Emergence of cytomegalovirus resistance to foscarnet in a patient receiving foscarnet salvage therapy for multidrug-resistant HIV infection

Boutolleau, David; Canestri, Ana; Burrel, Sonia; Wirden, Marc; Seang, Sophie; Clavel-Osorio, Cyril; Marcelin, Anne–Geneviève; Katlama, Christine; Agut, Henri

doi:10.1016/j.jcv.2012.02.008

Cited by 10 publications

(5 citation statements)

References 23 publications

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“…This mutation conferred resistance to FOS and borderline resistance to GCV, and the patient was treated successfully with artesunate. A patient was also reported who received prolonged FOS as salvage therapy for human immunodeficiency virus and developed FOS resistance . In both of these cases, the development of FOS resistance occurred after prolonged therapy, in stark contrast to only 28 days of therapy in our patient.…”

Section: Discussionmentioning

confidence: 56%

“…Indeed, prolonged antiviral exposure, coupled with ongoing viral replication because of host immune suppression and/or inadequate antiviral dosing, are the primary risk factors for the development of resistance . In 27 kidney transplant recipients, the mean duration of GCV therapy before detection of resistance was 108 days (range 41–205 days) .…”

Section: Discussionmentioning

confidence: 99%

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UL54 foscarnet mutation in an hematopoietic stem cell transplant recipient with cytomegalovirus disease

Gregg

Hakki

Kaul

2014

Transplant Infectious Dis

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Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 99%

UL54 foscarnet mutation in an hematopoietic stem cell transplant recipient with cytomegalovirus disease

Gregg

Hakki

Kaul

2014

Transplant Infectious Dis

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“…While we were not able to assess the impact of PFA–ZDV–DTG regimen on cytomegalovirus (CMV) infection resistance to foscarnet, it should be kept in mind that CMV resistance may occur in patient receiving foscarnet‐based salvage therapy [Boutolleau et al, ].…”

Section: Discussionmentioning

confidence: 99%

Foscarnet, zidovudine and dolutegravir combination efficacy and tolerability for late stage HIV salvage therapy: A case‐series experience

Delory

Papot

Rioux

et al. 2016

Journal of Medical Virology

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Salvage therapy including foscarnet (PFA), zidovudine (ZDV) and an optimized background ART (OBT) has been shown to be effective in patients with advanced HIV infection, and no therapeutic options. Dolutegravir (DTG) may offer a more active combination. Objective was to describe efficacy and tolerability of PFA-ZDV-DTG containing regimen. In our cohort, we identified patients who: (i) had plasma HIV-1 RNA load (pVL) >50 c/ml (>100 for HIV-2) on combination ART (cART); (ii) had at least 1 PI/r, 1 NRTI, 1 NNRTI (for HIV-1), and at least 1 raltegravir resistance mutations; (iii) were naive to DTG; and (iv) initiated on a PFA-ZDV-DTG containing-regimen with 48 weeks (W48) of follow-up. Out of 5 patients, 2 were infected with HIV-2. At PFA-ZDV-DTG initiation, CD4 cell count was (/mm(3) ) of 64, 40, 10, in HIV-1, and 37, 199, in HIV-2 infected patients; and pVL (log10 c/ml) of 4.8, 5.1, 4.4, in HIV-1, and 3.6, 4.2, in HIV-2 infected patients, respectively. Median OBT genotypic sensitivity score was 1.5 [1-2]. PFA was discontinued in one patient, due to an acute renal failure. At W48, one HIV-1 infected patient had a pVL <50 c/ml and two <200 c/ml; the two HIV-2 infected patients had pVL >100 c/ml. No lack of treatment adherence was observed. In treatment experienced HIV-infected patients, failing cART and without other therapeutic options, a PFA-ZDV-DTG combination therapy could be effective. Renal adverse events should be monitored.

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“…At the time of the diagnosis of HCMV retinitis, the patient had a high viral load, which may have contributed to the observed negative response to treatment. On the other hand, other factors, including profound immunosuppression, previous exposure to antiviral drugs, and persistently low levels of HCMV DNA, are also thought to be responsible for the failure to treat HCMV ( 6 ). Of note, at the beginning of GCV treatment, the CD4 + cell count was 8 CD4 + cells/mm 3 .…”

Section: Discussionmentioning

confidence: 99%

“…Despite the fact that nowadays treatment of HCMV infection is usually successful, it continues to represent a significant proportion of cases with end-organ disease in patients with AIDS ( 5 ). HCMV infection treatment failure could involve risk factors such as profound immunosuppression, previous exposure to anti-HCMV drugs, or persistent low-level HCMV replication ( 6 ). Nevertheless, retinitis relapse in patients with AIDS is mostly a result of the development of HCMV GCV resistance caused by prolonged treatment periods ( 2 ) and low adherence to ART.…”

Section: Introductionmentioning

confidence: 99%

Late emergence of A594V and L595W mutations related to ganciclovir resistance in a patient with HCMV retinitis and long-term HIV progression

Slavov

Vilar

Wagatsuma

et al. 2015

Braz J Med Biol Res

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The emergence of ganciclovir (GCV) resistance during the treatment of human cytomegalovirus (HCMV) infection is a serious clinical challenge, and is associated with high morbidity and mortality. In this case report, we describe the emergence of two consecutive mutations (A594V and L595W) related to GCV resistance in a patient with HCMV retinitis and long-term HIV progression after approximately 240 days of GCV use. Following the diagnosis of retinitis, the introduction of GCV did not result in viral load reduction. The detected mutations appeared late in the treatment, and we propose that other factors (high initial HCMV load, previous GCV exposure, low CD4+ cell count), in addition to the presence of resistance mutations, may have contributed to the treatment failure of HCMV infection in this patient.

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Emergence of cytomegalovirus resistance to foscarnet in a patient receiving foscarnet salvage therapy for multidrug-resistant HIV infection

Cited by 10 publications

References 23 publications

UL54 foscarnet mutation in an hematopoietic stem cell transplant recipient with cytomegalovirus disease

UL54 foscarnet mutation in an hematopoietic stem cell transplant recipient with cytomegalovirus disease

Foscarnet, zidovudine and dolutegravir combination efficacy and tolerability for late stage HIV salvage therapy: A case‐series experience

Late emergence of A594V and L595W mutations related to ganciclovir resistance in a patient with HCMV retinitis and long-term HIV progression

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