David N. Chernoff

Cardiac manifestations of human immunodeficiency virus infection: a two-dimensional echocardiographic study.

To determine the prevalence of cardiac abnormalities in patients with human immunodeficiency virus (HIV) infection, two-dimensional Doppler echocardiography was performed on 70 consecutive patients with HIV infection, including 51 with acquired immunodeficiency syndrome (AIDS), 13 with AIDS-related complex and 6 with asymptomatic HIV infection. Of the 70 patients, 36% were hospitalized and 64% were ambulatory at the time of evaluation. The average age was 37 years; 93% were homosexual men. Echocardiographic findings included dilated cardiomyopathy in eight patients (11%), pericardial effusions in seven patients (10%) (one with impending tamponade), pleural effusion in four patients (6%) and mediastinal mass in one patient (1%). Among the 25 hospitalized patients, echocardiographic abnormalities were noted in 16 (64%), whereas among the 45 ambulatory patients, the only abnormality noted was mitral valve prolapse in 3 patients (7%) (p less than 0.0001). Dilated cardiomyopathy was the only echocardiographic lesion more common in the 25 hospitalized patients than in 20 hospitalized control patients with acute leukemia. Symptoms of congestive heart failure responded to conventional therapy. Cardiac lesions were associated with active Pneumocystis carinii pneumonia and low T helper lymphocyte counts. Dilated cardiomyopathy of unknown origin may be more common than was previously recognized in hospitalized, acutely ill patients with AIDS, but is uncommon in ambulatory patients with HIV infection. Echocardiography should be considered in the evaluation of dyspnea in hospitalized patients with HIV infection, especially those with dyspnea that is out of proportion to the degree of pulmonary disease.

PREVENTION OF PNEUMOCYSTIS CARINII PNEUMONIA BY INHALED PENTAMIDINE

The efficacy and toxicity of pentamidine inhaled once a month to prevent Pneumocystis carinii pneumonia (PCP) was investigated in 102 patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC). The cohort was compared with historical controls after a mean duration of prophylaxis of 6.38 months. 86% and 15% of the patients had AIDS or ARC, respectively. 50% of patients had had one previous episode of PCP, 9% had had two episodes, and 3% had had three. 11 patients acquired PCP. Among these 51 patients with one prior episode of PCP, the PCP-free survival after 3.03, 4.7, and 6.38 months of prophylaxis was 98%, 92%, and 82%, respectively. Compared with those for historical controls, the data suggest that inhaled pentamidine can delay relapse by 6 months and reduce the rate of relapse by 50%. PCP acquired while patients were inhaling pentamidine prophylactically was mild and had a case-fatality rate of only 9%. Further investigation of the prophylactic value of inhaled pentamidine is warranted.

Natural history of HIV-associated salivary gland disease

To describe the natural history of HIV-associated salivary gland disease, which is characterized by enlarged major salivary glands and/or xerostomia in HIV-infected persons, we assessed 22 patients at an initial and follow-up examinations (median span of examinations, 15 months). Sixteen patients (73%) had bilateral parotid gland enlargement, 17 had symptoms of dry mouth, and 11 had both conditions. Parotid gland enlargement remained unchanged in 10 patients, it progressed in 2, and it regressed in 4 during treatment with zidovudine or steroids. Those patients with parotid gland enlargement had a significantly lower mean stimulated parotid flow rate (0.27 ml/min/per gland) than a control group of HIV+ persons without salivary gland disease (0.48 ml/min/per gland) (p less than 0.05), whereas the mean unstimulated whole salivary flow rates did not did not differ significantly between the two groups. The mean salivary flow rate of the study group did not change during the observation period. When HIV-associated salivary gland disease was diagnosed, 5 patients (23%) had AIDS, and at follow-up 10 (46%) had AIDS. Seven of these had Kaposis sarcoma. The mean peripheral blood CD4 cell count was 280 and 225 per mm3 at the initial and follow-up examinations, respectively. The corresponding CD8 counts were 1138 and 900. The pathogenesis of HIV-associated salivary gland disease may include hyperplasia of intra-parotid lymphoid tissue. Because HIV-associated salivary gland disease can clinically resemble Sjögrens syndrome, the differential diagnosis of bilateral parotid enlargement should include HIV infection.

Intravenous or inhaled pentamidine for treating Pneumocystis carinii pneumonia in AIDS: a randomized trial.

