Risk factors for incident diabetes mellitus among HIV-infected patients receiving combination antiretroviral therapy in Taiwan: a case–control study

Objectives

Recent studies suggest that patients with HIV infection are at increased risk for incident diabetes mellitus (DM). We investigated the incidence and risk factors of DM among HIV‐infected patients receiving combination antiretroviral therapy (CART) in Taiwan.

Methods

Incident cases of DM were identified among HIV‐infected patients at the National Taiwan University Hospital between 1993 and 2006. A retrospective case–control study was conducted after matching cases with controls for sex, age at HIV diagnosis, year of HIV diagnosis, mode of HIV transmission and baseline CD4 lymphocyte count. A multivariate analysis was performed to identify risk factors for incident DM among HIV‐infected patients.

Results

In 824 HIV‐infected patients eligible for analysis, 50 cases of incident DM were diagnosed, resulting in an incidence of 13.1 cases per 1000 person‐years of follow‐up. In total, 100 matched controls were identified. Risk factors for incident DM were a family history of DM [odds ratio (OR) 2.656; 95% confidence interval (CI) 1.209–5.834], exposure to zidovudine (OR 3.168; 95% CI 1.159–8.661) and current use of protease inhibitors (OR 2.528; 95% CI 1.186–5.389).

Conclusions

Incident DM was associated with a family history of DM, exposure to zidovudine and current use of protease inhibitors in HIV‐infected patients receiving CART in Taiwan.     

Critical illness in HIV-infected patients in the era of combination antiretroviral therapy

As HIV-infected persons on combination antiretroviral therapy (ART) are living longer and rates of opportunistic infections have declined, serious non-AIDS-related diseases account for an increasing proportion of deaths. Consistent with these changes, non-AIDS-related illnesses account for the majority of ICU admissions in more recent studies, in contrast to earlier eras of the AIDS epidemic. Although mortality after ICU admission has improved significantly since the earliest HIV era, it remains substantial. In this article, we discuss the current state of knowledge regarding the impact of ART on incidence, etiology, and outcomes of critical illness among HIV-infected patients. In addition, we consider issues related to administration of ART in the ICU and identify important areas of future research.     

Outcomes in HIV-infected patients on antiretroviral therapy with tuberculosis

HIV-infected patients with active tuberculosis (TB) having CD4 counts < 100/mm3 and who were antiretroviral therapy (ART) na?ve were reviewed retrospectively to determine the outcomes of their tuberculosis infection. All patients received ART at or after receiving anti-TB treatment. Clinical manifestations, treatment regimens and outcomes were analyzed. Of 101 patients, 62 (61.4%) completed TB treatment. Of these, 53.2% were treated with a 6-month standard TB regimen, while the rest were treated with prolonged TB regimens. The median interval between anti-TB treatment and ART was 68 days (range: 0-381). Among the clinically cured patients 66.1% received rifampin concomitantly with nevirapine, and 32.3% received rifampin concomitantly with efavirenz. The treatment success rate was 75.6%, with a mortality rate of 6.1%. The risk factors for death were resistant TB (p = 0.03) and poor compliance (p < 0.05). Seven point nine percent had multi-drug resistant TB. Possible or probable immune reconstitution inflammatory syndrome (IRIS) was seen in 15 cases (14.9%). No life-threatening IRIS was reported, and it did not affect disease outcome (p = 0.5). A shorter time between anti-TB treatment and ART onset was associated with the occurrence of IRIS (31 days vs 90 days; p < 0.05). Regarding adverse drug effects, 44.6% had side effects due either to anti-TB drugs or ART. Sixty-six point one percent of them occurred within the first 2 months of TB treatment, and 43 (76.8%) had to stop or change either anti-TB treatment or ART. The mortality rate with TB and HIV on ART was low and the occurrence of IRIS did not carry any additional mortality.     

Gynecomastia in HIV-infected patients receiving antiretroviral therapy

Thirty-four HIV-positive men with gynecomastia were seen in an HIV outclinic during a 20-month period (incidence of 2.4 cases/100 patients receiving HAART per year). It developed mainly in subjects having good immunologic and virologic status, after an average of 3 years of HAART. No hormone abnormalities were found, or association with specific drugs. Although initially unilateral, more than half of cases progressed to bilateral gynecomastia. Spontaneous resolution occurred in most subjects with 12 months without modifying therapy.     

