Paromomycin: no more effective than placebo for treatment of cryptosporidiosis in patients with advanced human immunodeficiency virus infection. AIDS Clinical Trial Group.

To evaluate the efficacy of paromomycin for the treatment of symptomatic cryptosporidial enteritis in human immunodeficiency virus-infected adults, we conducted a prospective, randomized, double-blind, placebo-controlled trial before the widespread introduction of highly active antiretroviral therapy (HAART). Seven units under the auspices of the AIDS Clinical Trials Group enrolled 35 adults with CD4 cell counts of < or = 150/mm(3). Initially, 17 patients received paromomycin (500 mg 4 times daily) and 18 received matching placebo for 21 days. Then all patients received paromomycin (500 mg q.i.d.) for an additional 21 days. Clinical definitions of response were measured by an average number of bowel movements per day in association with concurrent need for antidiarrheal agents that was lower than that before study entry. There was no treatment response during the placebo-controlled phase of the study according to protocol-defined criteria (P=.88). Three paromomycin recipients (17.6%) versus 2 placebo recipients (14.3%) responded completely. Rates of combined partial and complete responses in the paromomycin arm (8 out of 17, 47.1%) and the placebo arm (5 out of 14, 35.7%) of the study were also similar (P=.72). The clinical course of cryptosporidiosis was quite variable. Paromomycin was not shown to be more effective than placebo for the treatment of symptomatic cryptosporidial enteritis. However, inadequate statistical power prevents definitive rejection of the usefulness of paromomycin as therapy for this infection.

Multifocal hepatic lesions in AIDS: an unusual presentation of steatosis.

Patients infected with HIV frequently have abnormal results on liver tests, leading to radiographic evaluation for hepatic lesions. The etiology of these lesions in patients infected with HIV is most often secondary to infections or tumors. Occasionally, focal abnormalities in the liver are identified in asymptomatic patients. The etiology and clinical course in this subset of patients are not known. However, because of concerns of tumor, an evaluation is usually warranted. We report an unusual case of multifocal hepatic steatosis presenting as multiple liver lesions in an HIV-positive patient with cutaneous Kaposi's sarcoma. This case emphasizes the importance of obtaining a tissue diagnosis in this patient population.

Prednisone improves renal function and proteinuria in human immunodeficiency virus-associated nephropathy.

PURPOSE: To determine if prednisone ameliorates the course of human immunodeficiency virus-associated nephropathy (HIV-AN). PATIENTS AND METHODS: Twenty consecutive HIV-infected adults with biopsy-proven HIV-AN (n = 17) or clinical characteristics of HIV-AN (n = 3) with serum creatinine concentrations > 177 mumol/L (2 mg/dL) or proteinuria > 2.0 g/d or both were prospectively evaluated and treated with prednisone at a dose of 60 mg/d for 2 to 11 weeks, followed by a tapering course of prednisone over a 2- to 26-week period. Serum creatinine concentration, 24-hour protein excretion, serum albumin, and steroid-related adverse effects were assessed before and after treatment. RESULTS: Nineteen patients had serum creatinine concentrations > 117 mumol/L (2 mg/dL). Two of them progressed to end stage renal disease (ESRD) in 4 to 5 weeks. In 17 patients serum creatinine levels decreased from 717 +/- 103 mumol/L (8.1 +/- mg/dL) (mean +/- SE) to 262 +/- 31 mumol/L (3.0 +/- 0.4 mg/dL) (P < 0.001). Five patients relapsed after prednisone was discontinued and were retreated. In these 5 the serum creatinine declined from 728 +/- 107 mumol/L (8.2 +/- 1.2 mg/dL) to 344 +/- 47 mumol/L (3.9 +/- 0.5 mg/dL) (P < 0.01) in response to the second course of prednisone. Twelve of 13 tested patients showed a reduction in 24-hour urinary protein excretion with an average decrement from 9.1 +/- 1.8 g/d to 3.2 +/- 0.6 g/d (P < 0.005). Serum albumin increased from 24.4 +/- 3.6 g/L to 29.3 +/- 2.6 g/L (P = NS) in the 11 patients with paired 24-hour urine collections for whom pre- and post-treatment determinations were available. In one non-azotemic patient with nephrotic syndrome, protein excretion declined from 15.2 to 2.2 g/day and the serum albumin increased from 4.0 g/L to 31.0 g/L. The 20 patients have been followed for a median of 44 weeks (range 8 to 107). Eight ultimately required maintenance dialysis. Eleven died from complications of HIV disease 14 to 107 weeks after institution of prednisone; none was receiving prednisone at the time of death. Seven are alive and free from ESRD a median of 25 weeks (range 8 to 81) from the initiation of prednisone therapy. Six patients developed a total of seven serious infections while receiving prednisone, including Mycobacterium avium-complex infection in 2 and CMV retinitis in 3. CONCLUSION: Prednisone improves serum creatinine and proteinuria in a substantial proportion of adults with HIV-AN. Corticosteroid-related side effects are not prohibitive. A prospective, randomized controlled trial is required to confirm these preliminary results.

