Progression of Liver Fibrosis in HIV/HCV Co-Infection: A Comparison between Non-Invasive Assessment Methods and Liver Biopsy.

OBJECTIVES: To evaluate the diagnostic performance of seven non-invasive tests (NITs) of liver fibrosis and to assess fibrosis progression over time in HIV/HCV co-infected patients. METHODS: Transient elastography (TE) and six blood tests were compared to histopathological fibrosis stage (METAVIR). Participants were followed over three years with NITs at yearly intervals. RESULTS: Area under the receiver operating characteristic curve (AUROC) for significant fibrosis (> = F2) in 105 participants was highest for TE (0.85), followed by FIB-4 (0.77), ELF-Test (0.77), APRI (0.76), Fibrotest (0.75), hyaluronic acid (0.70), and Hepascore (0.68). AUROC for cirrhosis (F4) was 0.97 for TE followed by FIB-4 (0.91), APRI (0.89), Fibrotest (0.84), Hepascore (0.82), ELF-Test (0.82), and hyaluronic acid (0.79). A three year follow-up was completed by 87 participants, all on antiretroviral therapy and in 20 patients who completed HCV treatment (9 with sustained virologic response). TE, APRI and Fibrotest did not significantly change during follow-up. There was weak evidence for an increase of FIB-4 (mean increase: 0.22, p = 0.07). 42 participants had a second liver biopsy: Among 38 participants with F0-F3 at baseline, 10 were progessors (1-stage increase in fibrosis, 8 participants; 2-stage, 1; 3-stage, 1). Among progressors, mean increase in TE was 3.35 kPa, in APRI 0.36, and in FIB-4 0.75. Fibrotest results did not change over 3 years. CONCLUSION: TE was the best NIT for liver fibrosis staging in HIV/HCV co-infected patients. APRI-Score, FIB-4 Index, Fibrotest, and ELF-Test were less reliable. Routinely available APRI and FIB-4 performed as good as more expensive tests. NITs did not change significantly during a follow-up of three years, suggesting slow liver disease progression in a majority of HIV/HCV co-infected persons on antiretroviral therapy.

[Serious course of a miliary tuberculosis in a 34-year-old patient with ulcerative colitis and HIV infection under concomitant therapy with infliximab]. / Schwerer Verlauf einer Miliartuberkulose bei einem 34-jährigen Patienten mit Colitis ulcerosa und HIV-Infektion unter einer TNF-alpha-Antikörper-Therapie.

A 34-year-old HIV-positive patient with ulcerative colitis was transferred to the authors' hospital because of progressive worsening of his general condition with intermittent fever, increasing lymphopenia, anemia, thrombopenia and neutropenia under anti-tumor necrosis factor-(TNF-)alpha therapy with infliximab. In spite of negative screening tests before initiation of infliximab therapy and intermittent tests during treatment, miliary tuberculosis was finally diagnosed and a tuberculostatic therapy was started. The patient's clinical condition worsened due to the development of a serious exudative necrotizing pancreatitis which was likely to be caused by the tuberculostatic treatment. Due to severe pulmonary infiltrates and pleural effusions with respiratory failure the patient finally passed away.

HIV-1 superinfection in an HIV-2-infected woman with subsequent control of HIV-1 plasma viremia.

A human immunodeficiency virus type 2 (HIV-2)-infected woman experienced asymptomatic superinfection with HIV-1 subtype AG. She did not have cross-neutralizing autologous HIV-1 antibodies before and shortly after HIV-1 superinfection. This evidence supports a mechanism other than cross-neutralizing antibodies for the mild course of HIV-1 infection in this woman.

Lepromatous leprosy with erythema nodosum leprosum as immune reconstitution inflammatory syndrome in an HIV-1 infected patient after initiation of antiretroviral therapy.

We present the case of an HIV infected male patient with erythema nodosum leprosum and function loss of the peroneus nerve as manifestations of lepromatous leprosy. Since symptoms occurred after initiation of antiretroviral therapy and recovery of the immune system, the clinical picture is suggestive of a rare form of an immune reconstitution inflammatory syndrome.