Favourable outcome of progressive multifocal leukoencephalopathy with mefloquine treatment in combination with antiretroviral therapy in an HIV-infected patient

A 33-year-old man who developed progressive multifocal leukoencephalopathy (PML) with HIV infection is reported. The patient exhibited rapid decline in neurological status after initiation of antiretroviral therapy (ART), which was attributed to the PML-immune re-constitution inflammatory syndrome. Following the administration of mefloquine in combination with ART, the patient's neurological status improved substantially. This case suggests that further investigation of the use of mefloquine might be warranted for treatment of PML in HIV-infected patients.     

云南省HIV-1感染儿童一线抗病毒治疗病毒学反弹影响因素研究

目的 观察云南省艾滋病病毒(HIV-1)感染儿童抗病毒治疗(ART)的疗效,探讨ART过程中出现病毒学反弹的影响因素.方法 通过"国家艾滋病抗病毒治疗信息系统"收集资料,并进行描述性分析,采用COX比例风险回归模型分析发生病毒学反弹的影响因素.结果 2005年1月1日至2015年12月31日,云南省随访治疗1年以上且在...     

Dyslipidaemia in HIV-infected patients: association with adherence to potent antiretroviral therapy

Metabolic complications are being increasingly recognized among HIV-infected patients treated with potent combination antiretroviral therapies. We sought to assess the association of dyslipidaemia with adherence to protease inhibitor (PI) therapy and with the markers of clinical response to antiretroviral therapy (CD4 count, HIV RNA viral level) through a prospective, cross-sectional cohort study. Fifty-six HIV-infected patients who were already on, or who were started on PI-containing antiretroviral therapy were monitored for the development of dyslipidaemias. Therapy with PI-containing antiretroviral therapy was significantly associated with elevated serum triglyceride level (>250 mg/dl) (52% vs 8%, P=0.001). Patients with an adherence rate of at least 80% to a PI-containing regimen were significantly more likely to have elevated low density lipoprotein (LDL) cholesterol level as compared to patients with an adherence rate of <80% (79% vs 26%, P=0.03). Patients with an adherence rate of at least 80% to a PI-containing regimen were also significantly more likely to have severe hypertriglyceridaemia (>800 mg/dl) as compared to patients with an adherence rate of <80% (21% vs 4%, P=0.04). Viral load at the last study visit did not correlate with total cholesterol (r=-0.39, P=0.30), LDL cholesterol (r=0.57, P=0.30), or triglyceride level (r=0.55, P=0.20). However, there was a significant correlation between the last viral load and high density lipoprotein (HDL) cholesterol (r=0.79, P=0.035), i.e. lower viral load was associated with higher HDL cholesterol level. In conclusion, dyslipidaemia in patients with HIV infection was significantly associated with adherence to PI-containing antiretroviral therapy. Patients who are adherent to PI-containing regimens at least 80% of the time warrant close monitoring for the development of dyslipidaemia.     

Risk factors for immune reconstitution inflammatory syndrome under combination antiretroviral therapy can be aetiology-specific

In order to discriminate general from aetiology-specific risk factors for immune reconstitution inflammatory syndrome (IRIS), we followed up, during six months, 99 patients with advanced HIV infection commencing antiretroviral therapy (ART) without active opportunistic infections or evident inflammation. IRIS predictors were determined by univariate analysis using clinical data from 76 ART-responding patients either completing follow-up or developing IRIS, and by multivariate analysis of inflammation, disease progression and nutrition status variables. We identified 23 primary IRIS events (30.3%). Univariate predictors for all IRIS events were higher platelet counts and lower CD4/CD8 ratio, whereas subclinical inflammation was the multivariate predictor. Platelets, alkaline phosphatase levels and %CD8 T-cells in univariate analysis also predicted mycobacteria-associated IRIS independently, remaining elevated during follow-up. Herpesvirus IRIS was predicted by platelets and inflammation. Indicators of advanced HIV disease and subclinical inflammation jointly predict IRIS, and some are specific of the underlying microbial aetiology, possibly explaining previous reports.     

