Racial and ethnic disparities in COVID-19 disease incidence independent of comorbidities, among people with HIV in the US.

OBJECTIVES: To define the incidence of clinically-detected COVID-19 in people with HIV (PWH) in the US and evaluate how racial and ethnic disparities, comorbidities, and HIV-related factors contribute to risk of COVID-19. DESIGN: Observational study within the CFAR Network of Integrated Clinical Systems cohort in 7 cities during 2020. METHODS: We calculated cumulative incidence rates of COVID-19 diagnosis among PWH in routine care by key characteristics including race/ethnicity, current and lowest CD4 count, and geographic area. We evaluated risk factors for COVID-19 among PWH using relative risk regression models adjusted with disease risk scores. RESULTS: Among 16,056 PWH in care, of whom 44.5% were Black, 12.5% were Hispanic, with a median age of 52 years (IQR 40-59), 18% had a current CD4 count < 350, including 7% < 200; 95.5% were on antiretroviral therapy, and 85.6% were virologically suppressed. Overall in 2020, 649 PWH were diagnosed with COVID-19 for a rate of 4.94 cases per 100 person-years. The cumulative incidence of COVID-19 was 2.4-fold and 1.7-fold higher in Hispanic and Black PWH respectively, than non-Hispanic White PWH. In adjusted analyses, factors associated with COVID-19 included female sex, Hispanic or Black identity, lowest historical CD4 count <350 (proxy for CD4 nadir), current low CD4/CD8 ratio, diabetes, and obesity. CONCLUSIONS: Our results suggest that the presence of structural racial inequities above and beyond medical comorbidities increased the risk of COVID-19 among PWHPWH with immune exhaustion as evidenced by lowest historical CD4 or current low CD4:CD8 ratio had greater risk of COVID-19.

Treatment of anemia in patients with HIV infection, Part 1: The need for adequate guidelines.

Anemia in HIV-infected individuals, still a common hematologic complication in the highly active antiretroviral therapy (HAART) era, is associated with shortened survival, increases in the rate of disease progression, and reduction in quality of life. Based on a thorough review of the literature, guidelines were developed for the assessment, diagnosis, monitoring, and treatment of anemia in patients with HIV/AIDS by a consensus committee consisting of nurses from academia and clinical practice. A major goal of this committee is to increase awareness within the nursing community of the prevalence of anemia in HIV-infected patients and its impact on their lives. Anemia developed in close to 90% of HIV-infected patients before the introduction of HAART, and it is still found in up to 46% of patients in the HAART era. Another goal is to encourage screening for anemia and the adaptation of a proposed classification system of anemia based on a graded decrease in hemoglobin levels.

Incidence of pancreatitis in HIV-infected patients receiving nucleoside reverse transcriptase inhibitor drugs.

BACKGROUND: Pancreatitis is a known adverse effect of the nucleoside reverse transcriptase inhibitors, particularly didanosine. Hydroxyurea has been used to potentiate the antiviral efficacy of didanosine, but recently there has been concern that severe and even fatal pancreatitis may be more likely to occur when hydroxyurea is used in combination with didanosine. We investigated the incidence of pancreatitis in patients using nucleoside analogues with or without hydroxyurea. METHODS: Data were obtained from patients followed longitudinally on the Johns Hopkins HIV Clinic. Incidence rates of pancreatitis were calculated for each antiretroviral regimen that included zidovudine, stavudine, didanosine (+ hydroxyurea), and didanosine + stavudine (+ hydroxyurea). Poisson regression was used to compare the relative rate of pancreatitis for each regimen adjusting for other covariates. RESULTS: A total of 2613 patients received at least one of the nucleoside reverse transcriptase inhibitor-containing regimens. There were 33 cases of pancreatitis. The crude incidence rate of pancreatitis ranged from 0.18 cases per 100 person-years on therapy for zidovudine to 6.25 cases per 100 person-years for didanosine + hydroxyurea. Compared to didanosine alone, and adjusting for CD4 cell count and other variables, the relative risk (RR) of pancreatitis was 8.56 [95% confidence interval) CI, 1.85-35.59] for didanosine + hydroxyurea, and 2.35 (95% CI, 0.46-11.89) for didanosine + stavudine + hydroxyurea. For any use of hydroxyurea, the RR = 4.01 (95% CI, 1.02-15.89). Other risk factors for pancreatitis included a CD4 cell count < 200 x 106 cells/l, female sex, and a history of pancreatitis. CONCLUSIONS: Our data show that the risk of pancreatitis is four-fold higher when hydroxyurea is used. The use of hydroxyurea with didanosine should probably be discouraged if other treatment options are available.

