Death In AIDS Patients Research Articles

MiR-769-3p inhibits cellular proliferation of KSHV-infected SH-SY5Y cells through targeting mTOR.

The infection by Kaposi's sarcoma-associated herpesvirus (KSHV) is one of the most common causes of death in AIDS patients. Our studies have found that KSHV can infect SH-SY5Y cells (named SK-RG) in vivo and mTOR was up-regulated, which results in remarkable enhancement of cell proliferation, migration. But the regulatory role of mTOR in KSHV infected neurons has not yet been fully elucidated. Here, we find that miR-769-3p is decreased in SK-RG cells, which can exert anti-KSHV effect through negatively regulating the expression of mTOR. The knockdown of mTOR or overexpress of miR-769-3p decreased the proliferation, migration ability and cell cycle related protein of SK-RG cells, and the expression of KSHV related genes. In contrast, activating mTOR function by 3BDO treatment weakened the cellular behaviors of miR-769-3p overexpressing cells. Meanwhile, overexpressed miR-769-3p and rapamycin showed a shared inhibition trend in the effects on cell proliferation and motility. Our data indicated that miR-769-3p can inhibit cell proliferation and migration by down regulating mTOR in KSHV infected SH-SY5Y cells, and can be a candidate molecule for anti-KSHV therapy.

Kaposi\u2019s sarcoma-associated herpesvirus infection promotes proliferation of SH-SY5Y cells by the Notch signaling pathway

BackgroundThe cancer caused by Kaposi’s sarcoma-associated herpesvirus (KSHV) infection is one of the major causes of death in AIDS patients. Some patients have neurological symptoms, which appear to be associated with KSHV infection, based on the neurotropic tendency of this virus in recent years. The objectives of this study were to investigate the effects of KSHV infection on neuronal SH-SY5Y cells and to identify differentially expressed genes.MethodsKSHV was collected from islk.219 cells. Real-time PCR was used to quantify KSHV copy numbers. KSHV was used to infect SH-SY5Y cells. The KSHV copy number in the supernatants and mRNA levels of latency-associated nuclear antigen (LANA), ORF26, K8.1 A, and replication and transcriptional activator (RTA) were detected by real-time PCR. Proteins were detected by immunohistochemistry. The effect of KSHV infection on cell proliferation was detected by MTT and Ki-67 staining. Cell migration was evaluated by Transwell and wound healing assays. The cell cycle was analyzed by flow cytometry. The expression of CDK4, CDK5, CDK6, cyclin D1, and p27 were measured by western blotting. The levels of cell cycle proteins were re-examined in LANA-overexpressing SH-SY5Y cells. Transcriptome sequencing was used to identify differentially expressed genes in KSHV-infected cells. The levels of Notch signaling pathway proteins were measured by western blotting. RNA interference was used to silence Notch1 and proliferation were analyzed again.ResultsSH-SY5Y cells were successfully infected with KSHV, and they maintained the ability to produce virions. KSHV-infected SH-SY5Y expressed LANA, ORF26, K8.1 A, and RTA. After KSHV infection, cell proliferation was enhanced, but cell migration was suppressed. KSHV infection accelerated the G0/G1 phase. CDK4, CDK5, CDK6, and cyclin D1 expression was increased, whereas p27 expression was decreased. After LANA overexpression, CDK4, CDK6 and cyclin D1 expression was increased. Transcriptome sequencing showed that 11,258 genes were upregulated and 1,967 genes were downregulated in KSHV-infected SH-SY5Y. The Notch signaling pathway played a role in KSHV infection in SH-SY5Y, and western blots confirmed that Notch1, NICD, RBP-Jĸ and Hes1 expression was increased. After silencing of Notch1, the related proteins and cell proliferation ability were decreased.ConclusionsKSHV infected SH-SY5Y cells and promoted the cell proliferation. KSHV infection increased the expression of Notch signaling pathway proteins, which may have been associated with the enhanced cell proliferation.

