Andrea Bedini

Discontinuation of Maintenance Therapy for Cryptococcal Meningitis in Patients with AIDS Treated with Highly Active Antiretroviral Therapy: An International Observational Study

We conducted a retrospective, multicenter study evaluating the safety of discontinuing maintenance therapy for cryptococcal meningitis after immune reconstitution. Inclusion criteria were a previous definitive diagnosis of cryptococcal meningitis, a CD4 cell count of >100 cells/microL while receiving highly active antiretroviral therapy (HAART), and the subsequent discontinuation of maintenance therapy for cryptococcal meningitis. The primary end point was relapse of cryptococcal disease. As of July 2002, 100 patients were enrolled. When maintenance therapy was discontinued, the median CD4 cell count was 259 cells/microL and the median plasma virus load was <2.30 log10 copies/mL, and serum cryptococcal antigen was undetectable in 56 patients. During a median follow-up period of 28.4 months (range, 6.7-64.5; 262 person-years), 4 events were observed (incidence, 1.53 events per 100 person-years; 95% confidence interval, 0.42-3.92). Three of these patients had a CD4 cell count of >100 cells/microL and a positive serum cryptococcal antigen test result during the recurrent episode. In conclusion, discontinuation of maintenance therapy for cryptococcal meningitis is safe if the CD4 cell count increases to >100 cells/microL while receiving HAART. Recurrent cryptococcal infection should be suspected in patients whose serum cryptococcal antigen test results revert back to positive after discontinuation of maintenance therapy.

Effect of treatment interruption monitored by CD4 cell count on mitochondrial DNA content in HIV-infected patients: a prospective study

Background:HIV infection per se and HAART can alter mitochondrial functionality, leading to a decrease in mitochondrial DNA content. Objective:To evaluate whether treatment interruption monitored by CD4 cell count can restore mitochondrial DNA content in peripheral blood lymphocytes. Methods:Mitochondrial DNA content was measured in platelet-free CD4 and CD8 T cells by real-time polymerase chain reaction; flow cytometry was used to identify and quantify activated CD4 and CD8 T lymphocytes. Results:The 30 patients had been treated for a mean of 107 months (range, 27–197). Median CD4 cell count at discontinuation was 702 cells/μl (range, 547–798). Median observational time from HAART discontinuation was 11.3 months (range, 4–26). Discontinuation of treatment provoked significant increases in mitochondrial DNA in CD8 T cells, which started only 6 months after therapy discontinuation [5.12 copies/cell per month from 0 to 6 months (P = 0.37) and 26.96 copies/cell per month from 6 to 12 months (P < 0.0001)]. Conclusions:This study is the first showing that mitochondrial DNA content can increase in peripheral blood lymphocytes during treatment interruption, but only after at least 6 months of interruption. Consequently, interruptions of shorter periods, whether by clinician or patient decision, are unlikely to allow restoration of mitochondrial DNA and so decrease HAART-related toxicity.

Discontinuation of secondary prophylaxis for Pneumocystis carinii pneumonia in human immunodeficiency virus-infected patients: A randomized trial by the CIOP Study Group

This subgroup analysis assessing secondary prophylaxis for Pneumocystis carinii pneumonia (PCP) describes a multicenter, open-labeled, randomized, controlled trial evaluating the discontinuation of PCP prophylaxis. The main inclusion criterion was a history of PCP and an increase in the CD4 cell count to >200 cells/microL associated with receipt of highly active antiretroviral therapy for >or=3 months. The primary end point was the development of definitive or presumptive PCP. A total of 146 patients were enrolled (77 in the treatment discontinuation arm). After >2 years, 1 definitive and 1 presumptive case of PCP were observed, both of which occurred in patients who discontinued therapy. In most patients, secondary prophylaxis for PCP can be safely discontinued after potent antiretroviral therapy is initiated, but the threshold of >200 CD4 cells/microL may not be considered absolutely safe. Patients who present with symptoms after discontinuation of secondary prophylaxis should be evaluated for PCP despite high CD4 count and complete virus suppression.

Kinetics of CD4 cells after discontinuation of antiretroviral therapy in patients with virological failure and a CD4 cell count greater than 500 cells/μl

After a median of 37 months on antiretroviral therapy, 16 patients were asked to discontinue treatment instead of changing it. After a median observation time of 10.5 months, most patients experienced a rapid and progressive decrease in their CD4 cell count, even without a high viral load rebound. This decline was unrelated to the CD4 cell count and HIV-RNA values at interruption, but was more profound in patients in whom the M184V mutation had disappeared after lamivudine discontinuation.

Fusarium verticillioides fungemia in a liver transplantation patient: successful treatment with voriconazole ☆

Fusarium is an opportunistic fungal pathogen which is emerging as a significant cause of morbidity and mortality in immunocompromised hosts. We present a rare case of F. verticillioides fungemia that occurred in a patient who underwent a second orthotopic liver transplantation for chronic rejection and completely responded to treatment with voriconazole.

