mycophenolic-acid and HIV-Infections

Acquired epidermodysplasia verruciformis (AEV) is a form of epidermodysplasia verruciformis (EV) that is most commonly found in immunocompromised or immunosuppressed patients. EV is commonly associated with human papillomavirus (HPV), which is often found in EV and AEV lesions. Clinical presentation of AEV in patients with organ transplantation, HIV+, congenital HIV+, hematological diseases, and other iatrogenic immunosuppression are reviewed. Treatment options include topical cidofovir, topical retinoids, topical imiquimod, topical glycolic acid, HPV 9-valent vaccine, acitretin, improving cellular immunity, and changing transplant medication to mycophenolate mofetil.

Topics: Acitretin; Cidofovir; Epidermodysplasia Verruciformis; HIV Infections; Humans; Imiquimod; Mycophenolic Acid; Papillomaviridae; Papillomavirus Infections; Vaccines

There is still no consensus on the optimal management of COVID-19 within the general population due to the emerging evidence base. High-risk groups, including kidney transplant recipients living with HIV present unique additional challenges. Here we discuss two kidney transplant recipients living with HIV with SARS-CoV-2 infection and their clinical course, and review the existing literature for this subset of challenging patients.

Topics: Adult; Anti-Bacterial Agents; Anti-HIV Agents; Atovaquone; CD4 Lymphocyte Count; CD4-CD8 Ratio; COVID-19; Dideoxynucleosides; Female; Glucocorticoids; Graft Rejection; HIV Infections; HIV-1; Humans; Immunocompromised Host; Immunosuppressive Agents; Kidney Transplantation; Lamivudine; Male; Middle Aged; Mycophenolic Acid; Pneumonia, Pneumocystis; Prednisolone; Raltegravir Potassium; RNA, Viral; SARS-CoV-2; Tacrolimus; Trimethoprim, Sulfamethoxazole Drug Combination

To describe the unusual occurrence of systemic lupus erythematosus (SLE) with nephritis in human immunodeficiency virus (HIV)-infected individuals.. Chart review-based report of a case of SLE with diffuse proliferative glomerulonephritis (DPGN) in an HIV-infected man, together with a literature review of previously published cases. We searched the English language medical literature from 1987 to 2009 using the following PubMed and Medline terms: "SLE," "HIV," "DPGN." In addition, we researched the role of mycophenolate mofetil (MMF) in the treatment of patients with HIV by using the keywords "MMF" and "HIV".. An 18-year-old male patient with vertically transmitted HIV-1 infection presented with malaise, weight loss, malar rash, arthritis, proteinuria, and hematuria. Kidney biopsy confirmed the diagnosis of lupus nephritis (Class IV). He was treated successfully with high-dose corticosteroids and MMF, which were added to his baseline treatment of highly active antiretroviral therapy. The review of the literature identified a total of 18 cases of SLE appearing in HIV+ individuals, of which 11 patients had lupus nephritis. Among the latter, there were only 5 cases of proliferative (focal or diffuse) glomerulonephritis, and their treatment consisted mainly of high-dose corticosteroids. The short-term outcome was favorable in 4 cases and 1 patient died.. Proliferative lupus nephritis is rare in HIV-infected patients. A detailed analysis of the cases may lead to important insights into the pathogenic mechanisms of both diseases. Considering its complex interaction with antiviral medications, MMF may be considered for the treatment of lupus with severe proliferative glomerulonephritis in HIV-infected individuals.

Topics: Adolescent; Adrenal Cortex Hormones; Anti-Retroviral Agents; Biopsy; Comorbidity; Dose-Response Relationship, Drug; Drug Therapy, Combination; Glomerulonephritis; HIV Infections; Humans; Immunosuppressive Agents; Kidney; Lupus Erythematosus, Systemic; Male; Mycophenolic Acid; Treatment Outcome