Analysis of survival and influencing factors of HIV/AIDS patients in Tianjin, 2004-2014

Objective: To understand the survival and influencing factors of HIV/AIDS patients in Tianjin. Methods: The data of HIV/AIDS cases reported in Tianjin during 2004-2014, which were collected from National AIDS Prevention and Control Information System, were analyzed by using life table and Kaplan Meier method to calculate survival time and the survival rate, and univariate and multivariate Cox regression analysis was conducted to identify the influencing factors for survival time. Results: For the 2 775 HIV/AIDS patients, 1 year, 3 years, 5 years, 10 years and 11 years cumulative survival rates were 91%, 88%, 86%, 79% and 79% respectively. The risk of death in AIDS patients was higher than that in people living with HIV (χ(2)=107.622, P<0.001); Factors affecting the survival of people living with HIV were the first time CD(4) value and antiviral treatment, and the influencing factors for survival of AIDS patients were the infection route, detection ways, first time CD(4) value and antiviral treatment. Conclusion: Early detection and early treatment can obviously reduce the risk for death of people living with HIV/AIDS. To improve the survival of HIV/AIDS patients, it is necessary to strengthen the early detection and early treatment of HIV infection.

Quantitative structure–activity relationships of dihydrofolatereductase inhibitors

Pneumocystis carinii is a nonpathogenic fungus found in respiratory tract of healthy humans. It is a major cause of death in AIDS patients. P. carinii dihydrofolatereductase inhibitors such as trimetrexate are currently used to treat P. carinii pneumonia. These drugs have several adverse side effects and, therefore, there is a critical need for the identification of novel dihydrofolatereductase inhibitors. In this work, quantitative structure – activity relationship models were derived for 395 stucturally diverse P. carinii dihydrofolatereductase inhibitors. A wide variety of molecular descriptors belonging to various structural properties were calculated for each molecule. Both linear (multiple linear regression) and non-linear (generalized regression neural network) models were developed to link the calculated descriptors as independent variables to their reported biological activity as dependent variable. Different variable transformation was performed on the both dependent and independent variables to obtain better multiple linear regression models. At first glance, it seemed applying variable transformation on the dependent variable was necessary to improve quality of the quantitative structure–activity relationships models because it made the model more predictive. Upon further inspection, the results were not necessarily surprising. In the other words, back-transforming predictions did not give unbiased estimations of pIC50. At the final trial, generalized neural network was employed to develop predictive quantitative structure–activity relationships model.

Plasma IL-6/IL-10 Ratio and IL-8, LDH, and HBDH Level Predict the Severity and the Risk of Death in AIDS Patients with Pneumocystis Pneumonia.

Objective. To identify blood biomarkers to predict severity and mortality in AIDS PCP patients. Methods. Biomarkers including clinical parameters and plasma inflammatory cytokines were assessed in 32 HIV-infected patients with Pneumocystis pneumonia (PCP) at time of admission. Predictive value of the biomarkers for clinical severity and in-hospital mortality was evaluated by corresponding ROC curve. Results. Levels of CRP, WBC, LDH, HBDH, and Ferritin were significantly higher in the severe and nonsurvivor AIDS PCP patients. These important biochemical indicators have inverse correlation with oxygenation index, especially levels of LDH (P = 0.008, R 2 = 0.258), HBDH (P = 0.001, R 2 = 0.335), and Ferritin (P = 0.005, R 2 = 0.237). Plasma IL-8 and IL-6 levels were significantly higher in patients with PaO2/FiO2 ≤ 200 mmHg and nonsurvivors than in those with PaO2/FiO2 > 200 mmHg and survivors. Severe and nonsurvival groups showed higher ratio of mean IL-6/IL-10 level (1.78 ± 1.56, P < 0.001; 1.11 ± 0.72, P = 0.043), larger AUC (95% CI 0.781–1.000, P < 0.001; 95% CI 0.592–0.917, P = 0.043), and more significantly inverse correlation with the oxygenation index. Conclusion. Plasma IL-8, LDH, and HBDH levels and IL-6/IL-10 ratio could be helpful for early evaluation of the severity and predicting fatal outcomes in AIDS PCP patients.

