Inflammatory Myositis Secondary to Anti-Retroviral Therapy in a Child; Case Report and Review of the Literature

2021 ◽  
pp. 1-7
Author(s):  
Marie Monaghan ◽  
Charlotte Loh ◽  
Stephen Jones ◽  
Agyepong Oware ◽  
Kathryn Urankar ◽  
...  

Here, we describe a five year old girl with congenital HIV who had a six-week onset of rapidly deteriorating mobility and progressive proximal muscle weakness, associated with a raised Creatine Kinase (CK) level of 4330 U/L [25–200 U/L], subsequently diagnosed with an inflammatory myositis. Potential causes were investigated by paediatric neurology and immunology teams. Her viral load had been undetectable over the preceding two years, excluding a primary HIV myositis. While MRI scanning did not show evidence of definite myositis, a muscle biopsy showed evidence of an inflammatory process, comprising a moderate endomysial, perimysial and perivascular mononuclear (CD8 + T cell) infiltrate with increased MHC expression. No particular features of dermatomyositis or immune-mediated necrotising myopathy were identified and there were no features of an inclusion body myositis. Given the absence of active HIV infection, the role of anti-retroviral medications was considered. She had had a recent switch in medication, from twice daily Raltegravir (an Integrase Strand Transfer Inhibitor, INSTI) to once daily Dolutegravir (an INSTI) while continuing on an established daily protocol of Abacavir and Lamivudine (Nucleoside Reverse Transcriptase Inhibitors). Changing the Dolutegravir back to Raltegravir, in combination with continuing Lamivudine and Abacavir for two months made no difference to her weakness or CK levels. Moreover, this drug regimen had been well-tolerated over the preceding 19 month period. Changing the anti-retroviral regime completely to a single drug class (Protease Inhibitors) of Ritonavir and Darunavir, resulted in a dramatic improvement in her symptomatology. Within ten days she regained the ability to stand and walk, with a reduction in her CK from 1700 U/L at time of switch to 403 U/L [25–200]. This case highlights the potential risk of developing inflammatory myositis from anti-retrovirals even 19 months into treatment.

2020 ◽  
Vol 75 (7) ◽  
pp. 1955-1960 ◽  
Author(s):  
Jordi Navarro ◽  
Ana González-Cordón ◽  
José Luís Casado ◽  
Jose I Bernardino ◽  
Pere Domingo ◽  
...  

Abstract Background The combination of boosted darunavir plus rilpivirine, once daily, could be a convenient, effective and well-tolerated two-drug regimen to achieve HIV suppression in HIV-infected patients. Methods Multicentre, retrospective cohort study in nine hospitals in Spain. All HIV-infected subjects starting boosted darunavir plus rilpivirine were included, irrespective of their viral load (VL). The primary objective was the percentage of patients with VL <50 copies/mL at 48 weeks. Secondary objectives included changes in CD4+ cell count, lipid profile and renal function. Results Eighty-one of 84 patients reached Week 48. Fifty-nine (70.2%) patients had VL <50 copies/mL at baseline and the rest had a median VL of 202 (IQR 98–340) copies/mL. Subjects had a median of 21 years of infection with six prior regimens. The main reasons for starting boosted darunavir plus rilpivirine were simplification (44%), kidney or bone toxicity (28.6%) and virological failure (17.9%). Historical genotypes from 47 patients showed 41 (87.2%) patients with NRTI RAMs, 21 (44.7%) with NNRTI RAMs, 12 (25.5%) with primary PI RAMs and 7 (14.9%) with integrase strand transfer inhibitor (INSTI) RAMs. One patient had low-level resistance to boosted darunavir and five patients had some resistance to rilpivirine. At 48 weeks, 71 (87.7%) patients had VL <50 copies/mL. According to undetectable or detectable baseline VL, effectiveness was 91.1% or 80%, respectively. There were four virological failures with no emergence of new RAMs. Three of these patients resuppressed viraemia while maintaining the same regimen. Conclusions The combination of boosted darunavir plus rilpivirine has shown good effectiveness and tolerability in this cohort of pretreated patients with a long-lasting HIV infection, exposure to multiple antiretroviral regimens and prior HIV resistance.


