Evidence suggests that integrase strand transfer inhibitors (INSTIs) are associated with greater weight gain than other antiretrovirals. This real-world study compares weight/body mass index (BMI) ...change between insured US patients with human immunodeficiency virus (HIV-1) initiating a protease inhibitor (PI) or INSTI.
A retrospective longitudinal study was conducted using Decision Resources Group's Real World Data Repository (7/17/2017-6/1/2019). Adult patients with HIV-1 who initiated a new PI or INSTI on or after 7/17/2018 (index date) and had ≥12 months of continuous pre-index clinical activity were included. Baseline characteristics were balanced using inverse probability of treatment weighting. The proportion of patients with ≥5% weight/BMI increases and mean weight/BMI change from pre- to post-index were compared using odds ratios (ORs) and mean differences (MDs).
20,367 patients (9993 PI, 10,374 INSTI) were included (mean age = 50 years; ∼30% females). Pre- and post-index weight and BMI measurements were available in 429 and 430 PI patients, and 397 and 383 INSTI patients, respectively (mean time between index and post-index measurements: ∼7 months). The PI cohort was 39%/49% less likely to experience ≥5% weight/BMI increase than the INSTI cohort, respectively (OR ≥5% weight gain = 0.61; p = .014; OR ≥5% BMI gain = 0.51; p < .001). Mean weight/BMI gain was significantly lower in the PI cohort than the INSTI cohort (weight MD = -1.90 kg -4.19 lbs, BMI MD = -0.61kg/m
2
; both p < .001).
Relative to INSTI, patients initiating a new PI were less likely to experience ≥5% weight/BMI gain post-index. Additionally, mean weight/BMI gain was lower in the PI than in the INSTI cohort.
Some HIV antiretroviral therapies (ART) have been associated with renal toxicities, which become of increasing concern as HIV-infected patients age and develop comorbidities. The objective of this ...study was to evaluate the relative impact of atazanavir (ATV)-based regimens on the renal function of adult patients with HIV. We conducted a systematic literature review by searching PubMed, EMBASE, Cochrane library, and the CRD from 2000 until March 2013. Major HIV-related conferences occurring in the past two years were also searched. All randomized clinical trials and large cohort studies assessing renal function in treatment-naïve and/or treatment-experienced HIV patients on ATV-based regimens were included. Fixed-effect mixed-treatment network analyses were carried out on the most frequently reported renal outcomes. 23 studies met the inclusion criteria, and change in estimated glomerular filtration rate (eGFR) from baseline to 48 weeks was identified as the main outcome. Two networks including, respectively, six studies (using the Cockcroft-Gault method) and four studies (using MDRD and CKD-EPI) were analysed. With CG network, ATV/r + TDF/FTC was associated with lower impact on the decline of eGFR than ATV/cobicistat + TDF/FTC but with higher decrease in eGFR than ATV/r + ABC/3TC (difference in mean change from baseline in eGFR respectively +3.67 and -3.89). The use of ATV/cobicistat + TDF/FTC led to a similar decline in eGFR as EVG/cobicistat/TDF/FTC. With respect to third agents combined with TDF/FTC, ATV/r had a lower increase in eGFR in comparison to EFV, and no difference was shown when compared to SQV/r and DRV/r. The effect of ATV-based regimens on renal function at 48 weeks appears similar to other ART regimens and appears to be modest regardless of boosting agent or backbone, although TDF containing backbones consistently leads to greater decline in eGFR.
: Antiretroviral therapy initiation is associated with declines in bone mineral density (BMD), which seem greatest with tenofovir disoproxil fumarate (DF)-containing regimens. Data comparing protease ...inhibitors are limited. This CASTLE substudy compared paired baseline with week 96 BMD in patients initiating tenofovir DF/emtricitabine plus atazanavir/ritonavir (n = 106) vs lopinavir/ritonavir (n = 70). In both groups, week 96 BMD declined significantly in arm, leg, trunk, and total body regions. Atazanavir/ritonavir was associated with smaller 96-week trunk and total body BMD declines compared with lopinavir/ritonavir multivariate-adjusted least squares mean difference +2.00% (95% confidence interval: 0.52 to 3.45; P = 0.008) and +1.24% (95% confidence interval: 0.13 to 2.35; P = 0.029), respectively. In addition, low baseline CD4 cell count (<50 cells per microliter) and increasing age were associated with larger declines in BMD.
Darunavir, cobicistat, emtricitabine, and tenofovir alafenamide can be used as a single-tablet regimen (STR, DRV/c/FTC/TAF) or multiple-tablet regimen (MTR, DRV/c+FTC/TAF) to treat patients with ...human immunodeficiency virus (HIV). This study described treatment patterns and predictors of adherence among patients with HIV initiated on DRV/c/FTC/TAF or DRV/c+FTC/TAF.
