Incident hypertension in older women and men with or at risk for HIV infection.

OBJECTIVES: Antiretroviral (ARV) therapy has prolonged the life expectancy of HIV-infected persons, increasing their risk of age-associated diseases, including atherosclerosis (AS). Decreased risk of AS has been associated with the prevention and control of hypertension (HTN). We conducted a cohort study of perimenopausal women and older men with or at risk of HIV infection to identify risk factors for incident HTN. METHODS: Standardized interviews, physical examinations, and laboratory examinations were scheduled at 6-month intervals. Interview data included demographics, medical, family, sexual behaviour and drug use histories, and physical activity. RESULTS: There were 330 women and 329 men eligible for inclusion in the study; 27% and 35% of participants developed HTN during a median follow-up period of 1080 and 1071 days, respectively. In gender-stratified analysis, adjusting for traditional HTN risk factors (age, race, body mass index, smoking, diabetes, family history of HTN, alcohol dependence, physical activity and high cholesterol), HIV infection was not associated with incident HTN in women [hazard ratio (HR) 1.31; 95% confidence interval (CI) 0.56, 3.06] or men (HR 1.67; 95% CI 0.75, 3.74). Among HIV-infected women, although exposure to ARVs was not significantly associated with incident HTN (HR 0.72; 95% CI 0.26, 1.99), CD4 T-cell count was positively associated with incident HTN (HR 1.15 per 100 cells/µL; 95% CI 1.03, 1.28). Among physically active HIV-infected men, exposure to ARVs was negatively associated with incident HTN (HR 0.15; 95% CI 0.03, 0.78). CONCLUSIONS: HIV infection was not associated with incident HTN in older men or women. This study provides additional evidence supporting a causal relationship between immune function and incident HTN, which warrants further study.

Resistance to experimental autoimmune encephalomyelitis in mice lacking the CC chemokine receptor (CCR)2.

Monocyte recruitment to the central nervous system (CNS) is a necessary step in the development of pathologic inflammatory lesions in experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis. Monocyte chemoattractant protein (MCP)-1, a potent agonist for directed monocyte migration, has been implicated in the pathogenesis of EAE. Here we report that deficiency in CC chemokine receptor (CCR)2, the receptor for MCP-1, confers resistance to EAE induced with a peptide derived from myelin oligodendrocyte glycoprotein peptide 35-55 (MOGp35-55). CCR2(-/)- mice immunized with MOGp35-55 failed to develop mononuclear cell inflammatory infiltrates in the CNS and failed to increase CNS levels of the chemokines RANTES (regulated on activation, normal T cell expressed and secreted), MCP-1, and interferon (IFN)-inducible protein 10 (IP-10) as well the chemokine receptors CCR1, CCR2, and CCR5. Additionally, T cells from CCR2(-/)- immunized mice showed decreased antigen-induced proliferation and production of IFN-gamma compared with wild-type immunized controls, suggesting that CCR2 enhances the T helper cell type 1 immune response in EAE. These data indicate that CCR2 plays a necessary and nonredundant role in the pathogenesis of EAE.

Abnormal thyroid function in older men with or at risk for HIV infection.

OBJECTIVES: The aim of the study was to evaluate the prevalence of and factors associated with abnormal thyroid function in older men with or at risk for HIV infection. METHODS: A cross-sectional analysis of 636 men > or =49 years old was carried out using data obtained from interviews, from measurements of body mass index (BMI), HIV-1 serology and viral load, CD4 cell count, hepatitis C virus (HCV) assays, thyroid-stimulating hormone (TSH) and free thyroid hormone levels. RESULTS: Participants were 54% black, 57% overweight/obese, 57% HIV seropositive, and 72% HCV seropositive; 38% reported recent cocaine or heroin use. Decreased TSH was found in 56 men (8.8%) and raised TSH in 23 men (3.6%). Only three men had abnormal free thyroxine levels. CONCLUSIONS: Abnormal TSH levels were noted in 12.4% of older men with or at risk for HIV infection, but nearly all reflected subclinical hyperthyroidism or subclinical hypothyroidism.

Shedding of PECAM-1 during HIV infection: a potential role for soluble PECAM-1 in the pathogenesis of NeuroAIDS.