Author(s):  
Hanh T Pham ◽  
Brunna M Alves ◽  
Sunbin Yoo ◽  
Meng A Xiao ◽  
Jing Leng ◽  
...  

Abstract Objectives The development of HIV drug resistance against the integrase strand transfer inhibitor dolutegravir is rare. We report here the transient detection, by near full-genome ultradeep sequencing, of minority HIV-1 subtype B variants bearing the S153F and R263K integrase substitutions in the proviral DNA from blood cells of one patient who successfully initiated dolutegravir-based ART, over 24 weeks. Our objective was to study the effects of these substitutions. Methods Strand transfer and DNA-binding activities of recombinant integrase proteins were measured in cell-free assays. Cell-based resistance, infectivity and replicative capacities were measured using molecular clones. Structural modelling was performed to understand experimental results. Results R263K emerged first, followed by the addition of S153F at Week 12. By Week 24, both mutations remained present, but at lower prevalence. We confirmed the coexistence of S153F and R263K on single viral genomes. Combining S153F or S153Y with R263K decreased integration and viral replicative capacity and conferred high levels of drug resistance against all integrase inhibitors. Alone, S153Y and S153F did little to infectivity or dolutegravir resistance. We identified altered DNA binding as a mechanism of resistance. The patient remained with undetectable viral loads at all timepoints. Conclusions Drug-resistant minority variants have often been reported under suppressive ART. Our study adds to these observations by unravelling a progression towards higher levels of resistance through a novel pathway despite continuous undetectable viral loads. Poorly replicative HIV drug-resistant minority proviral variants did not compromise viral suppression in one individual treated with dolutegravir.


2011 ◽  
Vol 16 (2) ◽  
pp. 253-256 ◽  
Author(s):  
Benjamin Young ◽  
Signe Fransen ◽  
Kenneth S Greenberg ◽  
Amy Thomas ◽  
Sharon Martens ◽  
...  

Author(s):  
William A Werbel ◽  
Diane M Brown ◽  
Oyinkansola T Kusemiju ◽  
Brianna L Doby ◽  
Shanti M Seaman ◽  
...  

Abstract Background Organ transplantation from donors with HIV to recipients with HIV (HIV D+/R+) presents risks of donor-derived infections. Understanding clinical, immunologic, and virologic characteristics of HIV+ donors is critical for safety. Methods We performed a prospective study of donors with HIV-positive and HIV false-positive (FP) testing within the HOPE in Action studies of HIV D+/R+ transplantation (ClinicalTrials.gov NCT02602262; NCT03500315; NCT03734393). We compared clinical characteristics in HIV+ versus FP donors. We measured CD4+ T cells, HIV viral load (VL), drug resistance mutations (DRMs), co-receptor tropism, and serum antiretroviral therapy (ART) detection using mass spectrometry in HIV+ donors. Results Between 03/2016-03/2020, 92 donors (58 HIV+, 34 FP), representing 98.9% of all US HOPE donors during this period, donated 177 organs (131 kidney, 46 liver). Each year the number of donors increased. Prevalence of hepatitis B (16% vs. 0%), syphilis (16% vs. 0%), and cytomegalovirus (91% vs. 58%) was higher in HIV+ versus FP donors; hepatitis C viremia was similar (2% vs. 6%). Most HIV+ donors (71%) had known HIV diagnosis, of whom 90% were prescribed ART and 68% had VL<400 copies/mL. Median CD4 count was 194 cells/uL (IQR=77-331); median CD4% was 27.0 (IQR=16.8-36.1). Major HIV DRMs were detected in 42%, including non-nucleoside reverse transcriptase inhibitors (33%), integrase strand transfer inhibitor (INSTI, 4%), and multiclass (13%). Serum ART was detected in 46% and matched ART by history. Conclusion Utilization of HIV+ donor organs is increasing. HIV DRMs are common, yet resistance that would compromise INSTI-based regimens is rare, which is reassuring regarding safety.


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