HIV Clinical Trials最新文献

{"title":"Characteristics associated with virologic failure in high-risk HIV-positive participants with prior failure: a post hoc analysis of ACTG 5251.","authors":"Gregory K Robbins,&nbsp;Susan E Cohn,&nbsp;Linda J Harrison,&nbsp;Laura Smeaton,&nbsp;Laura Moran,&nbsp;David Rusin,&nbsp;Marjorie Dehlinger,&nbsp;Theresa Flynn,&nbsp;Sara Lammert,&nbsp;Albert W Wu,&nbsp;Steven A Safren,&nbsp;Nancy R Reynolds","doi":"10.1080/15284336.2016.1189754","DOIUrl":"https://doi.org/10.1080/15284336.2016.1189754","url":null,"abstract":"<p><strong>Unlabelled: </strong>Patients with prior virologic failure (VF) are at an increased risk of subsequent failure, emergence of resistance, and death. This analysis identifies outcomes and correlates of VF in a high-risk population.</p><p><strong>Methods: </strong>A5251 was designed to evaluate an enhanced adherence counseling intervention delivered by nurses from a central call site on virologic suppression. Due to slow enrollment, the study was closed prematurely and revised study endpoints were evaluated (week 24 VF (HIV-1 RNA ≥200 copies/ml) and non-perfect adherence (<100% self-reported using both the ACTG adherence questionnaire and visual analog scale (VAS)).</p><p><strong>Results: </strong>Fifty-nine participants were enrolled, 43 (73%) black non-Hispanic and 23 (39%) women. Median prior antiretroviral regimen changes were three and the co-morbidity in this population was higher than typical for HIV clinical trials. At week 24 (n = 41), 24 (59%) failed to reach virologic suppression (HIV-1 RNA <200 copies/ml) and 25 (63%) reported non-perfect adherence. Higher depression (CES-D10) and adverse illness perceptions (IPQ-B) were associated with week 24 non-adherence. Early clinical assessments (week 12 HIV-RNA ≥200 copies/mL and non-perfect adherence) as well as higher depression and adverse illness perceptions were associated with week 24 VF.</p><p><strong>Discussion: </strong>In this high-risk population, the proportion of participants with suboptimal adherence and VF was unacceptably high. Interventions to address this treatment gap are clearly needed. Depression and a higher illness perception score, failure to achieve virologic suppression by week 12, and less than perfect adherence could be used to target individuals for early interventions in treatment-experienced, high-risk individuals at high risk for VF.</p>","PeriodicalId":13216,"journal":{"name":"HIV Clinical Trials","volume":"17 4","pages":"165-72"},"PeriodicalIF":0.0,"publicationDate":"2016-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15284336.2016.1189754","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34679160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Can Probiotics Reduce Inflammation and Enhance Gut Immune Health in People Living with HIV: Study Designs for the Probiotic Visbiome for Inflammation and Translocation (PROOV IT) Pilot Trials.","authors":"Connie J Kim,&nbsp;Sharon L Walmsley,&nbsp;Janet M Raboud,&nbsp;Colin Kovacs,&nbsp;Bryan Coburn,&nbsp;Rodney Rousseau,&nbsp;Robert Reinhard,&nbsp;Ron Rosenes,&nbsp;Rupert Kaul","doi":"10.1080/15284336.2016.1184827","DOIUrl":"https://doi.org/10.1080/15284336.2016.1184827","url":null,"abstract":"<p><strong>Objectives: </strong>Despite substantial improvements in HIV outcomes with combination antiretroviral therapy (cART), morbidity and mortality remain above population norms. The gut mucosal immune system is not completely restored by cART, and the resultant microbial translocation may contribute to chronic inflammation, inadequate CD4 T-cell recovery, and increased rates of serious non-AIDS events. Since the microbial environment surrounding a CD4 T cell may influence its development and function, we hypothesize that probiotics provided during cART might reduce inflammation and improve gut immune health in HIV-positive treatment-naïve individuals (PROOV IT I) and individuals with suboptimal CD4 recovery on cART (PROOV IT II).</p><p><strong>Methods: </strong>These prospective, double-blinded, randomized, placebo-controlled, multicenter pilot studies will assess the impact of the probiotic Visbiome at 900 billion bacteria daily. Forty HIV positive cART-naïve men will be randomized in the PROOV IT I study, coincident with antiretroviral initiation, and be followed for 24 weeks. In PROOV IT II, 36 men on cART, but with a CD4 T-cell count below 350 cells/mm(3) will be followed for 48 weeks. The primary outcome for both studies is the comparison of blood CD8 T-cell immune activation. Secondary analyses will include comparison of blood inflammatory biomarkers, microbial translocation, blood and gut immunology and HIV levels, the bacterial community composition, diet, intestinal permeability, and the safety, adherence and tolerability of the study product.</p><p><strong>Discussion: </strong>These studies will evaluate the ability of probiotics as a safe and tolerable therapeutic intervention to reduce systemic immune activation and to accelerate gut immune restoration in people living with HIV.</p>","PeriodicalId":13216,"journal":{"name":"HIV Clinical Trials","volume":"17 4","pages":"147-57"},"PeriodicalIF":0.0,"publicationDate":"2016-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15284336.2016.1184827","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34614982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrase Strand Transfer Inhibitors (INSTIs) Resistance Mutations in HIV-1 Infected Turkish Patients.","authors":"M Sayan,&nbsp;A Gündüz,&nbsp;G Ersöz,&nbsp;A İnan,&nbsp;A Deveci,&nbsp;G Özgür,&nbsp;F Sargın,&nbsp;G Karagöz,&nbsp;A İnci,&nbsp;D İnan,&nbsp;A Ülçay,&nbsp;I Karaoğlan,&nbsp;S Kaya,&nbsp;S S Kutlu,&nbsp;K Süer,&nbsp;A Çağatay,&nbsp;H Akalın","doi":"10.1080/15284336.2016.1153303","DOIUrl":"https://doi.org/10.1080/15284336.2016.1153303","url":null,"abstract":"<p><strong>Objectives: </strong>Integrase strand transfer inhibitor (INSTI) is a new class of antiretroviral (ARV) drugs designed to block the action of the integrase viral enzyme, which is responsible for insertation of the HIV-1 genome into the host DNA. The aim of this study was to evaluate for the first time INSTI resistance mutations in Turkish patients.</p><p><strong>Methods: </strong>This study was conducted in Turkey, between April 2013 and April 2015 using 169 HIV-1-infected patients (78 ARV naive patients and 91 ARV-experienced patients). Laboratory and clinical characteristics of ARV naive and ARV-experienced patients were as follows: gender (M/F): 71/7 and 80/11, median age: 38 and 38.4; median CD4(+) T-cell: 236 and 216 cells/mm(3), median HIV-1 RNA: 4.95+E5 and 1.08E+6 copies/ml. Population-based seqeunces of the reverse transcriptase, protease, and integrase domains of the HIV-1 pol gene were used to detect HIV-1 drug resistance mutations.</p><p><strong>Result: </strong>INSTI resistance mutations were not found in recently diagnosed HIV-1-infected patients. However, ARV-experienced patients had major resistance mutations associated with raltegravir and elvitegravir; the following results were generated:F121Y, Y143R, Q148R and E157Q (6/91 - 6.6%).</p><p><strong>Conclusions: </strong>The prevalence of INSTI resistant mutations in ART-experienced patients suggested that resistance testing must be incorporated as an integral part of HIV management with INSTI therapies.</p>","PeriodicalId":13216,"journal":{"name":"HIV Clinical Trials","volume":"17 3","pages":"109-13"},"PeriodicalIF":0.0,"publicationDate":"2016-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15284336.2016.1153303","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34342382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improvement of BMD after Switching from Lopinavir/R Plus Two Nucleos(T)ide Reverse Transcriptase Inhibitors to Lopinavir/R Plus Lamivudine: OLE-LIP Substudy.","authors":"M Crespo,&nbsp;J Navarro,&nbsp;M Martinez-Rebollar,&nbsp;D Podzamczer,&nbsp;P Domingo,&nbsp;J Mallolas,&nbsp;M Saumoy,&nbsp;G M Mateo,&nbsp;A Curran,&nbsp;J Gatell,&nbsp;E Ribera","doi":"10.1080/15284336.2016.1149929","DOIUrl":"https://doi.org/10.1080/15284336.2016.1149929","url":null,"abstract":"<p><strong>Objective: </strong>To compare 48-week changes in bone mineral density (BMD) and body fat distribution between patients continuing lopinavir/ritonavir and two NRTIs and those switching to lopinavir/ritonavir and lamivudine.</p><p><strong>Methods: </strong>Substudy of a randomized, open-label, multicenter OLE study was carried out. Adult HIV-infected patients with <50 copies/mL for ≥6 months were randomized (1:1) to continue lopinavir/ritonavir and two NRTIs or switching to lopinavir/ritonavir and lamivudine. Dual-energy X-ray absorptiometry (DXA) was performed at baseline and after 48 weeks to measure bone composition and body fat distribution in both the groups.