Human immunodeficiency virus (HIV) infection is characterized by viral entry into the central nervous system (CNS), which is mediated, in part, by the transmigration of HIV-infected monocytes into the brain. The elaboration of chemokines and other factors by these infected cells contributes to CNS inflammation and cognitive impairment in a significant number of HIV-infected individuals. Recently, we demonstrated that HIV-infected monocyte transmigration into the CNS is enhanced greatly by the chemokine CC chemokine ligand 2 (CCL2)/monocyte chemoattractant protein-1. Platelet endothelial cell adhesion molecule-1 (PECAM-1) plays an important role in leukocyte transmigration across the endothelium of the systemic vasculature by mediating homophilic interactions between endothelial cells (EC)-EC and EC-leukocytes, thus preserving vessel integrity. The role of PECAM-1 in HIV-infected leukocyte transmigration across the blood brain barrier (BBB) and NeuroAIDS has not been characterized. We demonstrate that in brain tissue from individuals with HIV encephalitis, there is an accumulation of cleaved, soluble forms of the extracellular region of PECAM-1 (sPECAM-1). In addition, HIV-infected individuals have elevated levels of sPECAM-1 in their sera. Our in vitro data demonstrate that HIV-infected leukocytes, when treated with CCL2, shed sPECAM-1, suggesting a mechanism of extracellular PECAM-1 cleavage and release dependent on HIV infection and CCL2. We hypothesize that sPECAM-1 production by HIV-infected leukocytes, resulting in the accumulation of sPECAM-1 within the CNS vasculature and the generation of truncated, intracellular forms of PECAM-1 within leukocytes, alters PECAM-1 interactions between EC-EC and EC-leukocytes, thus contributing to enhanced transmigration of HIV-infected leukocytes into the CNS and changes in BBB permeability during the pathogenesis of NeuroAIDS.

Inhibitors of purine nucleoside phosphorylase: effects of 9-deazapurine ribonucleosides and synthesis of 5'-deoxy-5'-iodo-9-deazainosine.

9-Deazapurine ribonucleosides constitute a new class of noncleavable purine nucleoside phosphorylase inhibitors that have at least 30-fold greater affinity for the enzyme than the corresponding C-nucleosides of the formycin B series. 9-Deazaguanosine, 9-deazainosine, and 5'-deoxy-5'-iodo-9-deazainosine competitively inhibited human erythrocytic purine nucleoside phosphorylase with Ki values of 29, 20, and 1.8 X 10(-7) M. The last compound is the most potent nucleoside inhibitor of the enzyme presently available and its synthesis is described. In contrast, 7,9-dideaza-7-thiainosine is a very weak inhibitor of the enzyme. When tested as an inhibitor of 2'-deoxyguanosine phosphorolysis in intact human erythrocytes and MOLT-3 human T-cell lymphoblastic leukemia cells, 5'-deoxy-5'-iodo-9-deazainosine was equipotent with 8-aminoguanosine (which is a precursor for 8-aminoguanine, Ki = 2 X 10(-7) M). Similarly, 5'-deoxy-5'-iodo-9-deazainosine and 8-aminoguanosine both potentiated the growth inhibition of human T-lymphocytic MOLT-3 cells by 2'-deoxyguanosine, reducing the 50% inhibitory concentration from approximately 2 X 10(-5) to approximately 2 X 10(-6) M.

Constitutive expression of cellular retinoic acid binding protein II and lack of correlation with sensitivity to all-trans retinoic acid in acute promyelocytic leukemia cells.