艾滋病并发症的影像学研究现状与临床应用

艾滋病患者死亡的主要原因是由于其机体免疫系统受到极度抑制甚至破坏而导致的多种并发症。依据病变起源可分为①人类免疫缺陷病毒病变(HIV)本身所致的病变。②机会性感染。③相关性肿瘤。艾滋病最常见的机会性感染是肺结核，双重感染时HIV和结核杆菌相互促进，相互影响，使患者病情更加复杂，并给患者带来沉重的身心负担和经济负担。因此，艾滋病的早期预防和并发症的正确诊断是提高患者治疗效果和生活质量的关键。 The complications of AIDS that due to their immune system suppression and even received extreme damage are main causes of death in AIDS patients. Lesions can be divided according to the origin: ① The human immunodeficiency virus disease (HIV) itself induced lesions; ② opportunistic infections; ③ related tumors. The most common opportunistic infection of AIDS is tuberculosis. Double infections of HIV and Mycobacterium tuberculosis affect each other, promote each other, so the patient’s condition is more complex, bringing heavy physical and mental burden and economic burden to patients. The keys for improving the therapeutic efficacy of AIDS and life quality of AIDS patients are early identification of HIV carriers, advanced prevention of AIDS complications and accurate diagnosis of AIDS.

Penicilliosis and AIDS in Haiphong, Vietnam: Evolution and predictive factors of death

ObjectivesThe study objective was to assess the lethality rates and the predictive factors for death in AIDS patients infected by Penicillium marneffei (Pm) in Hai Phong, Vietnam. MethodsA retrospective cohort study was conducted by reviewing 103 medicals records of confirmed cases from June 2006 to August 2009. ResultsPenicilliosis-related mortality was very high (33%). The majors risk factors of death were: (i) patient lacking complete treatment, a regimen with both of secondary prophylaxis by itraconazole and HAART (OR=52.2, P<0.001); (ii) patients having received only secondary prophylaxis (OR=21.2, P<0.001); (iii) patients coinfected by hepatitis C (OR=2.3, P=0.02) and tuberculosis (OR=1.97, P=0.04). Penicilliosis occurred in 28 cases after initiation of ART, probably caused by IRIS, with the same signs and symptoms as “common” penicilliosis. However, the diagnosis of IRIS was ruled out because the viral load could not be assessed. ConclusionsPenicilliosis is very frequent in the North of Vietnam. A good compliance to a complete treatment with healing antifungal (Amphotericin B) then secondary prophylaxis (Itraconazole) associate with ART, prolongs survival, prevents relapse, and also allows discontinuing a secondary prophylaxis in a half of the cases.

Public Health Implications of Cryptococcal Infection among HIV Patients on Antiretroviral Therapy in Hospital in Shika, Nigeria

Cryptococcal meningitis is a leading cause of death in AIDS patients and contributes substantially to the high early mortality in antiretroviral treatment (ART) programs in low-resource settings. A hospital-based seroprevalence of cryptococcal antigen among HIV patients on ART program was determined using the Alpha cryptococccal Antigen EIA KIT. The prevalence was low in the study area probably because the ART monitoring program used helped in reducing the incidence of cryptococccal infection. Routine screening of HIV patients is needed for early detection of the infection before unset of complicating clinical signs.

