HIV epidemics with a significant injection drug use component. We estimated the effectiveness and cost effectiveness of strategies for using oral PrEP in various combinations with methadone maintenance treatment (MMT) and antiretroviral treatment (ART) in Ukraine, a representative case for mixed HIV epidemics.Methods and FindingsWe developed a dynamic compartmental model of the HIV epidemic in a population of non-IDUs, IDUs who inject opiates, and IDUs in MMT, adding an oral PrEP program (tenofovir/emtricitabine, 49% susceptibility reduction) for uninfected IDUs. We analyzed intervention portfolios consisting of oral PrEP (25% or 50% of uninfected IDUs), MMT (25% of IDUs), and ART (80% of all eligible patients). We measured health care costs, quality-adjusted life years (QALYs), HIV prevalence, HIV infections averted, and incremental cost effectiveness. A combination of PrEP for 50% of IDUs and MMT lowered HIV prevalence the most in both IDUs and the general population. ART combined with MMT and PrEP (50% access) averted the most infections (14,267). For a PrEP cost of $950, the most cost-effective strategy was MMT, at $520/QALY gained versus no intervention. The next most cost-effective strategy consisted of MMT and ART, costing $1,000/QALY gained compared to MMT alone. Further adding PrEP (25% access) was also cost effective by World Health Organization standards, at $1,700/QALY gained. PrEP alone became as cost effective as MMT at a cost of $650, and cost saving at $370 or less.ConclusionsOral PrEP for IDUs can be part of an effective and cost-effective strategy to control HIV in regions where injection drug use is a significant driver of the epidemic. Where budgets are limited, focusing on MMT and ART access should be the priority, unless PrEP has low cost.

Rare occurrence of occult hepatitis C virus in apparently uninfected injecting drug users: a two‐centre, masked, case–control study

Occult hepatitis C virus (HCV) is a phenomenon where serum HCV RNA is not detected by sensitive commercial assays, but viral RNA is detected by ultrasensitive techniques. Occult HCV infection has not previously been studied in highly exposed, but apparently uninfected (EU) individuals. Two studies examining occult infection in EU subjects were undertaken - an initial two-centre, masked, case-control study based on cross-sectional samples (n = 35 subjects) and a single-centre confirmatory study based on longitudinal samples (n = 32 subjects). Plasma and peripheral blood mononuclear cells were tested for HCV RNA using an ultrasensitive nested polymerase chain reaction assays. Two EU subjects in the first study (10%) and one in the second study (3%) were found to have consistently detectable HCV RNA. Occult HCV infection occurs in high-risk, apparently uninfected subjects.

Vitamin D deficiency and persistent proteinuria among HIV-infected and uninfected injection drug users

Vitamin D deficiency and persistent proteinuria among HIV-infected and uninfected injection drug users

Frailty, HIV Infection, and Mortality in an Aging Cohort of Injection Drug Users

BackgroundFrailty is associated with morbidity and premature mortality among elderly HIV-uninfected adults, but the determinants and consequences of frailty in HIV-infected populations remain unclear. We evaluated the correlates of frailty, and the impact of frailty on mortality in a cohort of aging injection drug users (IDUs).MethodsFrailty was assessed using standard criteria among HIV-infected and uninfected IDUs in 6-month intervals from 2005 to 2008. Generalized linear mixed-model analyses assessed correlates of frailty. Cox proportional hazards models estimated risk for all-cause mortality.ResultsOf 1230 participants at baseline, the median age was 48 years and 29% were HIV-infected; the frailty prevalence was 12.3%. In multivariable analysis of 3,365 frailty measures, HIV-infected IDUs had an increased likelihood of frailty (OR, 1.66; 95% CI, 1.24–2.21) compared to HIV-uninfected IDUs; the association was strongest (OR, 2.37; 95% CI, 1.62–3.48) among HIV-infected IDUs with advanced HIV disease (CD4<350 cells/mm3 and detectable HIV RNA). No significant association was seen with less advanced disease. Sociodemographic factors, comorbidity, depressive symptoms, and prescription drug abuse were also independently associated with frailty. Mortality risk was increased with frailty alone (HR 2.63, 95% CI, 1.23–5.66), HIV infection alone (HR 3.29, 95% CI, 1.85–5.88), and being both HIV-infected and frail (HR, 7.06; 95%CI 3.49–14.3).ConclusionFrailty was strongly associated with advanced HIV disease, but IDUs with well-controlled HIV had a similar prevalence to HIV-uninfected IDUs. Frailty was independently associated with mortality, with a marked increase in mortality risk for IDUs with both frailty and HIV infection.