The up-regulation of cellular retinoic acid binding protein-II (CRABP-II) has been invoked as an important mechanism of clinically acquired resistance to all-trans retinoic acid (RA) therapy in acute promyelocytic leukemia (APL). To test this hypothesis, we used quantitative reverse transcription-PCR and fast performance liquid chromatography procedures to examine the levels of CRABP-II mRNA and RA binding activity in APL patient samples. We found that CRABP-II mRNA in APL cells from pretreatment patients (n = 36) was constitutively expressed at relatively high levels (median, 0.92; range, 0.16-4.13) relative to the level in CRABP-H protein-expressing NB4 cells (arbitrarily set at 1.0 unit). Consistent with this finding, the RA binding activity of CRABP in APL cells from three pretreatment cases (range, 27.2-53.2 fmol/mg protein) was similar to that of NB4 cells (22.6 +/- 5.4 fmol/mg protein). Furthermore, in the pretreatment samples, there was no association between CRABP-H mRNA expression level and APL cellular sensitivity to RA-induced differentiation in vitro. After 45 days of remission induction therapy on Eastern Cooperative Oncology Group protocol E2491, CRABP-II mRNA was modestly increased from day 0 values in patients treated with either RA (median increase, 0.41) or chemotherapy (median increase, 0.56), and there was no significant difference between the two treatment groups (P = 0.91). In patients studied after relapse from RA therapy (n = 7), there was a significant decline in APL cell sensitivity to RA-induced differentiation in vitro compared with patients after relapse from chemotherapy (n = 5; P = 0.015-0.055 at three RA concentrations tested), but in the RA relapse cases, there was no change from pretreatment levels of CRABP-II mRNA (median, 0.98) or, in three relapse cases studied, of RA protein binding activity (range, 22.1-70.7 fmol/mg protein). Taken together, our data strongly imply that variations in CRABP-II expression and RA binding activity are not causally related to the development of clinically acquired APL cellular RA resistance, but rather, they suggest that constitutive expression of CRABP-II could have a facilitative role in the response of APL cells to RA.

An effective hospital-based pneumococcal immunization program.

We studied a hospital-based pneumococcal immunization program. Ninety (66%) of 136 patients on the study unit (group 1) and 97 (80%) of 122 patients on the control unit (group 2) were candidates for pneumococcal vaccine based on age of 65 years or older or underlying medical condition, or both, and absence of prior vaccination. In group 1, an infection control nurse identified candidates at the time of discharge and offered vaccine. No intervention was made in group 2. Seventy (78%) of vaccine candidates in group 1 were vaccinated at the time of hospital discharge compared with none of 97 candidates in group 2 (P less than .001). A hospital-based program offering vaccine at the time of hospital discharge can significantly improve immunization rates and successfully immunize the majority of hospitalized individuals at high risk from pneumococcal infection.

Pneumococcal vaccine in the hospital. Improved use and implications for high-risk patients.

A randomized trial of a program to improve pneumococcal immunization was undertaken. Also studied were the prevalence of high-risk conditions for serious pneumococcal disease among hospital admissions and prior hospitalization of patients with pneumococcal bacteremia. During two successive winters, 56% of 1,062 medical patients were identified by admission diagnosis or age as having a high-risk condition. None had received prior vaccination. During the trial period, identifying candidates for vaccination increased immunization from two (2.1%) of 95 to ten (10.4%) of 96 in year 1 and from two (2.1%) of 96 to 19 (20%) of 95 in year 2. Among adults with pneumococcal bacteremia, 33 (54%) of 61, including 32 (64%) of 50 with high-risk conditions, had documentation of prior hospitalization within five years. A hospital-based program can increase pneumococcal immunization rates and would be directed at patients in whom serious pneumococcal disease is likely to develop.

The treatment of Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome.

Forty-four episodes of Pneumocystis carinii pneumonia (PCP) occurred in 36 of 70 patients with the acquired immunodeficiency syndrome. Thirty-four patients with 40 episodes of PCP were treated with trimethoprim-sulfamethoxazole. Therapy was successful in 18 episodes (45%), but was unsuccessful in 15 episodes (37.5%). In the latter cases, two patients died within 72 hours; 13, of whom nine died, had therapy changed to pentamidine. In seven additional episodes (17.5%), trimethoprim-sulfamethoxazole was changed to pentamidine due to adverse reactions; all patients survived. Seven patients (26% of survivors) developed recurrent PCP. Twenty-two patients (65%) developed adverse reactions to trimethoprim-sulfamethoxazole, including leukopenia (20), hepatotoxicity (12), fever (eight), rash (six), and immediate reactions (two). Reactions were most common during the second week of therapy. Patients with the acquired immunodeficiency syndrome who have PCP have a high trimethoprim-sulfamethoxazole failure rate, due either to adverse reactions or unresponsive infection. Late recurrence is common.