Effect of antiretroviral therapy on the incidence of bacterial pneumonia in patients with advanced HIV infection.

To determine the relationship of combination antiretroviral therapy and bacterial pneumonia, we assessed incidence of and risk factors for bacterial pneumonia in 1,898 human immunodeficiency virus (HIV)-infected patients with CD4 cell counts < 200/mm(3) followed in the Johns Hopkins HIV clinic between 1993 and 1998. A total of 352 episodes of bacterial pneumonia occurred during 2,310 patient-years of follow-up. Incidence of bacterial pneumonia decreased from 22.7 episodes/100 person-years (py) in the first half of 1993 to 12.3 episodes/100 py in the first half of 1996, reaching a nadir of 9.1 episodes/100 py in the second half of 1997 (p < 0.05). The use of protease inhibitor-containing regimens was associated with a decreased risk of bacterial pneumonia (risk ratio [RR] 0.55, 95% CI 0.31 to 0.94). Lower CD4 cell counts (RR 2.22, 95% CI 1.54 to 3.18), injection drug use as HIV transmission category (RR2.0, 95% CI 1.43 to 2.76), and prior Pneumocystis carinii pneumonia (RR 3.88, 95% CI 1.65 to 9.16) were also significantly associated with bacterial pneumonia. Trimethoprim-sulfamethoxazole and macrolide use were not significantly associated with risk of bacterial pneumonia. There has been a dramatic decline in the incidence of bacterial pneumonia resulting from the use of combination antiretroviral therapy containing protease inhibitors.

Incidence of neuropathy in HIV-infected patients on monotherapy versus those on combination therapy with didanosine, stavudine and hydroxyurea.

BACKGROUND: Sensory neuropathy is a common adverse effect of the nucleoside analogue anti-retroviral drugs didanosine (ddl) and stauvudine (d4T). These drugs are increasingly being used in combination, and it is not currently known whether the incidence of neuropathy is higher with combination compared to individual drug use. It is also not known if hydroxyurea, used to potentiate the antiviral efficacy of these drugs, may also increase the risk of neuropathy. The purpose of this analysis is to investigate if the combination of ddl and d4T, with or without hydroxyurea, has a higher incidence of neuropathy than a single drug regimen. METHODS: Data were obtained from patients followed longitudinally by the Johns Hopkins AIDS Services. Incidence rates of development of neuropathy were calculated for each of five regimens: ddl (+/- hydroxyurea), ddl + d4T (+/- hydroxyurea), and d4T. Cox proportional hazard regression was used to compare the relative risk of neuropathy for each regimen adjusting for CD4 cell count, other drugs received, and time on therapy. RESULTS: A total of 1116 patients received at least one of the five regimens. There were 117 cases of neuropathy. The crude incidence rate of neuropathy ranged from 6.8 cases per 100 person-years for ddl to 28.6 cases per 100 person-years for ddl + d4T + hydroxyurea. Compared with ddl alone, and adjusting for CD4 cell counts and other variables, the relative risk of neuropathy was 1.39 [95% confidence interval (CI): 0.84-2.32] for d4T alone, 2.35 (95% CI: 0.69-8.07) for ddl + hydroxyurea, 3.50 (95% CI: 1.81-6.77) for ddl + d4T, and 7.80 (95% CI: 3.92-15.5) for ddl + d4T + hydroxyurea. CONCLUSIONS: Based on the data, the risk of neuropathy is additive or even synergistic for ddl + d4T + hydroxyurea compared with ddl or d4T alone. The combination of ddl + d4T also increases the risk of neuropathy but less than when hydroxyurea is included.

Stavudine in zidovudine (ZDV)-experienced compared with ZDV-naive patients.

