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。     

Factors associated with renal dysfunction within an urban HIV-infected cohort in the era of highly active antiretroviral therapy

Background

Kidney disease remains a prevalent problem in HIV care. The contribution of highly active antiretroviral therapy (HAART), HIV disease factors and traditional factors needs further evaluation.

Methods

A cross‐sectional study of all patients seen at an HIV outpatient clinic during 2005 was performed. All data were collected from medical record review. Multivariate regression modelling was used to identify independent predictors of lower glomerular filtration rate (eGFR) and chronic renal failure (CRF) from factors significant in univariate analysis. eGFR was calculated using the simplified modification of diet in renal disease equation. Results were compared with those for persons from the National Health and Nutrition Examination Survey (NHANES) matched for age, race and gender.

Results

Of 845 HIV‐infected persons, 64% were men and 34% were Caucasian, and the mean age was 39.8 years. Thirty per cent of the patients had proteinuria and 43% had eGFR<90 mL/min/1.73 m². Persons on HAART (63%) had a lower mean eGFR than those not on HAART (92.0 vs. 101.6). In multivariate analyses, significant predictors of eGFR decline were diagnoses of hypertension, hyperlipidaemia, proteinuria, use of tenofovir or stavudine, and lower viral load. Compared with those in NHANES, HIV‐infected persons had a lower mean eGFR (94.9 vs. 104.2) and a higher prevalence of CRF (8%vs. 2%).

Conclusion

In this cohort, the prevalence of CRF is low, but remains higher than that of the general population. Clinicians should routinely screen for early asymptomatic kidney disease to address risk factors that can be treated.     

Characterization of viro-immunological responses in a closely followed cohort of heavily pretreated patients: evidence from the GenPheRex Study

Objectives

To assess prevalence and predictive factors of viro‐immunological discordant trends in a cohort of heavily pretreated patients.

Methods

Factors associated with viro‐immunological discordant trends either as categorical or continuous measures have been studied in 159 heavily pretreated HIV‐positive patients from a multicentre prospective study of real‐ vs. virtual‐phenotype. Univariate and multivariate logistic regressions were used to assess risk factors for categorical discordant responses, ceasing follow‐up at week 32 since enough patients had been on the original drug combination for a sufficient amount of time to evaluate their immune response. Complementary linear regression analysis was performed over the entire 48 weeks' follow‐up considering CD4 and plasma viral load (pVL) as continuous measures.

Results

Among 58 virological responder patients (≥1 log₁₀ HIV‐1 RNA copies/mL decrease) and 101 virologically non‐responders, immunological discordances (increase in CD4 count ofP<0.001), also the use of protease inhibitors (PIs) in the salvage regimen (HR 36.57, 95%CI 15.45–57.68; P<0.001) and >8 months on treatment (HR 41.64, 95%CI 19.27–64.01; P<0.001) correlated with highly significant immune recovery.

Conclusions

These data confirm that therapy, possibly including PIs, should be continued in heavily pretreated patients and that hard‐to‐reach pVL undetectability is not essential to obtain immunologic recovery; however, this is strongly increased by the degree of pVL reduction that should be achieved.