</p><p><strong>Results: </strong>Forty-one patients (dual-therapy, n = 23; triple-therapy, n = 18) of 239, who received at least one dose of study medication, completed the study: median age, 42 years, 71% male, 73% Caucasian. At week 48, total BMD increased by 1.04% (95% CI, 0.06 to 2.01%) among patients switching to dual-therapy, whereas no significant changes occurred in patients maintaining triple-therapy. Dual-therapy and older age were independently associated with total BMD increase. Among patients discontinuing tenofovir-DF, a significant increase was seen in total BMD (1.43; 95% CI, -0.04 to 2.91) and total hip (1.33%; 95% CI, 0.44 to 2.22%). A non-statistically significant decrease in femoral and spinal BMD was observed in patients who discontinued abacavir and in those continuing triple-therapy. Regarding fat distribution, no significant changes were seen in both the treatment groups.</p><p><strong>Discussion: </strong>BMD increased following switching to lopinavir/ritonavir plus lamivudine in HIV-infected patients on suppressive triple-therapy with lopinavir/ritonavir and two NRTIs including tenofovir-DF.</p>","PeriodicalId":13216,"journal":{"name":"HIV Clinical Trials","volume":"17 3","pages":"89-95"},"PeriodicalIF":0.0,"publicationDate":"2016-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15284336.2016.1149929","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34342380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fosamprenavir/ritonavir in patients with viral hepatitis coinfection: an observational multicohort study.","authors":"Paola Nasta,&nbsp;Dominique Salmon,&nbsp;Antonella d'Arminio Monforte,&nbsp;Jeanne M Pimenta,&nbsp;Carlo Cerini,&nbsp;Mariarosaria Giralda,&nbsp;Maria Winnock,&nbsp;Alessandro Cozzi-Lepri","doi":"10.1080/15284336.2016.1150409","DOIUrl":"https://doi.org/10.1080/15284336.2016.1150409","url":null,"abstract":"Objective: Safety and tolerability evaluation of adapted dose regimens containing fosamprenavir/ritonavir (FPV/r) in HIV-infected subjects with viral hepatitis co-infection. Methods: A retrospective multicohort analysis was conducted. Subjects from three European cohorts who started FPV/r or lopinavir/ritonavir (LPV/r) as a comparator contributed data to a centralized database. Subjects were divided into five groups by treatment regimen and level of hepatic impairment (aspartate aminotransferase [AST] platelet ratio index [APRI] score < or ≥2). Multivariable Cox regression analyses controlling for demographic factors, baseline CD4 count, FIB-4 score, use of antiretroviral therapy, and laboratory markers (bilirubin and platelet count) were performed to identify factors independently associated with risk of developing adverse events or safety events (eg, drug discontinuation, alanine aminotransferase (ALT) elevation, hepatic decompensation/death). Results: A total of 1096 patients contributed data to the study. Fosamprenavir/ritonavir (except in subjects with APRI ≥2 receiving standard dose) was associated with a higher two-year risk of drug discontinuation compared with LPV/r. Restricting the analysis to discontinuations due to adverse events (AEs), only subjects who received the reduced dose were more likely to discontinue ≥1 drug in the FPV/r regimen. There were no statistical differences in ALT elevation between groups. Incidence of hepatic decompensation events was similar among groups except for subjects who received non standard doses of FPV, though the number of events was small. Conclusions: Fosamprenavir/ritonavir discontinuation rate due to AEs or ALT elevation was similar across all European-approved FPV/r doses and to that of LPV/r subjects. Although liver tolerated antiretrovirals, such as integrase inhibitor and entry inhibitor, the use of FPV/r is acceptable in HIV infected patients with viral hepatitis.","PeriodicalId":13216,"journal":{"name":"HIV Clinical Trials","volume":"17 3","pages":"96-108"},"PeriodicalIF":0.0,"publicationDate":"2016-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15284336.2016.1150409","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34342381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A cross-sectional study to evaluate the association of hyperbilirubinaemia on markers of cardiovascular disease, neurocognitive function, bone mineral density and renal markers in HIV-1 infected