Noya Galai

Viral infections in short-term injection drug users: the prevalence of the hepatitis C, hepatitis B, human immunodeficiency, and human T-lymphotropic viruses.

OBJECTIVES The purpose of this study was to estimate the prevalence and correlates of four blood-borne viral infections among illicit drug injectors with up to 6 years of injecting experience. METHODS We analyzed data from 716 volunteers recruited in 1988 and 1989. Test results for hepatitis C virus (HCV), hepatitis B virus (HBV), human immunodeficiency virus, type 1 (HIV), and human T-lymphotropic virus types I and II (HTLV) were examined across six sequential cohorts defined by duration of drug injection. RESULTS Overall, seroprevalence of HCV, HBV, HIV, and HTLV was 76.9%, 65.7%, 20.5% and 1.8%, respectively, and 64.7%, 49.8%, 13.9%, and 0.5%, respectively, among those who had injected for 1 year or less. Among the newest initiates, HCV and HBV were associated with injecting variables, and HIV was associated with sexual variables. CONCLUSIONS The high rates of HCV, HBV, and HIV infections among short-term injectors emphasizes the need to target both parenteral and sexual risk reduction interventions early. Renewed efforts at primary prevention of substance abuse are indicated.

HIV Infection Is Associated with an Increased Risk for Lung Cancer, Independent of Smoking

BACKGROUND Human immunodeficiency virus (HIV)-infected persons have an elevated risk for lung cancer, but whether the increase reflects solely their heavy tobacco use remains an open question. METHODS The Acquired Immunodeficiency Syndrome (AIDS) Link to the Intravenous Experience Study has prospectively observed a cohort of injection drug users in Baltimore, Maryland, since 1988, using biannual collection of clinical, laboratory, and behavioral data. Lung cancer deaths were identified through linkage with the National Death Index. Cox proportional hazards regression was used to examine the effect of HIV infection on lung cancer risk, controlling for smoking status, drug use, and clinical variables. RESULTS Among 2086 AIDS Link to the Intravenous Experience Study participants observed for 19,835 person-years, 27 lung cancer deaths were identified; 14 of the deaths were among HIV-infected persons. All but 1 (96%) of the patients with lung cancer were smokers, smoking a mean of 1.2 packs per day. Lung cancer mortality increased during the highly active antiretroviral therapy era, compared with the pre-highly active antiretroviral therapy period (mortality rate ratio, 4.7; 95% confidence interval, 1.7-16). After adjusting for age, sex, smoking status, and calendar period, HIV infection was associated with increased lung cancer risk (hazard ratio, 3.6; 95% confidence interval, 1.6-7.9). Preexisting lung disease, particularly noninfectious diseases and asthma, displayed trends for increased lung cancer risk. Illicit drug use was not associated with increased lung cancer risk. Among HIV-infected persons, smoking remained the major risk factor; CD4 cell count and HIV load were not strongly associated with increased lung cancer risk, and trends for increased risk with use of highly active antiretroviral therapy were not significant. CONCLUSIONS HIV infection is associated with significantly increased risk for developing lung cancer, independent of smoking status.

Failure of T-cell homeostasis preceding AIDS in HIV-1 infection

We and others have postulated that a constant number of T lymphocytes is normally maintained without regard to CD4+ or CD8+ phenotype (‘blind’ T-cell homeostasis). Here we confirm essentially constant T-cell levels (despite marked decline in CD4+ T cells and increase in CD8+ T cells) in homosexual men with incident human immunodeficiency virus, type 1 (HIV-1), infection who remained free of acquired immunodeficiency syndrome (AIDS) for up to eight years after seroconversion. In contrast, seroconverters who developed AIDS exhibited rapidly declining T cells (both CD4+ and CD8+) for approximately two years before AIDS, independent of the time between seroconversion and AIDS, suggesting that homeostasis failure is an important landmark in HIV disease progression. Given the high rate of T-cell turnover in HIV-1 infection, blind T-cell homeostasis may contribute to HIV pathogenesis through a CD8+ T lymphocytosis that interferes with regeneration of lost CD4+ T cells.

Time to initiating highly active antiretroviral therapy among HIV-infected injection drug users.