Intravenous drug abusers and the acquired immunodeficiency syndrome (AIDS). Demographic, drug use, and needle-sharing patterns.

We studied the demographic characteristics, drug use patterns, and sexual habits of intravenous (IV) drug abusers to further define this population at risk for acquired immunodeficiency syndrome (AIDS). Sixteen IV drug abuser patients with AIDS, 24 IV drug abuser patients with AIDS-related complex (ARC), and 14 IV drug abuser controls without evidence of AIDS or ARC were evaluated. The subjects in each group were similar demographically, in drug use practice, and in sexual orientation and experience. Of the AIDS and ARC patients, 34 (88%) of 40, including all seven homosexual men, shared needles, as did all drug abusers without AIDS or ARC. Seventy-four percent of patients, including all homosexual men, attended "shooting galleries," where anonymous multiple-partner needle sharing took place. Needle sharing supports the hypothesis of AIDS transmission by a blood-borne route, can explain the spread of AIDS and the high rate of seropositivity to the putative AIDS agent among IV drug abusers, and is a logical link between IV drug abusers and male homosexuals, the two largest groups with AIDS.

Viral sensing at the blood-brain barrier: new roles for innate immunity at the CNS vasculature.

Neurotropic viral infections are a major source of disease worldwide and represent a growing burden to public health. While the central nervous system (CNS) is normally protected from viral infection by the blood-brain barrier (BBB), many viruses are able to cross the BBB and establish CNS infection through processes that largely remain poorly understood. A growing body of recent research has begun to shed light on the viral and host factors that modulate BBB function, contributing to both protective and pathological disease processes. Central to these studies have been the actions of host cytokines and chemokines, which have increasingly been shown to be key regulators of BBB physiology. This review summarizes recent advances in understanding how BBB function governs both viral pathogenesis and host immune responses during neurotropic viral infections.

Frequency of pulmonary tuberculosis in patients undergoing sputum induction for diagnosis of suspected Pneumocystis carinii pneumonia.

OBJECTIVE: To determine the frequency of pulmonary tuberculosis (TB) in patients with suspected Pneumocystis carinii pneumonia (PCP). DESIGN: Prospective study of sputum specimens from subjects undergoing diagnostic sputum induction for PCP and medical chart review. SETTING: University hospital in the Bronx, New York City. PATIENTS: A total of 373 consecutive adults with induced sputum specimens adequate for acid-fast smear and mycobacterial culture. MAIN OUTCOME MEASURES: Direct immunofluorescence for PCP, acid-fast stain, and mycobacterial culture of all induced sputum specimens. Determination of demographic characteristics, HIV risk factors, and HIV serological status. Clinical and radiographic findings of patients with TB. RESULTS: Proven symptomatic HIV infection was present in 251 of the 373 (67%) patients prior to sputum induction. PCP was detected in 136 out of 519 (26%) specimens, Mycobacterium tuberculosis in 10 (1.9%) specimens from nine patients. Smear was positive for acid-fast bacilli in nine (1.7%), of which seven (78%) grew M. tuberculosis and two (22%) M. avium complex. Pulmonary TB was found in nine of the 373 (2.4%) patients [95% confidence intervals (CI), 1.1-4.6]. Smears were positive for acid-fast bacilli in seven out of 10 (70%) specimens with M. tuberculosis compared with two out of 65 (3%) with other mycobacteria (P < 0.0001). Of 66 specimens that grew mycobacteria despite negative acid-fast smears, three (4.5%) were M. tuberculosis (95% CI, 0-13.3). Of the nine patients with TB, six had prior known TB, chest radiographs atypical for PCP, or both; two others had positive acid-fast smears. Only a single patient (0.27%; 95% CI, 0-0.79) had pulmonary TB, which remained unsuspected after acid-fast smear of induced sputum. CONCLUSIONS: Pulmonary TB occasionally occurs in patients with suspected PCP and in most cases is suggested by medical history, clinical findings, or acid-fast stain of induced sputum.

CD4+ lymphocyte level and rate of decline as predictors of AIDS in intravenous drug users with HIV infection.

