• DOI:10.7326/0003-4819-124-7-199604010-00003
• Corpus ID: 20023137

Natural History of Opportunistic Disease in an HIV-Infected Urban Clinical Cohort

@article{Moore1996NaturalHO,
  title={Natural History of Opportunistic Disease in an HIV-Infected Urban Clinical Cohort},
  author={R. D. Moore and Richard E. Chaisson},
  journal={Annals of Internal Medicine},
  year={1996},
  volume={124},
  pages={633-642}
}

• R. Moore, R. Chaisson
• Published 1 April 1996
• Medicine
• Annals of Internal Medicine

Since the beginning of the human immunodeficiency virus (HIV) epidemic, opportunistic infections and cancers have been recognized as common complications of HIV infection [1-3]. As immunosuppression from HIV infection progresses, the overall incidence of opportunistic disease increases [4, 5]; however, the risk for individual opportunistic illnesses varies with the specific degree of immunosuppression [6]. For example, infections with herpesviruses, Candida species, or pyogenic bacteria may occur in asymptomatic persons with moderate immunosuppression [7], whereas the risk for Pneumocystis carinii pneumonia markedly increases when the CD4+ count is less than 200 cells/mm3 [8, 9]. Mycobacterium avium complex bacteremia, cytomegalovirus infection, and non-Hodgkin lymphoma typically develop when the CD4+ count is less than 100 cells/mm3 [10-12]. Because of the substantial morbidity and mortality associated with opportunistic illness, much effort has been directed toward developing preventive interventions. One of the more successful targets of preventive therapy has been P. carinii pneumonia, for which the use of trimethoprim-sulfamethoxazole and other interventions has reduced the associated morbidity and mortality [13-16]. Other preventive interventions include those for M. avium complex bacteremia, deep fungal infections such as cryptococcosis, Candida esophagitis, toxoplasmosis, and tuberculosis [17-20]. Nevertheless, opportunistic illnesses continue to be a ubiquitous complication of advanced HIV infection that exacts a heavy toll in terms of morbidity and mortality. Since 1985, the Johns Hopkins Hospital and University have operated a comprehensive primary and subspecialty clinical practice for treating patients with HIV infection. In this practice, patient management is individualized according to the needs and preferences of patients and their clinicians, but prophylaxis for opportunistic illness generally adheres to accepted treatment guidelines [21]. This practice allows the opportunity to assess the development over time of opportunistic disease as a complication of HIV infection, the distribution of the CD4+ counts at which opportunistic disease occurs, the duration of survival after opportunistic disease develops, and the effect of preventive interventions introduced in the past several years on the occurrence of opportunistic infections and cancers in clinical practice. The contemporary natural history of opportunistic disease in an urban population may be particularly relevant given the recent trends toward higher rates of HIV infection and the acquired immunodeficiency syndrome (AIDS) in women, members of racial and ethnic minority groups, and injection drug users [22, 23]. Methods Study Sample The Johns Hopkins AIDS Service provides longitudinal primary and subspecialty care for many HIV-infected patients in the Baltimore metropolitan area. To be registered in the clinic, patients must have a previous diagnosis of HIV infection. Each new patient has an initial comprehensive medical and psychosocial evaluation by a physician or physician's assistant, a nurse, and a social worker. In this evaluation, standardized instruments are used to collect extensive demographic, clinical, laboratory, pharmaceutical, and psychosocial characteristics [24]. Thereafter, similar data are collected every 6 months by review of all ambulatory and inpatient medical records, supplemented by automated reviews of Johns Hopkins Health System databases and reviews of all available records from facilities other than Johns Hopkins. Trained medical records technicians abstract these data onto standard data collection instruments. To ensure a high rate of longitudinal follow-up, medical records from other institutions in which the patients may have received care are routinely sought. Information on death is obtained from patient charts and from a separate death registry maintained by the clinic that receives reports from families, funeral homes, other medical institutions, and local coroners. In addition, the names of patients whose vital status is unknown for more than 12 months are searched for in the death records of the Maryland Bureau of Vital Records and the National Death Index. Nurses and physicians associated with the HIV clinic check the validity of a 10% sample of all collected data. If systematic error is identified, personnel are retrained, and the affected variable is reabstracted on all patients. The entry dates of our study population currently extend from July 1989 to December 1994. Follow-up extends to April 1995. Only about 12% of patients in the study group were censored before dying. Definitions We focused on opportunistic diseases that are included in Category C of the AIDS surveillance criteria of the Centers for Disease Control and Prevention [25]. The following diagnoses and criteria were used in our analyses: 1. Pneumocystis carinii pneumonia: a) microbiological identification using induced sputum or bronchoalveolar lavage fluid or b) symptomatic presentation with compatible chest radiologic study and clinical response to an appropriate therapeutic regimen. 