Monica Guffanti

Efficacy of Low-Dose Intermittent Subcutaneous Interleukin (IL)–2 in Antiviral Drug–Experienced Human Immunodeficiency Virus–Infected Persons with Detectable Virus Load: A Controlled Study of 3 IL-2 Regimens with Antiviral Drug Therapy

To evaluate the safety and efficacy of 3 regimens of intermittent subcutaneous (sc) interleukin (IL)--2 in a phase 2 study, 61 antiviral drug-experienced human immunodeficiency virus (HIV)--positive patients were randomly assigned to one of the following study arms: antiretroviral therapy (ART) plus IL-2 (12 million IU [MIU] by continuous intravenous infusion, followed by 7.5 MIU twice a day, sc, every 8 weeks); ART plus IL-2 (7.5 MIU twice a day, sc, every 8 weeks); ART plus IL-2 (3 MIU twice a day, sc, every 4 weeks); or ART alone. A significant increase of circulating CD4 cells was observed in IL-2--treated subjects, compared with those given ART alone. Low doses of IL-2 were better tolerated. Despite the incomplete suppression of viral replication, IL-2 with ART did not increase either plasma viremia or cell-associated HIV DNA levels. Low doses of intermittent sc IL-2 induced a stable increase of peripheral CD4 cells that was indistinguishable from those associated with higher, less well-tolerated doses of IL-2.

Cytomegalovirus Pneumonia in AIDS Patients: Value of Cytomegalovirus Culture From BAL Fluid and Correlation With Lung Disease

OBJECTIVES To verify the value of cytomegalovirus (CMV) cultures of BAL fluid vs postmortem lung histopathology in detecting CMV pneumonia, and to correlate the BAL viral dose with the number of CMV inclusion bodies (CMV-IB) in the lung tissue of AIDS patients. DESIGN Retrospective analysis of 434 BALs and 40 autopsies involving 307 AIDS patients; clinical follow-up lasted 10 months. PATIENTS AND METHODS The 40 patients who died within 20 days of undergoing BAL were divided on the basis of histopathologic findings into subjects with and without CMV-IB in the lung tissue. The relationship between the BAL viral dose and CMV lung infection was evaluated by counting the early antigen (CMV-EA) positive cells/200 microL of BAL and the number of CMV-IB/mm2 of lung tissue. RESULTS The predictive value of BAL virus isolation for the diagnosis of CMV pneumonia was 61% for positive and 100% for negative results. The patients with the largest number of CMV-IB had CMV-EA counts from 2 to 840; in those with a moderate and small number, the CMV-EA counts were, respectively, from 11 to 700 and 2 to 300. Among the patients surviving up to 10 months after the BAL index sample, the frequency of recurrent extrapulmonary CMV abnormalities was 27% in those with positive and 7% in those with negative cultures. CONCLUSIONS BAL CMV cultures from AIDS patients have a very high negative and relatively low positive predictive value for CMV pneumonia. The presence and replication of CMV in the lung may lead to systemic dissemination as suggested by the higher probability of CMV extrapulmonary diseases. Viral titers do not seem to be related to the degree of lung damage.

Clinical Investigations: InfectionCytomegalovirus Pneumonia in AIDS Patients: Value of Cytomegalovirus Culture From BAL Fluid and Correlation With Lung Disease

OBJECTIVES To verify the value of cytomegalovirus (CMV) cultures of BAL fluid vs postmortem lung histopathology in detecting CMV pneumonia, and to correlate the BAL viral dose with the number of CMV inclusion bodies (CMV-IB) in the lung tissue of AIDS patients. DESIGN Retrospective analysis of 434 BALs and 40 autopsies involving 307 AIDS patients; clinical follow-up lasted 10 months. PATIENTS AND METHODS The 40 patients who died within 20 days of undergoing BAL were divided on the basis of histopathologic findings into subjects with and without CMV-IB in the lung tissue. The relationship between the BAL viral dose and CMV lung infection was evaluated by counting the early antigen (CMV-EA) positive cells/200 microL of BAL and the number of CMV-IB/mm2 of lung tissue. RESULTS The predictive value of BAL virus isolation for the diagnosis of CMV pneumonia was 61% for positive and 100% for negative results. The patients with the largest number of CMV-IB had CMV-EA counts from 2 to 840; in those with a moderate and small number, the CMV-EA counts were, respectively, from 11 to 700 and 2 to 300. Among the patients surviving up to 10 months after the BAL index sample, the frequency of recurrent extrapulmonary CMV abnormalities was 27% in those with positive and 7% in those with negative cultures. CONCLUSIONS BAL CMV cultures from AIDS patients have a very high negative and relatively low positive predictive value for CMV pneumonia. The presence and replication of CMV in the lung may lead to systemic dissemination as suggested by the higher probability of CMV extrapulmonary diseases. Viral titers do not seem to be related to the degree of lung damage.

Ten-year survival among HIV-1-infected subjects with AIDS or non-AIDS-defining malignancies.