Cross-sectional study to evaluate factors associated with adherence to antiretroviral therapy by Brazilian HIV-infected patients

Antiretroviral therapy success is highly dependent on the ability of the patient to fully adhere to the prescribed treatment regimen. We present the results of a cross-sectional study that evaluates the predictive value of a self-administered questionnaire of adherence to antiretroviral (ARV) therapy. Study participants were interviewed using a 36-item Patient Medication Adherence Questionnaire (PMAQ) designed to assess knowledge about ARV therapy, motivation to adhere to treatment, and behavioral skills. Plasma HIV-1 RNA levels were correlated with the results obtained from the PMAQ. Of the 182 study participants, 82 (45%) were receiving their initial ARV regimen. Of the remaining patients, 39 (21%) and 61 (34%) were on a second or additional ARV regimen, respectively. An undetectable viral load was documented in 47/62 (76%) patients on their first regimen who reported missing medication on less than 4 days in the last 3 months. The PMAQ had a higher predictive value of plasma viral suppression for patients in the initial regimen than for patients in salvage therapy. The overall predictive value of the PMAQ to identify adherence was 74%, and 59% for nonadherence, with an overall efficacy of 64%. Of the 74 patients (45%) who did not understand the concept of antiretroviral therapy, 80% were failing or had previously failed the ARV treatment. Of 35 patients with doubts about their HIV status or skeptical of the benefits of ARV therapy, 29 (84%) were nonadherent. Despite the positive predictive value of PMAQ in identifying adherence, self-reported adherence is not a sufficiently precise predictor of treatment success to substitute for viral load monitoring. On the other hand, the use of such an instrument to identify factors associated with nonadherence provides an excellent opportunity to apply early intervention designed to specifically address factors that might be contributing to the lack of adherence prior to regimen failure.     

Lipodystrophy and metabolic syndrome in HIV-infected patients treated with antiretroviral therapy

Lipodystrophy (lipo) and metabolic derangements associated with an increased cardiovascular risk are observed frequently in human immunodeficiency virus (HIV)-infected patients who receive antiretroviral treatment (ART). The objective of the study was to provide detailed biochemical information about metabolic syndrome in this condition. One hundred forty-six HIV-infected male and female patients on ART for more than 6 months were compared with 156 body mass index (BMI)-matched healthy subjects. Lipodystrophy was diagnosed upon patient and physician concordance. Metabolic syndrome was defined according to the Adult Treatment Panel III criteria. Plasma adiponectin (AD) and leptin were measured by radioimmunoassay. Insulin resistance (IR) was assessed by the homeostasis model assessment (HOMA). The prevalence of metabolic syndrome was higher in HIV-infected patients on ART than in non-HIV-infected healthy controls (15.8% vs 3.2%; P < .001). Patients with metabolic syndrome are older (44.6 +/- 6 vs 39.8 +/- 8 years; P = .004), have an increased BMI (24.9 +/- 3.8 vs 22.9 +/- 9.8 kg/m(2); P = .01), present with a reduced AD-to-leptin ratio log(10) (-0.19 +/- 0.4 vs 0.5 +/- 0.4; P = .04), and show increased IR (HOMA, 5.6 +/- 2.7 vs 3.8 +/- 2.2; P = .001; plasma fasting insulin, 22.9 +/- 9.8 vs 16.6 +/- 9.7 ng/mL; P < .001). In multivariate analysis, the diagnosis of lipo and HOMA were independently and significantly related to metabolic syndrome. In conclusion, the prevalence of metabolic syndrome is significantly increased in HIV-infected patients on ART and its presence is associated with lipo, increased age and BMI, IR, and a reduced plasma AD-to-leptin ratio.     

Prevalence and factors associated with idiopathic hypercalciuria in HIV patients on combination antiretroviral therapy

Idiopathic hypercalciuria may lead to bone loss via three pathogenic mechanisms described in HIV-negative patients: intestinal hyperabsorption, kidney loss and bone hyperabsorption. We conducted a cross-sectional study in a cohort of 217 HIV-positive antiretroviral-experienced patients, identifying hypercalciuria in 67 patients: the prevalence was 30.9% (95% confidence interval 27.4-37.0). The occurrence of hypercalciuria in subjects with normal values of parathormone may indicate an absorptive form of hypercalciuria. In this sample, other bone turnover markers and T-scores were not related to the condition. The results of this study show a high prevalence of idiopathic hypercalciuria in a group of antiretroviral-experienced patients. The consequences and the exact causes of this metabolic complication are not yet known and further investigation is needed.