ObjectiveStudies have shown that HIV-infected injection drug users (IDUs) are less likely to receive antiretroviral therapy than non-drug users. We assess factors associated with initiating highly active antiretroviral therapy (HAART) in HIV-infected IDUs. MethodsA cohort study of IDUs carried out between 1 January 1996 and 30 June 1999 at a community-based study clinic affiliated to the Johns Hopkins University, Baltimore, Maryland. The participants were a total of 528 HIV-infected IDUs eligible for HAART based on CD4+ cell count. The main outcome measure was the time from treatment eligibility to first self-reported HAART use, as defined by the International AIDS Society–USA panel (IAS–USA) guidelines. ResultsBy 30 June 1999, 58.5% of participants had initiated HAART, most of whom switched from mono- or dual-combination therapy to a HAART regimen. Nearly one-third of treatment-eligible IDUs never received antiretroviral therapy. Cox proportional hazards regression showed that initiating HAART was independently associated with not injecting drugs, methadone treatment among men, having health insurance and a regular source of care, lower CD4+ cell count and a history of antiretroviral therapy. ConclusionsSelf-reported initiation of HAART is steadily increasing among IDUs who are eligible for treatment; however, a large proportion continues to use non-HAART regimens and many remain treatment-naive. Although both groups appear to have lower health care access and utilization, IDUs without a history of antiretroviral therapy use would have more treatment options available to them once they become engaged in HIV care.

Survival of critically ill patients hospitalized in and out of intensive care units under paucity of intensive care unit beds

Objective:The demand for intensive care beds far exceeds their availability in many European countries. Consequently, many critically ill patients occupy hospital beds outside intensive care units, throughout the hospital. The outcome of patients who fit intensive care unit admission criteria but are hospitalized in regular wards needs to be assessed for policy implications. The object was to screen entire hospital patient populations for critically ill patients and compare their 30-day survival in and out of the intensive care unit. Design:Screening teams visited every hospital ward on four selected days in five acute care Israeli hospitals. The teams listed all patients fitting a priori developed study criteria. One-month data for each patient were abstracted from the medical records. Setting:Five acute care Israeli hospitals. Patients:All patients fitting a priori developed study criteria. Interventions:None. Measurements and Main Results:Survival in and out of the intensive care unit was compared for screened patients from the day a patient first met study criteria. Cox multivariate models were constructed to adjust survival comparisons for various confounding factors. The effect of intensive care unit vs. other departments was estimated separately for the first 3 days after deterioration and for the remaining follow-up time. Results showed that 5.5% of adult hospitalized patients were critically ill (736 of 13,415). Of these, 27% were admitted to intensive care units, 24% to specialized care units, and 49% to regular departments. Admission to an intensive care unit was associated with better survival during the first 3 days of deterioration, after we adjusted for age and severity of illness (p = .018). There was no additional survival advantage for intensive care unit patients (p = .9) during the remaining follow-up time. Conclusions:The early survival advantage in the intensive care unit suggests a window of critical opportunity for these patients. Under economic constraints and dearth of intensive care unit beds, increasing the turnover of patients in the intensive care unit, thus exposing more needy patients to the early benefit of treatment in the intensive care unit, may be advantageous.

High HIV Prevalence and Risk Behaviors in Men Who Have Sex with Men in Chennai, India

ObjectiveTo estimate HIV and sexually transmitted disease (STD) prevalence and behavioral risk characteristics of men who have sex with men (MSM) in Chennai, India. MethodsA cross-sectional population-based random sample survey was conducted in 2001. Randomly selected residents of 30 slums in Chennai were interviewed for behavioral risk factors through face-to-face interviews. Sera and urine were examined for syphilis, HIV-1, gonorrhea, and chlamydia. Logistic regression analyses were used to assess associations between MSM status and HIV infection and to identify risk characteristics of MSM. ResultsOf 774 men, 46 reported (5.9%) sex with other men. MSM were more likely to be seropositive for HIV (odds ratio [OR] = 8.57; 95% confidence interval [CI]: 1.83, 40.23) and were more likely to have a history of STD (OR = 2.66; 95% CI: 1.18, 6.02) than non-MSM. Men who used illicit drugs in past 3 months (adjusted odds ratio [AOR] = 4.01; 95% CI: 1.92, 8.41), ever exchanged money for sex (AOR = 3.93; 95% CI: 1.97, 7.84), or were ever tested for HIV (AOR = 3.72; 95% CI: 1.34, 10.34) were significantly more likely to report sex with men. ConclusionsMSM in Chennai slums are at high risk for HIV. HIV prevention strategies aimed at changing unsafe drug and sexual practices should target the general population of men, with specific attention to areas with high rates of MSM.