Vitamin D deficiency and persistent proteinuria among HIV-infected and uninfected injection drug users

Proteinuria occurs commonly among HIV-infected and uninfected injection drug users (IDUs) and is associated with increased mortality risk. Vitamin D deficiency, highly prevalent among IDUs and potentially modifiable, may contribute to proteinuria. To determine whether vitamin D is associated with proteinuria in this population, we conducted a cross-sectional study in the AIDS Linked to the IntraVenous Experience (ALIVE) Study. 25(OH)-vitamin D levels were measured in 268 HIV-infected and 614 HIV-uninfected participants. The association between vitamin D deficiency (<10 ng/ml) and urinary protein excretion was evaluated by linear regression. The odds of persistent proteinuria (urine protein-to-creatinine ratio >200 mg/g on two occasions) associated with vitamin D deficiency was examined using logistic regression. One-third of participants were vitamin D-deficient. Vitamin D deficiency was independently associated with higher urinary protein excretion (P < 0.05) among HIV-infected and diabetic IDUs (P-interaction < 0.05 for all). Persistent proteinuria occurred in 18% of participants. Vitamin D deficiency was associated with greater than six-fold odds of persistent proteinuria among diabetic IDUs [odds ratio (OR) 6.29, 95% confidence interval (CI) 1.54, 25.69] independent of sociodemographic characteristics, comorbid conditions, body mass index, and impaired kidney function [estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m(2)]; no association, however, was observed among nondiabetic IDUs (OR 1.06, 95% CI 0.64, 1.76) (P-interaction <0.05). Vitamin D deficiency was associated with higher urinary protein excretion among those with HIV infection and diabetes. Vitamin D deficiency was independently associated with persistent proteinuria among diabetic IDUs, although not in nondiabetic persons. Whether vitamin D repletion ameliorates proteinuria in these patients requires further study.

Loss of Virus-specific T-Cell Responses in HCV Exposed Uninfected Injection Drug Users With Drug Rehabilitation

Hepatitis C virus (HCV)-specific T lymphocyte responses have been demonstrated in peripheral blood from injection drug users (IDUs) persistently HCV antibody and RNA negative despite high-risk behavior. We have termed these apparently HCV resistant cases "Exposed Uninfecteds" (EUs), and have studied the evolution of T-cell responses to determine if they are protective in nature. Twenty-one EU cases were studied using a questionnaire to ascertain injecting behavior details. Peripheral blood mononuclear cells were isolated from whole blood and an interferon-gamma (IFN-γ) enzyme-linked immunosorbent spot (ELISPOT) assay used to detect T-cell responses to a panel of HCV proteins. EU cases were subdivided by injecting drug patterns into (1) cases in rehabilitation who stopped injecting, (2) prisoners (infrequent/noninjectors), and (3) cases who continued to inject. EUs continuing to inject had significantly stronger (P < .01) and more frequent (P < .05) HCV-specific IFN-γ ELISPOT responses than controls or noninjecting EUs. EUs in rehabilitation lost their T-cell responses during follow-up, while those continuing to inject maintained them. HCV-specific T-cell responses in EU cases wane within months of cessation of injection drug use. Maintenance of these T-cell responses appears to be dependent on continuing HCV exposure through injection drug use.