Few data are available regarding the 10‐year survival among subjects with HIV and cancer. The aim of this study was to evaluate the 10‐year survival of HIV‐infected subjects with AIDS‐defining malignancies (ADM) or non‐AIDS‐defining malignancies (NADM). This was a single center, retrospective, observational study of subjects with HIV infection and a subsequent cancer diagnosis; the data were collected from January 1991 to April 2010. Malignancies were divided into ADM or NADM on the basis of the Centre of Diseases Control‐1993 classification. Survival curves were estimated using Kaplan–Meyer method and compared by the log‐rank test. Six hundred and fifteen (9.5%) of the 6,495 subjects recorded in the San Raffaele Infectious Diseases Database developed a malignancy: 431 (70%) an ADM and 184 (30%) a NADM. In the case of ADM, survival was more favorable when cancer was diagnosed during post‐highly active antiretroviral therapy (HAART) era (10‐year survival: 43.2% ± 4.4%) than when diagnosed during the pre‐HAART era (10‐year survival: 16.4% ± 2.7%; log‐rank test: p < 0.001). The same was true in the case of NADM (10‐year survival: 44.7% ± 5.5% vs. 33.3 ± 9.6%; log‐rank test: p = 0.03). An evaluation of survival probability by cancer type showed higher survival rates during the post‐HAART era in the case of non‐Hodgkin lymphoma (10‐year survival: 42.1% ± 5.3% vs. 11.4% ± 3.3%; log‐rank test: p = <0.001), Kaposis sarcoma (10‐year survival: 44.0% ± 8.4% vs. 23.5% ± 3.9%; log‐rank test: p < 0.001) and Hodgkins disease (10‐year survival: 49.5% ± 14.5% vs. 40.0% ± 12.7%; log‐rank test: p = 0.005). Despite the better cancer prognosis during the post‐HAART era, the 10‐year survival of HIV‐infected subjects with an ADM or NADM is poor.

Disseminated rhodococcus equi infection in HIV infection despite highly active antiretroviral therapy

BackgroundRhodococcus equi (R.equi) is an acid fast, GRAM + coccobacillus, which is widespread in the soil and causes pulmonary and extrapulmonary infections in immunocompromised people. In the context of HIV infection, R.equi infection (rhodococcosis) is regarded as an opportunistic disease, and its outcome is influenced by highly active antiretroviral therapy (HAART).Case presentationWe report two cases of HIV-related rhodococcosis that disseminated despite suppressive HAART and anti-rhodococcal treatment; in both cases there was no immunological recovery, with CD4+ cells count below 200/μL. In the first case, pulmonary rhodococcosis presented 6 months after initiation of HAART, and was followed by an extracerebral intracranial and a cerebral rhodococcal abscess 1 and 8 months, respectively, after onset of pulmonary infection. The second case was characterized by a protracted course with spread of infection to various organs, including subcutaneous tissue, skin, colon and other intra-abdominal tissues, and central nervous system; the spread started 4 years after clinical resolution of a first pulmonary manifestation and progressed over a period of 2 years.ConclusionsOur report highlights the importance of an effective immune recovery, despite fully suppressive HAART, along with anti-rhodococcal therapy, in order to clear rhodococcal infection.

Clinical, virologic, and immunologic outcomes in lymphoma survivors and in cancer-free, HIV-1-infected patients: a matched cohort study.

The objective of this study was to compare immunologic, virologic, and clinical outcomes between living human immunodeficiency virus (HIV)‐infected individuals who had a diagnosis of lymphoma versus outcomes in a control group of cancer‐free, HIV‐infected patients.

Unboosted atazanavir with lamivudine/emtricitabine for patients with long-lasting virological suppression.

Unboosted atazanavir (ATV) including regimens have been investigated as a ritonavir‐sparing simplification strategy. No data are available on removal of one NRTI in subjects effectively treated with unboosted atazanavir+2NRTIs. We present the 48‐week virological efficacy and safety of unboosted atazanavir plus lamivudine (3TC) or emtricitabine (FTC) (lamivudine/emtricitabine/Reyataz©, LAREY Study).

Susac’s syndrome as HIV-associated immune reconstitution inflammatory syndrome

Susac’s Syndrome (SS) is an autoimmune endotheliopathy of cerebral, retinal and cochlear arterioles. We report of an HIV-infected woman who developed a first SS episode following a spontaneous reduction of plasma viral load and several relapses six years later, following initiation of combined antiretroviral therapy (cART). Corticosteroids and intravenous immunoglobulins alone did not control the disease, which improved after combined treatment with acyclovir and ganciclovir. SS onset in HIV infection and relapses during cART-induced immune reconstitution are consistent with the dysimmune nature of the disease. The response to anti-herpes drugs suggests a viral contribute in this case of SS.

Prevalence of type 2 diabetes mellitus and its predictive factors in Italy: a comparison between HIV-infected and uninfected subjects

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK