Introduction
Pneumocystis carinii pneumonia (PCP) is the most common serious opportunistic infection associated with AIDS in developed countries [1]. PCP prophylaxis has been found to be highly effective and has been widely recommended for persons whose CD4 counts are less than 200 × 106/l or less than 20% of total circulating lymphocytes, or who have had a previous episode of PCP [2-12].
Despite these recommendations, studies have shown that PCP prophylaxis is less likely to be received by racial and ethnic minorities, women, and individuals with a history of injecting drug use [13-16]. However, two of these studies were conducted among patients at a single institution [13,14] and one study was conducted among persons receiving special community-based services [15], thereby limiting the ability to generalize these results to a broader group of HIV-infected patients.
To obtain population-based information regarding characteristics of individuals who did not receive PCP prophylaxis, we examined the use of primary and secondary PCP prophylaxis among San Francisco residents whose AIDS-defining opportunistic illness was PCP in 1993.
Methods
A retrospective chart review of all San Francisco residents who were reported to the San Francisco Department of Public Health (SFDPH) with PCP as their first AIDS-defining opportunistic illness was conducted in 1993.
As part of ongoing surveillance, the SFDPH collects demographic, risk, and clinical data on all residents diagnosed with AIDS. Previous studies have found that over 95% of AIDS cases from hospitals and 88% of cases diagnosed in outpatient settings were reported in San Francisco [17,18].
Insurance status was based on insurance at the time of diagnosis with PCP. All types of private and public insurance were grouped together. We were unable to assess the impact of insurance on secondary PCP prophylaxis because all uninsured persons with PCP are eligible for Medicaid.
Through chart review, information was also collected on utilization of primary and secondary PCP prophylaxis, duration of hospitalization, and 30-day survival. For individuals who did not receive PCP prophylaxis prior to developing PCP, the reasons for not receiving these medications were ascertained from the medical record.
Individuals were categorized as eligible for primary PCP prophylaxis if the CD4 lymphocyte count obtained closest to the diagnosis of PCP was less than 200 × 106/l or less than 20% of total at any time prior to the diagnosis of PCP or within 3 months (92 days) after the diagnosis. CD4 counts obtained after the PCP diagnosis were included because patients who have not had a CD4 lymphocyte measurement performed prior to developing PCP usually have one performed during, or shortly after their episode of pneumonia. Excluding these patients would have biased our results by systematically eliminating a group of patients for whom not receiving medical care was an important reason for lack of PCP prophylaxis. All individuals were considered eligible for secondary PCP prophylaxis because it is recommended for all HIV-infected patients with a prior episode of PCP [8].
The cost of hospital care for preventable cases of PCP was calculated using a conservative estimate of the efficacy of primary PCP prophylaxis. Clinical trials comparing either trimethoprim-sulfamethoxazole or aerosolized pentamidine with placebo have found PCP prophylaxis to be at least 68% effective [2,4,6]. We therefore estimated that 68% of the cases of PCP among persons not receiving prophylaxis could have been prevented. The percentage of patients who were hospitalized in the medical unit and in the intensive care unit for treatment of PCP was calculated and multiplied by the number of preventable cases of PCP in order to estimate the number of patients who received care in whom PCP could have been prevented. The median number of days that patients without primary prophylaxis received care in the hospital medical unit and in the intensive care unit was calculated and multiplied by the estimated number of patients who received care to determine the total number of preventable hospital medical unit and intensive care unit days. The cost of hospital care was estimated using 1993 charges for care in the medical unit and in the intensive care unit at a local university hospital. These charges were applied to the number of estimated days in the hospital medical unit and in the intensive care unit to derive the total charges for hospital stay. To provide a more accurate reflection of true costs, the Medicare cost-to-charge ratio for this hospital for 1993 (0.43) was then applied to the total charges for hospitalization [19].
Statistical analysis
Proportions were assessed using the χ2 test and medians were compared using the Wilcoxon rank-sum test. Multiple logistic regression was conducted to determine independent predictors of receiving prophylaxis. All analyses were performed using SAS for Windows (SAS Institute, Cary, North Carolina, USA).
Results
Characteristics of the sample
In 1993, 386 patients were reported with PCP as their AIDS-defining opportunistic illness. Medical charts were available for 341 (88%) of these patients. The demographic characteristics of the patients whose charts were available did not differ from the characteristics of patients whose charts were unavailable (P > 0.05). The majority of individuals with PCP were aged between 35 and 45 years (52%), white (71%), homo-/bisexual men (82%), and insured (80%).
