Diagnosis and management of central nervous system histoplasmosis.

Two cases of Histoplasma meningitis are presented, illustrating the difficulty in diagnosis and treatment. The first case occurred in a patient with acquired immunodeficiency syndrome as a relapse of disseminated histoplasmosis and resolved after prolonged treatment and ongoing antiretroviral therapy. The second case occurred in a cardiac allograft recipient as meningitis and focal brain lesions that responded to liposomal amphotericin B, but the patient died shortly after therapy was completed. Unfortunately, there are no prospective studies addressing the diagnosis and management of patients with histoplasmosis of the central nervous system from which to provide evidence-based guidelines for care. In the absence of such data, an approach will be presented on the basis of our experience and opinions.

HCV-coinfection is associated with diabetes and CD4 decline.

In February 2001, Dr. Robert Zackin became the first HIV-infected individual to receive a heart transplant. A biostatistician whose research focus is HIV, Dr. Zackin was the senior author of the paper published in the New England Journal of Medicine summarizing his case and providing 2-year follow-up from his successful transplant (N Engl J Med 2003;348:2323-8). Recently, Dr. Deborah J Cotton spoke with Dr. Zackin about life as both patient and researcher, the controversies surrounding solid-organ transplantation in HIV-infected individuals, and surviving AIDS and advanced cardiomyopathy.

Erroneously low or undetectable plasma human immunodeficiency virus type 1 (HIV-1) ribonucleic acid load, determined by polymerase chain reaction, in West African and American patients with non-B subtype HIV-1 infection.

The polymerase chain reaction (PCR) assay for plasma human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) inadequately quantitates virus load for some non-B HIV-1 subtypes because of genetic diversity in the gag region targeted by the PCR primers. Unexpectedly low or undetectable plasma HIV-1 RNA findings by PCR were a clue to non-B HIV-1 infections in patients in whom plasma HIV-1 RNA was found to be substantially higher when determined by a branched-chain deoxyribonucleic acid assay.

Detection and significance of splenomegaly on chest radiographs of HIV-infected outpatients.

AIM: The purpose of this study was to determine the prevalence of splenomegaly on chest radiographs of HIV-infected outpatients and to correlate with CD4 cell counts, opportunistic conditions, liver disease and the presence of intrathoracic disease on chest radiographs. METHODS: We reviewed sequential chest radiographs of 200 HIV Clinic outpatients at the Jacobi Medical Center, Bronx, New York, mixed with chest radiographs of 137 outpatients of unknown HIV status (control group) for the presence of splenomegaly and intrathoracic disease. Chest radiographic assessment of splenomegaly was correlated with computed tomography (CT) or ultrasound (US) in 90 out of 337 patients (27%). Clinical charts of all HIV-infected patients were reviewed for CD4 cell count, liver disease and opportunistic conditions including those associated with splenomegaly. The HIV-infected patients were divided into four groups by ascending CD4 cell count: Group 1 (0-50 cells/mm3), Group 2 (51-200 cells/mm3), Group 3 (201-500 cells/mm3) and Group 4 (>500 cells/ mm3). There were 118 men and 82 women with a mean age of 40 (range 20-60) years. Mean CD4 was 180 (range 2-1108) cells/mm3. We also reviewed all autopsies (n = 239) performed on HIV-infected patients between 1983 and 1995 at our institution to correlate splenic size with splenic pathology in that population. RESULTS: Splenomegaly was present on chest radiographs in 82 (41%) HIV-infected patients including: 36/84 (43%) Group 1, 23/49 (47%) Group 2, 18/46 (39%) Group 3, and 5/21 (24%) Group 4 (P = NS). Splenomegaly was present in 30/97 (31%) patients with no evidence of liver disease or opportunistic conditions known to be associated with splenomegaly. Forty-nine HIV-infected patients had 63 opportunistic conditions known to be associated with splenomegaly (mycobacterial and fungal infections, Kaposi sarcoma and lymphoma), half of whom had splenomegaly. Splenomegaly was present on chest radiographs in 18/137 (13%) controls. The presence or absence of splenomegaly on CT or US agreed with chest radiography in 89%. Among the autopsied patients, 135/239 (56%) had splenomegaly (splenic weight > or = 240 g). No specific pathogen was present in 93/135 (69%) enlarged spleens. In contrast, one or more opportunistic conditions were present in 26/104 (25%) normal weight spleens. CONCLUSION: In conclusion, splenomegaly is common in HIV-infected patients and was present in 41% of this series. Splenomegaly may be seen in HIV-infected patients without associated opportunistic conditions or liver disease and in the absence of specific splenic pathology. Chest radiography plays an important role in detecting splenomegaly and may lead to earlier diagnosis of HIV infection.