OBJECTIVE: To assess the effect of prior zidovudine (ZDV) use on subsequent response to stavudine (D4T)-containing regimens. DESIGN: Analysis of data from prospective observational database. METHODS: Patients were ZDV-experienced if they had previously received more than 90 days of ZDV and ZDV-naive if they had never received ZDV. HIV-1 RNA and CD4 cell counts were compared at 3, 6, and 12 months after initiation of D4T. Univariate and multivariate analyses were performed, adjusting for baseline HIV-1 RNA and CD4 cell count, age, sex, race, HIV transmission category, time since enrollment, and protease inhibitor use. RESULTS: No difference was found between ZDV-experienced (n = 130) and naive (n = 98) patients in age, sex, race, transmission category, use of a concurrent protease inhibitor, or baseline CD4 cell count and HIV-1 RNA. There was no difference in the median decline in HIV-1 RNA (-1.29 log10 copies/ml for experienced patients versus -1.19 log10 copies/ml for naive patients; P = 0.39), in achieving HIV-1 RNA < 400 copies/ml at 3 months (51% versus 49%; P = 0.79) or 6 months (48% versus 56%; P = 0.33). There was no difference in CD4 cell response (+73 x 10(6)/l versus + 87 x 10(6)/l; P = 0.51). By multivariate adjustment in a repeated measures analysis, there was no significant difference in achieving undetectable HIV-1 RNA or in CD4 cell response between experienced and naive patients. CONCLUSION: No difference in response to a D4T-containing regimen between ZDV-experienced and naive patients was found over a 1-year period. In contrast to previous trials, most patients in this study also received a protease inhibitor. These findings may be more relevant in the current era of highly active antiretroviral therapy.

Anemia and survival in HIV infection.

Several clinical studies have suggested that anemia is an independent risk factor for dying in patients with HIV disease. We analyzed data from a large urban HIV clinical practice in Baltimore to assess the annual incidence of anemia, the risk of dying in patients who develop anemia, and the association between recombinant human erythropoietin use to treat anemia and subsequent survival. In 2348 patients observed between 1989 and 1996, 498 (21%) developed at least grade 1 anemia (hemoglobin <9.4 g/dl); 95 (4%) developed grade 4 anemia (hemoglobin <6.9 g/dl). Development of anemia was associated with decreased survival, independent of other prognostic factors. Use of erythropoietin was more likely in patients of nonminority race, those who did not inject drugs, those with a lower CD4 count or AIDS, and those being treated for cytomegalovirus disease (p < .05). Adjusting for these factors as well as severity of anemia, age, diagnosis of opportunistic disease, blood transfusion, and antiretroviral therapy in a time-dependent Cox proportional hazards analysis, erythropoietin use (n=91) was associated with a decreased hazard of dying (relative hazard [RH]=0.57; 95% confidence interval [CII, 0.40-0.81; p=.002). Although we cannot rule out a treatment selection bias, adjusting for available prognostic factors and factors potentially associated with a decision to use erythropoietin suggests that erythropoietin for treatment of anemia is associated with improved survival in HIV disease.

Impact of opportunistic disease on survival in patients with HIV infection.

OBJECTIVE: To assess the impact of opportunistic diseases on survival in patients with HIV disease. METHODS: A cohort of 2081 patients followed for a mean of 30 months was studied. Time-dependent Cox proportional hazards analyses were performed using incident opportunistic diseases and CD4 cell counts as independent variables. RESULTS: During follow-up, 730 (35%) patients died. The occurrence of Pneumocystis carinii pneumonia (PCP), cytomegalovirus (CMV) disease, Mycobacterium avium complex (MAC) disease, Candida esophagitis, Kaposi's sarcoma, lymphoma, progressive multifocal leukoencephalopathy (PML), dementia, wasting, toxoplasmosis, and cryptosporidiosis were all significantly associated with death, independently of CD4 cell count (all P<0.001 for opportunistic diseases controlling for CD4 cell count). The magnitude of increased risk was greatest for lymphoma [relative hazard (RH), 7.2], PML (RH, 3.9), MAC (RH, 3.0) and CMV (RH, 2.2). Cryptococcosis (RH, 0.94) and herpes zoster (RH, 0.85) were not associated with death. In a multivariate Cox proportional hazards analysis, MAC [RH, 2.56; 95% confidence interval (CI), 2.1-3.1], CMV (RH, 1.63; 95% CI, 1.3-2.1), toxoplasmosis (RH, 1.85; 95% CI, 1.3-2.6), PCP (RH, 1.29; 95% CI, 1.1-1.5), and CD4 cell count were significantly associated with death. Patients who had opportunistic diseases had significantly greatly monthly declines in CD4 counts (-11 x 10(6)/l per month) than those who did not (-6 x 10(6)/l per month; P <0.001). CONCLUSION: Most opportunistic diseases increase the risk of death independently of CD4 cell count. These data support the hypothesis that opportunistic diseases enhance HIV pathogenesis and further underscore the importance of prophylaxis.

