Oral lesions in HIV/AIDS patients undergoing highly active antiretroviral treatment including protease inhibitors: a new face of oral AIDS?

The objective of this work was to assess the prevalence of human immunodeficiency virus-related oral lesions (HIV-ROL) in HIV-positive/acquired immunodeficiency syndrome (AIDS) patients receiving highly active antiretroviral therapy (HAART) including HIV-protease inhibitors. One hundred fifty-five (154) AIDS patients (69 intravenous drug users [IDU], 53 heterosexuals, 29 males who have sex with males, 1 transfused, and 2 of unknown contagious source) receiving HAART, were examined. We found the following prevalences: HIV-ROL 53.2%; oral candidiasis 34.4%; hairy leucoplakia 26.6%; xerostomia 15.5%; herpes simplex labialis 1.9%; HIV/periodontitis-gingivitis 0.6%. No cases of Kaposi's sarcoma were observed. The highest prevalence of HIV-ROL was found in the IDU group, and in patients with viral load more than 10,000 copies and CD4(+) cell count less than 200. Using our historical controls, this suggests that the prevalence of all oral lesions, particularly oral candidiasis, herpes simplex labiali, Kaposi's sarcoma, and periodontal disease has decreased more than 30% after the institution of HAART.     

The Changing Clinical Spectrum of Human Immunodeficiency Virus (HIV)-Related Oral Lesions in 1,000 Consecutive Patients: A 12-Year Study in a Referral Center in Mexico

In developing countries, the variations in the clinical spectrum of human immunodeficiency virus (HIV)-related oral lesions over time, and the possible effects of antiretroviral therapy, have not been described. In this study we evaluate the clinical spectrum of oral lesions in a series of HIV-infected patients when first examined at the acquired immunodeficiency syndrome (AIDS) clinic of a tertiary care institution in Mexico City, Mexico, and the changes observed over 12 years. All HIV-infected adult patients had an oral examination performed by specialists in oral pathology and medicine who used established clinical diagnostic criteria for oral lesions. Four periods were defined according to the evolving pattern of antiretroviral use: the first 2 were before the introduction of highly active antiretroviral therapy (HAART) and the last 2 were during more established use of HAART. For the statistical analysis the chi-square test for contingency tables and the chi-square test for trend were utilized. For dimensional variables, except age, the Kruskal-Wallis or Mann-Whitney rank sum tests were used when applicable and trend was tested with the Spearman correlation coefficient. Age was tested through analysis of variance (ANOVA) and linear regression analysis. Alpha value was set at p = 0.05 for each test. In the 12-year study, 1,000 HIV-infected patients were included (87.9% male). At the baseline examination, oral lesions strongly associated with HIV were present in 47.1% of HIV-infected patients. Oral candidosis (31.6%), hairy leukoplakia (22.6%), erythematous candidosis (21.0%), and pseudomembranous candidosis (15.8%) were the most frequent lesions. Oral Kaposi sarcoma (2.3%), HIV-associated periodontal disease (1.7%), and oral non-Hodgkin lymphoma (0.1%) were less frequent. HIV-related oral lesions decreased systematically-by half during the course of the 4 study periods (p < 0.001). Except for Kaposi sarcoma, all oral lesions strongly associated with HIV showed a trend to decrease significantly during the study period. No apparent variation in the occurrence of salivary gland disease or human papillomavirus-associated oral lesions was found. A significant trend to a lower prevalence was observed in the group of patients who were already taking antiretroviral therapy, non-HAART and HAART (p < 0.001 and p = 0.004, respectively). Only a discrete reduction, barely significant, was noted among untreated patients (p = 0.060). By Period IV (1999-2001), those who received HAART showed the lowest prevalence of oral lesions strongly associated with HIV (p < 0.001). Patients with oral lesions strongly associated with HIV had significantly lower median CD4+ counts and higher viral loads than those without oral lesions strongly associated with HIV (p < 0.001 and p = 0.005, respectively). When CD4+ counts were correlated with prevalence of oral candidosis, a consistently negative association was found; this association prevailed even after the study group was partitioned according to period. In this selected cohort of 1,000 patients with HIV infection, the clinical spectrum of HIV-related oral lesions has changed over the 12-year study, with a decreased prevalence of most oral lesions. Our findings probably represent improvements in medical care of HIV-infected persons, earlier detection of HIV-infected patients at the AIDS clinic, the increasing use of prophylactic drugs to prevent secondary AIDS-related opportunistic infections, and, perhaps most important, the availability of potent antiretroviral therapy in recent years, since the introduction of HAART.     