The NK Receptor NKp30 Mediates Direct Fungal Recognition and Killing and Is Diminished in NK Cells from HIV-Infected Patients

Natural killer (NK) cells are a subset of immune effectors that directly bind and kill fungi via a perforin-dependent mechanism. The receptor mediating this activity and its potential role in disease remain unknown. Using an unbiased approach, we determined that NKp30 is responsible for recognition and killing of the fungal pathogens Cryptococcus and Candida. NKp30 was required for NK cell-fungal conjugateformation, phosphatidylinositol 3-kinase (PI3K) signaling, and perforin release. Because fungal infections are a leading cause of death in AIDS patients, we examined NKp30 expression in HIV-infected patients. NK cells from these patients had diminishedNKp30 expression, defective perforin release, and blunted microbicidal activity. Surprisingly, interleukin-12 (IL-12) restored NKp30 expression and fungal killing. Thus, the NKp30 receptor plays a critical role in NK cell antifungal cytotoxicity, and diminished expression of NKp30 is responsible for defective antifungal activity of NK cells from HIV-infected patients, which can be corrected with IL-12.

Drug Repurposing Screen Reveals FDA-Approved Inhibitors of Human HMG-CoA Reductase and Isoprenoid Synthesis That Block Cryptosporidium parvum Growth

Cryptosporidiosis, a diarrheal disease usually caused by Cryptosporidium parvum or Cryptosporidium hominis in humans, can result in fulminant diarrhea and death in AIDS patients and chronic infection and stunting in children. Nitazoxanide, the current standard of care, has limited efficacy in children and is no more effective than placebo in patients with advanced AIDS. Unfortunately, the lack of financial incentives and the technical difficulties associated with working with Cryptosporidium parasites have crippled efforts to develop effective treatments. In order to address these obstacles, we developed and validated (Z' score = 0.21 to 0.47) a cell-based high-throughput assay and screened a library of drug repurposing candidates (the NIH Clinical Collections), with the hopes of identifying safe, FDA-approved drugs to treat cryptosporidiosis. Our screen yielded 21 compounds with confirmed activity against C. parvum growth at concentrations of <10 μM, many of which had well-defined mechanisms of action, making them useful tools to study basic biology in addition to being potential therapeutics. Additional work, including structure-activity relationship studies, identified the human 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitor itavastatin as a potent inhibitor of C. parvum growth (50% inhibitory concentration [IC(50)] = 0.62 μM). Bioinformatic analysis of the Cryptosporidium genomes indicated that the parasites lack all known enzymes required for the synthesis of isoprenoid precursors. Additionally, itavastatin-induced growth inhibition of C. parvum was partially reversed by the addition of exogenous isopentenyl pyrophosphate, suggesting that itavastatin reduces Cryptosporidium growth via on-target inhibition of host HMG-CoA reductase and that the parasite is dependent on the host cell for synthesis of isoprenoid precursors.

Integrating Cryptococcal Antigen Screening and Pre-Emptive Treatment into Routine HIV Care

Cryptococcal meningitis is a leading cause of death in AIDS patients in sub-Saharan Africa. Cryptococcal antigen (CRAG) can be detected weeks before onset of symptoms, and those who are asymptomatic but CRAG positive have a high risk of subsequent cryptococcal meningitis and mortality. A new CRAG point of care immunochromatographic test is available that is remarkably easy to administer without laboratory infrastructure or expertise and has excellent sensitivity and specificity. We review the benefits of targeted CRAG screening, developments in CRAG diagnostics, and evidence regarding treatment options that can be implemented into routine HIV care in areas of high cryptococcal burden. Based on published CRAG+ prevalence rates of 2%-12%, the cost to save one life is between $20 to $140 in sub-Saharan Africa. We provide recommendations for implementation, pre-emptive treatment, and identify the gaps in our current knowledge.

