Discontinuation of maintenance therapy for cytomegalovirus retinitis in HIV-infected patients receiving highly active antiretroviral therapy

OBJECTIVE: To study the safety of discontinuing cytomegalovirus (CMV) maintenance therapy among patients with cured CMV retinitis receiving highly active antiretroviral therapy (HAART). METHODS: Patients with a history of CMV retinitis who were receiving anti-CMV maintenance therapy and who had a CD4 cell count > 75 x 10(6) cells/l and a plasma HIV RNA level < 30000 copies/ml while on HAART were included in a multicentre prospective study. Maintenance therapy for CMV retinitis was discontinued at enrolment and all the patients were monitored for 48 weeks by ophthalmological examinations and by determination of CMV markers, CD4 cell counts and plasma HIV RNA levels. T helper-1 anti-CMV responses were assessed in a subgroup of patients. The primary study endpoint was recurrence of CMV disease. RESULTS: At entry, the 48 assessable patients had been taking HAART for a median of 18 months. The median CD4 cell count was 239 x 10(6) cells/l and the median HIV RNA load was 213 copies/ml. Over the 48 weeks, 2 of the 48 patients had a recurrence of CMV disease. The cumulative probability of CMV retinitis relapse was 2.2% at week 48 (95% confidence interval, 0.4-11.3) and that of all forms of CMV disease 4.2%. CMV blood markers remained negative throughout follow-up. The proportion of patients with CMV-specific CD4 T cell reactivity was 46% at baseline and 64% at week 48. CONCLUSIONS: CMV retinitis maintenance therapy may be safely discontinued in patients with CD4 cell counts above 75 x 10(6) cells/l who have been taking HAART for at least 18 months.     

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.     

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。     

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.     

Risk of pneumocystosis after early discontinuation of prophylaxis among HIV-infected patients receiving highly active antiretroviral therapy

Background  

Risk of pneumocystosis after discontinuation of primary or secondary prophylaxis among HIV-infected patients before CD4 counts increase to ≧200 cells/μL (early discontinuation) after receiving highly active antiretroviral therapy (HAART) is rarely investigated.     

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.     

Management of opportunistic infection prophylaxis in the highly active antiretroviral therapy era

Prophylaxis and maintenance therapy against opportunistic infections are a mainstay of management of HIV-infected patients and have led to a significant improvement in quality of life and survival. Antiretroviral combination therapy (ART) has markedly changed the natural course of HIV infection. Incidence of opportunistic infections (OIs) has declined and survival after an OI has improved. Achieving a CD4 count of 200 cells/μL after 6 months of ART is a valuable marker for low risk of OI afterwards. Therefore, recommendations on prophylaxis and maintenance therapy need to be redefined. Criteria for discontinuation, such as a CD4 count rise above threshold values and time above threshold values as response to ART, should be evaluated for the most frequent OIs. Reliable data in favor of discontinuation of primary prophylaxis against Pneumocystis carinii pneumonia, toxoplasmic encephalitis, and Mycobacterium avium infection have been published. Discontinuation of maintenance therapy against P. carinii pneumonia is possible, and may be safe against cytomegalovirus retinitis, M. avium, and cryptococcosis and toxoplasmosis in selected patients. Pharmacologic interactions between drugs used for OI prophylaxis and antiretroviral drugs need to be taken into account.     

Polyomavirus JCV excretion and genotype analysis in HIV-infected patients receiving highly active antiretroviral therapy

OBJECTIVE: To assess the frequency of shedding of polyomavirus JC virus (JCV) genotypes in urine of HIV-infected patients receiving highly active antiretroviral therapy (HAART). METHODS: Single samples of urine and blood were collected prospectively from 70 adult HIV-infected patients and 68 uninfected volunteers. Inclusion criteria for HIV-infected patients included an HIV RNA viral load < 1000 copies, CD4 cell count of 200-700 x 106 cells/l, and stable HAART regimen. PCR assays and sequence analysis were carried out using JCV-specific primers against different regions of the virus genome. RESULTS: JCV excretion in urine was more common in HIV-positive patients but not significantly different from that of the HIV-negative group [22/70 (31%) versus 13/68 (19%); P = 0.09]. HIV-positive patients lost the age-related pattern of JCV shedding (P = 0.13) displayed by uninfected subjects (P = 0.01). Among HIV-infected patients significant differences in JCV shedding were related to CD4 cell counts (P = 0.03). Sequence analysis of the JCV regulatory region from both HIV-infected patients and uninfected volunteers revealed all to be JCV archetypal strains. JCV genotypes 1 (36%) and 4 (36%) were the most common among HIV-infected patients, whereas type 2 (77%) was the most frequently detected among HIV-uninfected volunteers. CONCLUSION: These results suggest that JCV shedding is enhanced by modest depressions in immune function during HIV infection. JCV shedding occurred in younger HIV-positive persons than in the healthy controls. As the common types of JCV excreted varied among ethnic groups, JCV genotypes associated with progressive multifocal leukoencephalopathy may reflect demographics of those infected patient populations.     

