Dyspepsia in HIV-infected patients under highly active antiretroviral therapy

BACKGROUND AND AIM: Upper gastrointestinal symptoms, mainly dyspepsia, are common adverse effects in patients under highly active antiretroviral therapy (HAART). Whether it is worthwhile to perform endoscopy early in their treatment is a matter of debate. We have done a prospective study of the prevalence and the etiology of endoscopic lesions in a large cohort of dyspeptic adult HIV-infected patients under HAART, according to their immunological status. METHODS: 528 (334 men and 194 women, mean age 38) HIV-infected patients under HAART with epigastric pain and/or nausea and vomiting underwent upper endoscopy. Patients were classified in two groups, according to CD4 cells counting (>200 cells/mm(3) or < or =200 cells/mm(3)). Gastric and duodenal biopsies were taken from normal mucosa and any lesion found. RESULTS: Gastric mucosa alterations were seen in 61.74% of patients (40.71% erythema, 18.38% erosion and 2.65% ulcer). Duodenum mucosa alterations were seen in 25.37% of patients, mainly erosions (19.50%) and ulcer (3.59%). There was no difference in endoscopic findings according to CD4 cell count groups. Chronic active gastritis was shown in 459 patients (86.93%). H. pylori infection was seen in 32.38%, and it was more prevalent in the group with CD4 > 200 (p < 0.01). Opportunistic infections and malignancies were seen exclusively in patients with CD4 < or = 200. CONCLUSIONS: Most of the endoscopic lesions in dyspeptic HIV-infected patients under HAART were not related to AIDS. Upper endoscopy was more helpful in dictating clinical treatment in patients with low CD4 counts (< or =200) and should be done earlier in this group.     

Adherence to highly active antiretroviral therapy in HIV-infected inmates

Adherence to highly active antiretroviral therapy (HAART) has been scarcely studied in correctional settings. Our study aims to evaluate the relationship between adherence and virological outcome and to determine factors related to adherence in correctional settings. A cross-sectional retrospective study was performed in Topas prison (Salamanca, Spain). 50 inmates starting HAART were studied. Adherence was estimated through a self-report questionnaire and variables related to adherence (covering individual factors, the illness itself and the therapeutic regimen) were recorded. HIV-RNA levels and CD4 lymphocyte count were measured before starting therapy and six months after. Statistical analysis was performed using univariate and multivariate methods. 21 inmates (42%) were considered adherent and 29 (58%) were non-adherent. Adherence to treatment, as measured by our questionnaire, was the only significant and independent factor associated with an undetectable viral load at six months of therapy. Five variables were significantly associated with adherence to treatment, four of them as predictor factors for good adherence: an active occupation inside prison, the absence of HIV-related symptoms, a good or average acceptance of treatment, and a higher academic background; previous injection drug use as a risk factor for HIV transmission was associated with non-adherence. A simple self-report questionnaire may be useful for assessing adherence in prison inmates. Recognizing variables associated with adherence is essential to identify prisoners at high risk of being non-adherents in order to develop strategies for improving compliance.     

Long-term kinetics of T cell production in HIV-infected subjects treated with highly active antiretroviral therapy

The long-term kinetics of T cell production following highly active antiretroviral therapy (HAART) were investigated in blood and lymph node in a group of HIV-infected subjects at early stage of established infection and prospectively studied for 72 wk. Before HAART, CD4 and CD8 T cell turnover was increased. However, the total number of proliferating CD4(+) T lymphocytes, i.e., CD4(+)Ki67(+) T lymphocytes, was not significantly different in HIV-infected (n = 73) and HIV-negative (n = 15) subjects, whereas proliferating CD8(+)Ki67(+) T lymphocytes were significantly higher in HIV-infected subjects. After HAART, the total body number of proliferating CD4(+)Ki67(+) T lymphocytes increased over time and was associated with an increase of both naive and memory CD4(+) T cells. The maximal increase (2-fold) was observed at week 36, whereas at week 72 the number of proliferating CD4(+) T cells dropped to baseline levels, i.e., before HAART. The kinetics of the fraction of proliferating CD4 and CD8 T cells were significantly correlated with the changes in the total body number of these T cell subsets. These results demonstrate a direct relationship between ex vivo measures of T cell production and quantitative changes in total body T lymphocyte populations. This study provides advances in the delineation of the kinetics of T cell production in HIV infection in the presence and/or in the absence of HAART.     