subjects on protease inhibitors.","authors":"T J Barber,&nbsp;G Moyle,&nbsp;A Hill,&nbsp;G Jagjit Singh,&nbsp;A Scourfield,&nbsp;H M Yapa,&nbsp;L Waters,&nbsp;D Asboe,&nbsp;M Boffito,&nbsp;M Nelson","doi":"10.1080/15284336.2016.1176305","DOIUrl":"https://doi.org/10.1080/15284336.2016.1176305","url":null,"abstract":"<p><strong>Background: </strong>Ongoing inflammation in controlled HIV infection contributes to non-AIDS comorbidities. High bilirubin appears to exhibit an anti-inflammatory effect in vivo. We therefore examined whether increased bilirubin in persons with HIV was associated with differences in markers of inflammation and cardiovascular, bone, renal disease, and neurocognitive (NC) impairment.</p><p><strong>Methods: </strong>This cross-sectional study examined inflammatory markers in individuals with stable HIV infection treated with two nucleoside reverse transcriptase inhibitors and a boosted protease inhibitor. Individuals recruited were those with a normal bilirubin (NBR; 0-17 μmol/L) or high bilirubin (>2.5 × upper limit of normal). Demographic and anthropological data were recorded. Blood and urine samples were taken for analyses. Pulse wave velocity (PWV) measurement, carotid intimal thickness (CIT), and calcaneal stiffness (CSI) were measured. Males were asked to answer a questionnaire about sexual function; NC testing was performed using CogState.</p><p><strong>Results: </strong>101 patients were screened, 78 enrolled (43 NBR and 35 HBR). Atazanavir use was significantly higher in HBR. Whilst a trend for lower CIT was seen in those with HBR, no significant differences were seen in PWV, bone markers, calculated cardiovascular risk (Framingham), or erectile dysfunction score. VCAM-1 levels were significantly lower in the HBR group. HBR was associated with lower LDL and triglyceride levels. NBR was associated with a calculated FRAX significantly lower than HBR although no associations were found after adjusting for tenofovir use. No difference in renal markers was observed. Component tests of NC testing revealed differences favouring HBR but overall composite scores were similar.</p><p><strong>Discussion: </strong>High bilirubin in the context of boosted PI therapy was found not to be associated with differences in with the markers examined in this study. Some trends were noted and, on the basis of these, a larger, clinical end point study is warranted.</p>","PeriodicalId":13216,"journal":{"name":"HIV Clinical Trials","volume":"17 3","pages":"123-30"},"PeriodicalIF":0.0,"publicationDate":"2016-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15284336.2016.1176305","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34354236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-classical monocytes predict progression of carotid artery bifurcation intima-media thickness in HIV-infected individuals on stable antiretroviral therapy.","authors":"Dominic C Chow, Jamie M Kagihara, Guangxiang Zhang, Scott A Souza, Howard N Hodis, Yanjie Li, Brooks I Mitchell, Beau K Nakamoto, Kalpana J Kallianpur, Sheila M Keating, Philip J Norris, Lindsay B Kohorn, Lishomwa C Ndhlovu, Cecilia M Shikuma","doi":"10.1080/15284336.2016.1162386","DOIUrl":"10.1080/15284336.2016.1162386","url":null,"abstract":"<p><strong>Background: </strong>Inflammation may contribute to cardiovascular disease (CVD) among antiretrovirally suppressed HIV-infected individuals. We assessed relationships of monocyte, CD8 T-cell activation and plasma biomarkers to changes in carotid artery intima-media thickness (CIMT).</p><p><strong>Methods: </strong>Longitudinal study of HIV-infected subjects ≥40 years and on stable antiretroviral therapy (ART) ≥3 months. Peripheral blood mononuclear cells were immunophenotyped by multiparameteric flow cytometry to quantify classical (CD14(++)CD16(-)), intermediate (CD14(++)CD16(+)), non-classical (CD14(low/+)CD16(++)) and transitional (CD14(+)CD16(-)) monocyte subsets and activated (CD38(+)HLA-DR(+)) CD8(+) T-cells at baseline. Plasma biomarkers were assessed by multiplex Luminex assay. High-resolution B-mode ultrasounds of right carotid arteries were obtained. Changes in CIMT over two years at the right common carotid artery (CIMTCCA) and right bifurcation (CIMTBIF) were outcome variables.