Use of PCP prophylaxis
A total of 114 (35%) out of 326 eligible patients received primary PCP prophylaxis (Table 1). Eleven individuals who had received prophylaxis prior to PCP discontinued therapy more than 1 month prior to developing PCP. These persons were classified as not having received primary PCP prophylaxis because the prophylaxis was unlikely to have been effective in preventing the episode of PCP.
Primary PCP prophylaxis was less commonly used among non-whites (22%) than whites (40%; P < 0.05) and less commonly used among uninsured (18%) than among insured persons (41%; P < 0.001). After adjustment for age, sex, and injecting drug use in logistic regression analysis, non-whites [odds ratio (OR), 0.49; 95% confidence intervals (CI), 0.28-0.87] and the uninsured (OR, 0.35; 95% CI, 0.17-0.73) remained less likely to have received primary prophylaxis.
A total of 216 (63%) out of 341 eligible patients received secondary PCP prophylaxis. The sociodemo-graphic characteristics of individuals who received secondary prophylaxis did not differ significantly from the characteristics of persons who did not receive secondary PCP prophylaxis in both the univariate and multivariate analyses (Table 1).
Reasons for lack of PCP prophylaxis prior to a diagnosis of PCP
Among clinically eligible patients who were not receiving PCP prophylaxis, the most common reasons (non-mutually exclusive) were that they were unaware of their HIV status (22%) and that they were not receiving medical care for their HIV disease prior to their diagnosis of PCP (10%; Table 2).
Hospitalization for treatment of PCP
A total of 245 (75%) patients were hospitalized for PCP treatment. Hospitalization rates were similar for those who had received primary prophylaxis (74%) and those who had not (76%; P = 0.65). For hospitalized patients who were eligible for primary PCP prophylaxis, a median of eight medical unit days was recorded both for individuals who had used prophylaxis and for those who had not used primary prophylaxis. Among hospitalized patients, 10.7% of those who had received PCP prophylaxis and 9.3% of those who had not received prophylaxis required care in the intensive care unit (P = 0.72). For patients who had received care in the intensive unit, a median of 6 days was spent in the intensive care unit for patients who had received primary PCP prophylaxis, and a median of 5 days for persons who had not received primary prophylaxis (P = 0.77). These analyses were repeated, excluding patients who had died during their hospitalization, because short hospitalizations might reflect patients who were very ill and died shortly after their admission. The median number of days in the medical unit and in the intensive care unit remained similar for persons who had received primary PCP prophylaxis and those who had not.
Cost of preventable disease
A total of 212 individuals did not receive primary PCP prophylaxis, resulting in 144 potentially preventable cases, an estimated 864 days in the medical unit and 50 days in the intensive care unit. At a daily rate of US$ 1070 for care in the medical unit and US$ 2375 for daily care in the intensive care unit, the total hospital charges would be US$ 949 208 and estimated cost would be US$ 408 482.
PCP mortality
Seven (2.2%) patients died within 30 days of their PCP diagnosis. Primary prophylaxis was received by three of these seven persons and was not associated with mortality (P = 0.7).
Discussion
In this population-based study, we found that primary PCP prophylaxis was less likely to have been received by non-white patients and by those who were uninsured. However, we did not find any significant sociodemographic differences in the use of secondary prophylaxis against PCP.
Our data suggest that differences in use of primary PCP prophylaxis reflect knowledge of HIV serostatus and utilization of medical care. Most of the patients who were not receiving primary prophylaxis were unaware they were infected with HIV or were not in care prior to developing AIDS; only a small proportion of patients declined treatment or had a medical contraindication to the regimens. Our findings are similar to those of Gallant et al. [14], who reported that 43% of patients diagnosed with PCP in Baltimore who were not receiving prophylaxis were not known to have HIV infection. Lack of medical care was also a cause of missed prophylaxis in our study as well as in a survey of patients hospitalized with a first AIDS diagnosis at San Francisco General Hospital. This study found that approximately 25% had not received care for their HIV disease prior to their hospital admission [20]. Since AIDS is usually preceded by milder symptoms [21], fear or denial may have contributed to these patients not seeking care [22]. Once patients have experience with the medical system, PCP prophylaxis use may increase. The Multicenter AIDS Cohort study found that AIDS patients with a previous hospitalization and those who had an outpatient medical visit were more likely to receive PCP prophylaxis [23].