Alendronate Treatment for Osteoporosis in Patients Infected with Human Immunodeficiency Virus

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In vitro activities of amphotericin B deoxycholate and liposomal amphotericin B against 604 clinical yeast isolates

We determined the in vitro antifungal activity of liposomal amphotericin B (L-AmB) against 604 clinical yeast isolates. Amphotericin B deoxycholate (D-AmB) was tested in parallel against all the isolates. Susceptibility testing was performed according to the Clinical and Laboratory Standards Institute (CLSI) M27-A3 method. Overall, L-AmB was highly active against the isolates (mean MIC, 0.42 µg ml−1; MIC90, 1 µg ml−1; 97.2 % of MICs were ≤1 µg ml−1) and comparable to D-AmB (mean MIC, 0.48 µg ml−1; MIC90, 1 µg ml−1; 97.3 % of MICs were ≤1 µg ml−1). The in vitro activity of D-AmB and L-AmB was correlated (R2 = 0.61; exp(b), 2.3; 95 % CI, 2.19–2.44, P<0.001). Candida albicans (mean MICs of D-AmB and L-AmB, 0.39 µg ml−1 and 0.31 µg ml−1, respectively) and Candida parapsilosis (mean MICs of D-AmB and L-AmB, 0.38 µg ml−1 and 0.35 µg ml−1, respectively) were the species most susceptible to the agents tested, while Candida krusei (currently named Issatchenkia orientalis) (mean MICs of D-AmB and L-AmB, 1.27 µg ml−1 and 1.13 µg ml−1, respectively) was the least susceptible. The excellent in vitro activity of L-AmB may have important implications for empirical treatment approaches and support its role in treatment of a wide range of invasive infections due to yeasts.

Congenital pyelectasis in children born from mothers on tenofovir containing therapy during pregnancy: report of two cases.

Given the success of highly active antiretroviral therapy in slowing HIV disease progression, an increasing proportion of HIV-infected women are choosing to become pregnant. Antiretroviral treatment decisions in these women must consider not only the immunological and virological efficacy of different drugs, but also their possible effects on the unborn baby. The FDA classifies antiretroviral drugs in five categories (A, B, C, D, and X) according to their possible teratogenic effect on humans or animal models [1]. The drugs with the most available safety data, due to their extensive use in Western and developed countries, are zidovudine, lamivudine, nevirapine, nelfinavir and saquinavir [2, 3]. At present, data concerning the teratogenicity of more recent drugs are lacking. Tenofovir disoproxil fumarate, a nucleotide reverse transcriptase inhibitor, is widely used in patients pre-exposed to other nucleoside analogues because of its efficacy and tolerability [4, 5]. The use of this drug during pregnancy is currently classified in FDA category B [6]. The routine use of prenatal ultrasonography has improved early identification of birth defects. Fetal urinary tract abnormalities are among the most commonly diagnosed prenatal malformations, with a reported prevalence as high as 1 per 100 pregnancies [7, 8]. Pyelectasis is defined as a renal pelvic dilatation, and is one of the most commonly founded urologic anomalies. The aim of this present communication is to describe a possible association between in utero tenofovir exposure and this renal congenital malformation. The Clinic of Infectious and Tropical Diseases of Modena, Italy, follows 1,200 patients with HIV infection. During pregnancy, all patients are followed by the same clinician and undergo a monthly blood test, which includes a baseline genotypic resistance test in patients with a detectable HIV plasma viral load using a polymerase chain reaction (Real Time HIV-1, Abbott Molecular). Patients undergo at least three ultrasonographic scans of the abdomen performed in order to confirm pregnancy and for dating in the first trimester, to look for congenital malformations at about 20 weeks of gestation, and at around 32 weeks or later to assess fetal growth. Ultrasonographic scans were performed by the same operator. In the period between January 2004 and June 2006, 33 HIVpositive pregnancies were followed in our clinic. None of the babies acquired HIV infection from their mothers; 7 of 33 women received tenofovir (21%) as a continuation of their previous antiretroviral regimen. Fetal pyelectasis was diagnosed by ultrasonography in two of seven patients receiving tenofovir as compared to 0 of 26 not receiving tenofovir.

Clinical and Microbiological Characteristics of Visceral Leishmaniasis Outbreak in a Northern Italian Nonendemic Area: A Retrospective Observational Study

Background. Visceral leishmaniasis (VL) caused by Leishmania infantum is endemic in the Mediterranean area. In the last decades a northward spread of the parasite has been observed in Italy. This paper describes a VL outbreak in Modena province (Emilia-Romagna, Northern Italy) between 2012 and 2015. Methods. Retrospective, observational study to evaluate epidemiological, microbiological characteristics, and clinical management of VL in patients referring to Policlinico Modena Hospital. Results. Sixteen cases of VL occurred in the study period. An immunosuppressive condition was present in 81.3%. Clinical presentation included anemia, fever, leukopenia, thrombocytopenia, and hepatosplenomegaly. Serology was positive in 73.3% of cases, peripheral blood PCR in 92.3%, and bone marrow blood PCR in 100%. Culture was positive in 3/6 cases (50%) and all the isolates were identified as L. infantum by ITS1/ITS2 sequencing. The median time between symptom onset and diagnosis was 22 days (range 6–131 days). All patients were treated with liposomal amphotericin b. 18.8% had a VL recurrence and were treated with miltefosine. Attributable mortality was 6.3%. Conclusions. VL due to L. infantum could determine periodical outbreaks, as the one described; thus it is important to include VL in the differential diagnosis of fever of unknown origin, even in low-endemic areas.

Invasive pulmonary and cerebral aspergillosis in a patient with Weil's disease.

We describe the successful medical treatment of invasive aspergillosis in a patient suffering from Weils disease with a combined therapy based on amphotericin B lipid complex and voriconazole.