Dynamics of Two Separate but Linked HIV-1 CRF01_AE Outbreaks among Injection Drug Users in Stockholm, Sweden, and Helsinki, Finland

Detailed phylogenetic analyses were performed to characterize an HIV-1 outbreak among injection drug users (IDUs) in Stockholm, Sweden, in 2006. This study investigated the source and dynamics of HIV-1 spread during the outbreak as well as associated demographic and clinical factors. Seventy Swedish IDUs diagnosed during 2004 to 2007 were studied. Demographic, clinical, and laboratory data were collected, and the V3 region of the HIV-1 envelope gene was sequenced to allow detailed phylogenetic analyses. The results showed that the Stockholm outbreak was caused by a CRF01_AE variant imported from Helsinki, Finland, around 2003, which was quiescent until the outbreak started in 2006. Local Swedish subtype B variants continued to spread at a lower rate. The number of new CRF01_AE cases over a rooted phylogenetic tree accurately reflected the transmission dynamics and showed a temporary increase, by a factor of 12, in HIV incidence during the outbreak. Virus levels were similar in CRF01_AE and subtype B infections, arguing against differences in contagiousness. Similarly, there were no major differences in other baseline characteristics. Instead, the outbreak in Stockholm (and Helsinki) was best explained by an introduction of HIV into a standing network of previously uninfected IDUs. The combination of phylogenetics and epidemiological data creates a powerful tool for investigating outbreaks of HIV and other infectious diseases that could improve surveillance and prevention.

Tobacco use and nicotine dependence among HIV-infected and uninfected injection drug users

Introduction Urban U.S. populations are burdened by intersecting epidemics of HIV infection, injection drug use, and cigarette smoking. Given the substantial morbidity attributable to tobacco in these populations, we characterized smoking behaviors, nicotine addiction, and tobacco exposure among HIV-infected and HIV-uninfected injection drug users (IDUs) in Baltimore, Maryland. Methods Smoking behaviors among participants in the ALIVE Study were assessed using interviewer-administered questionnaires. Smoking history and nicotine dependence (Fagerstrom Index scores) were compared by HIV and drug injecting status. Serum cotinine (a nicotine metabolite) was measured for a sample of participants by enzyme immunoassay. Results Among 1052 participants (29.7% HIV-infected, 39.8% active injectors), 85.2% were current smokers and 9.3% were former smokers. Smoking prevalence, age at smoking initiation, and cumulative tobacco exposure were similar by HIV status. Median Fagerstrom scores of 4 for HIV-infected and HIV-uninfected smokers indicated moderate nicotine dependence. Daily cigarette consumption was identical by HIV status (median 10 cigarettes), although HIV-infected participants were less likely to smoke 1+ pack daily compared to HIV-uninfected participants (18.0% vs. 26.9%, p = 0.001). Compared to former injectors, active injectors had higher smoking prevalence (90.5% vs. 81.7%, p = 0.0001), greater daily cigarette consumption (30.7% vs. 19.6% smoked 1+ pack daily, p = 0.0001), and slightly higher Fagerstrom scores (median 5 vs. 4). Cotinine levels paralleled self-reported cigarette consumption. Discussion Tobacco use is extremely common among inner-city IDUs. Smoking behavior and nicotine dependence did not materially differ by HIV status but were associated with active drug injection. Cessation efforts should target the dual dependence of cigarettes and drugs experienced among this population.

Distribution of CCR5 genotypes and HLA Class I B alleles in HIV-1 infected and uninfected injecting drug users from Rio de Janeiro, Brazil

Host genetic factors play an important role in the HIV epidemic dynamics, and have been considered in studies assessing susceptibility/resistance to HIV-1 infection as well as clinical evolution. Class I and Class II HLA alleles have been associated with the heterogeneity of HIV-1 infection susceptibility, as protective or risk factors for HIV-1 transmission. Moreover, a 32-base pair deletion in the HIV-1 CCR5 gene-coding region confers resistance to HIV-1 infection in homozygous individuals for the deleted allele. In this study, DNA samples from HIV-1 infected and uninfected injecting drug users (IDUs) from Rio de Janeiro were PCR amplified to determine CCR5 genotypes based on the presence of the CCR5Δ32 mutation and typed for the HLA-B locus, in an attempt to assess possible associations between these genetic factors and susceptibility/resistance to HIV-1 infection. The distribution of CCR5 genotypes between the two IDU groups did not differ. The homozygous mutant genotype Δ32/Δ32 was not found in this study. Except for HLA-B*45 (4.0% vs. 3.0%; p = 0.04) and for B*51 (12.1% vs. 4.4%; p = 0.002), no statistically significant differences were made evident when analyzing the frequencies of each HLA-B allele between Caucasian and non-Caucasian IDUs. The most frequent HLA-B alleles were B*15; B*35; B*44 and B*51. Although some differences in the allele frequencies could be observed between the two IDU groups, none of these was statistically significant. Therefore, no putative association between these genetic markers and susceptibility/resistance to HIV-1 infection could be made evident in the present study. So far, the assessment of genetic markers among the IDU population has been restricted to North American, European, and Asian studies and this report represents a pioneer descriptive study of the distribution of CCR5 genotypes and HLA-B alleles in Rio de Janeiro, Brazil.

