Increase in visceral adipose tissue in a woman living with HIV after introduction of integrase strand transfer inhibitor.

Integrase strand transfer inhibitors (INSTIs) are a class of antiretroviral drugs with high virologic efficacy and excellent tolerability. Recent evidence showed a possible link of dolutegravir-based regimens with weight gain, and a relationship between raltegravir use and changes in adipose tissue density and metabolic abnormalities, with an increased cardiovascular risk, has been suggested. We describe a case where dolutegravir monotherapy led to a decrease in adipose tissue density.

Multidrug-resistant Combined Infections in a Liver Transplanted Patient: Case Report.

We report a case of successfully treated multiple liver abscesses in a liver-transplanted patient, sustained by combined multidrug-resistant infections. Two months after a liver transplant, a computed tomography scan revealed the presence of multiple abscesses in the liver graft. Blood cultures and abscessual liver fluid were both positive for acquired colistin- and carbapenem- resistant Klebsiella pneumoniae and an extended-spectrum of beta-lactamases-producing Enterobacter aerogenes. The treatment strategy consisted of different prolonged antimicrobial combinations and draining of the abscesses with complete recovery of the liver lesions.

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

BACKGROUND: The 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 PRESENTATION: A 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. CONCLUSIONS: To 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.

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.

Granulocyte macrophage colony-stimulating factor as an adjuvant for hepatitis B vaccination: a meta-analysis.

The efficacy of granulocyte macrophage colony-stimulating factor (GM-CSF) to enhance the immune response to hepatitis B virus vaccine has been object of several reports. We searched for randomized controlled clinical trials comparing GM-CSF given concomitantly to hepatitis B virus vaccine to vaccine given alone or with placebo. Data on rates of seroconversion (anti-HBs titers >10 IU/ml) from 13 studies (734 subjects) produced combined estimates that favored GM-CSF as compared to controls: rate ratio after a single immunization was 1.54 [95% confidence interval (CI), 1.04-2.27] and 1.20 (95% CI, 1.02-1.42) at the end of the vaccination cycle. Using a logistic approach a significant dose/response effect of GM-CSF was seen. Moreover, in renal failure patients who have responded to the vaccine, GM-CSF increased anti-HBs titers. Our findings suggest that GM-CSF induced a significant effect in terms of response rate and achievement of an earlier seroconversion to the vaccine in the overall populations examined, in renal failure patients and in healthy individuals.

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.

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). STUDY DESIGN AND METHODS: Since October 2001, at the Transfusion Service of Verona, single-donation NAT testing for HCV and HIV-1 (Procleix TMA HIV-1/HCV Assay) of all blood donations has been performed. CASE REPORT: A case of acute HIV-1 infection detected by HIV NAT in a repeat blood donor who donated during the preseroconversion window period is reported. All blood components donated were discarded, and the donor started antiretroviral therapy 2 weeks after blood donation. HIV-1 p24 antigen was still negative 10 days after the HIV-1 RNA-positive blood donation. Seroconversion was documented by Day 41 after donation. CONCLUSION: This case report testifies that HIV NAT screening of blood donation is effective in preventing the transmission of HIV infection through blood components.

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

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.