Pulmonary disease due to infection by Mycobacterium avium complex in patients with AIDS.

We reviewed the clinical, radiographic, and histologic features of nine patients with AIDS and pulmonary disease due to Mycobacterium avium complex (MAC). Pulmonary MAC disease was defined by (1) the isolation of MAC from two or more lower respiratory tract specimens or from a single lung biopsy sample, (2) an infiltrate revealed by chest radiography, and (3) the absence of other identified pulmonary pathogens or malignancies. Pulmonary MAC disease was present in five (2.5%) of 200 patients with disseminated MAC infection and in four additional patients without evidence of dissemination, as assessed by blood culture. The median CD4 cell count at the time of presentation was 90/microL. Pulmonary MAC disease was the initial AIDS-defining infection in five patients and presented within a median of 5 months after the initial infection in four patients. Radiographic patterns for these nine patients included consolidating or nodular infiltrates and cavitation. The histopathology of pulmonary MAC disease was characterized by granulomatous inflammation, often associated with necrosis and few evident organisms. The conditions of all patients treated with multidrug regimens clinically improved.

Effect of corticosteroid therapy on human immunodeficiency virus-associated nephropathy.

PURPOSE: Human immunodeficiency virus-associated nephropathy (HIV-AN) occurs predominantly in blacks and is characterized histologically by focal segmental glomerulosclerosis or mesangial proliferation and a lymphohistiocytic tubulointerstitial infiltrate. Patients manifest heavy proteinuria and, once azotemia occurs, progress rapidly to end-stage renal disease within 2 to 6 months. No treatment has been shown to be useful for HIV-AN. The purpose of this study was to determine the effect of corticosteroid agents on the progression of HIV-AN. PATIENTS AND METHODS: Four consecutive HIV-infected adults with fewer than 200 CD4 cells/microL, moderate to severe renal insufficiency, proteinuria greater than 2 g per 24 hours, and HIV-AN demonstrated by renal biopsy were treated with 60 mg of prednisone daily for 2 to 6 weeks. Patients were followed with respect to serum creatinine level, 24-hour protein excretion, adverse drug reactions, and the occurrence of opportunistic infections. RESULTS: CD4 counts ranged from 30 to 80 cells/microL before therapy with steroids. The mean (+/- SD) pretreatment serum creatine concentration was 9.1 +/- 5.7 mg/dL and decreased to 3.3 +/- 1.8 mg/dL (P < 0.05) after 2 to 6 weeks of corticosteroid therapy. Twenty-four hour protein excretion did not change (5.2 +/- 2.4 g pretreatment versus 4.6 +/- 4.1 g posttreatment). One patient was able to discontinue dialysis after 10 days. Two patients developed Mycobacterium avium-complex infections and steroid-associated psychosis. One of these patients developed a recurrence of genital herpes, and the other developed dermatomal zoster. None of the four required dialysis during a 1.5- to 5.5-month period of follow-up after cessation of steroid treatment. CONCLUSION: In selected patients with HIV-AN, short-term treatment with corticosteroid agents improves renal function and prevents the development of end-stage renal disease during a 1.5- to 5.5-month period of observation, but may be associated with an increased risk of opportunistic infection.