Alternative therapy use in HIV-infected patients receiving highly active antiretroviral therapy

The extent of use of alternative therapies, psychosocial and disease-specific variables predictive of alternative therapy use, and factors motivating the use of alternative therapies in HIV-infected patients receiving highly active antiretroviral therapy (HAART) have not been well defined. Types of alternative therapies used, demographic and medical data, coping (Billing and Moos inventory of coping with illness styles), social support (Irwing and Sarason questionnaire), sense of personal control (Pearlin's Mastery scale), quality of life (Medical Outcome Study scale), health beliefs, and adherence rate were prospectively assessed in 118 HIV-infected patients receiving HAART. Of 38% (45/118) of the patients who used alternative therapies, 56% (25/45) began using alternative therapies since the initiation of HAART. While Caucasian patients were more likely to use alternative therapies than all other patients (P = 0.015), new users of alternative therapies were more likely to be African-American (P = 0.022). Alternative therapy users reported less satisfaction with their emotional support (P = 0.027), and had greater psychological distress (P = 0.048), but were more likely to utilize problem-focused coping (P = 0.015). Patients who used alternative therapies were less likely to believe that HAART was beneficial (P = 0.06). Physicians were unaware of patients' alternative therapy use in 40% (18/45) of all patients who used alternative therapies, in 67% of herbal therapy users, and in 100% of dietary supplement users. Adherence to antiretroviral therapy, CD4 count, and HIV-RNA level were neither predictive nor affected by alternative therapy use. Despite scepticism about the benefits of HAART, resort to alternative therapies did not undermine adherence with antiretroviral therapy. Although able actively to cope with their illness, users of alternative therapies had greater psychological distress and were less satisfied with their emotional support. Interventions aimed at promoting their psychological well-being and enhancing the emotional support should be considered in these patients.     

Thymopoiesis in HIV-infected adults after highly active antiretroviral therapy.

The thymus of HIV-seropositive patients can enlarge as CD4+ T cell counts increase on highly active anti-retroviral therapy (HAART). This may indicate development of new T cells or represent mature peripheral T cells recirculating to the thymus. To define the etiology of the enlargement, the thymuses of two HIV-infected individuals on HAART were biopsied. For more than 3 years before initiation of HAART, both patients (38 and 41 years of age) had documented CD4+ T lymphopenia. Peripheral blood samples were obtained to assess circulating CD4+ CD45RA+ CD62L+ T cells, which were thought to have recently developed in the thymus. Peripheral blood T cells from both patients and thymocytes from the second patient were also tested for levels of DNA episomes formed during T cell receptor gene rearrangement (T cell receptor rearrangement excision circles, TRECs). With HAART, peripheral blood CD4+ T cell counts increased from approximately 60/mm(3) to 552/mm(3) and 750/mm(3) for patients 1 and 2, respectively. Thymic biopsies from both patients showed normal thymus histology with active thymopoiesis. Percentages of peripheral blood CD4+ CD45RA+ CD62L+ T cells and quantitation of T cell TRECs also reflected active thymopoiesis in both patients. Thus, in these two HIV-seropositive adults examined after initiation of HAART, thymic enlargement represented active thymopoiesis. Thymopoiesis in adult AIDS patients may contribute to immune reconstitution even after prolonged CD4+ T lymphopenia.     

接受高效抗反转录病毒治疗HIV感染者的巨细胞病毒性视网膜炎

高效抗反转录病毒治疗(highly active antiretroviral therapy,HAART)出现以前,巨细胞病毒性视网膜炎的诊断属于AIDS终末期事件,通常发生在CD4~+T淋巴细胞50/μl的HIV感染者中,诊断后的中位存活时间为6周~6个月。HAART的出现显著降低了巨细胞病毒性视网膜炎的发病率及AIDS患者病死率。但在发展中国家,由于缺乏常规筛查,巨细胞病毒性视网膜炎的发病率通常被低估,且普遍缺乏相关数据及管理策略。本文对近10年国内外免疫缺陷患者巨细胞病毒性视网膜炎的研究及发表数据进行回顾,提出应尽早开始HAART,并加强对严重免疫缺陷患者巨细胞病毒性视网膜炎进行筛查和早期诊断治疗的公共卫生策略。     

Nutritional aspects of HIV-infected children receiving highly active antiretroviral therapy

The presentation of the nutritional problems of HIV-infected children is changing over time with improved antiretroviral regimens. Early reports of HIV infection in the 1980s, included such problems as malnutrition and wasting. However, as treatment and prophylactic regimens improve, the current nutritional problems of HIV-infected children in developed countries include truncal obesity and insulin resistance in addition to malnutrition. Background data on the wasting syndrome, etiology of malnutrition, nutritional effects of highly active antiretroviral therapies, and nutritional intervention strategies for HIV-infected children will be presented.     