This study tested whether donor-derived HIV-specific immune responses could be detected when viral replication was completely suppressed by the continuous administration of highly active antiretroviral therapy (HAART). A regimen of fludarabine and 200 cGy total body irradiation was followed by infusion of allogeneic donor peripheral blood cells and posttransplantation cyclosporine and mycophenolate mofetil. Viral load, lymphocyte counts, and HIV-1-specific CD8(+) cell immune responses were compared before and after hematopoietic cell transplantation (HCT). Uninterrupted administration of HAART was feasible during nonmyeloablative conditioning and after HCT. The HIV RNA remained undetectable and no HIV-associated infections were observed. CD8(+) T-cell responses targeting multiple epitopes were detected before HCT. After HCT a different pattern of donor-derived HIV-specific CTL responses emerged by day +80, presumably primed in vivo. We conclude that allogeneic HCT offers the unique ability to characterize de novo HIV-1-specific immune responses. This clinical trial was registered at ClinicalTrials.gov (identifier: NCT00112593).

Topics: Adult; Antiretroviral Therapy, Highly Active; CD8-Positive T-Lymphocytes; Cyclosporine; Epitopes; Hematopoietic Stem Cell Transplantation; HIV Infections; HIV-1; Humans; Immune System; Immunosuppressive Agents; Leukemia, Myeloid, Acute; Male; Mycophenolic Acid; Transplantation, Homologous

We evaluated the safety, tolerability and antiretroviral activity of beta-D-2,6-diaminopurine dioxolane (DAPD; amdoxovir) with or without mycophenolate mofetil (MMF) in HIV-1 infection following extensive antiretroviral therapy (ART).. Oral DAPD 500 mg twice daily with placebo or MMF 500 mg twice daily was added to failing ART. HIV-1 RNA viral load (VL) decline to week 2 was analyzed by intent-to-treat, using rank-based tests. Patients with VL decline > 0.5 log10 copies/ml at week 2 (virologic response, VR) optimized ART and continued therapy for up to 96 weeks.. Forty adults with median VL 4.5 log10 copies/ml, median 184 CD4+ cells/microl, and a median of 6 nucleoside reverse transcriptase inhibitor (NRTI) mutations (range, 1-8) were randomized. Median VL reduction at week 2 was -0.26 log10 copies/ml (P < 0.0001). Response to DAPD/placebo (median -0.37 log10 copies/ml) was unexpectedly greater than to DAPD/MMF (median -0.23 log10 copies/ml), although this difference was not statistically significant (P = 0.59). MMF appeared to lower concentrations of DAPD and its metabolite dioxolane guanosine. Of 10 patients with VR (DAPD 7, DAPD/MMF 3), four persisted beyond week 24. VR was more frequent with < or = 5 baseline NRTI mutations (P = 0.12) or < 4 thymidine-associated mutations (TAMs) without E44D or V118I (P = 0.08). Twenty-three patients received extended DAPD +/- MMF; five beyond week 24. Few adverse events were related to study medications.. The addition of DAPD +/- MMF to failing therapy appears safe and well tolerated. DAPD had significant activity at week 2 (mean -0.35 log10) in heavily pretreated patients that was not augmented by MMF.

Topics: Adult; Aged; Dioxolanes; Double-Blind Method; Drug Resistance, Viral; Drug Therapy, Combination; Female; HIV Infections; HIV-1; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Purine Nucleosides; RNA, Viral; Treatment Outcome; Viral Load

Mycophenolate mofetil has been proposed for HIV-1 therapy because of its guanine-depleting effect, which is expected to interfere with HIV-1 replication directly by hampering reverse transcription and indirectly via inhibition of CD4+ T cell proliferation. However, treatment with mycophenolate mofetil might also compromise lymphocyte reconstitution and HIV-specific immunity. Therefore we longitudinally studied the effects of mycophenolate mofetil in combination with HAART on T cell proliferation, lymphocyte reconstitution, and HIV-specific CD4+ and CD8+ T cell responses in six therapy-naive, acute or chronic HIV-1-infected patients, as compared to eight patients treated with HAART alone. T cell proliferation in whole blood cultures of patients treated with mycophenolate mofetil was inhibited. Strikingly, ex vivo Ki67 expression within T cells was not influenced by treatment with mycophenolate mofetil. In vitro studies showed that Ki67 expression occurs at an early step of the cell cycle and was not inhibited by guanine depletion. When treatment with mycophenolate mofetil was stopped a transient increase in apoptosis and Ki67-expressing T cells was detected. This observation together with near complete inhibition of T cell proliferation in whole blood cultures during treatment with mycophenolate mofetil indicated that T cell proliferation was inhibited in patients treated with mycophenolate mofetil. Still, there was no evidence for detrimental effects of treatment with mycophenolate mofetil in addition to HAART on CD4+ T cell reconstitution or HIV-specific immunity.