Oral candidosis as a clinical marker of immune failure in patients with HIV/AIDS on HAART

Oral candidosis (OC) has been proposed as a clinical marker of highly active antiretroviral therapy (HAART) success or failure. The principal objective of this work was to assess whether the presence OC is associated with immunologic or virologic failure in patients with HIV/AIDS undergoing HAART. One hundred fifty-one patients with HIV/AIDS from Regional Hospital "Carlos Haya," Malaga, Spain, were examined orally. All patients had been undergoing HAART for a minimum of 6 months prior to oral examination. OC diagnosis was in accordance with World Health Organization-Centers for Disease Control (WHO-CDC) criteria. Age, gender, route of HIV infection, CD4 lymphocyte counts, and viral load were taken from the medical records. In regard to HAART response the patients were classified as: virologic- responders (viral load < 50 copies per milliliter), virologic nonresponders (viral load >50 copies per milliliter); immunologic responders (CD4 cells counts > 500 per milliliter), and immunologic nonresponders (CD4 cells counts < 500 per milliliter). Prevalence of OC was determined for each group. The presence of OC was closely related to immune failure (p 0.006; odds ratio [OR] 3.38 95% confidence interval [CI] 1.262-12.046) in patients with HIV/AIDS undergoing HAART. The probability of immune failure in the presence of OC was 91% for men who have sex with men, 95.5% for heterosexuals, and 96% for intravenous drug users. In conclusion, OC should be considered a clinical marker of immune failure in patients with HIV/AIDS undergoing HAART.     

Evaluation of lymph node virus burden in human immunodeficiency virus-infected patients receiving efavirenz-based protease inhibitor--sparing highly active antiretroviral therapy

Although efavirenz-containing regimens effectively suppress plasma levels of human immunodeficiency virus (HIV) RNA, it is now clear that undetectable plasma viremia may not reflect a lack of viral replication. Because lymphoid tissue is an active site of HIV replication, the lymph node virus burden was analyzed in persons who received highly active antiretroviral therapy (HAART) containing either efavirenz or a protease inhibitor (PI). Testing with in situ hybridization revealed no detectable follicular dendritic cell-associated HIV RNA in either group, and only 2 of 8 persons in the efavirenz group and 1 of 4 in the PI group had detectable RNA in lymph node mononuclear cells (LNMC) when tested by use of nucleic acid sequencebased amplification. Low levels of replication-competent HIV were identified in both groups by use of quantitative coculture assays. There was no evidence of development of resistance to either regimen in virus isolated from LNMC. These data support the use of efavirenz as an alternative to a PI in initial HAART regimens.     

Declining prevalence of opportunistic gastrointestinal disease in the era of combination antiretroviral therapy

OBJECTIVE: Opportunistic disorders (OD) are the most frequent GI manifestations of the acquired immunodeficiency syndrome (AIDS). Since the introduction of highly active antiretroviral therapy (HAART), there appears to be have been a reduction in the incidence of many of these OD; however, the effect of HAART on the prevalence of GI OD has not been well studied. METHODS: From 4/95 through 3/98, all HIV (HIV)-infected patients undergoing GI endoscopy were prospectively identified; mucosal biopsies were obtained in a standardized fashion and histological specimens were examined by a single GI pathologist. Patients were divided into three groups based on the time of evaluation: group I: 4/95 to 3/96; group II: 4/96 to 3/97; and group III: 4/97 to 3/98. RESULTS: A total of 166 patients (90% men; mean age 36+/-10 yr; median CD4 lymphocyte count 62 cells/microl, range 2-884, median viral RNA level 1,357 copies/ml, range undetectable to 7,721,715) underwent 279 upper and/or lower endoscopies during the study period. There were no statistical differences in patients' demographics and indications for endoscopy although the CD 4 lymphocyte count was higher in group III. The percentage of patients receiving HAART at the time of endoscopy increased from 0% to 57% over the three periods (p<0.01), and the percentage of patient receiving combination antiretroviral therapy increased from 37% to 82% over the study period (p<0.01). In contrast, the prevalence of OD decreased from 69% (group I) to 13% (group III) (p<0.01), whereas the prevalence of non-OD, including a normal endoscopy increased from 31% to 87% (p<0.01). CONCLUSIONS: GI OD now seem to be an uncommon problem in HIV-infected patients undergoing endoscopy despite a low CD4 lymphocyte count, and this reduction of OD was associated with the use of HAART.     

