Francesco Meneghetti

Regression of AIDS-related Kaposi's sarcoma following antiretroviral therapy with protease inhibitors: biological correlates of clinical outcome

The clinical response of AIDS-related Kaposis sarcoma (KS) to highly active antiretroviral therapy (HAART), a combination of human immunodeficiency virus type 1 (HIV-1) protease and reverse transcriptase inhibitors, was studied in 11 patients, all but one with progressive KS. CD4+ cell counts, plasma HIV-1 RNA levels, and antibody titres to lytic ORF65 and latency-associated human herpes virus type 8 (HHV-8) proteins were determined in sequential samples. Six complete and three partial clinical responses were achieved in a median time of 6 and 3 months, respectively, and confirmed after a median time of 16 months on HAART. 2 patients showed disease progression. A consistent decrease in HIV-1 RNA levels, paralleled by an increase in CD4+ cell counts, was observed in all patients who showed complete or partial clinical response; HIV-1 RNA levels remained persistently high in the two patients who progressed, despite a change in HAART. HHV-8 antibody titres were generally higher in patients with mucosal/visceral involvement compared with patients with limited disease; a decrease in ORF65 antibody titre was significantly associated with a clinical response. These results indicate that HAART is effective for AIDS-related KS; the clinical response correlates with a decrease in plasma HIV-1 RNA levels, an increase in CD4+ lymphocytes, and a decrease in antibodies to ORF65 HHV-8 protein.

Severe Hepatic Failure Related to Nevirapine Treatment

markable. Laboratory evaluations were significant for a leukocyte count of 1,500/mm (normal value, 4,500–11,000/mm) and macrocytic anemia (hematocrit, 30%; hemoglobin level, 9.8 g/dL; mean corpuscular volume, 104.6 fL). The absolute neutrophil and lymphocyte counts were 870 and 600/mm, respectively. The blood urea nitrogen level was 34 mg/dL (normal value, 7–22 mg/dL), and the creatinine level was 1.8 mg/dL (normal value, 0.6–1.3 mg/dL). Blood cultures were negative. Direct fluorescent antibody staining of fluid from one of the vesicles was positive for HSV, and viral cultures subsequently yielded HSV. A punch biopsy of one of the lesions revealed epidermal ulceration with florid viral cytopathic changes consistent with herpesvirus infection. Secondary bacterial colonization was noted. The patient was treated with intravenous acyclovir (5 mg/kg three times a day), and there was subsequent resolution of the lesions with scarring. Ecthyma refers to a cutaneous infection resembling impetigo but affecting areas deeper in the skin. The lesions are characterized by localized, well-demarcated, erythematous plaques with ulceration that reaches the dermis. Therefore, the lesions often have a central eschar and cause scarring [1]. Ecthyma is almost always secondary to streptococcal and staphylococcal infections, in particular Streptococcus pyogenes infection; therefore, treatment for ecthyma generally consists of oral antimicrobials that are active against S. pyogenes and Staphylococcus aureus. However, mucormycosis [2, 3], molluscum contagiosum [4], cutaneous diphtheria [5], and gonococcal infections [6] have all been associated with ecthyma-like cutaneous eruptions. Review of the literature with use of MEDLINE revealed no previously reported cases of an ecthyma-like presentation of HSV infection. On the basis of nomenclature, ecthyma should be distinguished from two similarly named conditions, ecthyma gangrenosum and contagious ecthyma. Ecthyma gangrenosum is a life-threatening condition secondary to bacterial septicemia with gram-negative bacteria, in particular Pseudomonas aeruginosa. It is characterized by well-demarcated, indurated, weeping, necrotic eschars in areas rich in apocrine glands. Contagious ecthyma, also known as orf, is a parapoxvirus infection of the skin acquired from sheep that is characterized by ulcerated erythematous nodules with white halos. A history of contact with sheep is almost invariably present. This case presents a novel manifestation of HSV infection in immunocompromised hosts. Other such manifestations include painful ulcerative lesions of the genitalia, perianal area, and lips and follicular facial lesions [7]. Moreover, HSV infections should be considered in the differential diagnosis of ecthyma-like skin lesions in immunocompromised patients, and biopsies and virological studies should be performed to exclude HSV infections.