Determinants of the Quantity of Hepatitis C Virus RNA

To test the hypothesis that person-to-person variability in blood levels of hepatitis C virus (HCV) RNA can be explained, the quantity of HCV RNA was assessed in 969 persons who acquired HCV infection in the context of injection drug use. Serum HCV RNA levels ranged from 200,000 to >120 million equivalents/mL (the linear range of the assay). The median log10 HCV RNA level was 0.46 higher in 468 human immunodeficiency virus (HIV)-positive persons than in 501 HIV-negative persons (P<.001). In addition, among HIV-negative persons, lower HCV RNA levels were independently associated with younger age (P<.001), ongoing hepatitis B infection (P=.005), and the absence of needle sharing (P=.02). However, >90% of the person-to-person HCV RNA level variability was not explained by these sociodemographic, environmental, and virologic factors. Additional research is necessary to ascertain what determines the level of HCV RNA in blood.

End-stage renal disease and chronic kidney disease in a cohort of African-American HIV-infected and at-risk HIV-seronegative participants followed between 1988 and 2004

Background:HIV-infected African-Americans are at increased risk of end-stage renal disease requiring renal replacement therapy (RRT). Objectives:To compare the incidence of RRT in HIV-infected and HIV-seronegative African-Americans and describe temporal trends in RRT and chronic kidney disease (CKD) in HIV infection. Design:Cohort study in Baltimore including 4509 HIV-infected and 1746 HIV-seronegative African-Americans. Methods:Incident RRT was defined by matching participant identifiers with the US Renal Data System; CKD was defined as an estimated glomerular filtration rate < 60 ml/min per 1.73m2 for ≥ 3 months. Standardized incidence ratios (SIR) and 95% confidence intervals (CI) were calculated by indirect adjustment. Risk factors for RRT were assessed by person-time methods and Poisson regression. Results:RRT was initiated in 24 HIV-seronegative subjects over 13 415 person-years of follow-up (SIR, 2.3; 95% CI, 1.5–3.4), in 51 HIV-infected participants without AIDS over 10 780 person-years (SIR, 6.9; 95% CI, 5.1–9.0), and in 125 participants with AIDS over 9833 person-years. SIR, 16.1; 95% CI, 13.4–19.2). In HIV-infected African-Americans, RRT incidences were 5.8 and 9.7/1000 person-years in the pre-HAART and HAART eras, respectively (adjusted rate ratio 1.2; 95% CI, 0.8–1.9). In supplementary analyses, CKD incidence declined significantly in the HAART era compared with pre-HAART, but the CKD period prevalence increased. Conclusions:Nearly 1% of HIV-infected African-Americans initiated RRT annually, a rate that was similar in the HAART and pre-HAART eras. While new cases of CKD decreased, the prevalence of CKD increased in the HAART era, primarily because survival in those with HIV-associated CKD has improved.

The second phase of priority settingGoodbye to the simple solutions: the second phase of priority setting in health careFairness as a problem of love and the heart: a clinician's perspective on priority settingIsrael's basic basket of health services: the importance of being explicitly implicit

What follows is the description of an improved hydraulic apparatus for the automatic adjustment of the inclination of the headlights of a motor vehicle, the adjustment being a dependent function of the axle load. The apparatus has a level sensor at each axle and each level sensor contains one metering piston and two positioning pistons. The rear axle level sensor is connected via two separate hydraulic lines to the front axle sensor, and the front axle sensor is in turn connected via two separate hydraulic lines to the positioning elements of the headlight housings. The internal construction of the two level sensors is substantially identical and is chosen such that the system is also suitable for manual adjustment.

Category of exposure to HIV and age in the progression to AIDS: Longitudinal study of 1199 people with known dates of seroconversion

Abstract 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. Key messages Many studies have found an age effect on progression to AIDS, but it is not clear if this is due to specific AIDS defining diseases such as neoplasms and if it differs by exposure groups or by sex Our study of 1199 subjects with known date of seroconversion to HIV showed that older subjects progressed to AIDS more rapidly in all exposure groups considered, for both men and women, and for different definitions of AIDS After adjustment for age at seroconversion, there was no evidence of different rates of progression among subjects belonging to different exposure categories Behavioural cofactors do not seem to play a major role in AIDS pathogenesis but age is of fundamental importance in disease progression