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Racial Differences in the Use of Drug Therapy for HIV Disease in an Urban Community

Richard D. Moore, David Stanton, Ramana Gopalan, and Richard E. Chaisson

N Engl J Med 1994; 330:763-768March 17, 1994

Abstract

Background

Guidelines for drug therapy in human immunodeficiency virus (HIV) disease are based primarily on the stage of the disease. To determine whether sociodemographic characteristics of patients influence drug therapy in practice, we analyzed the use of antiretroviral therapy and prophylactic therapy for Pneumocystis carinii pneumonia (PCP) in an urban population infected with HIV.

Methods

All patients presenting for the first time to our HIV clinic from March 1990 through December 1992 were enrolled. Data on sociodemographic and clinical variables and on drug use were collected at the time of presentation and after six months. We asked whether patients with CD4+ cell counts of 500 or less per cubic millimeter were receiving antiretroviral therapy at the time of presentation, and whether patients with CD4+ cell counts of 200 or less per cubic millimeter were receiving PCP prophylaxis.

Results

Among the 838 patients enrolled, 656 (79 percent) were blacks, 167 (20 percent) were non-Hispanic whites, and 15 (2 percent) were Asian or Hispanic or were not racially classified. There were no racial differences in the stage of HIV disease at the time of presentation. However, there were racial disparities in the receipt of antiretroviral therapy: 63 percent of eligible whites but only 48 percent of eligible blacks received such therapy (P = 0.003). PCP prophylaxis was received by 82 percent of eligible whites but only 58 percent of eligible blacks (P<0.001). There were no significant differences in the receipt of drug therapy with respect to age, sex, mode of HIV transmission, type of insurance, income, education, or place of residence. In a logistic-regression analysis, race was the feature most strongly associated with the receipt of drug therapy. When blacks were compared with whites, the adjusted relative odds were 0.59 (95 percent confidence interval, 0.38 to 0.93) for the receipt of an antiretroviral agent and 0.27 (95 percent confidence interval, 0.13 to 0.56) for the receipt of PCP prophylaxis.

Conclusions

Among patients infected with HIV, blacks were significantly less likely than whites to have received antiretroviral therapy or PCP prophylaxis when they were first referred to an HIV clinic. This disparity suggests a need for culturally specific interventions to ensure uniform access to care, including drug therapy, and uniform standards of care.

Media in This Article

Table 1Base-Line Characteristics of the 838 HIV-Infected Patients in the Study Cohort.
Table 2Use of Antiretroviral Agents at Presentation in Patients with CD4+ Lymphocyte Counts of 500 Cells per Cubic Millimeter or Less.
Article

Since the approval in 1987 of zidovudine, the first clinically effective form of antiretroviral therapy,1 a number of prophylactic and therapeutic drugs have been introduced for the treatment of patients with human immunodeficiency virus (HIV) disease2-12. In addition, over the past few years the most effective drug regimens and dosing schedules have been defined, as well as the stages of disease at which several of these drugs are most effectively used. The guidelines of the National Institute of Allergy and Infectious Diseases for the treatment of HIV-infected persons specify that antiretroviral therapy with zidovudine should begin when the CD4+ lymphocyte count falls to 500 cells per cubic millimeter or less13. This recommendation is based on the results of two clinical trials demonstrating the efficacy of zidovudine therapy for early treatment14,15. One of the most common opportunistic infections associated with advanced HIV infection is Pneumocystis carinii pneumonia (PCP)16. The guidelines of the Public Health Service specify that prophylactic treatment for PCP should begin when the CD4+ lymphocyte count reaches 200 cells per cubic millimeter or less17.