The case of the undetectable viral load.

AIDS: A case study is presented of an African-American gay man who tested positive for HIV in 1996 after going to a clinic for treatment of fever, mouth ulcers, and a dermatomal vesicular rash. He began treatment, was judged to be adherent to his regimen, and remained well clinically. However, despite a significant virologic response, his CD4 cell count never rose. Since these clinical findings were inconsistent and puzzling, the clinician suspected the man had a variant HIV-1 subtype that was not being measured by the viral load test, the Roche RT-PCR. The viral load testing process is described. This case demonstrates the difficulty in measuring viral load reductions in patients with variant subtypes of HIV-1. Viral load testing remains an important component of treatment management, but clinicians need to be reminded that it is not always accurate.^ieng

Another undectectable viral load: HIV-2.

AIDS: A case study is presented of a pregnant woman from Ghana whose prenatal screening indicated that she was HIV-positive. She was given AZT and 3TC to prevent transmitting the virus to her newborn, but declined to take the drugs, thinking they were unnecessary. The baby tested positive, and further testing of the mother revealed that they were infected with HIV-2, not HIV-1 for which they had been tested. HIV-2 is a lentivirus capable of causing the same clinical syndrome as HIV-1 with regard to CD4-cell depletions and opportunistic infections in some people. HIV-2 is not transmitted as easily via sexual intercourse or childbirth as is HIV-1. Common in West Africa, HIV-2 may be more widely spread than HIV-1. Treatment options for the patient are described.^ieng

Asymptomatic but discouraged.

AIDS: A case study is presented of a 62-year-old man diagnosed with AIDS in 1992. His treatment history is described briefly. Although the man remains asymptomatic, he is discouraged by his high viral loads despite antiretroviral treatment regimens, and by the lack of viral resistance to his drugs as demonstrated by genotyping. His case is reviewed by Elizabeth Jenny-Avital, MD, and Carlos Del Rio, MD, who discuss further treatment options.^ieng

Approach to the diagnosis of pulmonary disease in patients infected with the human immunodeficiency virus.

Patients infected with the human immunodeficiency virus are predisposed to develop a variety of common and uncommon infectious and neoplastic pulmonary diseases. Clinical information that can stratify the risk of occurrence of these pulmonary conditions includes: 1) CD4 cell count-the most important determinant; 2) concurrent antimicrobial therapy; 3) prior travel history; 4) known latent infections that may reactivate: and 5) underlying respiratory disease. Specific pulmonary diseases are discussed including: bacterial pneumonia, bronchitis, mycobacterial and fungal infections, pneumocystis carinii pneumonia, toxoplasmosis, cytomegalovirus, Kaposi sarcoma, lymphoma, and lung cancer. A differential diagnosis can be generated based on the chest radiographic pattern. Focal or multifocal areas of consolidation usually represent conventional bacterial pneumonia or, less commonly, tuberculosis. In severely immunocompromised patients, unusual diseases causing consolidation should be considered including: Rhodococcus infection, nocardiosis, cryptococcosis, aspergillosis, and lymphoma. Nodules can be present in tuberculosis, histoplasmosis, cryptococcosis, and Kaposi sarcoma. Interstitial opacities are common in pneumocystis carinii pneumonia, histoplasmosis, and cytomegalovirus pneumonia. Cavitation and cysts are features of pneumocystis carinii pneumonia, tuberculosis, aspergillosis, and lung cancer. Disease of the airways is increasingly recognized in those with acquired immunodeficiency syndrome. Lymphadenopathy is most common in mycobacterial infection, but can be a feature of fungal infection, lymphoma, Kaposi sarcoma, and lung cancer. The combined use of clinical information, knowledge of typical conditions associated with the human immunodeficiency syndrome, and radiographic patterns offers a useful approach to the diagnosis of pulmonary disease in the patient with the human immunodeficiency virus.