OBJECTIVE To evaluate the efficacy and toxicity of aerosolized pentamidine and of reduced-dose intravenous pentamidine for the treatment of mild to moderate Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN Randomized open study with serial pulmonary function testing and measurement of pentamidine concentrations in plasma and bronchoalveolar lavage fluid. PATIENTS Of 44 men and 1 woman with a mild to moderate first episode of P. carinii pneumonia (Pao2 greater than or equal to 7.3 kPa [55 mm Hg]), 23 received aerosolized pentamidine and 22, intravenous pentamidine. INTERVENTIONS Pentamidine isethionate, 600 mg by inhalation using a Respirgard II nebulizer (Marquest Medical Products, Inc., Englewood, Colorado) or 3 mg/kg body weight intravenously, administered once daily for 2 to 3 weeks. MEASUREMENTS AND MAIN RESULTS The planned 60-patient study was stopped after 45 patients had been enrolled. The rates (aerosolized compared with intravenous pentamidine) of initial failure, early recrudescence of symptoms, and relapse were 12% and 19% (difference, 7%; 99% confidence interval [CI], - 23% to 37%; P = 0.67), 35% and 0% (difference, 35%; CI, 13% to 58%; P = 0.02), and 24% and 0% (difference, 24%; CI, 4% to 49%; P = 0.03). The rates (aerosolized compared with intravenous pentamidine) of major toxicity were 0% (0 of 17 patients) and 10% (2 of 21 patients) (difference 10%; CI, -1% to 29%; P = 0.24). The mean (+/- SD) pentamidine concentration in bronchoalveolar lavage fluid for patients receiving aerosolized pentamidine was 96.6 +/- 65.1 ng/mL compared with 14.4 +/- 17.7 ng/mL for patients receiving intravenous treatment. Trough concentrations of pentamidine in plasma increased from 0 to 25.4 +/- 16.4, 56.5 +/- 26.1, and 61.1 +/- 56.0 ng/mL at the end of weeks 1, 2, and 3 of intravenous therapy, respectively. CONCLUSIONS The data suggest that reduced-dose intravenous pentamidine was more effective than aerosolized pentamidine for treating mild to moderate P. carinii pneumonia. Systemic absorption during aerosolized therapy was minimal; daily doses of intravenous pentamidine resulted in increased accumulation of pentamidine in plasma.

Elevated serum concentrations of IgE antibodies to environmental antigens in HIV-seropositive male homosexuals.

Forty-five homosexual male subjects with human immunodeficiency virus (HIV) infection, who received care during a 4-month period in an ambulatory center for acquired immunodeficiency syndrome (AIDS), were classified according to their principal presentation with characteristic secondary infections (CDC group IV C, N = 28), cancers (IV D, N = 10), or limited or no symptoms (groups II, III, IV A, or IV B, N = 7). The incidence of allergic rhinitis and conjunctivitis increased after HIV seroconversion by approximately twofold in patients of groups IV C and IV D. The mean serum concentration of IgE was significantly higher for group IV C than for the other HIV-seropositive groups and for a control group of 45 HIV-seronegative homosexual male subjects from the same community who were studied concurrently. More patients in groups IV C and IV D had positive RASTs for a panel of environmental antigens than patients in the other HIV-seropositive groups and the HIV-seronegative control group. Patients with AIDS presenting with typical secondary infections thus have a high frequency of some clinical and laboratory manifestations of allergic diseases.

Does HIV cause salivary gland disease

HIV-associated salivary gland disease (HIV-SGD) is characterized by enlargement of the major salivary glands and/or xerostomia. HIV does not appear to play a direct role in this disease since it was detected by immunohistochemistry in only occasional lymphocytes in labial salivary glands in two out of six patients; it was not found in the salivary gland epithelial cells. Moreover, HIV was not found in any of 21 saliva samples from seven patients. We conclude that HIV-SGD is not caused by direct infection of the salivary glands with HIV.

Oral histoplasmosis in HIV-infected patients: A report of two cases

Histoplasmosis is a fungal infection caused by the organism Histoplasma capsulatum. Disseminated disease usually occurs in immunosuppressed patients or in patients with chronic illnesses. Although relatively uncommon, histoplasmosis has been reported in patients with AIDS, and oral lesions have been noted on multiple sites and in various clinical presentations. We present two HIV-positive cases with oral lesions as the initial signs of histoplasmosis. Both patients responded well to IV amphotericin B but later suffered recurrences despite being maintained on systemic antifungal therapy.

The Significance of HIV Viral Load Assay Precision: A Review of the Package Insert Specifications of Two Commercial Kits

Quantification of HIV-1 RNA levels is a vital tool in the medical management of individuals infected with HIV. The commercially available US Federal Drug Administration (FDA)-approved assays vary in their ability to accurately measure and detect significant changes in plasma viral load. A more precise assay can accurately distinguish true clinically significant biologic changes in viral plasma load from background noise, or systematic variation. These differences in precision between assays are profound at low, near-cutoff levels, but also occur throughout the dynamic range of the assays. This review examines the precision specifications, expressed as fold changes in test and retesting, across the dynamic ranges of the Bayer Versant bDNA assay, and the two available versions of the Roche Amplicor Monitor PCR assays. Highly validated data from their respective package inserts are analyzed to confirm each assay’s performance throughout its dynamic range. The precision of a viral load assay is critical to patient management, and gives the clinician a clearer picture of the patient’s true virologic status that is attributable to infection or treatment as opposed to systematic variation in assays.