HIV infection has disproportionately affected racial and ethnic minorities in the United States18. Despite clinical recommendations that uniform standards of prescription-drug therapy be followed regardless of sociodemographic factors (such as sex, race, and age) or behavioral factors, such as the mode of HIV transmission (e.g., injection-drug use or homosexual contact), there is evidence to suggest dissimilar demographic patterns of prescription-drug use19-21. The reasons for the differences in the use of drug therapy are unknown. Physicians' prescribing practices may vary inappropriately according to the patient's sociodemographic characteristics. The patient's ability to pay, the presence of certain types of behavior, such as injection-drug use, and other social barriers may also affect access to, and receipt of, appropriate therapy.

To quantify sociodemographic differences in prescription-drug use in patients with HIV infection and to delineate the associated factors, we analyzed drug use in a heterogeneous urban cohort of HIV-infected patients presenting for comprehensive HIV care.

Methods

The Johns Hopkins Hospital AIDS Service provides long-term primary and subspecialty care for the majority of HIV-infected patients in the Baltimore metropolitan area. To be registered in the clinic, patients must have had HIV infection diagnosed by a Maryland physician. In our patients, the mean interval between such a diagnosis and entry into the clinic was 19 months. Since December 1988, every new patient has undergone a comprehensive medical and psychosocial evaluation by either a physician or a physician's assistant, along with a nurse and a social worker, using standardized instruments to collect extensive data on demographic, clinical, laboratory, pharmaceutical, and psychosocial characteristics22.

In this study, we assessed data collected at enrollment and also at follow-up six months later. Data on the use of drug therapy were obtained for all three antiretroviral drugs licensed at the time of the study: zidovudine, didanosine, and zalcitabine. Data were also collected on the drugs used for PCP prophylaxis: trimethoprim-sulfamethoxazole, aerosolized pentamidine, and dapsone. Information about drug use was obtained from the patients' reports and from accompanying medical records when available.

To determine whether there were demographic differences in the stage of HIV disease at presentation, we divided the patients into three groups according to CD4+ lymphocyte count ( ≤ 200, 201 to 500, and >500 cells per cubic millimeter) and assessed each group with respect to age, sex, race, mode of HIV transmission, insurance coverage, place of residence, income, and level of education. These variables were categorized as follows: age, as 30 years or less, 31 to 44 years, and 45 or more years; race was defined as black, white, or other (all the patients in this category were Asian or Hispanic or could not be classified). The mode of HIV transmission was defined as homosexual contact, injection-drug use, homosexual contact combined with injection-drug use, heterosexual contact, or other. Insurance coverage was defined as Medicaid coverage, commercial insurance (including Blue Cross-Blue Shield and private insurance), no insurance, or other (including Medicare and membership in a health maintenance organization [HMO]). Level of education was defined as not including a high-school degree, including a high-school degree, or including education beyond the high-school level. Place of residence was defined as East Baltimore (the clinic catchment area), all other parts of Baltimore, and areas outside Baltimore. Data on income included legal income only. Some data were missing for race, insurance coverage, education, income, and place of residence.

From interviews with each patient and the medical record, we determined whether the patient could identify and name a source from which he or she had obtained medical care before visiting our clinic for the first time. A usual source of care was defined as a personal physician, physician's assistant, or nurse practitioner or a clinic, HMO, or other practice entity known to provide comprehensive care. However, we did not have information on the extent or regularity of the care provided by these sources. Determinations of a usual source of care were made only for patients with base-line CD4+ lymphocyte counts of 500 cells per cubic millimeter or less.

Since antiretroviral therapy is indicated only for patients with CD4+ lymphocyte counts of 500 cells per cubic millimeter or less, we restricted our analysis of the use of these drugs to those patients. Since PCP prophylaxis is indicated only for patients with CD4+ lymphocyte counts of 200 cells per cubic millimeter or less, we restricted our analysis of the use of this prophylaxis to those patients. This was consistent with our subsequent findings, since only 8 percent of patients with CD4+ lymphocyte counts greater than 500 cells per cubic millimeter had received antiretroviral therapy and only 9 percent of patients with CD4+ counts greater than 200 cells per cubic millimeter had received PCP prophylaxis. In our cohort, the most commonly used antiretroviral drug was zidovudine (92 percent); only a small number of patients used didanosine (5 percent) or zalcitabine (3 percent). The drugs used for PCP prophylaxis included trimethoprim-sulfamethoxazole (59 percent), aerosolized pentamidine (27 percent), and dapsone (13 percent).

