Clinical monitoring and correlates of nephropathy in SIV-infected macaques during high-dose antiretroviral therapy

Sanders-Beer, Brigitte E.; Spano, Yvette Y; Golighty, Dawn; Lara, Abigail; Hebblewaite, Diane; Nieves-Duran, Lourdes; Rhodes, Lowrey; Mansfield, Keith G.

doi:10.1186/1742-6405-8-3

Cited by 11 publications

(5 citation statements)

References 21 publications

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“…In building our model of allo-HCT during suppressed SHIV infection, we encountered several challenges. First was the risk of renal insufficiency, a well-described toxicity of cART, most commonly attributed to tenofovir 56 , 57 . NHP transplant recipients were treated with cART for at least 6 months pre-transplant, and then continued to receive drugs post-HCT.…”

Section: Discussionmentioning

confidence: 99%

Evidence for persistence of the SHIV reservoir early after MHC haploidentical hematopoietic stem cell transplantation

et al. 2018

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Allogeneic transplantation (allo-HCT) has led to the cure of HIV in one individual, raising the question of whether transplantation can eradicate the HIV reservoir. To test this, we here present a model of allo-HCT in SHIV-infected, cART-suppressed nonhuman primates. We infect rhesus macaques with SHIV-1157ipd3N4, suppress them with cART, then transplant them using MHC-haploidentical allogeneic donors during continuous cART. Transplant results in ~100% myeloid donor chimerism, and up to 100% T-cell chimerism. Between 9 and 47 days post-transplant, terminal analysis shows that while cell-associated SHIV DNA levels are reduced in the blood and in lymphoid organs post-transplant, the SHIV reservoir persists in multiple organs, including the brain. Sorting of donor-vs.-recipient cells reveals that this reservoir resides in recipient cells. Moreover, tetramer analysis indicates a lack of virus-specific donor immunity post-transplant during continuous cART. These results suggest that early post-transplant, allo-HCT is insufficient for recipient reservoir eradication despite high-level donor chimerism and GVHD.

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Section: Discussionmentioning

confidence: 99%

Evidence for persistence of the SHIV reservoir early after MHC haploidentical hematopoietic stem cell transplantation

et al. 2018

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“…Similarly, the study conducted at Chiang Mai University Hospital, Thailand showed that lower baseline CD4 cell count was one of the main factors significantly associated with ART failure. 28 …”

Section: Discussionmentioning

confidence: 99%

First-line antiretroviral treatment failure and associated factors in HIV patients at University of Gondar Teaching Hospital, Gondar, Northwest Ethiopia

Ayalew¹,

Kumilachew²,

Belay³

et al. 2016

HIV

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BackgroundAntiretroviral therapy (ART) restores immune function and reduces HIV-related adverse outcomes. But treatment failure erodes this advantage and leads to an increased morbidity and compromised quality of life in HIV patients. The aim of this study was to determine the prevalence and factors associated with first-line ART failure in HIV patients at the University of Gondar Teaching Hospital.Patients and methodsA retrospective study was conducted on 340 adults who had started ART during the period of September 2011 to May 2015. Data regarding patients’ sociodemographics, baseline characteristics, and treatment-related information were collected through review of their medical charts. Data were analyzed using SPSS version 21. Descriptive statistics, cross-tabs, and binary and multiple logistic regressions were utilized. P<0.05 was used to declare association.ResultsAmong the 340 patients enrolled, 205 were females (60.3%). The mean age at ART initiation was 34.4 years. A total of 14 (4.1%) patients were found to have treatment failure. The median duration of treatment failure from initiation of treatment was 17.5 months (8–36 months). Poor adherence to treatment and low baseline CD4 cell count were found to be significant predictors of treatment failure.ConclusionThe prevalence of first-line ART failure was 4.1%. Treatment failure was most likely to occur for the patients who had poor drug adherence and those who were delayed to start ART till their CD4 cell count became very low (<100 cells/mm3).

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“…Renal toxicity with either acute or chronic overdosage of PMPA has been demonstrated but can be avoided with appropriate dosing [52,63]. While the NRTIs didanosine (ddI) and stavudine (d4T) have demonstrated anti-SIV activity, a significant proportion of macaques receiving this regimen have developed diabetes after >25 weeks of dosing, likely due to ddI toxicity [8,56].…”

Section: Cart Drugsmentioning

confidence: 99%

Considerations in the development of nonhuman primate models of combination antiretroviral therapy for studies of aids virus suppression, residual virus, and curative strategies

Prete¹,

Lifson²

2013

Current Opinion in HIV and AIDS

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Purpose of review Animal models will be critical for preclinical evaluations of novel HIV eradication and/or functional cure strategies in the setting of suppressive combination antiretroviral therapy (cART). Here, the strengths, limitations, and challenges of recent efforts to develop nonhuman primate (NHP) models of cART-mediated suppression for use in studies of persistent virus and curative approaches are discussed. Recent findings A number of combinations of NHP species and viruses that recapitulate key aspects of human HIV infection have been adapted for cART-mediated suppression studies. Different cART regimens implementing drugs targeting multiple different steps of the viral life cycle have provided varying levels virologic suppression, dependent in part upon the host species, virus, drug regimen and timing, and virologic monitoring assay sensitivity. New, increasingly sensitive virologic monitoring approaches for measurements of plasma viral RNA, cell- and tissue-associated viral RNA and DNA, and the replication-competent residual viral pool in the setting of cART in NHP models are being developed to allow for the assessment of persistent virus on cART and to evaluate the impact of viral induction/eradication strategies in vivo. Summary Given the vagaries of each specific virus and host species, and cART regimen, each model will require further development and analysis to determine their appropriate application for addressing specific experimental questions.

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Clinical monitoring and correlates of nephropathy in SIV-infected macaques during high-dose antiretroviral therapy

Cited by 11 publications

References 21 publications

Evidence for persistence of the SHIV reservoir early after MHC haploidentical hematopoietic stem cell transplantation

Evidence for persistence of the SHIV reservoir early after MHC haploidentical hematopoietic stem cell transplantation

First-line antiretroviral treatment failure and associated factors in HIV patients at University of Gondar Teaching Hospital, Gondar, Northwest Ethiopia

Considerations in the development of nonhuman primate models of combination antiretroviral therapy for studies of aids virus suppression, residual virus, and curative strategies

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