Appendicitis in HIV-infected patients during the era of highly active antiretroviral therapy

Background

Limited studies have suggested increased incidence rates and unusual clinical presentations of appendicitis among HIV‐infected patients during the pre‐highly active antiretroviral therapy (HAART) era. Data in the HAART era are sparse, and no study has evaluated potential HIV‐related risk factors for the development of appendicitis.

Methods

We retrospectively studied 449 HIV‐infected patients receiving care at a US Naval hospital involving 4750 person‐years (PY) of follow‐up. We also evaluated the rates of appendicitis among HIV‐negative persons at our medical facility. We compared demographics, HIV‐specific data, and HAART use in HIV‐infected patients with and without appendicitis.

Results

Sixteen (3.6%) of 449 patients developed appendicitis after HIV seroconversion. The incidence rate was 337 cases/100 000 PY, more than fourfold higher than among HIV‐negative persons. Eighty‐eight per cent of cases among HIV‐infected patients had an elevated white blood count at presentation, 39% were complicated, and 64% required hospitalization. HIV‐infected patients with appendicitis compared with those who did not develop appendicitis were less likely to be receiving HAART (25 vs. 71%, P<0.001), had higher viral loads (3.5 vs. 1.7 log₁₀ HIV‐1 RNA copies/mL, P=0.005), and were younger (median age of 30 vs. 41 years, P<0.002). In the multivariate model, receipt of HAART remained protective [odds ratio (OR) 0.21, P=0.012] for appendicitis, while younger age was positively associated (OR 1.08, P=0.048) with appendicitis.

Conclusion

Acute appendicitis occurs at higher incidence rates among HIV‐infected patients compared with the general population. Our study demonstrates that the lack of HAART may be a risk factor for appendicitis among HIV‐infected patients; further studies are needed.     

Neurocognitive performance enhanced by highly active antiretroviral therapy in HIV-infected women

OBJECTIVE: To determine whether highly active retroviral therapy (HAART) is associated with better neurocognitive outcome over time among HIV-infected women with severely impaired immune function. METHODS: A semiannual neurocognitive examination on four tasks was administered: Color Trail Making, Controlled Oral Word Association, Grooved Pegboard and Four-Word Learning. This protocol was initiated in the HIV Epidemiological Research study (HERS) study when a woman's CD4 cell count fell to < 100 x 10(6) cells/l. Immune function (CD4), viral load status and depression severity (CESD) were also assessed semi-annually, along with an interview to determine medication intake and illicit drug use. RESULTS: HAART was not available to any participant at the time of enrollment (baseline), while 44% reported taking HAART at their most recent visit (mean duration of HAART 36.3 +/- 12.6 months). HAART-treated women had improved neurocognitive performance compared with those not treated with HAART. Women taking HAART for 18 months or more showed the strongest neurocognitive performance with improved verbal fluency, psychomotor and executive functions. These functions worsened among women not taking HAART. Substance abuse status, severity of depressive symptoms, age and educational level did not influence the HAART treatment effects on neurocognitive performance. Neurocognitive improvements were strongly associated with the magnitude of CD4 cell count increases. CONCLUSIONS: HAART appeared to produce beneficial effect on neurocognitive functioning in HIV-infected women with severely impaired immune systems. Benefits were greatest for women who reported receiving HAART for more than 18 months.     

Recurrent pulmonary sarcoidosis in HIV-infected patients receiving highly active antiretroviral therapy

HIV infection and sarcoidosis occur in the same age group, but there are only a few reports of the coexistence of the two disorders in the same individual. This infrequent occurrence has been attributed to the paucity of functioning CD4(+) lymphocytes required for granuloma formation in patients with HIV infection. We report two patients with a history of remote sarcoidosis who later in life contracted HIV infection and developed recurrent, progressive pulmonary sarcoidosis while receiving highly active antiretroviral therapy (HAART). Progressive pulmonary sarcoidosis should be added to the differential diagnosis in patients receiving HAART for HIV infection who develop diffuse lung disease with recovery of CD4(+) lymphocyte population.     