2. Mycobacterium avium complex bacteremia: isolation from blood culture required but respiratory isolation alone not included. 3. Cytomegalovirus infection: retinitis diagnosed by clinically compatible examination by an ophthalmologist; colitis and esophagitis diagnosed by histopathologic confirmation of cytomegalovirus inclusions. 4. Mycobacterium tuberculosis disease: isolation in culture from pulmonary specimen, blood, or other tissue. 5. Toxoplasma gondii encephalitis: symptomatic clinical presentation with compatible computed tomographic scan or magnetic resonance image of the brain and response to appropriate therapy; nonresponse to therapy shown by histopathologic evidence of the organism; neurologist-confirmed diagnosis. 6. Candida esophagitis: symptomatic presentation of dysphagia or difficulty in swallowing with endoscopic evidence of invasive fungi or with clinical response to appropriate therapy. 7. Cryptococcal meningitis: evidence or culture of the organism in the cerebrospinal fluid. 8. Disseminated herpes simplex viral disease: identification of organism in tissue; includes chorioretinitis, visceral organ infection, central nervous system infection, or widespread cutaneous involvement. 9. Cryptosporidiosis: symptomatic clinical presentation with identification in stool specimen or intestinal biopsy specimen. 10. Kaposi sarcoma: typical clinical appearance or histopathologic confirmation. 11. Non-Hodgkin lymphoma: histopathologic confirmation of high-grade cancer. 12. Progressive multifocal leukoencephalopathy: symptomatic neurologic presentation with compatible radiologic imaging study of the brain and confirmation with or without biopsy by a neurologist. 13. The wasting syndrome: involuntary loss of more than 10% of the baseline body weight with chronic diarrhea or chronic weakness and enigmatic fever; no specific cause despite appropriate evaluation. 14. AIDS dementia complex: disabling cognitive and neurologic motor dysfunction interfering with activities of daily living; neurologist-confirmed diagnosis. 15. Herpes zoster: clinical presentation with pain and compatible dermatologic or disseminated rash. Analysis Our analyses focused on opportunistic disease that was diagnosed after enrollment into the Johns Hopkins HIV Clinic. We used the date at which each of these infections or cancers was diagnosed for the first time in the patient, with one exception: We analyzed both the first diagnosis of P. carinii pneumonia (primary P. carinii pneumonia) and the second diagnosis of P. carinii pneumonia (secondary P. carinii pneumonia). We limited the study group to patients whose CD4+ lymphocyte count at enrollment was less than 300 cells/mm3, because these infections or cancers seldom occur at higher CD4+ counts. We calculated the incidence rate of each diagnosis by using the number of new diagnoses of the opportunistic disease that occurred after entry into the clinic as the numerator and the total number of person-years in patients who had not yet been assigned that specific diagnosis as the denominator. We calculated Poisson 95% CIs using standard formulas [26]. We further compared the incidence rates between the earlier period (1989 through 1992) and later period (1993 through 1995) using Poisson regression [27]. This definition of earlier and later periods provided an approximately equal amount of person-time in each comparison group. We also assessed the association between preventive drug therapy and the incidence of selected opportunistic infections using multivariate Poisson regression with adjustment for CD4+ lymphocyte count. These preventive therapies included prophylaxis for primary and secondary P. carinii pneumonia (trimethoprim-sulfamethoxazole, aerosolized pentamidine), toxoplasmosis (trimethoprim-sulfamethoxazole), M. avium complex bacteremia (rifabutin), and candidiasis and cryptococcal meningitis (fluconazole). Dapsone could not be analyzed because it was used infrequently. We defined these drugs as being used for preventive therapy if they were given regularly (usually once daily; trimethoprim-sulfamethoxazole, however, could be given three times weekly). Patients developing the opportunistic infection of interest were considered to have preventive therapy failure only if therapy had first been used at least 90 days before diagnosis. This decision was made to minimize the chance that these drugs were started as therapy in patients already suspected of having the infection. We next determined the nearest CD4+ lymphocyte count within a maximum of 6 months before the diagnosis of each of the opportunistic illnesses. For each opportunistic disease, we examined the distribution of CD4+ counts, including the mean, median, and first and third quartiles (that is, the 25th and 75th percentiles). We then calculated the probabi