Swiss multicenter study evaluating the efficacy, feasibility and safety of peginterferon-alfa-2a and ribavirin in patients with chronic hepatitis C in official opiate substitution programs.

BACKGROUND: Though patients in opiate substitution programs are commonly infected with HCV, due to safety and efficacy concerns, they are rarely treated with interferon and ribavirin. METHODS: In a multicenter study, HCV-infected patients in opiate maintenance treatment programs received 180 microg pegylated interferon-alfa-2a once weekly, plus daily ribavirin for 24 weeks (genotypes 2, 3), or 48 weeks (genotypes 1, 4). RESULTS: Of the 67 patients enrolled, 31 (46%) had HCV genotypes 1 or 4, and 36 (54%) had genotypes 2 or 3. Intent-to-treat analysis showed end-of-treatment virologic response in 75% of patients (81% of genotypes 2 or 3; 65% of genotypes 1 or 4), and a sustained virologic response in 61% of patients (72% of genotypes 2 or 3; 48% of genotypes 1 or 4). Fifteen patients (22%) did not complete the study, in 5 (8%) cases because of severe adverse events. CONCLUSIONS: Drug users with chronic HCV infection, regularly attending an opiate maintenance program in which close collaboration between hepatologists/internists and addiction specialists is assured, can be treated effectively and safely with pegylated interferon-alfa-2a and ribavirin. Treatment results are very similar to those in other patient groups, and thus therapy should also be considered for this population.

Emergence of polyfunctional CD8+ T cells after prolonged suppression of human immunodeficiency virus replication by antiretroviral therapy.

Progressive human immunodeficiency virus type 1 (HIV-1) infection is often associated with high plasma virus load (pVL) and impaired CD8(+) T-cell function; in contrast, CD8(+) T cells remain polyfunctional in long-term nonprogressors. However, it is still unclear whether CD8(+) T-cell dysfunction is the cause or the consequence of high pVLs. Here, we conducted a longitudinal functional and phenotypic analysis of virus-specific CD8(+) T cells in a cohort of patients with chronic HIV-1 infection. During the initiation and maintenance of successful antiretroviral therapy (ART), we assessed whether the level of pVL was associated with the degree of CD8(+) T-cell dysfunction. Under viremic conditions, HIV-specific CD8(+) T cells were dysfunctional with respect to cytokine secretion (gamma interferon, interleukin-2 [IL-2], and tumor necrosis factor alpha), and their phenotype suggested limited potential for proliferation. During ART, cytokine secretion by HIV-specific CD8(+) T cells was gradually restored, IL-7Ralpha and CD28 expression increased dramatically, and PD-1 levels declined. Thus, prolonged ART-induced reduction of viral replication and, hence, presumably antigen exposure in vivo, allows a significant functional restoration of CD8(+) T cells with the appearance of polyfunctional cells. These findings indicate that the level of pVL as a surrogate for antigen load has a dominant influence on the phenotypic and functional profile of virus-specific CD8(+) T cells.

Acute interstitial nephritis of HIV-positive patients under atazanavir and tenofovir therapy in a retrospective analysis of kidney biopsies.

We performed a retrospective analysis on kidney biopsies of 30 human immunodeficiency virus (HIV)-positive patients. Twenty-two of them received highly active antiretroviral therapy (HAART). Tenofovir containing HAART together with atazanavir, a new protease inhibitor, was administered to three patients. All of them developed acute renal failure. The kidney biopsies of these patients showed an acute interstitial nephritis or a chronic interstitial nephritis with an acute component. Withdrawal of atazanavir and tenofovir resulted in recovery of renal function in all three patients. Acute interstitial nephritis was observed only in 1 of 19 patients without atazanavir or tenofovir treatment. We conclude that acute interstitial nephritis and consecutive acute renal failure is a relevant side effect of atazanavir and tenofovir therapy in HIV-positive patients.