OBJECTIVE: To examine the relationship between rate of loss of CD4+ T lymphocytes and risk of AIDS in HIV-infected intravenous drug users (IVDU) enrolled in a methadone program in the Bronx, New York. DESIGN: Serial CD4 percentages (CD4%) among lymphocytes before AIDS diagnosis were recorded at approximately 6-month intervals for 190 HIV-antibody-positive subjects. METHODS: A nested case-control study was performed, in which all subjects who developed AIDS were compared with those who remained AIDS-free. The relationship between CD4% decline and AIDS risk was evaluated using proportional-hazards regression. RESULTS: Analyses that used a single baseline CD4% measurement to adjust for CD4+ lymphocyte count suggested that both low (1-5 CD4% per semester) and high (> 5 CD4% per semester) rates of decline might be related to AIDS risk: relative risks were 1.83 and 1.44, although the 95% confidence intervals (Cl) included 1.0 in each case. Adjustment for current level of CD4% eliminated the association between low rates of CD4% decline and AIDS risk, but not that between high rates of decline and AIDS risk (adjusted relative risk, 1.80; 95% Cl, 0.57-5.70). Serial observations showed that a rate of decline of CD4% > 5 per semester was a significant predictor of AIDS risk after controlling for level of CD4% achieved (adjusted relative risk, 3.58; 95% Cl, 1.07-11.95). CONCLUSIONS: IVDU who develop AIDS have a greater rate of CD4 cell loss than subjects who remain AIDS-free. A low rate of CD4+ lymphocyte depletion is not an important predictor of the immediate onset of AIDS in HIV-infected IVDU, compared with CD4+ lymphocyte level, but a high rate of CD4+ decline can be.

Tampons as a self-administered collection method for the detection and quantification of genital HIV-1.

OBJECTIVE: To assess the detection and quantitation of HIV-1 from tampon eluents in comparison with cervicovaginal lavage (CVL) and plasma specimens from the same women. METHODS: Ninety-seven tampon, 105 CVL, and 104 plasma specimens from 105 HIV-1 seropositive women were analyzed using Version 3 of the Chiron bDNA assay, with sensitivity of 50 HIV-1 RNA copies/ml. Data analyses used McNemar's test, Wilcoxon signed rank test, and Mantel--Haenszel chi-squared and odds ratios with 95% confidence intervals to assess differences in proportions. RESULTS: In women for whom both plasma and genital specimens were available, HIV-1 was detected less frequently in genital specimens: [tampons (33/97, 34%) and CVL (48/104, 46%)] than plasma specimens (86/104, 83%) (P < 0.001 for both plasma versus tampon and for plasma versus CVL). However, the proportion of genital specimens with detectable virus did not differ significantly by collection method (P = 0.14). Among women with detectable virus using both collection methods (n = 23), viral load was similar for tampon eluents (median, 355 copies/ml; range, 52--120,898) and CVL specimens (median, 265 copies/ml; range, 61--35,637;P = 0.88). CONCLUSION: Tampon eluent specimens are slightly less sensitive than CVL specimens in the detection of genital HIV-1, although quantification of viral load, when detectable by both methods, was similar.

Effectiveness of isoniazid chemoprophylaxis for HIV-infected drug users at high risk for active tuberculosis.

OBJECTIVE: To define the effectiveness of chemoprophylaxis, outside of a clinical trial setting, in preventing tuberculosis among tuberculin-reactive and anergic HIV-infected drug users at high risk of developing active tuberculosis. DESIGN: An observational cohort study. SETTING: Methadone maintenance treatment program with on-site primary care. PARTICIPANTS: Current or former drug users enrolled in methadone treatment. INTERVENTIONS: Annual skin testing for tuberculosis infection and anergy was performed, and eligible patients were offered daily isoniazid for 12 months and followed prospectively. MAIN OUTCOME MEASURE: The development of active tuberculosis. RESULTS: A total of 155 persons commenced chemoprophylaxis. Among tuberculin reactors, tuberculosis rates were 0.51 and 2.07/100 person-years in those completing 12 months versus those not taking prophylaxis [rate ratio 0.25, 95% confidence interval (CI) 0.06-1.01]. Among anergic individuals, comparable rates were 0 and 1.44/100 person-years. Lower tuberculosis rates among completers were not attributable to differences in immune status between the treated and untreated groups. CONCLUSION: The completion of isoniazid chemoprophylaxis was associated with a marked reduction in tuberculosis risk among tuberculin reactors and anergic persons in this high-risk population. These data support aggressive efforts to provide a complete course of preventative therapy to HIV-infected tuberculin reactors, and lend weight to the findings of others that isoniazid can reduce the rate of tuberculosis in high-risk anergic HIV-infected persons.