Biomarkers Could Predict Death in AIDS Patients With Severe Inflammation

Biomarkers Could Predict Death in AIDS Patients With Severe Inflammation

A Replication-Limited Recombinant Mycobacterium bovis BCG Vaccine against Tuberculosis Designed for Human Immunodeficiency Virus-Positive Persons Is Safer and More Efficacious than BCG

Tuberculosis is the leading cause of death in AIDS patients, yet the current tuberculosis vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG), is contraindicated for immunocompromised individuals, including human immunodeficiency virus-positive persons, because it can cause disseminated disease; moreover, its efficacy is suboptimal. To address these problems, we have engineered BCG mutants that grow normally in vitro in the presence of a supplement, are preloadable with supplement to allow limited growth in vivo, and express the highly immunoprotective Mycobacterium tuberculosis 30-kDa major secretory protein. The limited replication in vivo renders these vaccines safer than BCG in SCID mice yet is sufficient to induce potent cell-mediated and protective immunity in the outbred guinea pig model of pulmonary tuberculosis. In the case of one vaccine, rBCG(mbtB)30, protection was superior to that with BCG (0.3-log fewer CFU of M. tuberculosis in the lung [P < 0.04] and 0.6-log fewer CFU in the spleen [P = 0.001] in aerosol-challenged animals [means for three experiments]); hence, rBCG(mbtB)30 is the first live mycobacterial vaccine that is both more attenuated than BCG in the SCID mouse and more potent than BCG in the guinea pig. Our study demonstrates the feasibility of developing safer and more potent vaccines against tuberculosis. The novel approach of engineering a replication-limited vaccine expressing a recombinant immunoprotective antigen and preloading it with a required nutrient, such as iron, that is capable of being stored should be generally applicable to other live vaccine vectors targeting intracellular pathogens.

AIDS: “It’s the bacteria, stupid!”

Acid-fast tuberculous mycobacterial infections are common in AIDS and are regarded as secondary "opportunistic infections." According to the National Institute of Allergy and Infectious Diseases, TB is the major attributable cause of death in AIDS patients. Could such bacteria play a primary or causative role in AIDS? Certainly, In screening tests for HIV, there is frequent, up to 70%, cross-reactivity, between the gag and pol proteins of HIV and patients with mycobacterial infections such as tuberculosis. By 1972, five years before gays started dying in the U.S., Rolland wrote Genital Tuberculosis, a Forgotten Disease? And ironically, in 1979, on the eve of AIDS recognition, Gondzik and Jasiewicz showed that even in the laboratory, genitally infected tubercular male guinea pigs could infect healthy females through their semen by an HIV-compatible ratio of 1 in 6 or 17%, prompting him to warn his patients that not only was tuberculosis a sexually transmitted disease, but also the necessity of the application of suitable contraceptives, such as condoms, to avoid it. Gondzik's solution and date of publication are chilling; his findings significant. Since 1982 Cantwell et al found acid-fast bacteria closely related to tuberculosis (TB) and atypical tuberculosis in AIDS tissue. On the other hand molecular biologist and virologist Duesberg, who originally defined retroviral ultrastructure, has made it clear that HIV is not the cause of AIDS and that the so-called AIDS retrovirus has never been isolated in its pure state. Dr. Etienne de Harven, first to examine retroviruses under the electron, agrees. In 1993 HIV co-discoverer Luc Montagnier reported on cell-wall-deficient (CWD) bacteria which he called "mycoplasma" in AIDS tissue. He suspected these as a necessary "co-factor" for AIDS. Remarkably, Montagnier remained silent on Cantwell's reports of acid-fast bacteria which could simulate "mycoplasma" in AIDS tissue. Mattman makes clear that the differentiation between mycoplasma and CWD bacteria is difficult at best and cites Pachas's 1985 study wherein one mycoplasma was actually mistaken for a CWD form of a bacterium closely related to the mycobacteria. It is important to realize that the statement "HIV is the sole cause of AIDS" is just a hypothesis. There are unanswered questions and controversy concerning the role of HIV "as the sole cause of AIDS." And until they are resolved, a cure is not possible. This paper explores the possible role of acid-fast tuberculous mycobacteria as "primary agents" in AIDS.