Topics: Acute Disease; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Chronic Disease; Drug Therapy, Combination; HIV Infections; HIV-1; Humans; Immunosuppressive Agents; Lymphocyte Activation; Male; Mycophenolic Acid; Treatment Outcome

The main goal of this study was to assess the role of mycophenolate mofetil (MMF) during interruption of highly active antiretroviral therapy (HAART). Seventeen patients with early-stage chronic HIV type 1 infection were treated with HAART for 12 months. They were then randomized (day 0) to receive MMF (HAART-MMF group, n = 9) or to continue the regimen (HAART group, n = 6) for 120 additional days. At day 120 in the HAART-MMF group, HAART was discontinued, and MMF administration was continued. The primary end point of the study was the number of individuals maintaining a plasma viral load (VL) set point of <200 copies/mL after at least 6 months off HAART. At day 120, all patients in both groups had undetectable plasma VLs. After 6 months off HAART, 5 of 9 patients in the HAART-MMF group versus 1 of 6 patients in the HAART group maintained a plasma VL of <200 copies/mL (P = 0.28). According to the ability of their plasma to inhibit cellular proliferation, patients were reclassified and divided into an inhibition group (n = 6) and a no inhibition group (n = 9). The doubling time of VL rebound was significantly higher in the inhibition group (mean +/- SE, 10.22 +/- 1.3) than in the no inhibition group (mean +/- SE, 4.6 +/- 1.6; P = 0.03). Moreover, 5 of 6 patients in the inhibition group maintained a plasma VL of <200 copies/mL versus 1 of 9 patients in the no inhibition group (P = 0.005) after 6 months off HAART. We found that combining MMF and HAART delayed VL rebound and improved control of viral replication without HAART but only when inhibition of lymphocyte proliferation was achieved.

Topics: Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Cell Line; Drug Administration Schedule; Female; HIV Infections; HIV-1; Humans; In Vitro Techniques; Lymphocyte Activation; Lymphoid Tissue; Male; Mycophenolic Acid; Pilot Projects; Virus Replication

To study the effect of mycophenolate mofetil (MMF) on the decay rate of plasma HIV-1 RNA and the latently infected cellular reservoir in treatment-naive patients starting antiretroviral therapy.. : Randomized trial.. A group of 19 HIV-1 infected patients (9 with a chronic and 10 with a primary infection) starting a triple antiretroviral drug regimen were randomized to a group with or without MMF. Plasma samples for HIV-1 RNA were taken and HLA-DR-CD4+ T cells were co-cultured for HIV-1 isolation. Slopes of plasma HIV-1 RNA and cellular viral load decay were calculated for the first 14 days and the first 24 weeks of treatment, respectively.. The median plasma HIV-1 RNA daily decay rate in chronically infected patients was 0.25 log10 copies/ml [interquartile range (IQR), 0.18-0.30] with MMF and 0.28 log10 copies/ml (IQR, 0.22-0.32) without MMF (P = 0.56); in primary infected patients, it was 0.31 log10 copies/ml (IQR, 0.31-0.32) with MMF and 0.32 log10 copies/ml (IQR, 0.26-0.34) without MMF (P = 0.75). The median daily decay rate of latently infected cells was 0.017 and 0.004 infected cells/10 cells in patients with and without MMF, respectively (P = 0.89). The increase in CD4 T cells was comparable between patients with and without MMF. After stopping MMF, there was an increase in the cellular reservoir in six of eight patients.. The addition of MMF to a triple class antiretroviral regimen in treatment-naive patients does not significantly increase the plasma HIV-1 RNA decay rate or the decay rate of the latently infected cellular reservoir.