Clindamycin and primaquine therapy for mild-to-moderate episodes of Pneumocystis carinii pneumonia in patients with AIDS: AIDS Clinical Trials Group 044.

The objective of this prospective, noncomparative study was to assess the safety and efficacy of clindamycin and primaquine therapy for mild-to-moderate pneumocystis pneumonia (defined as a difference of < 40 mm Hg between the alveolar and the arterial oxygen determinations) in patients with AIDS. In the first part of the study, 22 patients were treated with iv clindamycin (900 mg every 8 hours) for the first 10 days, and then their therapy was switched to oral clindamycin (450 mg every 6 hours) for an additional 11 days. In the second part of the study, 38 patients were treated entirely with oral clindamycin (600 mg every 8 hours). All patients were treated with oral primaquine base (30 mg once daily). Fifty-five (92%) of 60 patients responded to the study treatment. Forty-six (77%) of 60 patients completed a full course of therapy. Of the nine patients with treatment-limiting toxic effects, four had only a mild rash. This study indicates that the combination of clindamycin and primaquine is an effective and well-tolerated therapy for mild-to-moderate pneumocystis pneumonia in patients with AIDS. Entirely oral therapy appears to be as effective as initial therapy with iv clindamycin.

Acquired immunodeficiency syndrome: case reporting at a university hospital.

BACKGROUND: Planning and allocating resources for care of patients with acquired immunodeficiency syndrome (AIDS) requires accurate assessment of disease incidence. OBJECTIVE: To assess the accuracy and completeness of AIDS case reporting at our institution, we reviewed all inpatient and outpatient records of patients with AIDS seen at University Hospitals of Cleveland, Ohio, between January 1983 and July 1990. METHODS: The patients were identified through review of hospital discharge summaries, ambulatory clinic listings, and laboratory identification of opportunistic infections. RESULTS: We found that 24 of 291 AIDS cases (8%) seen at this institution had not been reported to state health departments. Of the 24 patients with unreported AIDS, 16 had received an AIDS diagnosis at other institutions, 11 had never been hospitalized at this institution, and 2 had used pseudonyms. CONCLUSIONS: Review of AIDS case reporting can ascertain the magnitude of underreporting; the profile of patients who were unreported may be used to evaluate the accuracy of reporting elsewhere and to identify systematic problems in case reporting methods.

Risk factors for HIV infection in homosexual men: the Cleveland men's study of risks in a low-prevalence area.

Detailed questionnaires concerning alcohol and drug use, sexual practices, and medical history were completed by 301 homosexual men living in the Cleveland metropolitan area. Their sera were subsequently tested for antibodies to the human immunodeficiency virus. Fifty-six (18.6%) were seropositive. In a univariate analysis, age, drug use, and four specific sexual practices were associated with seropositivity. In a multiple logistic regression analysis, intravenous drug use and receptive anal-genital sex remained independent predictors of seropositivity.

The safety and efficacy of zidovudine (AZT) in the treatment of subjects with mildly symptomatic human immunodeficiency virus type 1 (HIV) infection. A double-blind, placebo-controlled trial. The AIDS Clinical Trials Group.