Previous studies have also found that PCP prophylaxis is less likely among non-whites [13-15]. The lower rates of care among non-whites may be due to cultural barriers to seeking medical care, less access to medical care facilities, differing beliefs about the efficacy of medical treatment, discrimination in the health-care setting, or other economic factors. Chaisson et al. [24] found that HIV disease progression and survival were not related to race, sex, drug use, or income among persons who received consistent medical care. Given the high cost of medical care, we were not surprised to find that persons without insurance were less likely to receive primary PCP prophylaxis. In a recent study [25], insurance status was not associated with use of aerosolized pentamidine for primary PCP prophylaxis. Had the investigators included other types of primary PCP prophylaxis, an association may have been found. Race was not a predictor of receipt of secondary prophylaxis in our study. Developing PCP may lessen barriers to care either because it is the first indication of HIV disease and results in contact with the medical system, or because persons who are diagnosed with AIDS at the time of their hospitalization for PCP are provided with public health insurance and other entitlements.
No decrease in frequency of hospitalization or in the length of stay among individuals who had received primary PCP prophylaxis was found. Our findings contrast with previous studies that have found that use of prophylaxis results in shorter hospital stays [26] or fewer hospitalizations and intensive care unit days [14]. The similarity in rate and duration of hospitalization may reflect both the higher socioeconomic status of AIDS patients in San Francisco as well as the large number of community support services available to promote outpatient management and reduce the length of hospital stays.
The cost of treating the estimated 144 patients with preventable PCP was nearly US$ 500 000. The cost of providing prophylaxis was not subtracted from the projected savings, and the other costs associated with the diagnosis and treatment of PCP, such as radiology, and other diagnostic and therapeutic procedures were not added to the total estimated costs of treating PCP. However, these costs are small compared with the daily hospital charges. Because a crude and conservative estimate of the effectiveness of PCP prophylaxis was used, we have probably underestimated the cost savings associated with providing all eligible patients with prophylaxis. A cost-effectiveness analysis estimated the cost savings associated with PCP prophylaxis at between US$ 98 million and US$ 124 million per year for every 100 000 persons treated [27].
Our study has several limitations. We relied on medical records and communication with clinicians to determine the use of prophylactic medication. Under-reporting of prophylaxis use may have occurred, especially among patients whose diagnosis and treatment of PCP occurred as outpatients, because our staff have limited access to private physician's office records. However, patients treated in private medical settings are more likely to be white, insured, and to be offered prophylaxis; including such patients in our study would have been likely to strengthen the association between being white and insured, and receiving prophylaxis. Relying on medical records to identify the predictors of prophylaxis use also prevented us from assessing the impact of socioeconomic status on use of prophylaxis because this information was not available in the medical record.
The criteria used for defining eligibility for use of primary PCP prophylaxis may have been too broad. In particular, individuals whose CD4 counts were less than 200 × 106/l or less than 20% of total circulating lymphocytes within 3 months of their PCP diagnosis were considered to have been eligible for primary prophylaxis. Individuals whose low CD4 counts occurred during or shortly after their episode of pneumonia may have had low CD4 counts as a result of PCP and would not have been clinically eligible prior to their acute illness. To evaluate this possibility, the analysis was repeated limiting eligibility for primary prophylaxis to patients with a low CD4 count prior to developing PCP. Non-whites and uninsured persons were still significantly less likely to have received primary PCP prophylaxis (non-whites versus whites: OR, 0.5; 95% CI, 0.2-1.0; uninsured versus insured: OR, 0.4; 95% CI, 0.2-0.9).
Fourteen individuals did not have a CD4 test result available prior to their PCP diagnosis or within 3 months of their diagnosis. These persons were classified as not clinically eligible for primary prophylaxis. Because these persons may in fact have met the criteria for primary prophylaxis, the data were reanalyzed, reclassifying them as eligible. Our results were essentially unchanged (non-whites versus whites: OR, 0.5; 95% CI, 0.2-0.8; uninsured versus insured: OR, 0.3; 95% CI, 0.2-0.7).
Our results may not be generalizable to cities other than San Francisco. However, given the strong AIDS activism and high community knowledge about AIDS in San Francisco, we believe that a similar study would find an even higher proportion of preventable cases of PCP elsewhere.