Topics: Adult; Antiretroviral Therapy, Highly Active; Enzyme Inhibitors; HIV Infections; HIV-1; Humans; Male; Middle Aged; Mycophenolic Acid; RNA, Viral

Mycophenolic acid (MPA) increases the activity of both abacavir (ABC) and didanosine (ddI) in vitro against wild-type and multinucleoside-resistant HIV. We treated 7 patients with diagnosed AIDS who did not respond to eight or more antiretroviral therapies in an open label pilot study with mycophenolate mofetil (MMF), ABC, ddI, amprenavir (APV), and ritonavir (RTV), with or without efavirenz (EFV). Therapy was well tolerated despite the patients' advanced disease states. No significant decline in lymphocyte or other blood counts was observed. Median HIV RNA was 5.26 log10 copies/ml at entry, 4.53 log10 copies/ml at 4 weeks, and 5.13 log10 copies/ml at 16 weeks. Median CD4+ count was 34 cells/microl at entry and 39 cells/microl at 16 weeks of therapy. CD4+ counts increased further in five study subjects on extended therapy to 25 weeks (median 27 cells/microl at entry, 66 cells/microl at close), despite loss of virologic suppression in 4 of 5 cases. MPA can induce apoptosis in lymphocytes in vitro. However despite viral rebound, cell surface markers of apoptosis and activation declined in total CD3+ cells and CD3+/CD4+ cells twofold to fourfold in 4 of 5 adherent study subjects at 16 weeks, reaching levels comparable with those found in seronegative donors. Although low-dose MMF appears safe in late-stage HIV disease, this study did not demonstrate virologic efficacy. Higher doses of MMF may be more effective. With careful monitoring of toxicities and pharmacokinetics, MMF deserves further testing in HIV therapy.

Topics: Adult; Anti-HIV Agents; CD4 Lymphocyte Count; Drug Resistance, Microbial; Drug Resistance, Multiple; Drug Therapy, Combination; Flow Cytometry; HIV Infections; HIV-1; Humans; Mycophenolic Acid; Pilot Projects; Reverse Transcriptase Inhibitors; RNA, Viral; Salvage Therapy; Treatment Outcome

Mycophenolic acid, a selective inhibitor of the de novo synthesis of guanosine nucleotides in T and B lymphocytes, has been proposed to inhibit human immunodeficiency virus (HIV) replication in vitro by depleting the substrate (guanosine nucleotides) for reverse transcriptase. Here we show that mycophenolic acid induced apoptosis and cell death in a large proportion of activated CD4+ T cells, thus indicating that it may inhibit HIV infection in vitro by both virological mechanisms and immunological mechanisms (depletion of the pool of activated CD4+ T lymphocytes). Administration of mycophenolate mophetil, the ester derivate of mycophenolic acid, to HIV-infected subjects treated with anti-retroviral therapy and with undetectable viremia resulted in the reduction of the number of dividing CD4 + and CD8+ T cells and in the inhibition of virus isolation from purified CD4+ T-cell populations. Based on these results, the potential use of mycophenolate mophetil in the treatment of HIV infection deserves further investigation in controlled clinical trials.

Topics: Anti-HIV Agents; Apoptosis; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Dose-Response Relationship, Drug; HIV Infections; Humans; Immunosuppressive Agents; Lymphocyte Activation; Mycophenolic Acid; T-Lymphocytes