CMV as a cofactor enhancing progression of AIDS

Background Cytomegalovirus (CMV) has been proposed as a cofactor driving HIV pathogenicity since the late 1980s. Potential mechanisms which CMV could use as a cofactor have been described in vitro and potential criteria for assessing cofactor activity in vivo have been proposed. Objective To determine if recent publications have added new information to these in vitro or in vivo studies since the author last reviewed this subject in 1998. Study design Literature survey prior to presenting an overview lecture. Results No new in vitro mechanisms have been described though several clinical cohort studies are consistent with the possibility that active CMV infection can act as a cofactor. One study published in 1999 showed that mortality in AIDS patients was driven more by CMV viral load than HIV viral load. Although highly active antiretroviral therapy (HAART) has now greatly controlled end organ disease caused by CMV, a recent study showed that CMV viraemia was still strongly associated with death in AIDS patients. Conclusions (1) CMV remains important in the era of HAART. (2) CMV has been underestimated as an important cofactor since the beginning of the AIDS epidemic.

Morbidity and survival in advanced AIDS in Rio de Janeiro, Brazil.

Opportunistic diseases (OD) are the most common cause of death in AIDS patients. To access the incidence of OD and survival in advanced immunodeficiency, we included 79 patients with AIDS treated at Hospital Evandro Chagas (FIOCRUZ) from September 1997 to December 1999 with at least one CD4 count <or=100 cells/mm(3). The incidence of OD was analyzed by Poisson's regression, and survival by Kaplan Meier and Cox analysis, considering a retrospective (before CD4 <or=100 cells/mm(3)) and a prospective (after CD4 <or=100 cells/mm(3)) period, and controlling for demographic, clinical and laboratory characteristics. The confidence interval estipulated was 95%. Mean follow-up period was 733 days (CI = 683-782). During the study 9 (11.4%) patients died. Survival from AIDS diagnosis was a mean of 2589 days (CI = 2363-2816) and from the date of the CD4 count CD4 <or=100 cells/mm(3) was a mean of 1376 (CI = 1181-1572) days. Incidence of OD was 0.51 pp/y before CD4 <or= 100 cells/mm(3) and 0.29 pp/y after CD4 <or= 100 cells/mm(3). A lower number of ODs before CD4 < 100 cells/mm(3) was associated with lower incidence rates after CD4 <or= 100 cells/mm(3). AIDS diagnosis based on CD4+ counts <or= 200 cells/mm(3) was associated with lower incidence rates after CD4 <or= 100 cells/mm(3). Baseline CD4 counts above 50 cells/mm(3) (HR = 0.13) and restoration of baseline CD4+ counts above 100 cells/mm(3) (HR = 0.16) were associated with a lower risk of death. Controlling both variables, only restoration of baseline counts was statistically significant (HR = 0.22, p = 0.04). We found a very low incidence of OD and long survival after CD4 < 100 cells/mm(3). Survival was significantly associated with restoration of baseline CD4 counts above 100 cells/mm(3).

Essential role of HIV type 1-infected and cyclooxygenase 2-activated macrophages and T cells in HIV type 1 myocarditis.

HIV-1 cardiomyopathy has become a major cause of death in AIDS patients, but its pathogenesis is unclear. We used an antigen retrieval technique and immunostaining to investigate the hearts of 15 AIDS patients, of whom 3 had dilated cardiomyopathy. Immunocytochemistry shows infiltration of the left ventricular myocardium with mononuclear cells, ranging from minimal to diagnostic of myocarditis. The infiltrates include macrophages and CD3(+) and CD8(+) T cells. The tight junction protein ZO-1 is disrupted at the site of monocyte-macrophage vascular penetration and the coronary vessels show fibrinogen leakage in the hearts of AIDS patients, but not in the normal heart. A subset of infiltrating macrophages is doubly positive for cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase. HIV-1 peptides gp120 and Nef are expressed in macrophages and T cells, but not in cardiomyocytes. COX-2 is expressed by both gp120-positive and gp120-negative macrophages. The hearts of AIDS patients separate into those showing minimal infiltrates with low COX-2 expression and those with dense infiltrates and high COX-2; all failing hearts are in the latter group. These data suggest that COX-2-activated and HIV-1-infected monocyte-macrophages and T cells play a crucial role in the progression of HIV-1 myocarditis to HIV-1 cardiomyopathy.

