Non-virological response to a dolutegravir-containing regimen in a patient harbouring a E157Q-mutated virus in the integrase region (original) (raw)
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American Journal of Transplantation, 2009
Solid organ transplantations (SOT) are performed successfully in selected HIV-infected patients. However, multiple and reciprocal drug-drug interactions are observed between antiretroviral (ARV) drugs and calcineurin inhibitors (CNIs) through CYP450 metabolization. Raltegravir (RAL), a novel HIV-1 integrase inhibitor, is not a substrate of CYP450 enzymes. We retrospectively reviewed the outcomes of 13 HIV-infected transplant patients treated by an RAL + two nucleosidic reverse transcriptase inhibitor (NRTI) regimen, in terms of tolerability, ARV efficacy (plasma viral load, CD4 cell count), drug interactions, RAL pharmacokinetics and transplant outcome. Thirteen patients with liver (n = 8) or kidney (n = 5) transplantation were included. RAL was initiated (400 mg BID) either at time of transplantation (n = 6), or after transplantation (n = 7). Median RAL trough concentration was 507 ng/mL (176-890), which is above the in vitro IC95 for wild type HIV-1 strains (15 ng/mL). Target trough levels of CNIs were promptly obtained with standard dosages of tacrolimus or cyclosporine. RAL tolerability was excellent. There was no episode of acute rejection. HIV infection remained controlled. After a median follow-up of 9 months (range: 6-14), all patients were alive with satisfactory graft function. The use of an RAL + two NRTI-based regimen is a good alternative in HIV-infected patients undergoing SOT.
HIV Medicine, 2019
ObjectivesHigh rates of clinical acute rejection after kidney transplantation have been reported in people living with HIV (PLHIV), probably as a consequence of drug interactions. We therefore investigated the incidence of acute rejection within 6 months of transplantation in HIV‐infected recipients treated with a protease‐inhibitor‐free raltegravir‐based regimen.MethodsThe Agence Nationale de Recherche sur le Sida et les Hépatites Virales (ANRS) 153 TREVE (NCT01453192) study was a prospective multicentre single‐arm trial in adult PLHIV awaiting kidney transplantation, with viral load < 50 HIV‐1 RNA copies/mL, CD4 T‐cell count > 200 cells/μL, and HIV‐1 strains sensitive to raltegravir, aiming to demonstrate 6‐month clinical acute rejection rates < 30%. Time to transplantation was compared with that for uninfected subjects matched for age, sex and registration date.ResultsIn total, 61 participants were enrolled in the study, and 26 underwent kidney transplantation. Two parti...
AIDS, 2007
Suspected immune reconstitution inflammatory syndrome associated with the proliferation of Kaposi's sarcoma during HAART HAART has reduced the incidence of AIDS-related Kaposi's Sarcoma (KS) and, in affected individuals, its use alone can lead to KS resolution [1]. We read with interest the recent report by Connick et al. [2] and wish to describe an additional case of suspected immune reconstitution inflammatory syndrome (IRIS) associated with the proliferation of KS during HAART. A 35-year-old African-American man with HIV disease since 1990 had cutaneous KS of the left lower extremity diagnosed by biopsy in June 2003. At that time he had several raised, violaceous lesions with some edema of the right leg. He was treated with radiation and one cycle of doxil chemotherapy, with some resolution of the KS lesions. He was subsequently lost to follow-up until July 2004, when he was admitted to hospital with cryptococcal meningitis complicated by papillitis with visual compromise, which responded to therapy. Approximately 2 months later, he was again placed on lamivudine, tenofovir, and efavirenz at a CD4 cell count of 103 cells/ml. Up to that time, his KS lesions had undergone only an incremental increase in the size of the existing lesions. When seen in follow-up one month later he reported excellent compliance with his antiretroviral regimen; but we noted an explosive increase in the size, vascular appearance and number of nodules (from seven to 15) along with a marked increase in lymphedema. At that time, his CD4 cell count had increased to 127 cells/ml. He was continued on HAART and started chemotherapy again with doxil. Three months later, his CD4 cell count was 156 cells/ml and he had significant regression of his KS lesions. Our patient's course is consistent with IRIS manifested by the proliferation of KS lesions, as the lesions were quiescent before the re-initiation of HAART; furthermore, he experienced an increase in his CD4 cell count. The regression of KS after the institution of HAART is well documented [3-5]. The responsible mechanisms are not well elucidated, but restored immunity to the KS-associated herpesvirus, decreased levels of angiogenic factors that stimulate KS proliferation, and direct angiogenesis-inhibitory effects of HIV-1 protease inhibitors could all be involved [6]. When HAART is started, the regression of lesions is expected. There are now, however, several cases [2,7,8] that have described the progression of disease, and further efforts to identify this mechanism are warranted. As stated by Connick and colleagues [2], it is also important for clinicians to realize that IRIS does not indicate the failure of HAART or a need for changes in the antiretroviral regimen.