Infection due to fluconazole-resistant Candida in patients with AIDS: prevalence and microbiology.

A cross-sectional study was conducted to assess the prevalence and microbiology of oral infection due to fluconazole-resistant Candida in patients with AIDS. Oral swab specimens for fungal cultures were obtained from 100 consecutive outpatients with CD4 lymphocyte counts of < 200/mm3. At least one fungal organism demonstrating in vitro resistance to fluconazole (minimum inhibitory concentration, > or = 8 micrograms/mL) was isolated from 26 (41%) of 64 patients for whom cultures were positive. When fluconazole-resistant C. albicans was isolated, in vitro resistance correlated with clinical thrush. None of 10 patients from whom only non-albicans species of Candida were isolated had active thrush. The patients from whom fluconazole-resistant Candida albicans was isolated had lower CD4 cell counts (median, 9/mm3), a greater number of treated episodes of thrush (median, 4.5), and a greater median duration of prior fluconazole treatment (231 days) than did patients from whom fluconazole-susceptible C. albicans was isolated (median CD4 cell count, 58/mm3 [P = .004]; median number of treated episodes of thrush, 2.0 [P = .001]; and median duration of prior fluconazole treatment, 10 days [P = .01]; respectively). In a multivariate analysis, the number of episodes and duration of fluconazole therapy were independent predictors of resistance.

Duration of the survival benefit of zidovudine therapy in HIV infection.

BACKGROUND: Zidovudine therapy improves survival in advanced human immunodeficiency virus (HIV) infection and delays progression from earlier stages to advanced stage of HIV disease. The duration of the benefit of zidovudine therapy, however, may be limited. OBJECTIVE: To quantitate the duration of the survival benefit of zidovudine therapy in a heterogeneous patient population receiving care for HIV infection in an urban clinic. METHODS: We analyzed data from 393 HIV-infected patients with CD4+ cell counts of 0.5 x 10(9)/L (500 cells/microliter.) or less who first presented for care at The Johns Hopkins HIV Clinic, Baltimore, Md, from July 1989 through December 1993. Follow-up extended to a maximum of 3 years (median, 2 years). Survival probabilities in patients who received and who did not receive zidovudine therapy were analyzed by Kaplan-Meier methods and by multivariate Cox proportional hazards regression analysis adjusting for both time-dependent and fixed prognostic covariates. RESULTS: Adjusting for baseline differences in CD4+ cell count, clinical stage of HIV disease, and prophylaxis for Pneumocystis carinii pneumonia, Cox regression analysis showed a significant effect of zidovudine compared with no treatment on the risk of dying during the first year of therapy (relative hazard for death, 0.32; 95% confidence interval [CI], 0.18 to 0.59). However, analysis of the time-dependent effect of zidovudine therapy showed that there was a diminishing relative hazard between treatment and no treatment of 0.75 (95% CI, 0.45 to 1.26) at 1 to 2 years of therapy and a relative hazard of 1.61 beyond 2 years (95% CI, 0.70 to 3.71). CONCLUSION: The survival advantage of zidovudine therapy is time dependent, lasting between 1 and 2 years in patients with CD4+ cell counts of 0.5 x 10(9)/L or less. Alternative antiretroviral treatment may be indicated at that time.

Risk factors for pneumococcal disease in human immunodeficiency virus-infected patients.

To identify risk factors for pneumococcal infection among human immunodeficiency virus-infected patients, a nested case-control study was done in an urban university human immunodeficiency virus clinic. Subjects with pneumococcal illness seen between 1 January 1990 and 1 July 1994 (n=85) were randomly matched to controls from the same population. Patients with pneumococcal disease were more likely than controls to be African Americans (adjusted odds ratio [OR]=3.92), have <200 CD4 cells/mm3 (adjusted OR=3.38), have a history of any pneumonia (adjusted OR=3.28), and have an albumin level of <3.0 g/dL (adjusted OR=6.25). Use of zidovudine (adjusted OR=0.38) and pneumococcal vaccination when the subject had >200 CD4 cells/mm3 (adjusted OR=0.22) were less common in cases than in controls. Similar results were found when only cases with infections of usually sterile sites were analyzed. Pneumococcal vaccine may be most protective when it is administered before advanced immunodeficiency develops.

Effects of an incentive and education program on return rates for PPD test reading in patients with HIV infection.

