Romualdo Mazzi

Nosocomial epidemic of active tuberculosis among HIV-infected patients.

In an investigation of a nosocomial outbreak of tuberculosis, 18 HIV-infected inpatients were found to have been exposed to Mycobacterium tuberculosis; active tuberculosis developed in 8, 7 within 60 days of diagnosis of the index case. The patients with lower total lymphocyte and CD4 lymphocyte counts were more likely to get the disease than were those with higher counts. A low score on multiple antigen skin testing was also associated with the development of active tuberculosis. 4 of the 18 patients had a positive tuberculin skin test before exposure to M tuberculosis; none of them subsequently got the disease.

Abacavir use and cardiovascular disease events: a meta-analysis of published and unpublished data

Background:The use of abacavir (ABC) has been associated with an increased risk of cardiovascular disease in some cohort studies. However, no excess risk of myocardial infarction (MI) with ABC therapy has been observed in individual randomized clinical trials (RCTs) and in the aggregated clinical trials database maintained by the manufacturer of ABC. Objective:To combine all the evidence from RCTs by means of meta-analysis to estimate the effect of combined antiretroviral therapy (cART) containing ABC on MI and overall major cardiovascular events (CVEs). Methods:Primary outcomes included MI, CVE, adverse events requiring discontinuation of treatment, and overall mortality. We used a conventional Mantel–Haenszel method, with risk ratio and 95% confidence intervals (CIs) or, in the presence of heterogeneity, a random-effect model. Results:Data were from 28 primary RCTs (9233 participants) comparing ABC-containing cART (4376 participants) to other regimens not containing ABC (4857 controls). MI data were available from 18 trials (31 episodes in 7054 patients) and CVE data from 20 trials (79 episodes in 7899 patients). Compared to the controls, ABC use did not increase significantly the occurrence of MI (risk ratio 0.73, 95% CI 0.39–1.35; P = 0.31), CVE (risk ratio 0.95, 95% CI 0.62–1.44; P = 0.80), overall mortality (risk ratio 1.20, 95% CI 0.63–2.27; P = 0.58), and adverse events requiring discontinuation of treatment (risk ratio 0.82, 95% CI 0.67–1.00; P = 0.05). Conclusion:This meta-analysis of RCTs does not support the hypothesis that ABC-containing cART regimens carry a greater risk of MI or major cardiovascular events relative to comparator cART.

Treatment of chronic hepatitis C in haemophilic patients with interferon and ribavirin: a meta-analysis

BACKGROUND Hepatitis C virus (HCV) infection is a major cause of morbidity and mortality among haemophilic patients who were treated with clotting factor concentrates before the availability of virus-inactivated factors in the mid 1980s. In order to analyse the effect of the current combination anti-HCV treatment [i.e. ribavirin plus interferon (IFN)] in this subset of HCV-infected patients, we performed a systematic review with meta-analysis of the available literature. METHODS The outcome was sustained viral suppression. When trials included for the main predictors two arms (positive and negative), the effect size was described as a comparative index [odds ratio (OR)] and a standard meta-analytical procedure was applied. However, when trials did not report the outcome in separate study arms, the effect size was a non-comparative index (success rate) and comparisons between predictor-positive and -negative studies were performed by meta-regression. RESULTS Data involving 824 haemophilic HCV-infected patients treated with IFN plus ribavirin were collected from 18 articles (14 prospective cohort studies, 1 retrospective study and 3 randomized controlled trials). The higher rate of sustained viral response was observed in human immunodeficiency virus (HIV)-negative naive haemophiliacs treated with pegylated-IFN in combination with ribavirin (61%, ranging from 45% for genotype 1 to 79% for non-1 genotypes). Genotype 1 (OR, 0.15; 95% CI, 0.09-0.25) and co-infection with HIV (OR, 0.25; 95% CI, 0.08-0.81) were strong predictors of worse response to IFN therapy. CONCLUSIONS Our meta-analysis shows that the pattern of response to combination anti-HCV therapy of chronically HCV-infected haemophiliacs is similar to that achieved in the general HCV-infected population.

Unusual, rapidly growing ulcerative genital mass due to herpes simplex virus in a human immunodeficiency virus-infected woman.

