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Highly active antiretroviral therapy (HAART) induces a substantial control of HIV viral replication, but it allows for only a partial immune reconstitution, thus prompting the rationale for the adjuvant use of immunomodulants. Based on its in vitro action as a major T cell growth factor, interleukin (IL)-2 has now been extensively investigated for its potential to correct the HIV-driven immune deficiencies, possibly translating into immunological control over HIV infection. Specific immunological end points have thus far been addressed within extensive Phase I/II trials, disclosing a broad insight into several aspects of the IL-2-mediated immune reconstitution allowing for interesting clinical speculation. Indeed, preliminary results indicate that adjuvant IL-2 induces a significant CD4 cell rescue in patients with no immune recovery following long-term HAART, thus standing as a valid and safe therapeutic option for these patients. Furthermore, in these patients, the IL-2-mediated immune reconstitution is characterized by a rise in both peripheral turnover and de novo T cell synthesis, with reversion of the skewed HIV-driven immunophenotypic pattern, a substantial increase in IL-7 production and in several markers of immune function. Combined, these findings indicate IL-2 has a beneficial effect in correcting the severe disruption in T cell homeostasis induced by HIV, through the interaction with T cells and cytokine microenvironment. However, whether or not these immunological effects translate into an actual immunological competency and therefore clinical benefit, still awaits demonstration from ongoing large, controlled clinical studies.

Twenty-two patients with CD4(+)cell counts

Among 324 cases of culture-proven tuberculosis from 1988 to 1996 in a hospital in Milan, Italy, 90 (27.8%) were due to Mycobacterium tuberculosis strains resistant to isoniazid and rifampin. Sixty-one of 69 isolates tested had identical restriction fragment length polymorphism patterns. The prevalent strain tested susceptible only to ethionamide and was also resistant to ethambutol, streptomycin, cycloserine, amikacin, kanamycin, terizodone, ofloxacin, rifabutin, rifapentin, and KRM 1648. The median survival time was 94 days. Multivariate analysis showed a trend toward better outcome in the period 1994-1996 (hazard ratio, 4.16; P<.001), and extrapulmonary localization of tuberculosis was the only other independent predictor of a negative outcome (hazard ratio, 2.1; P = .019). The delay from symptoms to beginning of therapy did not seem to be a determining factor in survival time. Standard antituberculosis therapy with four drugs (isoniazid, rifampin, ethambutol, and pyrazinamide) had a higher efficacy than did other regimens with fewer drugs but without a statistically significant difference.

We evaluated the sensitivity and specificity of a nested polymerase chain reaction (PCR) to the Mycobacterium tuberculosis IS6110 sequence on formalin-fixed paraffin-embedded tissue samples from patients with tubercular and other granulomatous lesions. Five groups of patients and samples were studied: (1) 28 samples from HIV-positive patients with tuberculosis, (2) 8 samples from HIV-negative patients with histologically suspected tuberculosis (confirmed by culture in 5 cases), (3) lymph nodes from 5 HIV-positive patients with Mycobacterium avium-intracellulare infection, (4) lymph nodes from 30 patients with sarcoidosis, and (5) specimens from 17 patients with other granulomatous diseases. The DNA was extracted from sections with a total thickness of 60 microm, and PCR amplified an internal fragment of 123 base pairs. All of the cases with M. tuberculosis infection were PCR-positive, although this sensitivity was partially related to the initial concentration of the DNA used for amplification. Two of the group 4 samples also were repeatedly positive, thus reducing the specificity of the method. All of the cases with granulomatous diseases other than sarcoidosis were negative. We propose a simplified and highly sensitive nested PCR for the diagnosis of M. tuberculosis infection on archived material in HIV-positive and HIV-negative patients.

Granulocyte functions were studied in 20 patients with acquired immunodeficiency syndrome (AIDS), 20 subjects with lymphadenopathy syndrome (LAS) and 15 symptom-free drug addicts (SFDA). Polymorphonuclear leucocyte (PMNL) phagocytosis and killing of C. albicans appeared normal in homosexual men with AIDS, while drug addicts with AIDS or LAS and SFDA showed a significant defect of these functions as compared to healthy controls. Migration of PMNL in response to a chemoattractant was normal in SFDA, but markedly defective both in LAS and in AIDS patients. In the AIDS group no significant differences were evident between homosexual men and drug addicts. We conclude that defective PMNL phagocytosis and killing, unlike defective migration, are somehow related to drug abuse rather than to infection with the causative agent of the immunodeficiency.