</p><p><strong>Results: </strong>We studied 50 subjects: 84% male, median age 49 (Q1, Q3; 46, 56) years, median CD4 count 461 (317, 578) cells/mm(3), and with HIV RNA ≤ 50 copies/mL in 84%. Change in CIMTBIF correlated with log values of baseline absolute count of non-classical monocytes (r = 0.37, p = 0.020), and with MCP-1 (r = 0.42, p = 0.0024) and TNF-α (r = 0.30, p = 0.036) levels. In multivariable linear regression, only non-classical monocytes and MCP-1 predicted the change in CIMTBIF, independent of Framingham Risk Score and baseline CIMTBIF. No correlation was noted between CD8 T-cell activation and CIMTBIF change. Monocyte subsets, CD8 T-cell activation, and biomarker concentrations were not correlated with changes in CIMTCCA.</p><p><strong>Conclusions: </strong>Our findings highlight the role of non-classical monocytes and MCP-1 in the progression of CIMTBIF in HIV-infected individuals on stable ART independent of traditional cardio-metabolic risk factors.</p>","PeriodicalId":13216,"journal":{"name":"HIV Clinical Trials","volume":"17 3","pages":"114-22"},"PeriodicalIF":0.0,"publicationDate":"2016-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4892178/pdf/nihms788088.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34354235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rare emergence of drug resistance in HIV-1 treatment -naïve patients after 48 weeks of treatment with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide","authors":"N. Margot, K. Kitrinos, M. Fordyce, S. McCallister, Michael D. Miller, C. Callebaut","doi":"10.1080/15284336.2016.1142731","DOIUrl":"https://doi.org/10.1080/15284336.2016.1142731","url":null,"abstract":"Tenofovir alafenamide (TAF), a novel prodrug of the NtRTI tenofovir (TFV), delivers TFV-diphosphate (TFV-DP) to target cells more efficiently than the current prodrug, tenofovir disoproxil fumarate (TDF), with a 90% reduction in TFV plasma exposure. TAF, within the fixed dose combination of elvitegravir /cobicistat / emtricitabine (FTC)/TAF (E/C/F/TAF), has been evaluated in one Phase 2 and two Phase 3 randomized, double-blinded studies in HIV-infected treatment-naive patients, comparing E/C/F/TAF to E/C/F/TDF. In these studies, the TAF-containing group demonstrated non-inferior efficacy to the TDF-containing comparator group with 91.9% of E/C/F/TAF patients having <50 copies/mL of HIV-1 RNA at week 48. An integrated resistance analysis across these three studies was conducted, including HIV-1 genotypic analysis at screening, and genotypic/phenotypic analysis for patients with HIV-1 RNA >400 copies/mL at virologic failure. Pre-existing primary resistance-associated mutations (RAMs) were observed at screening among the 1903 randomized and treated patients: 7.5% had NRTI-RAMs, 18.2% had NNRTI-RAMs, and 3.4% had primary PI-RAMs. Pre-treatment RAMs did not influence treatment response at Week 48. In the E/C/F/TAF group, resistance development was rare; seven patients (0.7%, 7/978) developed NRTI-RAMs, five of whom (0.5%, 5/978) also developed primary INSTI-RAMs. In the E/C/F/TDF group, resistance development was also rare; seven patients (0.8%, 7/925) developed NRTI-RAMs, four of whom (0.4%, 4/925) also developed primary INSTI-RAMs. An additional analysis by deep sequencing in virologic failures revealed minimal differences compared to population sequencing. Overall, resistance development was rare in E/C/F/TAF-treated patients, and the pattern of emergent mutations was similar to E/C/F/TDF.","PeriodicalId":13216,"journal":{"name":"HIV Clinical Trials","volume":"17 1","pages":"78 - 87"},"PeriodicalIF":0.0,"publicationDate":"2016-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15284336.2016.1142731","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"59913440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of once-daily darunavir/ritonavir versus atazanavir/ritonavir on insulin sensitivity in HIV-infected persons over 48 weeks: results of an exploratory substudy of METABOLIK, a phase 4, randomized trial","authors":"E. Overton, P. Tebas, B. Coate, R. Ryan, Amy Perniciaro, Yaswant K. Dayaram, G. De La Rosa, B. Baugh","doi":"10.1080/15284336.2016.1141468","DOIUrl":"https://doi.org/10.1080/15284336.2016.1141468","url":null,"abstract":"Background: The phase 4, METABOLIK trial demonstrated that changes in metabolic parameters with darunavir with low-dose ritonavir (DRV/r) were comparable to those observed with atazanavir with low-dose ritonavir (ATV/r). A comprehensive assessment of the effects of