AIDS-defining Disease Research Articles

Changing case-definition for AIDS

The US Centers for Disease Control (CDC) plan to expand the AIDS surveillance case-definition for the US in december 1992. The definition will add pulmonary tuberculosis, recurrent pneumonia, and invasive cervical cancer to the list of 23 AIDS-defining diseases, and will classify all HIV-positive adolescents and adults without any of the 26 diseases, but with less than 200 CD4 T lymphocytes/ul, as having AIDS. Accordingly, many more infected individuals will meet the AIDS case-definition. This article briefly discusses the pros and cons of the CDC's action. As severe HIV morbidity increases with better and more drug therapy and prophylaxis, alternative methods of monitoring HIV morbidity are needed to plan health care. While CD4 counts may help plan and provide care, many countries have not developed quality assurances schemes for such measures. Many HIV-infected individuals will be classified as having AIDS for 2 additional years, and the broader definition will not affect patient access in most European nations. Other ways exist to monitor the prevalence of severe HIV morbidity. Other developed countries should also recognize 26 AIDS-defining conditions, yet use CD4 only to classify HIV, and not define AIDS.

Should pulmonary tuberculosis be an AIDS-defining diagnosis in patients infected with HIV?

Between 1983 and 1989, we cared for 56 patients with tuberculosis and human immunodeficiency virus (HIV) infection. In 37 patients (66%), tuberculosis occurred before any other AIDS-defining disease (group 1); in 10 (18%) it occurred during the same month as another AIDS-defining disease (group 2); and in 9 (16%), after the diagnosis of AIDS (group 3). Tuberculosis was entirely pulmonary in 14 patients (25%), entirely extrapulmonary in 9 (16%), and both pulmonary and extrapulmonary in 33 (59%). The frequency of extrapulmonary involvement was similar in patients from group 1 and from groups 2 and 3 (combined): 76% versus 74%. Needle biopsy of the liver revealed hepatic involvement in 18 patients (32%). The mean CD4 lymphocyte count was 232/mm 3 when tuberculosis was entirely pulmonary, and 243/mm 3 when extrapulmonary disease was present (difference not significant). In group 1, the onset of both pulmonary and extrapulmonary tuberculosis occurred at the same stage of HIV infection, 12 and 10 months, respectively, before any other AIDS-defining disease. Treatment, planned to last 1 year, was highly effective, despite frequent side-effects. Among the 32 patients who completed treatment, relapse of tuberculosis occurred in 2 (6%) with a mean follow-up of 16 months (0–53 months) after completion. Our results suggest that pulmonary tuberculosis should be included in the criteria for diagnosis of AIDS.

Treatment of Tuberculosis in Patients with Advanced Human Immunodeficiency Virus Infection

Infection with the human immunodeficiency virus (HIV) increases the risk of tuberculosis and may interfere with the effectiveness of antituberculosis chemotherapy. To examine the outcomes in patients with both diagnoses, we conducted a retrospective study of all 132 patients listed in both the acquired immunodeficiency syndrome (AIDS) and tuberculosis case registries in San Francisco from 1981 through 1988. At the time of the diagnosis of tuberculosis, 78 patients (59 percent) did not yet have a diagnosis of AIDS, 18 patients (14 percent) were given a concomitant diagnosis of AIDS (as determined by the presence of an AIDS-defining disease other than tuberculosis), and the remaining 36 patients (27 percent) already had AIDS. The manifestations of tuberculosis were entirely pulmonary in 50 patients (38 percent), entirely extrapulmonary in 40 patients (30 percent), and both pulmonary and extrapulmonary in 42 patients (32 percent). The treatment regimens were as follows: isoniazid and rifampin supplemented by ethambutol for the first two months, 52 patients; isoniazid and rifampin supplemented by pyrazinamide and ethambutol for the first two months, 39 patients; isoniazid and rifampin, 13 patients; isoniazid and rifampin supplemented by pyrazinamide for the first two months, 4 patients; and other drug regimens, 17 patients. The intended duration of treatment for patients whose regimen included pyrazinamide was six months, and for patients who did not receive pyrazinamide, nine months. Seven patients received no treatment because tuberculosis was first diagnosed after death. Sputum samples became clear of acid-fast organisms after a median of 10 weeks of therapy. Abnormalities on all chest radiographs taken after three months of treatment were stable or improved except for those of patients who had new nontuberculous infections. The only treatment failure occurred in a man infected with multiple drug-resistant organisms who did not comply with therapy. Adverse drug reactions occurred in 23 patients (18 percent). For all 125 treated patients, median survival was 16 months from the diagnosis of tuberculosis. Tuberculosis was a major contributor to death in 5 of the 7 untreated patients and 8 of the 125 treated patients. Three of 58 patients who completed therapy had a relapse (5 percent); compliance was poor in all 3. Tuberculosis causes substantial mortality in patients with advanced HIV infection. In patients who comply with the regimen, conventional therapy results in rapid sterilization of sputum, radiographic improvement, and low rates of relapse.