CDC International HIV Prevention Research Activities Among Injection Drug Users in Thailand and Russia

The Centers for Disease Control and Prevention (CDC) has participated in collaborative HIV prevention research activities in injection drug users (IDUs) with the Bangkok Metropolitan Administration (BMA) in Bangkok, Thailand, from 1995 to the present and with the Orel AIDS Center in Orel Oblast, Russia, from 2001 to 2003. Studies in Bangkok have included an HIV prevention trial preparatory cohort from 1995 to 1998, a seroconverter cohort from 1998 to the present, a phase III trial of the AIDSVAX B/E gp120 HIV vaccine from 1999 to 2003, and a phase II/III HIV prophylaxis trial with tenofovir scheduled to begin in 2005. Activities in Orel included a review of HIV surveillance data in 2001, focus group discussions and a case-control study with HIV-infected and -uninfected IDUs in 2001, a cross-sectional study with the female sex partners of male IDUs in 2002, and a community outreach intervention in 2002-2003. In Bangkok, 1,209 IDUs were enrolled in the preparatory cohort which revealed an HIV incidence of 5.8% per 100 person-years; 133 HIV-infected IDUs have been followed in the seroconverter cohort with >85% follow-up and HIV and tuberculosis care provided; 2,546 IDUs were enrolled in the HIV vaccine efficacy trial which was successfully completed with a follow-up rate of >95%, although the vaccine was not shown to be effective at reducing HIV incidence; and 1,600 IDUs will be enrolled in the daily tenofovir HIV prophylaxis trial in 2005. In Orel, initial focus group discussions and epidemiologic studies revealed low HIV knowledge and high rates of unsafe injecting and sexual practices among IDUs and their female sex partners; and educational campaigns and the community outreach intervention were developed and implemented. A steady decline in new HIV infections in IDUs was then observed in Orel in 2002-2003. CDC has participated in the conduct of successful collaborative HIV prevention research activities in Thailand and Russia over the past decade. The establishment of long-term relationships with in-country public health and community partners has been instrumental in the success of these efforts.

HIV-specific CD8 T-cell activity in uninfected injection drug users is associated with maintenance of seronegativity

To determine whether HIV-exposed, uninfected subjects (EUs) having HIV-specific effector activity are at a reduced risk for seroconverting compared with EUs with no HIV-specific effector responses. Twenty-eight intravenous drug users (IVDU) with documented risk for HIV infection over a 1-year period were screened for the presence of HIV-specific CD8+ effector cell activity. Group I included 18 IVDUs who remained seronegative despite exposure to HIV through needle sharing with partner(s) known to be HIV infected. Group II included 10 IVDUs who seroconverted after similar HIV exposure. The enzyme-linked immunospot (ELIspot; Mabtech AB, Nacka, Sweden) assay was used to measure the frequency of HIV-specific interferon-gamma secreting cells. Peripheral blood mononuclear cells (PBMC) were stimulated with a panel of synthetic HIV peptides in a major histocompatibility complex class I antigen-restricted fashion. PBMC from group II were obtained from timepoints 7 months or less before seroconversion. Twelve of 18 (66.7%) persistently seronegative subjects versus none of 10 seroconverters exhibited detectable HIV-specific effector responses at the sampling date (P < 0.001; Fisher's exact test). This represents an odds ratio of 40.38 (95% confidence intervals 2.95 to > 3000). EUs who have developed HIV-specific effector responses are at a reduced risk for seroconversion compared with EUs who do not develop this type of immunity. This observation supports the hypothesis that HIV-specific effector responses are a correlate of immune protection from HIV infection.