We attempted to determine whether the patients' use of antiretroviral therapy or PCP prophylaxis at the time of enrollment differed according to demographic characteristics. We compared drug use between demographic strata by the chi-square test23 and sought to determine whether differences in other base-line variables could explain demographic differences in use. The comparisons were performed again by the chi-square test after the demographic groups were stratified according to CD4+ lymphocyte counts at enrollment. We performed a multivariate analysis using logistic regression to assess the associations between multiple variables and drug use23. One of the laboratory values obtained was the mean corpuscular volume. This value is elevated in most patients who take zidovudine and was used as a marker of compliance with zidovudine therapy24. The t-test was used to compare the average mean corpuscular volume between groups23. Two-tailed P values are presented for all statistical analyses.

The research protocol was approved by the Johns Hopkins Joint Committee on Clinical Investigation. Informed consent was not required for this observational study.

Results

The demographic characteristics of the HIV-infected patients presenting to the clinic from March 1990 through December 1992 are shown in Table 1Table 1Base-Line Characteristics of the 838 HIV-Infected Patients in the Study Cohort.. The cohort was predominantly male (69 percent) and black (79 percent), with injection-drug use as the primary mode of HIV transmission (47 percent). The majority of patients (56 percent) were 31 to 44 years of age. At presentation, the patients were evenly divided into three groups with regard to CD4+ lymphocyte counts: those with 200 cells per cubic millimeter or less (34 percent), those with 201 to 500 cells per cubic millimeter (36 percent), and those with more than 500 cells per cubic millimeter (30 percent). We further analyzed the demographic characteristics according to the CD4+ lymphocyte count at presentation. Men were more likely than women to present first to the clinic after the CD4+ lymphocyte count had declined to 500 cells per cubic millimeter or less; similarly, persons 31 years old or older were more likely than younger persons to present after such a decline in the CD4+ count. There were no differences among patients according to CD4+ lymphocyte count at presentation with respect to race or other characteristics, including insurance coverage, place of residence, annual income, and level of education.

We examined the frequency of prescription-drug use at presentation according to these demographic categories (Table 2Table 2Use of Antiretroviral Agents at Presentation in Patients with CD4+ Lymphocyte Counts of 500 Cells per Cubic Millimeter or Less.). Blacks were less likely than whites (48 vs. 63 percent) to have received any of the antiretroviral drugs (P = 0.003). Patients less than 30 years old, those without insurance, and those from East Baltimore were less likely than the other patients to be receiving antiretroviral drugs at entry, although these differences were not statistically significant. Similarly, blacks were significantly less likely than whites (58 vs. 82 percent) to have received prophylaxis for PCP at presentation (P<0.001) (Table 3Table 3PCP Prophylaxis at Presentation in Patients with CD4+ Lymphocyte Counts of 200 Cells per Cubic Millimeter or Less.). No other significant differences were found.

To determine whether the differences between racial groups in the use of antiretroviral drugs and PCP prophylaxis were associated with other cofactors, we analyzed the use of these therapies according to race and other demographic characteristics. Table 4Table 4Percentages of Blacks and Whites Receiving Antiretroviral Therapy or PCP Prophylaxis at Presentation. shows that there was less frequent use of antiretroviral therapy and PCP prophylaxis at the time of first presentation by blacks than by whites according to most other demographic variables. This suggests that racial differences in drug therapy occur regardless of the patient's other characteristics, including income, insurance status, mode of HIV transmission, and place of residence. We also examined the time from the diagnosis of HIV infection to entry into the clinic for patients with CD4+ lymphocyte counts of 500 cells per cubic millimeter or less and found that this interval was somewhat shorter for blacks (mean, 20 months; 95 percent confidence interval, 18 to 22) than for whites (mean, 25 months; 95 percent confidence interval, 20 to 30).