Longitudinal changes in serum lipids among HIV-infected men on highly active antiretroviral therapy

OBJECTIVE: The aim of the study was to describe longitudinal changes in serum lipids among HIV-infected men receiving highly active antiretroviral therapy (HAART) with long-term follow-up. METHODS: A total of 304 HIV-infected men who initiated HAART and who had serum lipid measurements prior to and for up to 7 years after HAART initiation were identified from the Multicenter AIDS Cohort Study (MACS). Mean levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were examined at biannual time-points. RESULTS: Significant lipid changes were seen within 0.5 years of HAART initiation but increases in TC (+1.09 mmol/L), LDL-C (+0.57 mmol/L), HDL-C (+0.16 mmol/L) and non-HDL-C (+0.91 mmol/L) reached peak levels 2-3 years after HAART initiation. Declines in serum TC, LDL-C and non-HDL-C in subsequent years occurred concurrently with a substantial increase in use of lipid-lowering medications (from 1% usage pre-HAART to 43% 6-7 years after HAART initiation) but the proportion of men who either were treated with cholesterol-lowering medication or had elevated cholesterol levels (>5.18 mmol/L) did not change during the 2-7-year interval after HAART. Mean HDL-C also decreased after 2-3 years and was low (<1.04 mmol/L) in 55% of HIV-infected men 6-7 years after HAART initiation. CONCLUSIONS: Atherogenic serum lipids increased early after the initiation of HAART, peaked at 2-3 years and remained high or required treatment thereafter. Low HDL-C levels persisted in the majority of men. The long-term effects of lipid abnormalities on cardiovascular risk and the effectiveness and toxicity of prolonged use of lipid-lowering medications in combination with HAART are not known.     

Oral candidiasis and seborrheic dermatitis in HIV-infected patients on highly active antiretroviral therapy

Background

Mucocutaneous manifestations such as oral candidiasis (OC) and seborrheic dermatitis (SD) are very common HIV‐related opportunistic events and are usually initial markers of immunodeficiency.

Aim

The purpose of this study was to evaluate the efficacy of highly active antiretroviral therapy (HAART) in the regression of HIV‐associated OC and SD.

Methods

In a prospective study, 120 HIV‐infected patients with OC and SD were divided into two groups: HAART‐treated patients (group 1, n=76) and non‐HAART‐treated patients (group 2, n=44). Non‐HAART‐treated patients were given antimicrobial therapy. Study subjects were matched for sex, age, risk, and stage of HIV infection. The results were analysed by χ² test and the Kaplan‐Meier method.

Results

At baseline, OC was evident in 59 (77.7%) of the HAART‐treated patients and in 34 (77.3%) of the non‐HAART‐treated patients, while SD was present in 19 (25.0%) of the HAART‐treated patients and in 17 (38.6%) of the non‐HAART‐treated patients. After a median follow‐up period of 22 months, regression of OC and SD occurred in 49 (83.1%) and 16 (84.2%) of the HAART‐treated patients, respectively. In the control group, regression of OC and SD occurred in only five (14.7%) and seven (41.2%) patients, respectively, during the same period.

Conclusions

HAART showed greater efficacy than standard antimicrobial therapy for the treatment of OC and SD in HIV‐infected patients.

     

Varicella-Zoster virus-specific cell-mediated immunity in HIV-infected children receiving highly active antiretroviral therapy

Herpes zoster (HZ) is a frequent complication of advanced human immunodeficiency virus (HIV) infection. We determined the effect of highly active antiretroviral therapy (HAART) on reconstitution of varicella-zoster virus (VZV)-specific cell-mediated immunity (VZV-CMI) in 56 VZV- and HIV-infected children. VZV-CMI did not change over the course of >/=3 years of observation, despite a reduction in HIV load. VZV-CMI correlated with lower HIV load but not with CD4 cell percentage. The incidence of HZ was unaffected by HAART. None of 5 patients who developed HZ during the study had VZV-CMI before developing HZ. After developing HZ, only the 2 HAART-compliant patients developed VZV-CMI. Thus, VZV-specific immune reconstitution in HIV infection may require antigenic reexposure, in addition to control of HIV replication.