SIR, Mycosis fungoides (MF) is characterized by clonal helper ⁄ memory (CD4+ CD45RO+) T-cells in the epidermis, whereas follicular mucinosis or alopecia mucinosis has perifollicular T-cell infiltrates and may clinically resemble alopecia areata. Bexarotene is the first retinoid X receptor (RXR)-selective retinoid shown to be effective for cutaneous T-cell lymphoma. Bexarotene has recently been shown to induce T-cell apoptosis in vitro. Although bexarotene oral and topical gel are effective for MF, this is the first report, to our knowledge, of reversal of associated alopecia. Five patients with alopecia secondary to MF or follicular mucinosis were observed among a cohort of over 90 patients receiving bexarotene therapy at the M.D. Anderson Cancer Center. Their demographic data, degree of hair loss, skin biopsy results and drug administration are shown in Table 1. The location of the hair loss was confined to the scalp in four patients and to the extremities in a fifth. All of the skin biopsy specimens revealed atypical CD4+ CD8+ perifollicular lymphocytic infiltrates, and two showed mucin deposits consistent with follicular mucinosis. Three patients had scaling with negative fungal cultures. Patients with early stage MF were treated with topical bexarotene therapy and advanced stage patients with oral bexarotene. The MF as well as the alopecia improved in all five patients, irrespective of the route of delivery. Hair regrowth began within 2–9 months and full regrowth was evident by 1Æ5 years. Patient 1. A 77-year-old Native American woman presented with a 3-month history of a single patch of alopecia accompanied by pruritus and mild tenderness, generalized xerosis, fatigue and a 4Æ5-kg unintentional weight loss. Asthma and childhood eczema were noted. There was a 4 · 5 cm alopecia areata-like lesion with scaling on the scalp (Fig. 1a) and macular erythema of less than 1%. An atypical CD4+ CD8– clonal lymphocytic infiltrate and mucin deposits were present in the follicular epithelium. After applying 1% bexarotene gel daily to the leg and scalp lesions, partial hair regrowth was present at 3 months (Fig. 1b), with full regrowth of terminal grey hair covering the former patch of alopecia at 5 months (Fig. 1c). Patient 2. A 64-year-old Hispanic man with dermatitis for 30 years developed generalized exfoliative erythroderma, patchy alopecia, and a skin biopsy consistent with MF. He had increased fatigue, chills, night sweats and intense pruritus. On examination, he had generalized exfoliative erythroderma and lymphadenopathy. On the scalp, multiple round alopecia areata lesions, patches of white hair, and exclamation point hairs were observed (Fig. 2a,b). An atypical CD4+ CD8+ dermal infiltrate with epidermotropism and a clonal T-cell receptor gene rearrangement were observed in

Prevalence trend and correlates of HHV-8 infection in HIV-infected patients.

&NA; To assess the circulation of human herpesvirus (HHV)‐8 infection over the years, two seroprevalence surveys were conducted, which tested sera from HIV‐infected individuals recruited 10 years apart (206 individuals from 1986 to 1988 and 177 individuals from 1997 to 1998). For all patients, antibodies to hepatitis C virus (HCV), hepatitis B virus (HBV), and HHV‐8 lytic and latent antigens were evaluated. HHV‐8 seroprevalence was higher among individuals recruited in the 1990s (31.6% for anti‐lytic, 8.5% for anti‐latent antibodies) compared with similar findings in those seen in the late 1980s (14.6% and 3.4% for anti‐lytic and anti‐latent antibodies, respectively), with a twofold increase of the risk of HHV‐8 infection. However, the increase was observed only among injecting drug users, whereas seroprevalence tended to slightly increase among those infected by sexual contact. At univariate analysis, time of recruitment and being homosexual men were factors associated with HHV‐8 infection, an association that remained after adjusting for age. HBV infection was significantly associated with HHV‐8 infection (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.3‐3.6), whereas those infected with HCV had a lower probability of having HHV‐8 antibodies (OR, 0.3; 95% CI, 0.20‐0.6). After controlling for age and gender, time of recruitment remained independently associated with HHV‐8 infection among injecting drug users. In conclusion, HHV‐8 seroprevalence appears to be increased during 10 years among HIV‐infected injection drug users but not among homosexual men, who remain those at the highest risk of infection.

Detection of an early HIV-1 infection by HIV RNA testing in an Italian blood donor during the preseroconversion window period.

BACKGROUND: The implementation of NAT technologies for HIV screening has further reduced the diagnostic window in recent HIV infection. There is still a debate regarding the cost effectiveness of genomic screening of blood donations for transfusion‐transmitted viruses (HBV, HCV, HIV).

Thymidine kinase and deoxycytidine kinase activity in mononuclear cells from antiretroviral-naive HIV-infected patients.