Evaluation of adherence to antiretroviral therapy in Italian HIV patients.

We studied factors associated with treatment adherence in 88 male and 21 female adults (age range, 24-65 years) with HIV infection undergoing therapy with HIV-1 protease inhibitors (PIs) in Italy. Data on sociodemographic variables, clinical and psychological symptoms, treatment compliance, physician/patient relationship, and psychosocial characteristics were obtained by means of semistructured interviews. Every subject also compiled two self-report questionnaires: Coping Orientations to Problem Experiences (COPE) and Medical Outcomes Study-HIV (MOS-HIV) in order to evaluate the use of coping strategies and quality of life. We found a high rate of adherence to HIV therapies (almost 90% of patients had taken at least 80% of medication in the previous 7 days). No significant differences were found between adherence and nonadherence groups as measured by self-report. Few significant differences were found when data laboratory were used. When a Bonferroni corrected p level of <0.001 was used, only a comparison on Mental Disengagement subscale of COPE was statistically significant.

Synercid plus vancomycin for the Treatment of Severe Methicillin-resistant Staphylococcus aureus and Coagulase-negative Staphylococci Infections: Evaluation of 5 Cases

Synercid (quinupristin/dalfopristin), the first semi-synthetic injectable streptogramin, is a promising alternative to glycopeptides against many Gram-positive multiresistant bacteria. Vancomycin is still considered an effective agent for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections but therapeutic failures with glycopeptides have been observed, even for the treatment of infections caused by S. aureus strains sensitive to vancomycin. Synercid, in combination with a glycopeptide, may address this problem without causing significant side effects due to the different toxicity patterns of the 2 antimicrobials. This study reports our experience with the combination of Synercid and vancomycin in 5 patients with severe infection caused by MRSA or methicillin-resistant coagulase-negative Staphylococcus.

Leuconostoc Species: A Case-cluster Hospital Infection

Leuconostoc species are members of the Streptococcacae family. They are generally regarded as non-pathogenic culture contaminants and are thought to be an uncommon cause of infection. We present a study of a case-cluster nosocomial infection due to Leuconostoc spp. Three patients were hospitalized at the time of the infection with significant underlying diseases and all had a compromised skin and mucous barriers. Two had received previous antibiotic therapy. This report highlights the importance of Leuconostoc spp. as an emerging pathogen, even though the modes of transmission and reservoirs of Leuconostoc spp. are as yet unknown.

CHEMO-IMMUNOTHERAPY OF ADVANCED AIDS-RELATED KAPOSI'S SARCOMA

Aims and background Kaposis sarcoma (KS) is the most common neoplastic complication of HIV infection and AIDS. Multiple cytotoxic chemotherapy regimens have been used with various response rates. We have evaluated the efficacy and toxicity of low-dose chemotherapy in patients with poor-prognosis AIDS-related KS and the role of interferon alpha (IFN-α) in complete responders. Methods Twenty-five previously untreated patients with advanced KS received bleomycin (BL) 10 mg/m2 and vinblastine (VB) 6 mg/m2 on days 1 and 15 every two weeks. After six cycles, patients in complete remission received IFN-alpha (3 million U s.c. 3 times/week) combined with antiretroviral therapy. All patients were evaluated for toxicity using the World Health Organization (WHO) toxicity schedule. Both Eastern Cooperative Oncology Group (ECOG) and AIDS Clinical Trials Group (ACTG) response criteria were used to evaluate response and survival. Results The overall response rate was 84% (95% confidence interval, 51–117%) with six complete remissions (24%) and 15 partial remissions (60%) by ECOG criteria, and 92% (95% confidence interval: 58–128%) with 17 partial remissions (68%) by ACTG criteria. The median duration of response on IFN-alpha treatment was 4.5 months (range, 2–10). The overall median survival duration for all 25 patients was 9 months (range, 2–39). Grade 3–4 anemia was observed in five patients and grade 3–4 neutropenia in two patients. No other clinically significant (> grade 3) toxicities were observed. Conclusions Combination of BL and VB is effective and well tolerated, even if new therapeutic options are developing. This disease remains a challenging problem, so larger studies using the combination of chemotherapy and/or IFN-alpha with antiretroviral treatment are warranted.