In a logistic-regression analysis, we examined whether racial differences in drug use could be explained by differences in other demographic factors at presentation (Table 5Table 5Multivariate Logistic-Regression Analysis of Demographic Characteristics Associated with Drug Use.). Racial differences continued to be present after adjustment for all the other factors. The relative odds for the receipt of antiretroviral therapy by blacks was 0.59 (95 percent confidence interval, 0.38 to 0.93), and the relative odds for the receipt of PCP prophylaxis was 0.27 (95 percent confidence interval, 0.13 to 0.56) (P = 0.02 and P<0.001, respectively). Significant differences were also found for age less than 31 years (relative odds, 0.63; 95 percent confidence interval, 0.43 to 0.94) and lack of insurance (relative odds, 0.60; 95 percent confidence interval, 0.39 to 0.93) for the receipt of antiretroviral therapy, and residence in East Baltimore (relative odds, 0.55; 95 percent confidence interval, 0.32 to 0.94) for PCP prophylaxis.

To assess whether patients for whom zidovudine had been prescribed were taking the drug at entry, we compared the mean corpuscular volume in patients who reported zidovudine use with that in patients not reporting such use and found means of 95 fl (95 percent confidence interval, 94 to 96) and 88 fl (95 percent confidence interval, 87 to 89), respectively (P<0.001). Notably, among blacks the average mean corpuscular volume in patients receiving zidovudine was 93 fl (95 percent confidence interval, 91 to 95), as compared with 88 fl (95 percent confidence interval, 87 to 89) in patients not receiving zidovudine. Among whites, the average mean corpuscular volume in patients receiving zidovudine was 101 (95 percent confidence interval, 98 to 104), as compared with 89 (95 percent confidence interval, 87 to 91) in patients not receiving the drug. The mean difference of 8 fl between blacks and whites was significant (P<0.001).

A usual source of care was identified by 67 of 113 whites (59 percent) and 150 of 437 blacks (34 percent) (P<0.001). Forty-nine of 67 whites (73 percent) and 92 of 150 blacks (61 percent) who identified a usual source of care had received an antiretroviral drug (P = 0.092). In the subgroup of patients with CD4+ lymphocyte counts of 200 cells per cubic millimeter or less, 32 of 39 whites (82 percent) and 46 of 78 blacks (59 percent) who identified a usual source of care had received PCP prophylaxis (P = 0.013).

Finally, the results of the six-month interim follow-up were similar among blacks and whites and represented 96 percent and 94 percent, respectively, of patients eligible for follow-up. No racial differences in the use of either antiretroviral therapy or PCP prophylaxis were found after six months. Antiretroviral therapy had been received by 81 percent of the blacks and 84 percent of the whites. PCP prophylaxis had been received by 92 percent of the blacks and 98 percent of the whites.

Discussion

Our analysis of an HIV-infected urban cohort showed that blacks were less likely than whites to have had either antiretroviral therapy or PCP prophylaxis prescribed before they came to our clinic for care. Because a provider may have prescribed a treatment for which the patient could not pay, it is notable that the data on insurance coverage and income did not explain this racial disparity. Nor did behavior such as injection-drug use, demographic characteristics such as sex and age, or socioeconomic factors such as the patient's level of education and place of residence appear to explain the racial difference.