Although the definition of AIDS was expanded in 1993 to include individuals with HIV infection whose CD4 lymphocyte count was less than 200 × 106/l, we included individuals who met the 1993 CDC AIDS case definition due to low CD4 counts if their first opportunistic illness was PCP. Of the 341 persons in our study, 141 met the AIDS case definition because of CD4 lymphocyte depletion prior to developing PCP. These individuals were included because, unlike other AIDS diagnoses, having a low CD4 count would not necessarily have resulted in these individuals receiving ongoing primary medical care. We felt that excluding persons whose prior CD4 count was less than 200 × 106/l would have inserted a selection bias into our sample, because individuals who had a previous low CD4 count are not necessarily different from persons who had a previous CD4 count greater than 200 × 106/l.
To assess the possible impact that including persons who had a previous low CD4 count might have on our results, the data was reanalyzed after limiting the sample only to those individuals who had a low CD4 count prior to developing PCP. Lack of health insurance and non-white race remained predictors of persons less likely to have received primary PCP prophylaxis (OR, 0.63 and 0.91, respectively).
Our findings of lower rates of primary PCP prophylaxis use among non-whites and the uninsured suggest that these characteristics function as barriers to receiving recommended services. As with other cities hit hard by the AIDS epidemic, San Francisco receives funding through the Ryan White Care Act to provide free and low cost medical care for uninsured persons. Disadvantaged persons may be unaware of these services or the services may be inaccessible. Further studies, especially those conducted outside health-care settings, are needed to delineate the barriers to health-care utilization and to help clarify the relationship between race and use of health services. The large proportion of persons in our study who were unaware of their HIV infection suggests that current programs to encourage HIV testing among high-risk persons may be inadequate. San Francisco promotes anonymous and confidential HIV testing through outreach programs, through counseling services at tuberculosis, drug treatment, and sexually transmitted disease clinics, and through advertisements posted in public venues. Efforts to evaluate the effectiveness of these programs at reaching high-risk persons should be expanded. Expanding the number of testing sites and providing testing services in especially high-risk neighborhoods may be useful. The availability of home collection kits for HIV testing may facilitate testing among those for whom confidentiality concerns preclude testing at a private physician office or at a counseling and testing clinic. Although all publicly funded HIV testing programs maintain a policy of referring HIV-infected persons for medical care, there is no systematic follow-up to ensure that individuals keep their appointments. Providing transportation and extended office hours may help persons to overcome difficulties in keeping their referral appointments. Strengthening ties between testing programs and medical services may reduce the barriers to HIV-infected persons receiving adequate care.
References
1. Hay JW, Osmond DH, Jacobson MA: Projecting the medical costs of AIDS and ARC in the United States. J Acquir Immune Defic Syndr 1987, 1:466-85.
2. Fischel MA, Dickenson GM, LaVoie L: Safety and efficacy of sulfamethoxazole and trimethoprim chemoprophylaxis for Pneumocystis carinii pneumonia in AIDS. JAMA 1988, 259:1185-1189.
3. Leoung GS, Feigal DW, Montgomery AB, et al.: Aerosolized pentamidine for prophylaxis against Pneumocystis cariniipneumonia. N Engl J Med 1990, 323:769-775.
4. Hirschel B, Lazzarin A, Chopard P, et al.: A controlled study of inhaled pentamidine for primary prevention of Pneumocystis cariniipneumonia. N Engl J Med 1991, 324:1079-1083.
5. Kemper CA, Tucker RM, Lang OS, et al.: Low-dose dapsone prophylaxis of Pneumocystis carinii pneumonia in AIDS and AIDS-related complex. AIDS 1990, 4:1145-1148.
6. Bozzette SA, Finkelstein DM, Spector SA, et al.: A randomized trial of three anti- Pneumocystis agents in patients with advanced human immunodeficiency virus infection. N Engl J Med 1995, 332:693-699.
7. Centers for Disease Control: Guidelines for prophylaxis against Pneumocystis carinii pneumonia for persons infected with human immunodeficiency virus. MMWR 1989, 38 (suppl 5):1-9.
8. Centers for Disease Control: Recommendations against Pneumocystis carinii pneumonia for adults and adolescents infected with human immunodeficiency virus. MMWR 1992, 41 (RR-4):1-10.