End-stage renal disease in the human immunodeficiency virus-positive population is increasing. Kidney transplant is the optimal therapy for this population rather than dialysis modalities if some criteria are met. These include undetectable plasma human immunodeficiency virus RNA, CD4 cell count over 200 cells/μL, and the absence of any AIDS-defining illness. Here, we describe the first living-donor kidney transplant in a human immunodeficiency virus-positive recipient in Turkey. The patient, a 52-year-old male diagnosed as human immunodeficiency virus positive, was on antiretroviral therapy, which consisted of 400 mg twice daily darunavir, 100 mg/day ritonavir, and 50 mg/day dolutegravir. He had been negative for human immunodeficiency virus RNA for the past 3 years. The patient developed renal insufficiency without any known cause and started hemodialysis. A living donor transplant from his son was performed, and the patient received ATG Fresenius-S (Neovii Biotech, Rapperswil, Switzerland) induction and a maintenance immunosuppression therapy consisting of methyl-prednisolone, mycophenolate mofetil, and tacrolimus. There were no incidences of delayed graft function or acute rejection. Because of tacrolimus and ritonavir interaction, tacrolimus trough levels were too high. With tacrolimus withdrawn, tacrolimus trough level decreased to detectable levels 2 weeks later. Antiretroviral therapy was continued on the same dosage. At month 4 posttransplant, the patient's creatinine level was 1.01 mg/dL. At present, the patient has had no complications and no episodes of rejection. Kidney transplant is the most favorable replacement therapy for HIV-positive patients who are under controlled AIDS care with highly active antiretroviral therapy. However, drug interactions should be carefully evaluated.

Topics: Acquired Immunodeficiency Syndrome; Drug Interactions; Graft Rejection; HIV; HIV Infections; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Ritonavir; RNA; Tacrolimus

The influence of patient characteristics and immunosuppression management on COVID-19 outcomes in kidney transplant recipients (KTRs) remains uncertain. We performed a single-center, retrospective review of all adult KTRs admitted to the hospital with confirmed COVID-19 between 03/15/2020 and 05/15/2020. Patients were followed from the date of admission up to 1 month following hospital discharge or study conclusion (06/15/2020). Baseline characteristics, laboratory parameters, and immunosuppression were compared between survivors and patients who died to identify predictors of mortality. 38 KTRs with a mean baseline eGFR of 52.5 ml/min/1.73 m

Topics: Adrenal Cortex Hormones; Adult; Aged; COVID-19; Female; Graft Rejection; HIV Infections; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Retrospective Studies; Risk Factors; Tacrolimus; Transplant Recipients

CD8+ encephalitis (CD8+E) is an emerging and incompletely understood HIV-associated neurological syndrome, typically presenting as a steroid-responsive subacute encephalopathy with prominent white matter changes in patients with apparently well-controlled HIV infection. Some cases can be associated with the phenomenon of 'viral escape' (disproportionate replication within the cerebrospinal fluid), but the most important pathophysiology of CD8+E is thought to involve an attack on HIV-infected CD4+ lymphocytes by autoreactive CD8+ cells. We report a case of CD8+E where the initial positive response to steroid treatment was followed by several relapses on withdrawal. This led to the use of mycophenolate mofetil (MMF) as a long-term steroid-sparing agent, which is the first time this approach has been reported in the literature. The patient has now been on treatment with MMF for 10 months and it has been possible to taper the steroids down to a minimal maintenance dose without further relapse.

Topics: Adult; CD8-Positive T-Lymphocytes; Drug Resistance; Drug Therapy, Combination; Encephalitis; Female; HIV Infections; Humans; Immunosuppressive Agents; Magnetic Resonance Imaging; Mycophenolic Acid; Prednisolone; Recurrence; Remission Induction; Treatment Outcome; Viral Load

Renal transplantation in HIV-positive patients with end-stage renal disease has in recent years become a successful treatment option. We report two patients who underwent renal transplantation using a combination of basiliximab, calcineurin inhibitors, mycophenolate mofetil (MMF), and steroids with a "non-interacting" antiretroviral combination therapy consisting of stavudine or abacavir, lamivudine, and nevirapine. We observed no acute rejection but a BK polyomavirus infection in both patients. In conclusion, a quadruple immunosuppression with an interleukin 2 receptor antagonist, a calcineurin inhibitor, MMF, and steroids appears to be advisable to prevent high rates of acute rejection, but if possible thereafter immunosuppression should be tapered rapidly (eg, MMF stop, prednisolone dose 5 mg/d). The selection of antiretroviral agents should avoid compounds that interact severely with the immunosuppression used.