Needle-exchange attendance and health care utilization promote entry into detoxification.

This study was undertaken to identify factors associated with entry into detoxification among injection drug users (IDUs), and to assess the role of needle-exchange programs (NEPs) as a bridge to treatment. IDUs undergoing semiannual human immunodeficiency virus (HIV) tests and interviews were studied prospectively between 1994 and 1998, during which time an NEP was introduced in Baltimore. Logistic regression was used to identify independent predictors of entry into detoxification, stratifying by HIV serostatus. Of 1,490 IDUs, similar proportions of HIV-infected and uninfected IDUs entered detoxification (25% vs. 23%, respectively). After accounting for recent drug use, hospital admission was associated with four-fold increased odds of entering detoxification for HIV-seronegative subjects. Among HIV-infected subjects, hospital admission, outpatient medical care, and having health insurance independently increased the odds of entering detoxification. After accounting for these and other variables, needle-exchange attendance also was associated independently with entering detoxification for both HIV-infected (adjusted odds ratio [AOR] = 3.2) and uninfected IDUs (AOR = 1.4). However, among HIV-infected subjects, the increased odds of detoxification associated with needle exchange diminished significantly over time, concomitant with statewide reductions in detoxification admissions. These findings indicate that health care providers and NEPs represent an important bridge to drug abuse treatment for HIV-infected and uninfected IDUs. Creating and sustaining these linkages may facilitate entry into drug abuse treatment and serve the important public health goal of increasing the number of drug users in treatment.

HIV infection among injecting drug users in the South Australian methadone program.

To investigate risk factors for infection with HIV among injecting drug users (IDUs) in South Australia. Retrospective case-control study comparing HIV-infected and uninfected IDUs who had received methadone at any time between January 1981 and June 1991. Most HIV-infected clients were diagnosed between 1985 and 1987. Men were more likely to be infected than women. A history of imprisonment was associated with a higher risk of infection on univariate but not multivariate analysis. Infected IDUs on average were three years younger than noninfected IDUs when they first injected drugs. Prevention programs should target young drug injectors. Prisons are important places to institute prevention programs.

Entry of human immunodeficiency virus infection into a population of injecting drug users, Victoria, 1990

To investigate the pathway by which the human immunodeficiency virus (HIV) is entering populations of injecting drug users (IDUs) in Victoria. A retrospective case-control study comparing the prevalence of self reported risk behaviour in HIV-infected and uninfected Victorian IDUs. Subjects were recruited by trained peer outreach workers from their personal networks, community agencies and Fairfield Hospital outpatients, and by a research worker from the major metropolitan prison. People who had been resident in Victoria for the past 12 months and had injected an illicit drug more than once in the previous three years were eligible to participate. Sixty-two such people (28 HIV-infected, 34 not infected) were included in the study. The two main hypothesised portals of entry were from the non-IDU homosexual population in Victoria, and from HIV-infected IDUs elsewhere. male homosexual contact was the most consistent risk factor identified by this study (odds ratio [OR], 6.2; 95% confidence interval [CI], 1.7-23.8). Having lived in or visited Sydney before 1986 was also associated with being infected with HIV (OR, 13.2; 95% CI, 1.5-603), and this was associated with homosexuality. Infected IDUs reported more sharing of injecting equipment than controls (OR, 9.0; 95% CI, 1.5-92.5), particularly with sexual partners; when this was the case, they were more likely to always use the injecting equipment after their partner (61% of cases, 0% of controls; OR, greater than or equal to 4.1; P = 0.0006). Men who have a history of both homosexual contact and injecting drug use represent the group of IDUs at highest risk of HIV infection in Victoria. Although heterosexual and homosexual IDUs may have limited contact only, a larger epidemic of HIV infection in heterosexual IDUs could spread from homosexual IDUs through the sharing of injecting equipment.