A retrospective longitudinal study was conducted using linked claims and electronic medical records from Decision Resources Group's Real World Data Repository (7/17/2017-6/1/2019). Treatment-naïve and treatment-experienced virologically suppressed adults with HIV-1 prescribed DRV/c/FTC/TAF or DRV/c+FTC/TAF (index date) were included. Six-month persistence (no treatment gaps >60 and >90 days) and adherence (proportion of days covered PDC) to the index regimen were evaluated among patients with ≥6 months of observation post-index. Predictors of low adherence (PDC<80%) were evaluated using a logistic regression model.
Among 2633 eligible patients (49.5 years old, 29% female, 37% African American/Black), 12% were treatment-naïve pre-index and 88% switched from a previous antiretroviral therapy; 84% initiated DRV/c/FTC/TAF and 16% initiated DRV/c+FTC/TAF. Among 822 DRV/c/FTC/TAF patients with ≥6 months of observation post-index, 80% and 86% had no >60- and >90-day gaps in DRV/c/FTC/TAF coverage, respectively, while among 204 DRV/c+FTC/TAF patients with ≥6 months of observation post-index, 69% and 75% had no >60- and >90-day gaps in DRV/c+FTC/TAF coverage, respectively. Mean (median) PDC for the index regimen was 81% (93%) for patients treated with DRV/c/FTC/TAF and 73% (83%) for patients treated with DRV/c+FTC/TAF. Predictors of low adherence included younger age (odds ratio OR=2.36, p=0.017), higher Quan-Charlson comorbidity index (OR=1.32, p=0.012), use of MTR regimen at index (OR=1.69, p=0.022), and prior low adherence (OR=2.56, p<0.001).
Among patients initiating a DRV/c-based regimen, those initiating STR had higher 6-month adherence/persistence than those initiating MTR, highlighting the potential benefits of the STR formulation, particularly among younger patients with multiple comorbidities and prior low adherence.
A theoretical concern exists that atazanavir (ATV) use during pregnancy may exacerbate physiologic neonatal hyperbilirubinemia. The aim of this substudy was to evaluate patterns of neonatal bilirubin ...following ATV/ritonavir (RTV) treatment of pregnant mothers and clinical and pharmacogenetic factors that may correlate. The design involved a subanalysis of study AI424182, a multicenter, open-label, prospective, single-arm Phase I study. The study had two treatment arms: (1) ATV/RTV 300/100 mg once daily or (2) ATV/RTV 400/100 mg once daily, both in combination with zidovudine/lamivudine 300/150 mg twice daily. Total bilirubin was assessed at baseline, each visit, and delivery day for mothers and on days 1 (delivery day), 3, 5, and 7 and weeks 2 and 6 for neonates. Blood samples were obtained for UGT1A1 genotyping and ATV cord blood concentration. Bilirubin elevation of any grade occurred in 14/40 neonates (35%). All Grade 3 to 4 bilirubin abnormalities (n=7) occurred after day 14. The pattern of neonatal bilirubin levels reported was consistent with neonatal physiologic elevations of bilirubin. Little correlation was observed between either maternal bilirubin levels over the last 4 weeks of pregnancy (including delivery) or ATV cord concentration and neonatal bilirubin. There was a significant association between UGT1A1 genotype and bilirubin grade in the maternal population (p=0.0006) but not neonates (p=0.49). Neither neonatal UGT1A1 genotype nor cord blood ATV concentration is a good predictor of neonatal hyperbilirubinemia. ATV/RTV treatment of mothers does not appear to exacerbate neonatal physiologic hyperbilirubinemia.
Introduction
PRINCE‐1 is an ongoing prospective, international, multicentre, nonrandomized, two‐stage clinical trial assessing safety and efficacy of once‐daily atazanavir (ATV) powder boosted with ...ritonavir (RTV) liquid plus optimized dual nucleoside reverse‐transcriptase inhibitor (NRTI) background therapy in antiretroviral (ARV)‐naïve and ‐experienced children with HIV‐1 infection aged ≥3 months to <6 years.
Methods
Children with HIV‐1 infection without prior ATV exposure and with a screening HIV‐1 RNA ≥1000 copies/mL were enrolled. The dosing of ATV powder, boosted with 80 mg RTV liquid, was based on three baseline weight bands (5 to <10 kg=150 mg, 10 to <15 kg=200 mg and 15 to <25 kg=250 mg).