HCV in an HIV-infected man.

AIDS: A case is reported of a 31-year-old former IV drug user who had been using AZT for one year. Results of a routine blood test showed that the patient was positive for hepatitis C viral (HCV) antibodies. Over a 5-year period, he was treated with a variety of antiretroviral agents, some of which were stopped because of increased liver enzymes and high bilirubin levels. The patient died in the fifth year of treatment due to complications of advanced liver disease, including hemorrhage, hepatorenal syndrome, and hepatic encephalopathy. Since HCV is nearly universal in IV drug users, serology should be performed in all HIV-infected patients with any history of IV drug use or cocaine snorting, and on all patients with signs of liver disease. Physicians treating co-infected patients must also be aware of subtle signs of asymptomatic liver disease.^ieng

Occult gastrointestinal Kaposi's sarcoma in an HIV-infected African man.

AIDS: A case report is presented of a 33-year-old HIV-positive African-American male who was diagnosed with occult gastrointestinal Kaposi's sarcoma (KS). Symptoms, diagnosis, and treatment efforts are detailed. It was hoped that treatment with a triple antiretroviral regimen would resolve his gastrointestinal symptoms, however, the patient experienced adverse effects which were attributed to the antiretroviral treatment. These adverse effects continued even after the treatment ceased; a decision was made to begin minimally active chemotherapy. The patient began improving dramatically after the first treatment. The case history presented suggests that widespread and severe KS does not necessarily indicate a hopeless prognosis, particularly in patients who can experience immune reconstitution as a result of antiretroviral therapy. Newer agents for treating visceral KS, the occurrences of KS in specific populations, and the emergence of KS-associated herpesvirus or human herpesvirus-8 were also discussed.^ieng

Hepatitis C.

Hepatitis C virus commonly causes chronic liver disease. Chronicity as a result of the failure of T-cell-mediated immunity, liver damage caused by cytotoxic T lymphocytes, and the evolution of genetic diversity characterize hepatitis C infection. Progression, typically silent, is determined by sex, age, alcohol and immune status. Interferon and ribavirin are effective in the substantial minority of patients with less advanced fibrosis and lower hepatitis C viral loads.

Effect of HIV status on chest radiographic and CT findings in patients with tuberculosis.

AIM: To compare the chest radiographic and chest CT findings of tuberculosis according to HIV status. PATIENTS AND METHODS: Ninety-eight HIV-tested patients with cultures positive for Mycobacterium tuberculosis (Mtb) between January 1991 and December 1993 whose clinical charts and radiographic records were available for review formed the study population. There were 67 HIV-positive patients (51 men, 16 women) and 31 HIV-negative patients (23 men, 8 women). Chest CT scans were available for review in 15 HIV-positive and four HIV-negative patients. RESULTS: On chest radiographs, HIV-positive patients had mediastinal lymphadenopathy (60% vs. 23%) and atypical infiltrates (55% vs. 10%) significantly more frequently than HIV-negative patients. Conversely, HIV-negative patients had infiltrates typical for reactivation tuberculosis (77% vs. 30%) and cavitation (52% vs. 18%) significantly more frequently than HIV-positive patients. The chest CT scans showed a similar trend, but significant differences were only seen regarding more frequent bilateral mediastinal lymphadenopathy in HIV-positive patients and more frequent cavitation in HIV-negative patients. CONCLUSION: This study demonstrates significant differences in chest radiographic and chest CT appearances of tuberculosis according to HIV status. HIV-positive patients have more frequent atypical infiltrates and mediastinal lymphadenopathy, and less frequent cavitation and infiltrates typical for reactivation tuberculosis than do HIV-negative patients.