Our HIV service is the principal referral site in Maryland for patients with HIV infection diagnosed elsewhere. As our analysis of patients' demographic characteristics at presentation shows, both black and white patients are referred to the clinic more often in later than in earlier stages of the disease, as demonstrated by the fact that 70 percent of patients had CD4+ lymphocyte counts of 500 cells per cubic millimeter or less. The slightly shorter interval between the diagnosis of HIV infection and presentation among blacks than among whites did not explain the differences in treatment. We learned whether the patient could identify a physician or comprehensive health care facility as a usual source of care, but we did not have detailed information about the extent to which these patients had used such resources before their first visit to us. With this qualification, our analysis suggested that blacks were less likely than whites to have a usual source of care through which they could receive appropriate HIV prophylactic-drug therapy before their referral to our clinic. Recent data indicate that HIV infection increasingly affects lower-income residents of inner cities, who are predominantly young and black25. This appears also to describe a group of people who have historically neither sought nor had access to medical care, particularly preventive medical care26. Blacks, especially younger men, are the group least likely to have a regular primary care physician27. A recent study showed that HIV-infected non-whites are more likely than whites with comparable CD4+ counts to be admitted to a hospital and less likely to use outpatient care28.

Barriers to the spread of information may also affect blacks more than whites. Beliefs about the benefits and risks of treating hypertension relate to differences between blacks and whites in the use of medical care29. Blacks appear to have less knowledge of heart-attack symptoms30 and the detection and treatment of cancer31. Misconceptions about HIV disease and the acquired immunodeficiency syndrome (AIDS) have been shown to be more common among blacks than whites,32 and distrust of health authorities may also be a barrier33. If we assume that the response of the mean corpuscular volume to zidovudine in blacks is similar to that in whites,24 our finding of a lower average mean corpuscular volume in blacks suggests that blacks may have lower compliance with zidovudine therapy than whites.

Still another potential barrier to care for blacks relates to the prescribing habits of care providers. There is evidence to suggest that the likelihood of a physician's recommending a therapeutic regimen may be influenced by the patient's race. Members of minority groups are less likely than non-Hispanic whites to be offered treatment (surgical or other) for coronary artery disease,34,35 analgesia for long-bone fractures,36 treatment of alcoholism,37 erythropoietin for end-stage renal disease,38 and rehabilitation after a mastectomy39. Our data indicate that among patients who identified a usual source of care, fewer blacks than whites received therapy. This is the case despite evidence indicating that there are probably no valid reasons for racial disparities in drug prescribing for HIV disease40-42.

Such barriers to care for young blacks contrast with the care received by the predominantly white, middle-class gay community, which has organized support systems through which medical care is actively sought, particularly in the early stages of the disease. The efforts of the gay community with regard to delivery of care and research in HIV disease represent a model of involvement by patients in medical care43. Our results suggest that there may be a need for culturally appropriate efforts to promote early preventive care in urban black populations. This need was emphasized in a recent review of barriers to the treatment of AIDS in intravenous drug users belonging to ethnic minorities44. One model for such an effort is a community-based partnership between an academic medical center and a high-risk urban black population, coordinated through churches45. Our six-month follow-up data suggest that without a referral center dedicated to the comprehensive treatment of HIV disease, inequalities in care may persist.

Although our results indicate that blacks may not have the same access as whites to recommended therapeutic care, we do not know whether these differences in access result in different outcomes. Our cohort does not have sufficient follow-up to permit us to determine whether rates of survival, progression to AIDS, or the development of PCP and other opportunistic conditions differ over time between blacks and whites. Two previous studies in urban communities found no racial differences in survival after a diagnosis of AIDS, although for the most part these studies predated contemporary antiretroviral and other therapy46,47. There are nearly 60,000 excess deaths per year among blacks as compared with whites48. Stroke, diabetes, severe hypertension, and renal failure are all more common in blacks than in whites26. The increasing shift of HIV disease to poor urban communities in which the lack of preventive care has resulted in increased morbidity and mortality from other diseases underscores the need for effective intervention to improve access to care.

Supported by a grant (R01-HS07809-01) from the Agency for Health Care Policy and Research and by a contract from the Maryland Department of Health and Mental Hygiene.

We are indebted to Darrell Forney, Sharon McAvinue, and Linda Locklear for their contributions to the creation and analysis of these data.

Source Information

From the Johns Hopkins University School of Medicine, 1830 E. Monument St., Rm. 8059, Baltimore, MD 21205, where reprint requests should be addressed to Dr. Moore.

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