Topics: Adult; Antibodies, Monoclonal; Basiliximab; Calcineurin Inhibitors; Drug Therapy, Combination; Female; Graft Rejection; HIV Infections; Hospitals, University; Humans; Immunosuppressive Agents; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Male; Mycophenolic Acid; Prednisolone; Recombinant Fusion Proteins; Steroids

The polyene antifungal agent Amphotericin B exhibits potent and broad spectrum fungicidal activity. However, high nephrotoxicity can hinder its administration in resource poor settings. Quantification of early fungicidal activity in studies of HIV patients with cryptococcosis demonstrate that 5-Fluorocytosine therapy in combination with Amphotericin B results in faster clearance than with Amphotericin B alone. In vitro synergy between the two drugs has also been reported but the mechanism by which 5-Fluorocytosine synergizes with Amphotericin B has not been delineated. In this study we set out to investigate the effect of genetic mutation or pharmacologic repression of de novo pyrimidine and purine biosynthesis pathways on the Amphotericin B susceptibility of Cryptococcus neoformans. We demonstrate that a ura- derivative of wild type Cryptococcus neoformans strain H99 is hypersensitive to Amphotericin B. This sensitivity is remediated by re-introduction of a wild type URA5 gene, but not by addition of exogenous uracil to supplement the auxotrophy. Repression of guanine biosynthesis by treatment with the inosine monophosphate dehydrogenase inhibitor, mycophenolic acid, was synergistic with Amphotericin B as determined by checkerboard analysis. As in Cryptococcus neoformans, a ura(-) derivative of Candida albicans was also hypersensitive to Amphotericin B, and treatment of Candida albicans with mycophenolic acid was likewise synergistic with Amphotericin B. In contrast, neither mycophenolic acid nor 5-FC had an effect on the Amphotericin B susceptibility of Aspergillus fumigatus. These studies suggest that pharmacological targeting of nucleotide biosynthesis pathways has potential to lower the effective dose of Amphotericin B for both C. neoformans and C. albicans. Given the requirement of nucleotide and nucleotide sugars for growth and pathogenesis of Cryptococcus neoformans, disrupting nucleotide metabolic pathways might thus be an effective mechanism for the development of novel antifungal drugs.

Topics: Amphotericin B; Antifungal Agents; Aspergillus fumigatus; Candida albicans; Cryptococcosis; Cryptococcus neoformans; Flucytosine; HIV Infections; Humans; Microbial Sensitivity Tests; Mycophenolic Acid; Nucleotides

One of the main concerns associated with renal transplantation in HIV-infected patients is the high risk of acute rejection, which makes physicians reluctant to use steroid-free immunosuppressive therapy in this subset of patients. However, steroid therapy increases cardiovascular morbidity and mortality. The aim of this study was to define the efficacy of a steroid-sparing regimen in HIV-infected renal transplant recipients. Thirteen HIV-infected patients were consecutively transplanted. The induction therapy consisted of basiliximab and methylprednisolone for 5 days followed by a calcineurin inhibitor plus mycophenolate acid. The mean follow-up was 50 ± 22 months. Eight patients (61.5%) experienced acute rejection, and 75% of the first episodes occurred within 2 months after transplantation. The probability of first acute rejection was 58% after 1 year and 69% after 4 years. Seven of eight patients recovered or maintained their kidney function after antirejection therapy and steroid resumption. At the last follow-up, seven of 13 patients (54%) had resumed steroid therapy. The 4-year patient and graft survivals were 100% and 88.9%, respectively. The benefits of this steroid-free regimen in HIV-infected renal recipients must be reconsidered because of the high rate of acute rejection. New immunosuppressive steroid-free strategies should be identi-fied in this set of patients.