To determine the impact of a food voucher incentive and patient education program on compliance with tuberculin skin test (PPD, purified protein derivative) performance in HIV-infected adults, we analyzed return rates for PPD reading for patients at our urban HIV clinic. The groups studied included patients who received no intervention (controls), patients offered a food voucher incentive, and patients offered a food voucher and patient education intervention. Return rates for PPD reading were 96 (35%) of 272 for the control group, 111 (48%, p = 0.004) of 229 for the food voucher group, and 96 (61%, p < 0.0001) of 158 for the food voucher and patient education group. By univariate analysis, black patients (p = 0.01), males (p = 0.01), older patients (p = 0.04), city residents (p = 0.001), and injection drug users were more likely to return for PPD reading. By logistic regression, food voucher, food voucher plus education, city residence, and male sex were significantly associated with return for PPD reading. Two simple, inexpensive interventions were found to increase compliance with tuberculin skin test performance in HIV-infected adults. Additional interventions are required to achieve better rates of return for PPD reading.

Risk factors for fluconazole-resistant candidiasis in human immunodeficiency virus-infected patients.

In a case-control study to identify risk factors for fluconazole-resistant oroesophageal candidiasis in human immunodeficiency virus-infected patients, 25 patients with clinical and in vitro fluconazole-resistant candidiasis were paired with controls who had treatment-responsive candidiasis and who had been observed for similar time periods. After their first episode of candidiasis, patients who later developed fluconazole resistance had more treated episodes than did matched controls (cases, 3.1; controls, 1.8; P = .004), lower median CD4 cell counts (11/mm3 vs. 71/mm/3; P = .004), and greater median durations of all antifungal therapy (419 vs. 118 days; P < .001) and of systemic azole therapy (272 vs. 14 days; P < .001). When paired with a second set of controls matched by CD4 cell count as well as first diagnosis of candidiasis, cases continued to show greater median exposure to azoles (272 vs. 88 days; P = .005). These data indicate that advanced immunosuppression and exposure to oral azoles are risk factors for the development of fluconazole resistance.

Neutropenia and bacterial infection in acquired immunodeficiency syndrome.

BACKGROUND: In human immunodeficiency virus (HIV) disease, neutropenia occurs most commonly in patients who are also severely immunosuppressed. It is not currently known whether neutropenia is an independent risk factor for the development of bacterial infection, which is a potentially serious complication of advanced HIV disease. METHODS: We compared the incidence of bacterial infection between 118 neutropenic patients (absolute neutrophil count [ANC], < 1 x 10(9)/L) and 118 nonneutropenic patients matched for CD4+ lymphocyte count, use of injecting drugs, and follow-up time from a demographically heterogeneous urban cohort of HIV-infected patients followed up longitudinally at the Johns Hopkins Hospital. The incidence of serious infection was analyzed separately for patients with an ANC of less than 1, less than 0.75, or less than 0.5 x 10(9)/L. RESULTS: There were no statistically significant associations found between neutropenia and several individual bacterial infections, including bacteremia, pneumonia, endocarditis, bacterial enterocolitis, and infection of normally sterile sites for any level of neutropenia. However, for all these infections combined, the adjusted relative risk for the occurrence of bacterial infection was 2.33 (95% confidence interval, 1.00 to 5.40; P = .05) for patients with an ANC of less than 1 x 10(9)/L and 7.92 (95% confidence interval, 1.18 to 53.2; P = .03) for those with an ANC of less than 0.5 x 10(9)/L. The incidence of serious bacterial infection ranged from two to three infections per 100 person-months of neutropenia for patients with an ANC of less than 1 x 10(9)/L and three to five infections per 100 person-months of neutropenia for patients with an ANC of less than 0.5 x 10(9)/L for all bacterial infections combined. CONCLUSIONS: Our matched cohort analysis indicates that neutropenia is an independent risk factor for bacterial infection in patients with advanced HIV disease. Given the incidence of infection, the cost-effectiveness of interventions to prevent neutropenia in advanced HIV disease should be assessed.

Race, sex, drug use, and progression of human immunodeficiency virus disease.