CYP2B6基因多态性与艾滋病患者HAART中依非韦仑血浆浓度的关联研究

目的研究依非韦仑（EFV）的血浆浓度与细胞色素P4502B6（CYP2B6）基因多态性的关系。方法用高效液相色谱仪（HPLC系统）测定深圳市东湖医院艾滋病专科门诊68例患者,服用EFV后8-12小时的EFV血浆浓度,用逆转录-聚合酶链反应检测所有患者的CYP2B6 516位点的G〉T基因频率。结果CYP2B6 516位点的基因型39例是GG型,26例是GT型,3例是TT型。各组EFV的血浆浓度分别是（3.3±1.2）μg/ml、（4.7±2.3）μg/ml、（9.0±0.8）μg/ml,其差异有显著的统计学意义（P〈0.01）。结论GT基因型频率在中国人相当常见,该基因型可出现较高的EFV血浆浓度;TT基因型虽然少见,但EFV血浆浓度异常升高。检测CYP2B6基因多态性可帮助临床个性化EFV用量。     

Initiating highly active antiretroviral therapy with newer protease inhibitors is associated with better survival compared to first-generation protease inhibitors or nevirapine

The high prevalence of comorbidity among HIV-infected patients in care such as hepatitis C virus (HCV) coinfection and mental illness may contribute to increased toxicity and decreased adherence to highly active antiretroviral therapy (HAART). Newer HAART regimens have less toxicity and better dosing characteristics than first-generation regimens, but it is not known whether they are associated with improved clinical outcomes. The purpose of this study was to examine the effect of patient factors and initial HAART regimen on survival among HIV-infected patients in routine care. We conducted an observational study of all HAART-na?ve patients in the University of Washington HIV cohort who initiated HAART between January 1996 and October 2005. Cox survival analyses were used to examine the association between time to death and treatment with first-generation protease inhibitors (PIs; indinavir, ritonavir, saquinavir), newer PIs (amprenavir, atazanavir, lopinavir, nelfinavir), efavirenz, or nevirapine, controlling for baseline characteristics, and calendar period. Of 694 patients, 84 (12%) died. In adjusted analyses, patients treated with a first-generation PI (hazard ratio [HR] 1.9, p = 0.04) or nevirapine (HR 2.0, p = 0.046) had twice the risk of death compared with those receiving a newer PI. Survival for patients treated with efavirenz did not differ from those receiving a newer PI (HR 1.1, p = 0.8). Greater disease severity (HR 1.7, p = 0.03), hepatitis C virus (HCV; HR 1.6, p = 0.05), and depression (HR 2.0, p = 0.007) were independent predictors of increased mortality. This study demonstrates significant improvement in survival among patients initiating HAART with newer PIs compared to first-generation PIs or nevirapine, and highlights the complexity of patient factors affecting the clinical outcomes of treatment.     

Prevalence of oral manifestations of HIV infection in Rio De Janeiro, Brazil from 1988 to 2004

