Hepatitis C virus (HCV) diversity in HIV-HCV-coinfected subjects initiating highly active antiretroviral therapy

Because of increased mortality and reduced treatment response rates in subjects coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), understanding the selection pressures underlying the evolution of HCV is important for the development of strategies to control both viruses. We therefore investigated diversity of HCV in 11 HIV-HCV-coinfected subjects initiating highly active antiretroviral therapy (HAART). Distinct categories of HCV virologic response to suppression of HIV were identified. The diversity of quasi species at several genomic regions was characterized over the course of a 48-week period. Consensus data suggested a shift in the virus population at all loci except the 5' untranslated region (UTR) after initiation of HAART. Intrasubject genetic distance and entropy were highest in hypervariable region (HVR)-1. In contrast, variation in the 5' UTR was limited. Positive immune selection pressure directed against HVR-1, but not other protein-coding regions, was also detected. These data suggest that there are several mechanisms by which suppression of HIV replication and a reconstituted immune system influence diversity of HCV in HIV-HCV-coinfected subjects.     

Time to initiating highly active antiretroviral therapy among HIV-infected injection drug users

OBJECTIVE: Studies have shown that HIV-infected injection drug users (IDUs) are less likely to receive antiretroviral therapy than non-drug users. We assess factors associated with initiating highly active antiretroviral therapy (HAART) in HIV-infected IDUs. METHODS: A cohort study of IDUs carried out between 1 January 1996 and 30 June 1999 at a community-based study clinic affiliated to the Johns Hopkins University, Baltimore, Maryland. The participants were a total of 528 HIV-infected IDUs eligible for HAART based on CD4+ cell count. The main outcome measure was the time from treatment eligibility to first self-reported HAART use, as defined by the International AIDS Society-USA panel (IAS-USA) guidelines. RESULTS: By 30 June 1999, 58.5% of participants had initiated HAART, most of whom switched from mono- or dual-combination therapy to a HAART regimen. Nearly one-third of treatment-eligible IDUs never received antiretroviral therapy. Cox proportional hazards regression showed that initiating HAART was independently associated with not injecting drugs, methadone treatment among men, having health insurance and a regular source of care, lower CD4+ cell count and a history of antiretroviral therapy. CONCLUSIONS: Self-reported initiation of HAART is steadily increasing among IDUs who are eligible for treatment; however, a large proportion continues to use non-HAART regimens and many remain treatment-naive. Although both groups appear to have lower health care access and utilization, IDUs without a history of antiretroviral therapy use would have more treatment options available to them once they become engaged in HIV care.     

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.     

Hepatitis C infection increases the risk of the modification of first highly active antiretroviral therapy in HIV-infected patients

We assessed predictors of discontinuation or change of the first regimen of highly active antiretroviral therapy in 465 HIV-infected adults, in the first year. A total of 187 patients modified their regimen: 45 discontinuing and 142 changing because of clinical/virological failure, intolerance/toxicity or non-adherence. Predictors of modification of the regimen were hepatitis C seropositivity, liver cirrhosis, higher baseline viral load, sex (women had a lower risk) and calendar year (lower risk staring in 2000).     

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.     

Hepatitis C virus quasispecies in HIV-infected women: role of injecting drug use and highly active antiretroviral therapy (HAART)

Despite the high frequency of HCV and HIV coinfection, little is known about HCV quasispecies in HIV-positive patients. The current analysis included 236 HIV+/anti-HCV+ women enrolled in the Women's Interagency HIV Study (WIHS). Hypervariable region 1 of the second envelope gene was analyzed by single-strand conformation polymorphism (SSCP). The relationship between the HCV quasispecies and clinical and demographic features were analyzed in multivariate models. Age over 40 years and high HCV RNA load were the only factors significantly associated with quasispecies complexity, assessed as the number of SSCP bands. High HIV and HCV plasma loads were associated with quasispecies stability over time, as reflected by stable SSCP band patterns. However, women who were actively injecting drugs were 3 times more likely to experience quasispecies changes than their noninjecting counterparts. No affect on HCV quasispecies dynamics was noted in relation to CD4 count or highly active antiretroviral therapy (HAART). CONCLUSION: among HIV/HCV coinfected patients, HCV quasispecies complexity and dynamics correlate more closely with HIV and HCV plasma loads than with CD4+ cell counts. Active drug use is associated with quasispecies changes probably due to repeated superinfections with new HCV strains. This needs to be considered when planning treatment and prevention strategies for HCV in coinfected individuals.     

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.     

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.     

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.     

Response to highly active antiretroviral therapy among severely immuno-compromised HIV-infected patients in Cambodia

BACKGROUND: HAART efficacy was evaluated in a real-life setting in Phnom Penh (Médecins Sans Frontières programme) among severely immuno-compromised patients. METHODS: Factors associated with mortality and immune reconstitution were identified using Cox proportional hazards and logistic regression models, respectively. RESULTS: From July 2001 to April 2005, 1735 patients initiated HAART, with median CD4 cell count of 20 (inter-quartile range, 6-78) cells/microl. Mortality at 2 years increased as the CD4 cell count at HAART initiation decreased, (4.4, 4.5, 7.5 and 24.7% in patients with CD4 cell count > 100, 51-100, 21-50 and < or = 20 cells/microl, respectively; P < 10). Cotrimoxazole and fluconazole prophylaxis were protective against mortality as long as CD4 cell counts remained < or = 200 and < or = 100 cells/microl, respectively. The proportion of patients with successful immune reconstitution (CD4 cell gain > 100 cells/microl at 6 months) was 46.3%; it was lower in patients with previous ART exposure [odds ratio (OR), 0.16; 95% confidence interval (CI), 0.05-0.45] and patients developing a new opportunistic infection/immune reconstitution infection syndromes (OR, 0.71; 95% CI, 0.52-0.98). Similar efficacy was found between the stavudine-lamivudine-nevirapine fixed dose combination and the combination stavudine-lamivudine-efavirenz in terms of mortality and successful immune reconstitution. No surrogate markers for CD4 cell change could be identified among total lymphocyte count, haemoglobin, weight and body mass index. CONCLUSION: Although CD4 cell count-stratified mortality rates were similar to those observed in industrialized countries for patients with CD4 cell count > 50 cells/microl, patients with CD4 cell count < or = 20 cells/microl posed a real challenge to clinicians. Widespread voluntary HIV testing and counselling should be encouraged to allow HAART initiation before the development of severe immuno-suppression.     

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.