OBJECTIVE: To evaluate the efficacy and safety of zidovudine early in the treatment of human immunodeficiency virus type 1 (HIV) infection. DESIGN: A double-blind, randomized, placebo-controlled trial with subject stratification by pretreatment CD4 T lymphocyte counts. SETTING: Multicenter trial at AIDS Clinical Trial units. SUBJECTS: Seven hundred eleven subjects with mildly symptomatic HIV infection. INTERVENTION: Three hundred fifty-one subjects were assigned to placebo and 360 to zidovudine, 200 mg orally every 4 hours. The median duration of follow-up was 11 months. MEASUREMENTS AND MAIN RESULTS: Fifty-one subjects developed the acquired immunodeficiency syndrome (AIDS), advanced AIDS-related complex, or death as a first critical event. For the stratum of subjects with more than 200 but less than 500 CD4 T lymphocytes/mm3 before treatment, 34 events occurred in placebo recipients and 12 in zidovudine recipients (P = 0.0002; relative risk [RR] estimate, 3.23 [95% CI, 1.67 to 6.24]). For the stratum of subjects with 500 to 799 CD4 T lymphocytes/mm3 before treatment, 2 events occurred in placebo recipients and 3 in zidovudine recipients. Candidiasis at study entry independently increased the risk for having an event (P = 0.005; RR estimate, 2.3 [95% CI, 1.29 to 4.12]); HIV antigenemia at study entry also increased this risk (P = 0.01; RR estimate, 2.1 [95% CI, 1.2 to 3.8]). Significant differences between the treatment groups in CD4 T-lymphocyte counts occurred in subjects with more than 200 but less than 500 CD4 T lymphocytes/mm3 after 4 weeks of therapy (P = 0.002). Differences persisted through week 52. Less prominent changes occurred in subjects with 500 or more CD4 T lymphocytes/mm3. Serum levels of HIV antigen decreased significantly in zidovudine recipients. Serious anemia and neutropenia occurred in 5% and 4% of zidovudine recipients, respectively, and in 0% and 1% of placebo recipients, respectively. CONCLUSION: Zidovudine delayed progression of HIV disease and produced little toxicity in subjects with mildly symptomatic HIV disease and less than 500 CD4 T lymphocytes/mm3.

Heightened complement sensitivity of acquired immunodeficiency syndrome lymphocytes related to diminished expression of decay-accelerating factor.

Although the human immunodeficiency virus can induce cytopathic changes in human lymphocytes in vitro, the mechanism(s) underlying progressive lymphopenia in patients with AIDS and AIDS-related complex has not been elucidated. To investigate this issue, peripheral blood lymphocytes of AIDS and AIDS-related complex patients and healthy control subjects were examined for their ability to resist homologous complement-mediated lysis. Upon sensitization with monoclonal antibodies to major histocompatibility complex class I antigen, as much as 48% lysis of patients' cells was observed in as little as a 1:32 dilution of human serum compared to 18 +/- 8% (mean +/- SD) lysis of controls' cells even in a 1:8 dilution of human serum. To investigate the mechanism of the abnormal complement sensitivity, AIDS and AIDS-related complex cells were analyzed for expression of decay-accelerating factor (DAF), a complement regulatory protein that functions intrinsically in blood cell membranes to prevent complement activation on their surfaces. Flow cytometric assays using anti-DAF monoclonal antibodies demonstrated that patients' lymphocytes and monocytes were DAF-deficient, in contrast to their polymorphonuclear leukocytes, which showed normal DAF levels. Expression of DAF was diminished on CD4+ as well as CD8+ T-lymphocyte subpopulations as opposed to expression of CD3, which was comparable in patients and controls. Incubation of normal lymphocytes with anti-DAF monoclonal antibodies or phosphatidylinositol-specific phospholipase C, an enzyme that cleaves DAF, enhanced lysis. Conversely, reconstitution of patients' cells with exogenous DAF reduced their lysis. The findings of heightened complement sensitivity and DAF deficiency of patients' lymphocytes in vitro suggest the possibility that the DAF deficit may contribute to the progressive lymphopenia of AIDS in vivo.