After the introduction of highly active antiretroviral therapy (HAART), several studies have shown a decrease in the prevalence of HIV-associated oral lesions. The goal of this study is to evaluate the prevalence of oral manifestations of HIV in Brazil. A retrospective epidemiologic analysis was performed of medical records of HIV-positive patients who attended Clementino Fraga Filho University Hospital and the Stomatology Clinic of Federal University of Rio de Janeiro from 1988 to 2004. Gender, age, mode of HIV transmission, level of education, history of opportunistic infections, smoking, CD4 counts, viral load, antiretroviral therapy, and presence and site of oral lesions were assessed. One thousand twelve medical records were reviewed, resulting in 1230 entries in the study's database: 920 men and 310 women. There was a positive correlation between the prevalence of women, patients older than 40 years of age, and patients with 11 years or less of education. HAART was associated with a lower prevalence of oral manifestations. The prevalence of oral manifestations decreased throughout the years, while an increase occurred in the prevalence of oral warts and HIV-associated salivary gland disease (SGD). This study implies a social trend of AIDS in Brazil with an increase in the number of females, people 40 years of age and older, and with lower educational background. In Brazil, it can also be observed a reduction in the prevalence of oral manifestations reported worldwide and an increase in the prevalence of oral warts and SGD. To our knowledge, no study of this time frame has been done in a Brazilian population.     

HIV/AIDS病人合并HCV感染对HAART不良反应的影响

目的研究合并丙型肝炎病毒(HCV)感染,对艾滋病病毒(HIV)/艾滋病(AIDS)病人接受高效抗反转录病毒治疗(HAART)后,不良反应发生的影响,为HIV/AIDS合并HCV感染的综合治疗提供依据。方法前瞻性观察167例合并HCV感染的HIV/AIDS患者(HIV/HCV组),接受HAART治疗2-5年出现不良反应的类型、频率、严重程度,以同期264例HIV/AIDS患者(HIV组)作为对照组。结果 167例合并HCV感染的HIV/AIDS患者中,163例(97.6%)出现疲乏症状,163例(97.6%)发生胃肠道反应,107例(64.1%)出现肝功能异常,98例(58.7%)出现血脂升高,83例(49.7%)出现药物性皮疹,56例(33.5%)出现腹泻,52例(31.1%)出现贫血。与HIV组相比,HIV/HCV组出现肝功能损害的频率较高(P<0.05),但严重程度无明显差异(P>0.05),其余不良反应发生的类型、频率及严重程度无显著性差异(P>0.05)。结论 HIV/AIDS病人在HAART过程中可发生多种不良反应,合并HCV感染时更容易发生肝功能损害,选择HAART方案时应尽量选择肝毒性少的药物。     

Nevirapine- versus efavirenz-based highly active antiretroviral therapy regimens in antiretroviral-naïve patients with advanced HIV infection

Objective

To compare virological and immunological responses to nevirapine (NVP)‐based and efavirenz (EFV)‐based highly active antiretroviral therapy (HAART) regimens in antiretroviral‐naïve patients with advanced HIV infection.

Methods

A retrospective observational cohort study was conducted on antiretroviral‐naïve HIV‐infected patients whose pretreatment CD4 cell counts were less than 100 cells/μL or whose viral loads were greater than 100 000 HIV‐1 RNA copies/mL.

Results

Baseline characteristics of patients in the NVP (n=24) and EFV (n=29) groups were not different. The proportion of patients with viral loads >100 000 copies/mL was higher in the EFV group. The probability of virological success estimated by the Kaplan‐Meier method showed that 3‐ and 6‐month success rates were 30.8% [95% confidence interval (CI): 16.7–52.2%] and 63.1% (95% CI: 44.7–81.3%) for the NVP group. The corresponding values were 41.2% (95% CI: 25.8–61.0%) and 62.9% (95% CI: 45.7–80.1%) for the EFV‐based group. The median success times of the two groups were about 4 and 3 months (P=0.678), respectively, for NVP and EFV. Cox's proportional hazard was used after adjusting for age, previous opportunistic infections (OIs), and viral load at baseline, and showed that patients who received the NVP‐based regimen had about 25% [hazard ratio (HR)=0.75, 95% CI: 0.37–1.51] less chance of virological success than patients who received the EFV‐based regimen (P=0.415). The median times to CD4≥100 cells/μL were 5.6 and 4.4 months for the NVP‐ and EFV‐based regimens, respectively (log‐rank test, P=0.144).

Conclusions

NVP‐ and EFV‐based HAART regimens as initial regimens in patients with advanced HIV infection are effective and comparable, in term of virological and immunological responses. However, further large‐scale randomized controlled clinical trials in this group of patients with advanced HIV infection are needed.