Topics: Adult; Calcineurin Inhibitors; Drug Therapy, Combination; Female; Follow-Up Studies; Graft Rejection; Graft Survival; HIV Infections; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Retrospective Studies; Risk Assessment; Steroids; Survival Analysis; Transplantation Immunology; Treatment Outcome; Young Adult

Topics: Adolescent; Female; HIV Infections; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Mycophenolic Acid

To evaluate the association between scleritis and systemic disease in a non-university, non-tertiary referral practice and to describe our experience with scleritis treatment.. Retrospective chart review.. The medical records of patients with scleritis between 2001 and 2007 were reviewed for associated systemic disease.. In our series of 86 patients with scleritis, 55 patients (64.0%) had isolated scleritis while 31 patients (36.0%) had associated systemic-disease. Twenty-six patients (83.9%) with systemic disease had diagnosed systemic disease at the time of initial scleritis presentation, while 5 patients (16.1%) were diagnosed following systemic work-up. Those diagnosed after systemic work-up were more likely to have systemic vasculitic disease as opposed to a rheumatic or infectious disease. Patients with and without associated systemic disease were likely to require systemic therapy at similar rates (93.5% and 92.7%, respectively). Five patients with steroid-refractory scleritis were treated with infliximab (Remicade; Centocor Inc, Horsham, Pennsylvania, USA) and all responded without evidence of adverse effect. Seven patients were treated with mycophenolate mofetil (CellCept; Roche Laboratories, Nutley, New Jersey, USA), of which three improved.. The association between scleritis and systemic disease in a community-based referral practice may be lower than in tertiary referral or university-based centers. Although thorough systemic disease evaluation is warranted in scleritis patients, most patients with associated systemic disease will have such a diagnosis prior to the development of scleritis. The need to institute aggressive systemic therapy cannot be predicted by the presence of an associated systemic disease. Infliximab and mycophenolate mofetil are useful additions to the scleritis practitioner's armamentarium for steroid-refractory scleritis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Antibodies, Monoclonal; Autoimmune Diseases; Child; Community Health Services; Female; Herpes Zoster; HIV Infections; Humans; Infliximab; Male; Middle Aged; Mycophenolic Acid; Referral and Consultation; Retrospective Studies; Sarcoidosis; Scleritis; Young Adult

A case of psoriasis and psoriatic arthritis in a 38-year-old white male patient infected with human immunodeficiency virus (HIV) treated safely and effectively with mycophenolate mofetil (MMF) is reported. Treatments for psoriasis and psoriatic arthritis are manifold, including topical, oral, intramuscular, intravenous, and subcutaneous therapies. These indicated treatments for psoriasis and psoriatic arthritis result in suppression of the immune system.

Topics: Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antiretroviral Therapy, Highly Active; Arthritis, Psoriatic; Clobetasol; HIV Infections; Humans; Male; Middle Aged; Mycophenolic Acid; Psoriasis; Skin

Liver transplantation (LT) for hepatitis C virus (HCV)-associated cirrhosis in human immunodeficiency virus (HIV)-infected patients was compared with non-HIV patients. Nine patients with HIV-HCV coinfection were compared with patients transplanted before and after each HIV patient (control group). Immunosuppression consisted in tacrolimus with steroids or mycophenolate mofetil. Acute cellular rejection and three-year actuarial patient survival were respectively 44% and 87.5% in HIV group and 22% and 93.7% in the control group (P=NS). Acute hepatitis C virus occurred earlier (2.3 vs. 4.3 months) and was more cholestatic (mean bilirubin: 10.8 vs. 1.6 mg/dL) in the HIV group. Eight (100%) HIV and nine (64.3%) control patients received antiviral treatment with pegylated interferon and ribavirin. One patient (11.1%) of the control group and one patient (20%) of the HIV group presented a sustained virologic response (P=NS). Short- to midterm results of LT in HIV-HCV co-infected patients were excellent and similar to non-HIV patients.