Protease inhibitor therapy is associated with markedly prolonged time to relapse and improved survival in AIDS patients with cytomegalovirus retinitis.

Prior to the use of highly active antiretroviral therapy (HAART), cytomegalovirus retinitis (CMV-R) in AIDS patients was characterized by multiple relapses and decreased survival. Recent data suggest that CMV-R in patients treated with HAART may remain relapse-free for long periods. We performed a study of the effects of HIV protease inhibitors (PIs) on the incidence of relapse and time to death in AIDS patients with CMV-R treated with anti-CMV therapy. Medical records of all AIDS patients with CMV-R at Parkland Memorial Health and Hospital System treated with anti-CMV agents were reviewed for date of diagnosis of CMV-R, date of CMV-R relapse, type and duration of anti-CMV therapy, and duration of PI therapy. Relapse rates in subjects treated with PIs were compared with the relapse rates in those who were not treated with PIs. The primary endpoint was the time to relapse and death as determined by Kaplan-Meier analysis. Multivariate analysis was performed by Cox proportional hazard model. One hundred and nine cases of CMV-R were identified in 75 patients. Median follow-up time was 247 days (range 31-1818 days). There were 0.54 relapses per 1000 patient days in the group treated with PIs compared with 1.83 relapses per 1000 patient days in the non-PI treatment group (relative risk [RR]=0.29, P<0.01). Time to relapse was increased in the PI treatment group compared with the non-PI treatment group (endpoint not reached vs 182 days, P<0.001, log-rank). Similarly, the time to relapse or death was increased in the PI group compared with the non-PI group (543 days vs 103 days, P<0.001, log-rank). Multivariate analysis utilizing the Cox proportional hazards model demonstrated that only PI therapy but not anti-CMV therapy was associated with decreased risk of CMV-R relapse or death. Only 3 patients with an undetectable HIV viral load and one patient with a CD4 count >120 cells/microl had a relapse. We conclude that patients with CMV-R treated with HAART containing a PI have increased time to relapse and have prolonged survival.

Association between Delirium and Death in AIDS Patients

The purpose of this study was to examine the relationship between delirium and death in AIDS patients. Forty-one patients admitted to a combination skilled nursing and assisted-living facility in 1994 were included in the retrospective chart review. Patients were grouped according to the presence versus absence of delirium during the first week of admission. Demographic characteristics and medical morbidity of the two groups were compared using the Chi-square statistic. Kaplan-Meier survival analysis was used to estimate survival functions during the study period for the delirious and nondelirious groups. Nine patients (22%) were found to have an episode of delirium in the first week of admission. There were no significant differences in demographic characteristics or medical morbidity between the delirious and nondelirious groups. Median days from admission to death for those with delirium (10 days) versus those without delirium (135 days) was significantly different (log rank = 19.03; p < 0.0001). Authors concluded that delirium is a marker for decreased survival in this sample of AIDS patients. Future research needs to demonstrate whether improved care of AIDS patients can prevent delirium or limit adverse outcomes associated with it.

A multicentre study on the causes of death among Italian injecting drug users. AIDS has overtaken overdose as the principal cause of death

The causes of death among injecting drug users (IDUs) are still being discussed worldwide. We analysed the causes of death among IDUs attending 26 centres for drug users in North-Eastern Italy from 1985 to 1994. The study of a total number of 1,022 deaths reveals the following: (1) AIDS has become the primary cause of death among IDUs since 1991 and is rising even in an area with a moderate HIV seroprevalence; (2) the mean age of death in AIDS patients proved higher than among patients who died of other causes (which may be due to the long incubation period of AIDS); (3) our data do not reveal higher HIV seroprevalence among IDUs who died of overdose and suicide as opposed to IDUs who died of other causes; (4) the mortality rate in IDUs is significantly higher when compared to that of the general population in the same age group.