Results
Of the 56 treated patients, 46 completed 48 weeks of therapy, 67.9% were from Africa and 60.7% were ART‐naïve. Median ages at baseline were 6, 35 and 55 months, and proportions with HIV‐1 RNA >100,000 were 85.7, 52.6 and 25% in the three baseline weight bands, respectively. No unexpected safety events occurred and no deaths were reported. Over 48 weeks, upper respiratory tract infections, diarrhoea, vomiting and Grade 3 to 4 hyperbilirubinaemia occurred in 35.7, 35.7, 28.6, and 9.4% of patients, respectively; five patients (8.9%) discontinued due to adverse events (AEs); and 11 patients (19.6%) experienced serious adverse events. At Week 48, using a modified intent‐to‐treat analysis (two patients were excluded because they switched to ATV capsules before Week 48), 61.1 and 74.1% of patients overall had an HIV‐1 RNA level <50 copies/mL and <400 copies/mL, respectively. Virologic suppression rates increased across the lowest to highest baseline weight bands (47.6, 68.4 and 71.4% had HIV‐1 RNA <50 copies/mL, and 66.7, 73.7 and 85.7% had HIV‐RNA <400 copies/mL, respectively) but did not differ meaningfully between ARV‐naïve and ‐experienced patients. Overall, the median change from baseline in CD4 cell count was +363 cells/mm3, and the median change from baseline in CD4 percent was +7.5%.
Conclusions
ATV powder boosted with RTV liquid once daily plus optimized dual NRTI background therapy was effective and well tolerated in this ART‐naïve or ‐experienced paediatric population aged ≥3 months to <6 years. No unexpected safety findings compared with those from previous ATV paediatric and adult studies were identified.
Despite the availability of 25 antiretroviral agents to treat HIV infection and the significant progresses made in the clinical pharmacology of HIV drugs, viral suppression and immune restoration ...remain problematic in a large number of HIV-infected persons. One of the main factors responsible for this partial therapeutic success is the difficulty patients have adhering consistently to antiretroviral therapy. Barriers to adherence are diverse and complex and evolve over time, complicating the monitoring of medication-taking behaviors. Consequently, multilevel interventions are often needed to address thoroughly adherence issues. Given the rapid and constant evolution of HIV treatments, innovative multidisciplinary programs integrating HIV pharmacotherapy specialists, as the “medication expert,” are being implemented. Because of his or her advanced knowledge of antiretrovirals, the HIV pharmacotherapy specialist is highly qualified to evaluate patients with complex regimens who are facing barriers to successful care and who need tailored interventions and long-term follow-up.
Abstract Background Response patterns to nivolumab differ from those seen with other approved targeted therapies. Objective To investigate the efficacy of nivolumab in previously treated patients ...with advanced renal cell carcinoma who were treated beyond (Response Evaluation Criteria In Solid Tumors) RECIST progression. Design, setting, and participants This was a subgroup analysis of patients treated with nivolumab in the phase 3 CheckMate 025 study. Patients continuing to tolerate therapy and exhibiting investigator-assessed clinical benefit were eligible to be treated beyond RECIST progression (TBP) and received therapy for ≥4 wk after first progression; patients not treated beyond RECIST progression (NTBP) received 0 wk to <4 wk of therapy after progression. Interventions Nivolumab 3 mg/kg intravenously every 2 wk. Results and limitations Of 406 nivolumab-treated patients, 316 (78%) progressed by RECIST criteria. Of those who progressed, 48% were TBP, 52% were NTBP. Before being TBP, objective response rate (95% confidence interval) was 20% (14–28) and 14% (9–21) in patients TBP and NTBP, respectively. Differences in clinical characteristics assessed at first progression between patients TBP versus NTBP included better Karnofsky performance status, less deterioration in Karnofsky performance status, shorter time to response, lower incidence of new bone lesions, and improved quality of life. Postprogression, 13% of all patients TBP (20/153) had ≥30% tumor burden reduction including patients with preprogression and postprogression tumor measurements ( n = 142) and complete/partial response (28%, 8/29), stable disease (6%, 3/47), and progressive disease (14%, 9/66) as their best response before being TBP. Incidence of treatment-related adverse events in patients TBP was lower after (59%) versus before (71%) progression. Limitations included potential bias from the nonrandomized nature of the analysis. Conclusions A subset of patients with advanced renal cell carcinoma and RECIST progression experienced tumor reduction postprogression with nivolumab, and had an acceptable safety profile. Clinical judgment remains essential when switching therapy. ClinicalTrials.gov Identifier: NCT01668784. Patient summary A subset of patients with advanced renal cell carcinoma and disease progression may continue to benefit from nivolumab treatment beyond progression as evidenced by tumor reduction postprogression and an acceptable safety profile.
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