Prognostic factors in acquired immunodeficiency syndrome.

To identify prognostic factors in acquired immunodeficiency syndrome (AIDS), the authors studied an inception cohort of 45 patients in a non-endemic area (Group I). The probability of survival was 67% six months after the diagnosis of AIDS and 32% at 12 months. As shown by multivariate Cox regression analysis, survivals were shorter (p less than 0.01) in patients 35 years old or older and in those who had anemia when AIDS was diagnosed. In patients with neither of these poor prognostic factors, the 12-month survival was 64%; in patients with one factor, it was 22%; and in patients with both factors, 0%. The prognostic significance of these two factors was validated in a second inception cohort of 50 patients (Group II): in patients with zero, one, and two poor prognostic factors, the 12-month survivals were 80%, 58%, and 26%, respectively. Other poor prognostic factors in Group I included disseminated Mycobacterium avium-intracellulare and the development of new opportunistic infections or neoplasms. The authors conclude that clinically important prognostic factors can be identified in AIDS patients. These findings should be considered in planning therapeutic trials and in counseling patients.

Lymphocytes of persons with the acquired immunodeficiency syndrome and related conditions express reactivity with the monoclonal antibody 4D12 reflective of in vivo lymphocyte activation.

We observed that lymphocytes obtained from healthy persons generally expressed infrequent reactivity with the monoclonal antibody 4D12, an antibody raised against a cell line infected by the human T-lymphotropic virus type I. As had been observed previously, persons bearing HLA-B5 cross-reactive antigens and certain other allotypes had frequent lymphocyte reactivity with 4D12. Lymphocytes obtained from persons infected by the human immunodeficiency virus were highly reactive with 4D12 as were lymphocytes obtained from persons with other viral or bacterial infections. Flow cytometric studies revealed greater 4D12 reactivity by larger lymphocytes, and in vitro studies demonstrated that lectin-stimulated lymphocytes acquired 4D12-reactive antigens. There was also a significant correlation between expression of 4D12-reactive antigens and the presence of the interleukin-2 receptor as recognized by the monoclonal antibody anti-Tac. Thus, the monoclonal antibody 4D12 recognizes a lymphocyte surface antigen frequently expressed among persons with various acute and chronic infections. This antigen is a marker of lymphocyte activation.

Augmentation of skin test reactivity and lymphocyte blastogenesis in patients with AIDS treated with transfer factor.

Nine patients with the acquired immunodeficiency syndrome (AIDS) were administered four doses of pooled transfer factor obtained from the lymphocytes of three healthy controls and three homosexuals with stable lymphadenopathy and serum antibody to the human immunodeficiency virus. Before receiving transfer factor, all patients exhibited anergy to skin test antigens. After four weeks of transfer factor therapy, six of seven patients tested had at least one skin test response. Lymphocyte blastogenic responses to phytohemagglutinin rose from a stimulation index of 6.77 +/- 1.31 before treatment to 19.77 +/- 6.24 after four weeks of transfer factor therapy. Smaller but significant increases were also seen in blastogenic responses to antigens. Improvements in immune responses diminished after administration of transfer factor was halted. Thus, administration of transfer factor to patients with AIDS resulted in partial immune reconstitution. Further studies are indicated to examine the clinical efficacy of this immune response modifier in the treatment of AIDS.

Molluscum contagiosum and the acquired immunodeficiency syndrome: clinical and immunological details of two cases.

We report here the clinical and immunological findings in two patients with molluscum contagiosum poxvirus infection and the acquired immunodeficiency syndrome (AIDS). These cases support earlier evidence that the molluscum contagiosum virus may act as cases support earlier evidence that the molluscum contagiosum virus may act as an opportunistic pathogen. There is now evidence that members of all five families of double stranded DNA-containing human viruses have been associated with unusual clinical manifestations in AIDS patients, and the significance of DNA virus infections in patients with AIDS is discussed.