these agents on insulin sensitivity will provide additional, relevant clinical information. Methods: In this substudy of METABOLIK, HIV-1–infected, antiretroviral agent–naïve male subjects aged ≥18 years with a viral load of >1,000 copies/mL were randomized to receive DRV/r 800/100 mg once daily (qd) or ATV/r 300/100 mg qd, both with a fixed dose of tenofovir disoproxil fumarate/emtricitabine 300/200 mg qd. The effects of DRV/r versus ATV/r on insulin sensitivity over 48 weeks were compared using the euglycemic hyperinsulinemic clamp, the preferred method to assess insulin sensitivity; primary end point was the effect on insulin sensitivity during the first 12 weeks. Results: Twenty-seven subjects completed the study. In the DRV/r arm (n = 14), median glucose disposal from baseline through weeks 12 and 48 was 9.3, 11.4, and 9.9 mg/kg*min, respectively; in the ATV/r arm (n = 13), these values were 8.9, 8.6, and 9.1 mg/kg*min, respectively. Median insulin sensitivity in the DRV/r arm at baseline, week 12, and week 48 was 24.0, 25.0, and 21.5 mg/kg*min per μIU/mL × 100, respectively; these values in the ATV/r arm were 20.7, 22.0, and 22.0 mg/kg*min per μIU/mL × 100, respectively. Most subjects had ≥1 adverse event, including three serious adverse events (n = 2 [DRV/r], n = 1 [ATV/r]). Conclusions: DRV/r and ATV/r displayed similar modest effects on insulin sensitivity using a euglycemic hyperinsulinemic clamp.","PeriodicalId":13216,"journal":{"name":"HIV Clinical Trials","volume":"17 1","pages":"72 - 77"},"PeriodicalIF":0.0,"publicationDate":"2016-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15284336.2016.1141468","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"59913427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Recombinant Human Growth Hormone and Rosiglitazone for HIV-Associated Abdominal Fat Accumulation on Adiponectin and other Markers of Inflammation.","authors":"Vivien Leung,&nbsp;Ya-Lin Chiu,&nbsp;Donald P Kotler,&nbsp;Jeanine Albu,&nbsp;Yuan-Shan Zhu,&nbsp;Kirsis Ham,&nbsp;Ellen S Engelson,&nbsp;Hoda Hammad,&nbsp;Paul Christos,&nbsp;Daniel S Donovan,&nbsp;Henry N Ginsberg,&nbsp;Marshall J Glesby","doi":"10.1080/15284336.2015.1126424","DOIUrl":"https://doi.org/10.1080/15284336.2015.1126424","url":null,"abstract":"<p><strong>Background/objective: </strong>In a previous report of HIV-infected patients with fat redistribution, we found that recombinant human growth hormone (rhGH) therapy reduced visceral adipose tissue (VAT) but increased insulin resistance, and that the addition of rosiglitazone reversed the negative effects of rhGH on insulin sensitivity. In this study, we sought to determine the effects of rhGH and rosiglitazone therapy on an array of inflammatory and fibrinolytic markers.</p><p><strong>Methods: </strong>72 patients with HIV-associated abdominal obesity and insulin resistance were randomized to treatment with rhGH, rosiglitazone, the combination of rhGH and rosiglitazone, or placebo for 12 weeks. Subjects with plasma and serum samples available at weeks 0 (n=63) and 12 (n=46-48) were assessed for adiponectin, C-reactive protein, homocysteine, interleukin-1, interleukin-6, tumor necrosis factor alpha, interferon gamma, fibrinogen, plasminogen activator inhibitor-1 antigen, and tissue plasminogen activator antigen.</p><p><strong>Results: </strong>Treatment with both rosiglitazone alone and the combination of rosiglitazone and rhGH for 12 weeks resulted in significant increases in adiponectin levels from baseline. Adiponectin levels did not change significantly in the rhGH arm alone . There were no significant changes in the other biomarkers among the different treatment groups.</p><p><strong>Discussion: </strong>In this study of HIV-infected patients with altered fat distribution, treatment with rosiglitazone had beneficial effects on adiponectin concentrations, an effect that was also seen with a combination of rosiglitazone and rhGH. RhGH administration alone, however, did not demonstrate any significant impact on adiponectin levels despite reductions in VAT.</p>","PeriodicalId":13216,"journal":{"name":"HIV Clinical Trials","volume":"17 2","pages":"55-62"},"PeriodicalIF":0.0,"publicationDate":"2016-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15284336.2015.1126424","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34750826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}