A prospective study of HIV disease progression in female and male drug users.

OBJECTIVE: To compare HIV disease progression and mortality in a cohort of female and male drug users. DESIGN: A prospective cohort study of 222 HIV-seropositive women and 302 HIV-seropositive men who attended a hospital-affiliated methadone maintenance program with on-site primary care. METHODS: Regression slopes of CD4+ cell decline were compared using the two sample t-test, and the distribution of AIDS-defining illnesses evaluated by Mantel-Haenszel chi2 test. Time to AIDS-defining clinical conditions and death were compared using the Kaplan-Meier log-rank test. Multivariate estimates of progression to clinical AIDS or death, for all participants, stratified by sex, were derived from Cox proportional hazards models. RESULTS: Ninety-five persons (43 women and 52 men) developed AIDS-defining conditions. Analyses of the rates of CD4+ cell decline, the distribution of first AIDS-defining illnesses, and the time to clinical AIDS did not differ by sex. In the multivariate model, sex was not associated with an AIDS outcome, whereas crack-cocaine use [hazards ratio (HR), 1.815; 95% confidence interval (CI), 1.151-2.863], CD4+ cell count (100 x 10(6)/l; HR, 0.589; 95% CI, 0.511-0.679), and two or more HIV-related symptoms (HR, 1.702; 95% CI, 1.125-2.576) were associated. Mortality rates (8.71 per 100 person-years in women and 9.85 per 100 person-years in men) were similar, using univariate or multivariate methods. CONCLUSIONS: There was little difference in clinical outcomes or mortality between HIV-seropositive female and male drug users with access to primary care. However, crack-cocaine use was independently associated with progression to clinical AIDS.

Additional evidence for lack of transmission of HIV infection by close interpersonal (casual) contact.

To further study the possibility of transmission of HIV infection by close personal but non-sexual, non-parenteral contact we have continued to enroll and evaluate household contacts of adult patients with AIDS. Two hundred and six household contacts of 90 patients with AIDS were evaluated with detailed interviews, physical examinations, and detection of HIV antibodies and p24 antigen from 1984 to 1987; 118 of these contacts were re-evaluated 6-12 months after cessation of household contact or death of the patient. The median duration of household contact from 18 months prior to symptoms in the AIDS patients to last contact was 23 months (range 3-101 months). The median time elapsed from first contact during this period to the last evaluation was 38 months (range 13-66 months). No household contact had signs or symptoms suggesting HIV infection. All 206 were negative for serum antibodies to HIV and HIV p24 antigen, despite extensive sharing of household facilities and items and personal interactions with AIDS patients. This study continues to show that household members without other risks remain at minimal to no risk for HIV transmission (95% confidence interval, 0-1.44) despite prolonged and substantial close non-sexual contact with AIDS patients, and after re-evaluation at a median of 10.9 months after initial evaluation.

Increased risk of bacterial pneumonia in HIV-infected intravenous drug users without AIDS.