     

Beneficial effects of protease inhibitors on body composition and energy expenditure: a comparison between HIV-infected and AIDS patients

OBJECTIVES: (i) To investigate whether protease inhibitor (PI) (nelfinavir)-containing highly active antiretroviral therapy (HAART) affects body composition differently in HIV-infected and AIDS patients without wasting syndrome. (ii) To delineate the changes in resting energy expenditure (REE) under PI therapy, and to determine whether sustained reductions in HIV RNA would decrease REE. DESIGN: Prospective longitudinal cohort study with individually matched healthy controls. SETTING: Tertiary care centre at a University Hospital. METHODS: HIV-seropositive (n = 20) and AIDS patients (n = 17) with a plasma viral load of at least 10000 copies/ml and 37 healthy volunteers were enrolled. All participants were weight stable, free of acute opportunistic infections, and naive to PI therapy. Patients underwent testing of bioelectrical impedance analysis (BIA), indirect calorimetry and food intake, shortly before the initiation of HAART and 24 weeks thereafter. RESULTS: Both patient groups gained weight, body mass index (BMI), and fat-free mass (FFM) (P < 0.05 versus baseline), whereas only AIDS patients gained fat mass. Increases were more pronounced in the AIDS group. REE was elevated compared with corresponding controls at baseline, and decreased similarly in HIV and in AIDS patients during PI therapy (P < 0.05). The reduction in the viral burden preceded the decrease in REE by several weeks. CONCLUSION: Body composition and metabolic parameters improved during PI therapy in HIV-infected and AIDS patients without wasting. Although an early reduction in viral load as a result of HAART does not seem to influence REE directly, sustained viral load suppression may promote a decrease in energy expenditure.     

HIV infection and high-density lipoprotein: the effect of the disease vs the effect of treatment

HIV infection is commonly associated with hypoalphalipoproteinemia. It is not clear how much the HIV infection and/or treatment contribute to the changes in high-density lipoprotein (HDL) levels. Blood lipids of HIV-positive males were assessed in a retrospective study. The following groups of patients were studied: (1) untreated for at least 6 months; (2) treatment with highly active antiretroviral therapy (HAART) without protease inhibitor (PI); (3) treatment with a HAART regimen that includes a PI (HAART/PI); (4) treatment with HAART that includes low-dose ritonavir and a PI (HAART/PI/boost). Lipoprotein levels were compared with those of age-matched HIV-negative healthy subjects. Compared with the control group, HDL-cholesterol (HDL-C) levels were 22%, 11%, 14%, and 11% lower for currently untreated HIV, HAART, HAART/PI, and HAART/PI/boost groups, respectively. Negative correlations were found among HDL-C level, peak and current viral load, and duration of the disease and the treatment. A positive correlation was found between HDL-C and current and nadir CD4 cell count and CD4 percentage. When patients were divided into subgroups based on duration of antiretroviral therapy, patients treated with HAART and HAART/PI for 3 to 6 years were significantly less likely to have high HDL-C levels compared with the control group and patients treated for 1 to 3 years. A 5-fold decrease in the proportion of subjects with high HDL-C and a 3-fold increase in those with low HDL-C were found in the group treated with HAART/PI/boost. These data suggest that hypoalphalipoproteinemia in patients with HIV is likely to be secondary to HIV infection itself.     

300例艾滋病患者高效抗逆转录病毒治疗后免疫重建规律探讨

目的探讨高效抗逆转录病毒治疗（HAART）对中国南部地区艾滋病患者的免疫重建规律。方法收集近3年来300例患者的完整资料,按基线CD4^＋T细胞数分为A、B、C三组,观察基线及治疗1、3、6、12月末CD4^＋T淋巴细胞数、12月末血浆病毒载量（VL）、临床症状和毒副作用。结果抗病毒治疗12月末300例患者CD4^＋T淋巴细胞计数平均上升127个／1,以治疗3月后增长明显,3、12月末与基线CD4^＋T淋巴细胞计数比较差异有显著性（P〈0．05）;12月末273例（91％）患者血浆病毒载量（VL）〈5copies/ml,27例（9％）患者病毒载量（VL）〉50copies/ml,高病毒载量A组16例,C组4例;A组与C组比较差异有显著性（P〈0．05）;药物不良反应主要是外周神经炎（35．4％）、骨髓抑制（18．2％）、皮疹（15．2％）、肝功能损害（12．1％）、乳酸酸中毒（12．1％）和肾结石（6．1％）。结论HAART治疗对中国南部地区的艾滋病患者有效,能够实现免疫重建,但存在较多毒副作用。     