BACKGROUND: The rates of progression of human immunodeficiency virus (HIV) infection and survival have been reported to differ among sociodemographic groups. It is unclear whether these differences reflect biologic differences or differences in access to medical care. METHODS: We measured disease progression and survival in a cohort of 1372 patients seropositive for HIV who were treated at a single urban center (median follow-up, 1.6 years). We calculated the rates of survival for the entire cohort and the rates of progression to the acquired immunodeficiency syndrome (AIDS) or death among the 740 patients who presented without AIDS. We used Cox proportional-hazards analysis to examine factors associated with progression to AIDS and death. RESULTS: Progression to AIDS or death was associated with a CD4 cell count of 201 to 350 per cubic millimeter (relative risk, 2.0; P < 0.001), the presence of symptoms at base line (relative risk, 2.0; P < 0.001), prior antiretroviral therapy (relative risk, 1.7; P = 0.003), and older age (relative risk per year of age, 1.02; P = 0.03). However, there was no relation between disease progression and sex, race, injection-drug use, income, level of education, or insurance status. In the entire cohort, a lower CD4 cell count, a diagnosis of AIDS, older age, and the receipt of antiretroviral therapy before enrollment were associated with an increased risk of death, whereas the use of prophylaxis against pneumocystis pneumonia, zidovudine use after enrollment, and having a job at base line were associated with lower risks of death. There was no significant difference in survival between men and women, blacks and whites, injection-drug users and those who did not use drugs, or patients whose median annual incomes were $5,000 or less and those whose incomes were more than $5,000. CONCLUSIONS: Among patients with HIV infection who received medical care from a single urban center, there were no differences in disease progression or survival associated with sex, race, injection-drug use, or socioeconomic status. Differences found in other studies may reflect differences in the use of medical care.

Racial and ethnic differences in outcome in zidovudine-treated patients with advanced HIV disease. Zidovudine Epidemiology Study Group.

UNLABELLED: OBJECTIVES--To determine if racial-ethnic differences exist in survival, disease progression, and development of myelosuppression in zidovudine-treated patients with advanced human immunodeficiency virus (HIV) disease. DESIGN--Prospective observational study. SETTING: -Hospital and private clinics in 12 metropolitan centers. PATIENTS: -The study included 754 non-Hispanic white, 165 black, and 106 Hispanic patients with the acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex (ARC) who received up to 2 years of zidovudine therapy. OUTCOME MEASURES--Survival, development of Pneumocystis carinii pneumonia (PCP), other opportunistic infections, and myelosuppression. RESULTS--At initiation of zidovudine therapy, Hispanic and particularly black patients had more advanced HIV disease than white patients, as indicated by lower baseline CD4+ counts, hematocrits, and AIDS-defining diagnoses. Black patients with AIDS also had a worse prognosis compared with white and Hispanic patients with AIDS. The product-limit survival rates at 2 years for white, black, and Hispanic patients with AIDS were 40%, 27%, and 39%, respectively (black vs white, P = .01; Hispanic vs white, P = .32, by the log-rank test). The respective proportions of patients who developed PCP at 2 years were 46%, 66%, and 44% (black vs white, P = .0001; Hispanic vs white, P = .86) and for other opportunistic infections the proportions were 56%, 63%, and 63%, respectively (black vs white, P = .03; Hispanic vs white, P = .09). There were no significant racial-ethnic differences in survival or in the development of opportunistic infections for patients with ARC, and there were no differences in the incidence of myelosuppression or dose reduction or suspension for patients with either ARC or AIDS. After adjusting for more advanced HIV disease (mainly low CD4+ counts and hematocrits), black race was no longer a significant independent predictor of survival. Adjustment for racial differences in the use of PCP prophylaxis accounted for most of the excess risk for the development of PCP in black patients compared with white patients with AIDS. CONCLUSIONS--Racial differences in survival and the development of opportunistic infections are mainly due to the more advanced HIV disease in black patients when zidovudine therapy is started and to their less frequent use of PCP prophylaxis. Innovative approaches are needed to ensure more widespread use of and earlier access to zidovudine therapy and PCP prophylaxis.

Analysis of physician and hospital differences in 'negative' coronary angiogram rates.

A direct relationship has been postulated between high "negative" coronary angiogram rates and physician payment. We conducted a prospective study of coronary angiography in a teaching and community hospital staffed, respectively, by cardiologists who were performing cardiac catheterization as salaried or fee-for-service physicians. The lower overall rate of negative angiograms at the teaching hospital correlated with the presence of a cardiac surgery unit and the increased referral of patients with documented coronary artery disease. The percentage of completely normal angiograms did not differ significantly between hospitals. The number of angiograms positive by a 70% occlusion criterion in patients not previously known to have coronary artery disease also did not differ greatly. Negative angiogram rates appeared to vary inversely with physician ability to set preangiogram probabilities of coronary artery disease. Our findings do not discount reimbursement as a strong incentive, but suggest other important determinants of coronary angiographic variation.