Virologic failure after 48 weeks of raltegravir-based regimen in low HIV-1 incidence setting
Antiviral Chemistry and Chemotherapy, 2020
Background With the advent of next generation integrase strand transfer inhibitors, the rates of virologic failure in treated subjects are expected to decrease. In this study, we analyzed the mutation patterns leading to virologic failure before and after starting integrase strand transfer inhibitor-based regimen as first-line or salvage therapy. Methods Between 2016 and 2019, blood samples were received from 258 patients with HIV-1 infection. Plasma HIV-1 RNA concentrations, and pol gene sequences were determined at baseline, and 16–48 weeks of treatment with integrase strand transfer inhibitor-based regimen. Only patients who did not achieve viral suppression at 48 weeks of integrase strand transfer inhibitor-based treatment were eligible for the current study. Results Virologic failure was observed in seven patients on raltegravir-based regimen. All patients with virologic failure but one were infected with CRF01_AE virus subtype. Raltegravir based-regimen was offered as first-li...
Experimental and Clinical Transplantation
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 methylprednisolone, 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.
MOJ Immunology
Background: Kidney damage appears to be a common complication of HIV infection in the modern era of antiretroviral therapy (ART). This cross sectional study evaluate the pattern, nature and character of elevation of two basic renal safety parameters (urinary uric acid and glucose) in over 57 HIV-infected patients exposed to tenofovir (TDF) (21), non-TDF (21) and drug naïve (15) patients. Methods: Urinary uric acid and glucose were assessed at commencement (V1) and after 4wks (V2), and after 12wks (V3) of patient exposure to therapy. Clinical features of both groups were comparable at commencement. Uricosuria and glucosuria were defined as urinary uric acid and glucose; ≥0.1mg/dl and ≥1.0 mg/dl respectively. Results: After 12 weeks of follow-up incidence of uricosuria and glucosuria were as as follows: [TDF (9), non-TDF (2) and drug naïve (3) (p=0.000)] and [TDF (9), non-TDF (3) and drug naïve (1) (p=0.000)] respectively. Fractional excretion of uric acid was also altered in the two treatment groups. Conclusion: The results show that treatment of HIV-infected patients with a TDF-based regimen compared to a non-TDF-based regimen produce alterations in safety biomarkers of renal pathophysiologic parameters (creatinine, glucosuria, Uricosuria and CD4) after a 12-weeks treatment period. In conclusion, TDF may be associated with subclinical renal tubular damage, inducing at a later stage major increased in urinary excretion of glucose and uric acid, as markers of early tubular injury.
LONG-TERM NONPROGRESSIVE HUMAN IMMUNODEFICIENCY VIRUS-1 INFECTION IN A KIDNEY ALLOGRAFT RECIPIENT
Transplantation, 1998
We report a unique case of a renal transplant patient with a long-term nonprogressive human immunodeficiency virus type-1 (HIV-1) infection and who is asymptomatic despite sustained immunosuppression. Renal function is normal, and HIV infection was probably acquired through blood transfusion before the transplant. Nonprogression may be due either to an effective immune control of HIV replication or to particular genetic aspects of the virus. Several virological investigations were carried out to verify if she is infected with an attenuated virus strain. Results show an unusual combination of high and stable CD4 count, ongoing viral replication and elevated viral loads. Attempts to isolate the virus from plasma were unsuccessful, but isolation was possible from peripheral blood mononuclear cells, and the virus was shown to be non-syncytium-inducing. Sequence analysis of the nef gene revealed no mutation. This exceptional lack of progression of HIV infection under immunosuppressive therapy requires further investigation.