Body composition changes in protease inhibitor-naive HIV-infected patients treated with two nucleoside reverse transcriptase inhibitors

Objectives

In the era of highly active antiretroviral treatment (HAART), there are insufficient data regarding lipodystrophy syndromes in HIV‐1‐infected patients treated with regimens that do not include protease inhibitors (PIs). We studied changes in body composition in HIV‐1‐infected patients before and 2 years after starting a non‐PI‐containing antiretroviral treatment regimen.

Methods

We studied retrospectively the whole body dual energy X‐ray absorptiometry (DEXA) scans of 23 PI‐naive HIV‐1‐infected patients (17 males, six females), aged 37.4 ± 9.3 years with mean CD4 count 401 ± 130 cells/µL. Thirteen patients were on zidovudine (ZDV) + lamivudine (3TC) and 10 on ZDV + didanosine (ddI). Subjects were evaluated before the beginning of antiretroviral treatment and approximately 24 months later. For each patient body weight, CD4 T‐cell counts, bone mineral content (BMC), bone mineral density (BMD) and whole body as well as regional fat and lean body mass were evaluated.

Results

A significant decrease in BMC was observed, although the T scores remained within the normal limits. Our patients also exhibited a significant decrease in body weight due almost exclusively to fat loss, while lean mass was minimally affected. Fat loss was statistically significant in the arms and legs, but not in the trunk. The above changes were most prominent in the ZDV + 3TC treatment group; in this group of patients, fat loss was also evident in the trunk. Patients on ZDV + ddI, on the other hand, only showed a significant increase in their legs' lean mass; they preserved their total fat mass and exhibited no other significant changes between the two assessments.

Conclusions

Dual NRTI therapy contributes to fat loss and reduction of bone mineral content in otherwise healthy, clinically stable, PI‐naive HIV‐infected adults. Compared with patients on ZDV + ddI, patients on ZDV + 3TC had a more prominent fat loss in all body regions.

     

艾滋病患者抗逆转录病毒治疗的肝毒性特点分析

目的分析包含非核苷类逆转录酶抑制剂联合抗逆转录病毒治疗（HAART）的肝毒性特点。方法回顾研究75例接受包含奈韦拉平或依非韦仑的联合抗逆转录病毒治疗的HIV／AIDs患者,对出现肝毒性者进行肝毒性分级,分析性别、年龄、HBV和／或HCV感染、其他肝毒性药物及NNRTIs种类对肝毒性发生的影响。结果75例接受HAART的HIV／AIDs患者中,45例（60.0％）发生至少1次肝毒性,其中肝毒性1级26例（57.8％）,2级16例（35.6％）,3级2例（4.4％）,4级1例（2.2％）;男性31例（68.9％）,女性14例（31.1％）,差异无统计学意义（X^2=0.658,P=0.428）;肝毒性组患者平均年龄（39±9）岁,无肝毒性组平均年龄（38±12）岁,差异无统计学意义（t=73,P=0.511）;合并HBV和／或HCV感染肝毒性组29例（64.4％）、无肝毒性组11例（36.7％）,差异有统计学意义（X^2=5.581,P=0.018）;应用基于NVP的HAART方案者肝毒性发生率为88.9％（32／36）：应用基于EFV的HAART方案者肝毒性发生率为33.3％（13／39）,差异有统计学意义（X^2=24.07,P=0.000）;同时应用抗结核药物或复方新诺明肝毒性组30例（66.7％）、无肝毒性组12例（40％）,差异有统计学意义（X^2=5.195,P=0.023）。结论包含NNRTIs的联合抗逆转录病毒治疗所致的肝毒性多为轻到中度,合并感染HBV和／或HCV、应用包含NVP的治疗方案和同时应用其他肝毒性药物的患者容易出现肝毒性,需要密切监测。     

Didanosine treatment of haemophilic patients infected with HIV

Twenty-six haemophilic patients with advanced HIV infection who had developed resistance or intolerance to zidovudine were treated with didanosine (ddI). 11 patients continue to take ddI at a median time of 14 months from commencement (range 7–18 months). Five of these patients showed an increase in CD4 lymphocyte count, reaching a maximum at a median time of 4 months. Four patients with HIV-related symptoms improved clinically. In general, the CD4 count and clinical improvements were not sustained. 11 patients discontinued ddI after a median of 3 months (range 3 days to 10 months), most commonly due to gastrointestinal side-effects. No case of pancreatitis or peripheral neuropathy was seen. Six patients, all with very advanced HIV disease, died. HIV-infected haemophilic patients who become resistant or intolerant to zidovudine may derive benefit from ddI, although this is usually transient.     

免疫检查点抑制剂相关致命性不良反应及管理策略

免疫检查点抑制剂(immune checkpointinhibitors, ICIs)是针对程序性死亡受体1(programmed cell death protein 1,PD-1)/程序性死亡受体配体1(programmed cell death protein ligand1,PD-L1)和细胞毒性T淋巴细胞相关抗原4(cytotoxic T lymphocyte associated antigen-4,CTLA-4)的单克隆抗体,主要通过阻断上述免疫检查点通路的抑制性免疫调节作用从而增强人体的抗肿瘤免疫反应。     

Cardiovascular events and all-cause mortality in patients with type 2 diabetes treated with dipeptidyl peptidase-4 inhibitors: An extensive meta-analysis of randomized controlled trials

AimsMeta-analyses of randomized trials on Dipeptidyl Peptidase-4 inhibitors (DPP4i) reported discordant results on major cardiovascular events (MACE), mortality, and heart failure. Aim of this meta-analysis of randomized trials is the assessment of the cardiovascular safety of DPP4i.Data synthesisA Medline, Embase, Cochrane database search for sitagliptin, vildagliptin, omarigliptin, saxagliptin, alogliptin, trelagliptin, anagliptin, linagliptin, gemigliptin, evogliptin, and teneligliptin was performed up to up January 1st, 2020. All trials with a duration ≥24 weeks and comparing the effects of DPP4i with placebo or active drugs were collected. Mantel–Haenszel odds ratio (MH-OR) with 95% Confidence Interval (95% CI) was calculated for all outcomes defined above. A total of 182 eligible trials were identified. DPP-4i were not associated with an increased risk of MACE (MH-OR 0.99 [0.93, 1.04]), all-cause mortality (MH-OR 0.99 [0.93, 1.06]), and heart failure (MH-OR 1.05 [0.96, 1.15]) with no significant differences across individual molecules, except for saxagliptin, which was associated with an increased risk of heart failure.ConclusionsAs a class, DPP4i are not associated with any increase or reduction of MACE, all-cause mortality, and heart failure. Saxagliptin seems to be associated with an increased risk of hospitalization for heart failure.