哈尔滨市艾滋病病人高效抗反转录病毒治疗效果评价

目的探讨哈尔滨市艾滋病（AIDS）病人的高效抗反转录病毒治疗（HAART）效果与不良反应。方法应用国家免费提供的抗病毒治疗药品,对符合治疗条件的HIV/AIDS病人进行规范抗病毒治疗,并检测病人的CD4＋T淋巴细胞计数与病毒载量。结果 HAART开始12个月后,病人CD4＋T淋巴细胞计数平均增长（241.61±148.02）个/μl,病毒载量均低于检测下限。结论抗病毒治疗效果显著,能够实现部分免疫重建,但也存在较多的不良反应。     

61例慢性肾脏病维持透析的HIV/AIDS患者血钙、血磷、全段甲状旁腺激素水平调查研究

目的了解广西地区维持性血液透析HIV/AIDS患者矿物质代谢紊乱情况及可能相关影响因素。方法收集2011—2016年在南宁市第四人民医院维持性血液透析3个月及以上合并HIV感染的61例患者作为观察组,根据其治疗情况,分为高效抗反转录病毒治疗(highly active antiretroviral therapy,HAART)组(51例)及非HAART组(10例),另选取30例非HIV感染维持血液透析大于3个月患者作为对照组。检测患者血钙、血磷及全段甲状旁腺激素(inact parathyroid hormone,i PTH)等矿物质代谢的评估指标,并对相关影响因素进行探讨。结果观察组中,血钙、血磷、i PTH的达标率分别为47.54%(29/61),24.59%(15/61)和21.31%(13/61);与对照组相比,在血钙、血磷、i PTH、HGB及ALB的平均值方面差异均有统计学意义(P均0.05);在观察组中,HAART患者血钙、i PTH指标均高于非HAART患者,血磷指标低于非HAART患者(P均0.05)。结论广西地区维持性血液透析HIV/AIDS患者矿物质代谢异常有其独特的临床表现,对于该人群的透析方式、HAART方案、影响因素值得进一步研究。     

Standard-dose efavirenz vs. standard-dose nevirapine in antiretroviral regimens among HIV-1 and tuberculosis co-infected patients who received rifampicin

Background

There is limited comparative data between efavirenz (EFV) 600 mg/day and nevirapine (NVP) 400 mg/day‐based antiretroviral therapy (ART) among HIV‐1 patients with tuberculosis (TB) and receiving rifampicin.

Methods

A retrospective cohort study was conducted in all ART‐naïve patients who were receiving rifampicin between January 2002 and December 2005.

Results

Of 188 patients, 77 and 111 patients were initiated on EFV‐based ART (EFV group) and NVP‐based ART (NVP group), respectively. Overall, median [interquartile range (IQR)] CD4 count was 36 (15–77) cells/μL and median (IQR) viral load was 5.6 (5.2–5.9) HIV‐1 RNA log copies/mL. At 48 weeks, 77.9% (60/77) in the EFV group and 67.6% (75/111) in the NVP group achieved HIV‐1 RNA <50 copies/mL (P=0.140, odds ratio =0.590, 95% confidence interval=0.302–1.153). At 24 and 48 weeks, respective median CD4 counts were 174 and 254 cells/μL in the EFV group and 156 and 218 cells/μL in the NVP group (P>0.05). By binary logistic regression, treatment group was not associated with HIV‐1 RNA <50 copies/mL (P>0.05). No patient in the EFV group and eight (7.2%) patients in the NVP group discontinued ART because of adverse reactions (P=0.084).

Conclusions

For HIV–TB co‐infected patients who receive rifampicin, efficacy of 600 mg EFV‐based and 400 mg NVP‐based ART may be similar, although adverse events tend to be higher in NVP‐based ART.