Objective:To evaluate whether an inter-individual variability in the activity of thymidine kinase (TK) and deoxycytidine kinase (dCK), which are involved in the first step of phosphorylation of some nucleoside analogues, exists in antiretroviral-naive, HIV-seropositive patients. Design:Forty-five randomly selected antiretroviral-naive HIV-infected patients were recruited, together with 26 healthy volunteers with no concurrent infection and under no pharmacological treatment. Methods:Peripheral blood mononuclear cells (PBMC) were isolated from venous blood and their TK and dCK activities evaluated. CD4 T cells and HIV-RNA were measured in HIV-infected patients, too. Results:There was a broad range of variability in TK activity in HIV-infected individuals. Furthermore, the activity in PBMC was significantly higher in HIV-infected individuals than in healthy volunteers. dCK activity in seropositive patients was significantly lower than in healthy volunteers. A marked inter-individual variability in dCK levels was observed in the HIV-infected group. No correlations were found between TK or dCK activities and plasma viral load, CD4 cell count, sex or age of patients. Conclusions:A marked range of inter-individual variability of TK and dCK activities in PBMC exists in HIV-infected individuals but not in healthy volunteers, indicating that the activity of enzymes with key roles in drug activation could vary greatly from one patient to another. Furthermore, TK expression is greater in HIV-infected individuals than in healthy volunteers. Better understanding of the viral or cellular factors that contribute to this variability, as well as their effect on responses to antiretroviral treatment, may aid optimization of the management of HIV-infected patients.

Recovery of Long-term Natural Protection Against Reactivation of CMV Retinitis in AIDS Patients Responding to Highly Active Antiretroviral Therapy

OBJECTIVES To see whether in severely immunosuppressed AIDS patients (with prior Cytomegalovirus retinal disease) who have significant increases in CD4+ lymphocytes following the initiation of highly active antiretroviral therapy (HAART) anti-Cytomegalovirus (CMV) maintenance therapy can be withdrawn with no subsequent progression of CMV retinitis. METHODS Eight patients with AIDS and one or more previous episodes of CMV retinitis interrupted anti-CMV maintenance therapy following the successful beginning of HAART. CD4 cell counts and HIV-RNA were monitored monthly while measurement of CMV antigenemia and ophthalmoscopy were carried every 2 weeks thereafter. RESULTS The HAART recipients in whom anti-CMV maintenance therapy had been interrupted had measureable increases of CD4+ T lymphocytes, substantial control of both HIV-RNA and CMV viraemia and did not show recurrence of retinitis during a mean follow-up of 98.4 weeks (range 78-120, SD 15.2). CONCLUSIONS Anti-CMV maintenance therapy can be interrupted with no subsequent progression of retinal damage over a long time in patients with AIDS who successfully respond to HAART with a significant increase in CD4 cell count.

Fluconazole therapy of disseminated cryptococcosis in AIDS patients with liver cirrhosis

Summary We report our experience with fluconazole in the treatment of disseminated cryptococcosis in 3 AIDS patients suffering for liver cirrhosis. All the patients were clinically cured. Fluconazole was well tolerated and no side effects were seen. Overall fluconazole seems to be an efficacious and safe agent for the treatment of cryptococcal infections, even in patients with liver impairment.

MOG antibody seropositivity in a patient with encephalitis: beyond the classical syndrome

BackgroundThe presence of circulating anti-myelin oligodendrocyte glycoprotein antibodies (MOG-Abs) has been described in sera of patients with different inflammatory conditions of the central nervous system. In adults the core clinical feature is usually characterised by acute myelitis and/or optic neuritis. We here report an atypical case with serum and cerebrospinal fluid MOG-Abs and a clinical picture suggestive for acute encephalitis.Case presentationA 31-year-old Indian man presented with altered mental status, slight fever, and ataxia. Brain magnetic resonance imaging noted a widespread involvement of the white matter associated with slight cortical and subcortical damage in absence of contrast enhancement. An extensive infectious screening resulted negative while autoimmune analysis revealed the presence of MOG-Abs, detected with live cell-based assay. After treatment with intravenous immunoglobulins a marked and prompt clinical and radiological improvement was observed.ConclusionsTo date, several areas of uncertainty still remain regarding clinical features and prognosis of subjects with MOG-Abs. The description of atypical cases is crucial, since recognition of this condition leads to prompt treatment and better prognosis, as in the case here reported.