Trends and Patterns of Opportunistic Diseases in Danish AIDS Patients 1980–1990

We analysed the AIDS-defining diseases in all 618 notified AIDS patients in Denmark by June 30, 1990, and looked for trends and associations over time. Pneumocystis carinii pneumonia (PCP) was the most commonly reported disease (47%), and showed some but insignificant changes over time. The number of patients reported with Kaposi's sarcoma (KS) declined significantly from 33% in 1980-84 to 12% in 1990. KS was reported 5 times as often in homosexual men as in all other AIDS patients while esophageal candidiasis was reported in one fifth of the patients and were reported twice as often in women as in homosexual men. Wasting and HIV encephalopathy were 2.5 times more often reported in women than in homosexual men. The overall survival rate was 56% (95% confidence interval: 51-61%) at 1 year and 21% (95% confidence interval: 15-28%) at 3 years. Significantly improved survival over time was observed in patients diagnosed with PCP. Patients reported with KS had a significantly better prognosis than those with PCP. Women in general had a bad prognosis.

Serum neopterin levels as predictor of AIDS

The reliability of laboratory parameters for the prediction of impending manifestation of AIDS in HIV-1 infected patients was investigated. Over a mean observation period of approximately 1 year (5 to 33 months) 56 patients were studied. Eleven patients progressed to AIDS (group 1) and 45 remained free of AIDS-defining disease (group 2). Eight candidate-predictor variables were measured on each patient at the beginning of the observation period: neopterin, hemoglobin, lymphocytes, CD4 counts, CD8 counts, platelets, gammaglobulins, and erythrocyte sedimentation rate. In a linear discrimination analysis, a stepwise entry of these parameters into the discriminant function was effected according to which variable added most to the separation into groups 1 and 2. Neopterin proved to be most discriminating with no improvement of separation when adding further variables. Thus, a final allocation rule was computed using neopterin alone. This rule assigns neopterin levels above 21.9 nmol/l to group 1 and levels below to group 2. We conclude, tentatively, that in HIV-infected patients neopterin levels of 22 nmol/l and over may indicate the manifestation of AIDS in the year to come.

3 - Viral Infections and Haematological Malignancies

In this prospective, multicentre cohort study, we analysed specific prognostic factors and the impact of timing of highly active antiretroviral therapy (HAART) on disease progression and death among 625 human immunodeficiency virus (HIV)-1-infected, treatment-naïve patients diagnosed with an AIDS-defining disease. HAART was classified as early (<30 days) or late (30–270 days). Deferring HAART was significantly associated with faster progression to a new AIDS-defining event/death overall (p 0.009) and in patients with Pneumocystis jiroveci pneumonia (p 0.017). In the multivariate analysis, deferring HAART was associated with a higher risk of a new AIDS-defining event/death (p 0.002; hazard ratio 1.83; 95% CI 1.25–2.68). Other independent risk factors for poorer outcome were baseline diagnosis of AIDS-defining lymphoma, age >35 years, and low CD4+ count (<50 cells/μL).