Although patients with AIDS have been noted to be at risk for bacterial pneumonia as well as opportunistic infections, little is known about the risk of bacterial pneumonia in HIV-infected populations without AIDS. To determine the incidence of bacterial pneumonia in a well defined population of intravenous drug users (IVDUs), and to examine any association with HIV infection, we prospectively studied 433 IVDUs without AIDS, enrolled in a longitudinal study of HIV infection in an out-patient methadone maintenance program. At enrollment, 144 (33.3%) subjects were HIV-seropositive, 289 (66.7%) were seronegative. Over a 12-month period, 14 out of 144 (9.7%) seropositive subjects were hospitalized for community-acquired bacterial pneumonia, compared with six out of 289 (2.1%) seronegative subjects. The cumulative yearly incidence of bacterial pneumonia was 97 out of 1000 for seropositives and 21 out of 1000 for seronegatives (risk ratio = 4.7, P less than 0.001). Eleven out of 14 (78.6%) cases among the seropositive patients were due to either Streptococcus pneumoniae [5] or Hemophilus influenzae [6]. Two out of 14 (14.3%) cases among the seropositives were fatal. Stratifying by level of intravenous drug use indicated that even among subjects not reporting active intravenous drug use at study entry, eight out of 82 (9.8%) seropositives compared with three out of 211 (1.4%) seronegatives were hospitalized for bacterial pneumonia over the study period (risk ratio = 6.9, P less than 0.01). This study shows a markedly increased incidence of bacterial pneumonia associated with HIV infection in IVDUs without AIDS.(ABSTRACT TRUNCATED AT 250 WORDS)

Laboratory markers and the risk of developing HIV-1 disease among injecting drug users.

OBJECTIVE: To characterize the progression to HIV-1 disease among injecting drug users (IDU) according to laboratory markers. DESIGN: Prospective study of cohort of HIV-1-seroprevalent IDU, with case-comparison component. METHODS: Different laboratory markers were examined as predictors of progression to HIV-1-associated diseases including AIDS in a cohort of 318 HIV-1-infected IDU. The cohort was enrolled from a methadone treatment program in the Bronx, New York, USA. The independent utility of non-CD4 cell markers was evaluated after adjustment for the association of low CD4 lymphocyte count with AIDS risk. Clinical events in the natural history of HIV-1 were related to changes in levels of two variables related to duration of infection, CD4 lymphocyte count and serum beta 2-microglobulin (beta 2M) concentration. RESULTS: On univariate analysis, AIDS incidence measured from baseline increased with declining CD4 lymphocyte number and percentage, increasing serum beta 2M level, low platelet count, low leukocyte count and p24 antigenemia. Among HIV-1-related outcomes prior to any AIDS diagnosis, the relative risk of pyogenic bacterial infections conferred by these markers was similar to the relative risk of AIDS. For all HIV-1 outcomes, the elevated risk encountered at CD4 lymphocyte number < or = 200 x 10(6)/l was entirely due to the high risk at < or = 150 x 10(6)/l. On multivariate analysis, control for CD4 lymphocyte count eliminated the association of any other marker with increased AIDS hazard. HIV-1-related outcomes tended to occur in this order: multiple constitutional symptoms, oral candidiasis, pyogenic bacterial infections and AIDS. CONCLUSIONS: In HIV-1-infected IDU, several laboratory markers may predict AIDS when analyzed individually. These are not, however, independently related to increased AIDS risk after adjustment for low CD4 lymphocyte count. A CD4 count < or = 150 x 10(6)/l is more strongly related to immediate risk of adverse outcome than a count of 200 x 10(6)/l. A progressive series of clinical events is associated with markers of duration of HIV-1 infection, prior to and including AIDS diagnosis.

Survival differences in patients with AIDS.

To define the clinical, demographic, and behavioral variables that may influence survival in patients with AIDS, we studied 526 patients with AIDS diagnosed through September 1987 who were cared for at a single medical center. A diversity of racial and ethnic backgrounds, ages, both men and women, and all risk behaviors except hemophilia were well represented. The initial AIDS defining diagnosis was the most powerful predictor of survival. The median survival was 12.8 months for patients presenting with Kaposi's sarcoma (p less than 0.001), 10.9 months for patients presenting with Pneumocystis carinii pneumonia (p less than 0.001), and 4.8 months for patients presenting with other infections or neoplasms (p less than 0.02). For the entire series, male sex and younger age were associated with more favorable survival (p less than 0.025). For those presenting with Pneumocystis carinii pneumonia, in addition to younger age (p less than 0.025), black race (p less than 0.025) and the combination of male sex and intravenous drug use (p less than 0.005) were associated with a more favorable survival. Within a setting of comparable clinical care, survival from the point of diagnosis of AIDS is associated most strongly with the initial AIDS diagnosis, but differences in age, gender, race, and risk behavior also exert an influence on survival.