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.     

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.     

Evolution of hepatitis B serological markers in HIV-infected patients receiving highly active antiretroviral therapy.

BACKGROUND: Evolution of serological markers of hepatitis B virus (HBV) carriage or infection has rarely been investigated among human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART). METHODS: During the period 1997-2002, a total of 633 HIV-infected patients were tested for HBV serological markers at baseline, including hepatitis B surface antigen (HBsAg), antibody to HBsAg (anti-HBs ), antibody to hepatitis B core antigen (anti-HBc), hepatitis C virus (HCV) antibody (anti-HCV) antibody, HCV RNA level, and HBV DNA level, all of which were retested at least 1 year apart. Medical records were reviewed to identify clinical characteristics associated with evolution of these serological markers. RESULTS: After a median duration of follow-up for 4.96 years, 161 patients (25.4%) had changes in HBV serological markers. Of 119 patients (18.8%) who tested positive for HBsAg at baseline, 6 (5.0%) developed anti-HBs, and 9 (7.6%) developed isolated anti-HBc. Of 270 patients (42.7%) who tested positive for anti-HBs, 18 (6.7%) lost anti-HBs. Of 179 patients (28.3%) in whom isolated anti-HBc had been detected, 73 (40.8%) developed anti-HBs, 18 (10.1%) lost all HBV markers, and 7 (3.9%) developed HBsAg. Of 65 patients (10.2%) who tested negative for all HBV markers, 13 (20%) developed anti-HBs, 13 (20%) developed isolated anti-HBc, and 4 (6.2%) developed HBsAg, indicating a high risk of HBV exposure. Patients in whom anti-HBc was detected at baseline were more likely to have acquired immunodeficiency syndrome (P=.008). Multivariate analysis revealed that an increase in the CD4 cell count after the commencement of HAART was significantly associated with persistence or subsequent development of anti-HBs in patients with anti-HBs or anti-HBc at baseline, respectively. CONCLUSIONS: Periodic measurements of HBV serological markers in HIV-infected patients are recommended, because new HBV infections and changes of HBV serological markers are not uncommon in patients with improved immunity after commencement of HAART.     

Withdrawal of Pneumocystis jirovecii prophylaxis in HIV-infected children under highly active antiretroviral therapy

OBJECTIVE: In HIV-infected adults Pneumocystis jirovecii pneumonia (PCP) prophylaxis can be safely withdrawn after immune reconstitution due to the introduction of highly active antiretroviral therapy (HAART). With regard to children only a small amount of data has been published. The present study investigated whether the withdrawal of PCP prophylaxis after immune reconstitution is safe in HIV-infected children. METHODS: A retrospective analysis at 10 European centers belonging to the Pediatric European Network on the treatment of AIDS (PENTA) using a standardized questionnaire. RESULTS: A total of 113 questionnaires were received. In 82 children the indication for PCP prophylaxis was provided following Centers for Disease Control (CDC) guidelines (72 primary and 10 secondary). Prophylaxis was withdrawn after the CD4 cell count increased above the age-related CDC thresholds. The observation period off prophylaxis was 335 years (300 years for primary and 35 years for secondary prophylaxis) and the median time per patient off prophylaxis was 4.1 years (range, 0.3-7.7 years). No episode of PCP occurred during the study period. In comparison with the incidence rate from historical data before the introduction of PCP prophylaxis and HAART, this was a significant reduction (P < 0.05). CONCLUSIONS: The increase in CD4 cell count provides functional reconstitution of the immune system in children. Our data suggests that the risk of developing a PCP after immune reconstitution is sufficiently low to withdraw PCP prophylaxis.