9. Lidman C, Berglund O, Tynell E, Lindback S, Elvin K: Aerosolized pentamidine as primary prophylaxis for Pneumocystis carinii pneumonia: efficacy, mortality and morbidity. AIDS 1994, 8:935-939.
10. Hardy WD, Feinberg J, Finkelstein DM, et al.: A controlled trial of trimethoprim-sulfamethoxazole or aerosolized pentamidine for secondary prophylaxis of Pneumocystis carinii pneumonia in patients with the acquired immune deficiency syndrome. N Engl J Med 1992, 327:1842-1848.
11. Schneider MM, Hoepelman AI, Eeftinck Schattenkerk JK, et al.: A controlled trial of aerosolized pentamidine or trimethoprim-sulfamethoxazole for primary prophylaxis of Pneumocystis carinii pneumonia in patients with human immunodeficiency virus infection. N Engl J Med 1992, 327:1836-1841.
12. Centers for Disease Control and Prevention: USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with the human immunodeficiency virus: a summary. MMWR 1995, 44 (RR-8):1-34.
13. Moore RD, Stanton D, Gopalan R, Chaisson RE: Racial differences in the use of drug therapy for HIV disease in an urban community. N Engl J Med 1994, 330:763-768.
14. Gallant JE, McAvinue SM, Moore RD, Bartlett JG, Stanton DL, Chaisson RE: The impact of prophylaxis on outcome and resource utilization in Pneumocystis carinii pneumonia. Chest 1995, 107:1018-1023.
15. Piette J, Stein M, Mor V, et al.: Patterns of secondary prophylaxis with aerosol pentamidine among persons with AIDS [letter]. J Acquir Immune Defic Syndr 1991, 4:826-827.
16. Turner BJ, Markson LE, McKee LJ, Houchens R, Fanning T: Health care delivery, zidovudine use, and survivial of women and men with AIDS. J Acquir Immune Defic Syndr 1994, 7:1250-1262.
17. Rauch KJ, Rutherford GW, Echenberg DF, et al.: Surveillance of acquired immunodeficiency syndrome in San Francisco: evaluating the completeness of reporting. 114th Annual Meeting of the American Public Health Association and Related Organizations. Las Vegas, September 1986 [abstract 035].
18. Lemp GF, Hirozawa AM, Cohen JB, Derish PA, McKinney KC, Hernandez SR: Survival for women and men with AIDS. J Infect Dis 1992, 166:74-79.
19. Anon: Notice of Amount of Program Reimbursement, Exhibit E, Issued June 30, 1995. Sacramento: Blue Cross of California, Medicare Fiscal Intermediary; 1993.
20. Hecht FM, Wachter RM, Heller K, Chesney M: Failure to obtain early care for HIV [abstract]. J Gen Intern Med 1994, 9 (suppl 2):55.
21. Holmberg SD, Buchbinder SP, Conley LJ, et al.: The spectrum of medical conditions an symptoms before acquired immunodeficiency syndrome in homosexual and bisexual men infected with the human immunodeficiency virus. Am J Epidemiol 1995, 141:395-404.
22. Katz MH, Bindman AB, Komaromy MS: Coping with HIV infection: why people delay care [letter]. Ann Intern Med 1992, 117:797.
23. Graham NMH, Jacobson LP, Kuo V, Shmiel JS, Morgenstern H, Zucconi SL: Access to therapy in the multicenter AIDS Cohort Study, 1989-1992. J Clin Epidemiol 1994, 47:1003-1012.
24. Chaisson RE, Keruly JC, Moore RD: Race, sex, drug use and progression of human immunodeficiency virus disease. N Engl J Med 1995, 333:751-756.
25. Loue S, Slymen DJ, Morgenstern H, Whalen C: Health insurance status and utilization in Pneumocystis carinii pneumonia. J Gen Intern Med 1995, 10:461-463.
26. Mallal SA, Martinez OP, French MA, James IR, Dawkins RL: Severity and outcome of Pneumocystis carinii pneumonia (PCP) in patients with known and unknown HIV status. J Acquir Immune Defic Syndr 1994, 7:148-153.
27. Freedberg KA, Tosten ANA, Cohen CJ, Cotton DJ: Primary prophylaxis for Pneumocystis carinii pneumonia in HIV-infected people with CD4 counts below 200/mm3 : a cost-effectiveness analysis. J Acquir Immune Defic Syndr 1991, 4:521-531.
© Lippincott-Raven Publishers.