Topics: Adult; Aged; Antiviral Agents; Case-Control Studies; Female; Hepatitis C, Chronic; HIV Infections; Humans; Immunosuppression Therapy; Liver Transplantation; Male; Middle Aged; Mycophenolic Acid; Steroids; Tacrolimus; Treatment Outcome

Mycophenolate mofetil (MMF), the bioavailable form of mycophenolic acid (MPA), has been proposed as adjuvant therapy for human immunodeficiency virus type 1 (HIV-1) infection. MPA can inhibit viral replication and might blunt virus-induced immunopathology. However, other effects of this inhibitor might be detrimental in an HIV-infected patient. We therefore studied the effect of MPA on selected cellular processes of relevance to HIV infection. We found that MPA did not alter the expression of the primary HIV coreceptor CCR5 on primary resting lymphocytes, but modestly increased CCR5 expression after activation. Conversely, MPA modestly decreased the secretion of the CCR5 ligand RANTES in resting lymphocytes, but had no effect after activation. It has been suggested that the use of inhibitors of host nucleoside metabolism may enhance clinical toxicities induced by HIV-1 nucleoside reverse transcriptase inhibitors (NRTIs). We found no evidence that MPA induced mitochondrial dysfunction or enhanced dysfunction induced by NRTIs in an HepG2 cell line model of mitochondrial toxicity. Further, MPA did not selectively enhance apoptosis in HIV-1-infected lymphocytes. Our findings support the testing of MMF to augment suppression of viral replication. However, careful study will be required to demonstrate that MMF is beneficial when used without antiretroviral therapy, to inhibit residual replication, or to deplete the pool of latently infected nonactivated cells.

Topics: Apoptosis; Cells, Cultured; Chemokine CCL5; Electron Transport Complex IV; HIV Infections; Humans; Leukocytes, Mononuclear; Mycophenolic Acid; Receptors, CCR5; RNA, Messenger

Although highly active antiretroviral therapy (HAART) has dramatically changed the epidemiological impact of HIV infection, many problems with currently used antiretroviral therapy have underscored the urgent need for additional therapeutic approaches. Structured treatment interruption trials, which can be considered an immune-based therapy with an autologous virus, have failed to control viral replication in most chronically HIV-1-infected patients. Alternative approaches could be the use of immunosuppressive drugs to enhance the control of viral replication mediated by their immune and antiviral properties. The use of immunosuppressive drugs may reduce the number of activated CD4 cells that support massive virus production and may prevent sequestration of CD4 T cells into lymphoid tissue, which is the place of antigen presentation and productive HIV infection. The strategy of using drugs that interfere with the HIV life-cycle, acting on the target cells of HIV rather than on viral enzymes, offers the advantage of avoiding the development of antiretroviral drug-resistant HIV mutants. However, it is not known if these approaches will clinically benefit long-term infection, by establishing a new immunological set-point that may affect the rate of disease progression. Caution is required when using HAART in combination with cytostatic drugs in HIV-1 infection until their impact and long-term safety have been investigated further in larger clinical trials.

Topics: Anti-HIV Agents; Antiretroviral Therapy, Highly Active; HIV Infections; Humans; Hydroxyurea; Immunosuppressive Agents; Mycophenolic Acid; Nucleic Acid Synthesis Inhibitors

Topics: Antiretroviral Therapy, Highly Active; HIV Infections; HIV Seropositivity; HIV-1; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid

Topics: Anti-HIV Agents; HIV Fusion Inhibitors; HIV Infections; HIV Integrase Inhibitors; HIV Protease Inhibitors; Humans; Immunosuppressive Agents; Mycophenolic Acid; Reverse Transcriptase Inhibitors

Topics: Anti-HIV Agents; Dideoxynucleosides; Drug Resistance, Microbial; Drug Resistance, Multiple; Drug Therapy, Combination; HIV Infections; HIV-1; Humans; IMP Dehydrogenase; Mycophenolic Acid; Reverse Transcriptase Inhibitors

Laboratory studies indicate that mycophenylate (CellCept) may increase the anti-HIV activity of abacavir (Ziagen). Mycophenylate suppresses the production of guanosine, which is critical to the replication of HIV. Although the combination of mycophenylate and abacavir has been shown to have a similar effect to that of the combination of Hydroxyurea and ddI, it may be more powerful and less toxic. These results are preliminary and must be confirmed by human studies, which are currently under way.

Topics: Dideoxynucleosides; Drug Synergism; Drug Therapy, Combination; Enzyme Inhibitors; HIV Infections; Humans; Immunosuppressive Agents; Mycophenolic Acid; Prodrugs; Reverse Transcriptase Inhibitors