艾滋病抗病毒治疗后机会感染的变化和分布状况

目的探讨艾滋病(AIDS)抗病毒治疗后机会感染疾病谱的变化及分布状况。方法采用回顾性分析的方法,对2006年9月-2008年12月期间,在郑州市第六人民医院接受门诊及住院治疗的128例HIV/AIDS病人,抗病毒治疗前后机会感染发生情况进行总结分析。结果 (1)128例HIV/AIDS病人中,高效抗反转录病毒疗法(HAART)治疗3-12月期间共发生100例次机会感染,主要为呼吸系统(46.09%)和消化系统(11.72%)感染,其中前4位机会感染是细菌性肺炎(29.69%)、肺结核(9.38%)、口腔念珠菌感染(7.81%)、带状疱疹(3.91%);与HAART治疗前相比,治疗后机会感染中细菌性肺炎、肺结核占绝大多数(86.46%),存在一定比例的口腔念珠菌感染和带状疱疹,AIDS晚期常见的机会感染如肺孢子菌肺炎、感染性腹泻及消耗综合征、中枢神经系统病变发病明显减少。(2)128例HIV/AIDS病人HAART治疗前机会感染发病率为80.47%,治疗后3-6月时下降至28.13%,治疗6-12月时为25.89%,3组相比差异有统计学意义(P<0.05)。HAART治疗后同时合并多种机会感染的病例减少。结论 HAART治疗后的机会感染发病率明显下降,机会感染疾病谱较治疗前有所不同,同时合并多种机会感染的几率减少。     

Epidemiology and risk of pulmonary disease

Although pulmonary diseases are important causes of illness and death in patients with human immunodeficiency virus (HIV) infection, advances in treatment and the demographics of HIV-infected populations are changing their incidence and manifestations. The rates of acquires immune deficiency syndrome (AIDS)- related mortality and opportunistic infections have fallen drastically since the introduction of highly active antiretroviral therapy (HAART) in 1996. The risk of developing specific disorders is related to the degree of immunosuppression, HIV risk group, area of residence, and use of antiretroviral treatments and prophylaxis against common infections. HIV-infected drug users are at increased risk for developing bacterial pneumonia and tuberculosis. Bronchitis and sinusitis occur commonly in the general population, but more frequently in HIV-infected persons. With progressive immunocompromise, the risk of developing bacterial pneumonia, Pneumocystis carinii pneumonia, and tuberculosis increases.     

Opportunistic and other infections in HIV-infected children in Latin America compared to a similar cohort in the United States

Opportunistic and other infections have declined since the introduction of highly active antiretroviral therapy (HAART) in developed countries but few studies have addressed the impact of HAART in HIV-infected children from developing countries. This study examines the prevalence and incidence of opportunistic and other infections in Latin America during the HAART era. Vertically HIV-infected children enrolled in a cohort study between 2002 and 2007 were followed for the occurrence of 29 targeted infections. Cross-sectional and longitudinal analyses were performed to calculate the prevalence of infections before enrollment and the incidence rates of opportunistic and other infections after enrollment. Comparisons were made with data from a U.S. cohort (PACTG 219C). Of the 731 vertically HIV-infected children 568 (78%) had at least one opportunistic or other infection prior to enrollment. The most prevalent infections were bacterial pneumonia, oral candidiasis, varicella, tuberculosis, herpes zoster, and Pneumocystis jiroveci pneumonia. After enrollment, the overall incidence was 23.5 per 100 person-years; the most common infections (per 100 person-years) were bacterial pneumonia (7.8), varicella (3.0), dermatophyte infections (2.9), herpes simplex (2.5), and herpes zoster (1.8). All of these incidence rates were higher than those reported in PACTG 219C. The types and relative distribution of infections among HIV-infected children in Latin America in this study are similar to those seen in the United States but the incidence rates are higher. Further research is necessary to determine the reasons for these higher rates.     

HIV1 and the gut in the era of highly active antiretroviral therapy

The gut and its gut-associated lymphoid tissue serve as a preferential site for HIV1 entry, active viral replication, reservoir, and HIV-mediated CD4 cell apoptosis. The widespread use of highly active antiretroviral therapy (HAART) has resulted in a significant decrease in the incidence of opportunistic enteric pathogens as a consequence of immune recovery. Nonetheless, patients with advanced HIV1 disease who were recently diagnosed or have poor response to HAART can still suffer from opportunistic infections with pathogens such as Cryptosporidium, microsporidia, Isospora belli, Cyclospora cayetanensis, Mycobacterium avium complex, and cytomegalovirus, among others. This review describes the impact of HIV1 infection on gut immune function, the salient features of the most common opportunistic enteric pathogens and HIV-associated enteropathy, and the effects of immune reconstitution after introduction of HAART.     

Impact of highly active antiretroviral therapy on organ-specific manifestations of HIV-1 infection

In the last 10 years, interesting results have been reported concerning the impact of highly active antiretroviral therapy (HAART) on the changing pattern of organ-specific manifestations of HIV-1 infection. There has been a clear step-wise reduction in the incidence of several opportunistic infections (OIs), particularly Pneumocystis carinii pneumonia, whereas a nonsignificant reduction in incidence has been observed for other organ-specific diseases, including invasive cervical cancer and Hodgkin disease. In addition, several organ-specific manifestations, including HIV-associated nephropathy, wasting syndrome and cardiomyopathy, are a direct consequence of damage by HIV-1, and so HAART may have a therapeutic effect in improving or preventing these manifestations. Finally, the introduction of HAART has seen the emergence of several complications, termed immune reconstitution inflammatory syndrome, which includes OIs such as cytomegalovirus vitritis, Mycobacterium avium complex lymphadenitis, paradoxical responses to treatment for tuberculosis, and exacerbation of cryptococcosis. Because not all HIV-1 organ-specific manifestations are decreasing in the HAART era, this review will analyse the influence of HAART on several organ-specific manifestations, and in particular OIs related to several organs, cerebral disorders and HIV-1-related neoplasia.     

Pneumocystis carinii pneumonia in HIV-infected patients in the HAART era

Since the advent of highly active antiretroviral therapy (HAART), the incidence of opportunistic infections (OI) in patients with HIV has markedly decreased. Despite this, there are still large numbers of Pneumocystis carinii pneumonia (PCP) cases at Cook County Hospital (CCH). To better understand this patient group, we performed a retrospective chart review of 120 pathologically proven cases of PCP from January 1998 to June 2001. One hundred four patients were included in the study. Sixty-nine percent of our patients were active substance abusers and 50% had previous knowledge of HIV disease. Of our patients, fewer than 5% were on HAART or PCP prophylaxis on study admission. The overall mortality rate was 14%. Of discharged patients, 65% were placed on HAART therapy and 59% of these achieved a viral load of less than 1000 copies per milliliter in the year postdischarge. Patients who failed to achieve a viral load less than 1000 copies per milliliter were more likely active substance abusers or had a viral load greater than 100,000 copies per milliliter prior to study admission. Our study shows that patients are still being admitted with PCP in the HAART era. Active substance abuse and failure to recognize HIV status contributed heavily to this late presentation of HIV disease. An aggressive approach toward HIV identification and substance abuse treatment may decrease admissions to the hospital for PCP and improve response to HAART therapy.     

Incidence and risk factors for immune reconstitution inflammatory syndrome during highly active antiretroviral therapy

BACKGROUND: There is little systematic information regarding the immune reconstitution inflammatory syndrome (IRIS). OBJECTIVE: To determine the incidence, risk factors, and long-term outcome of IRIS in HIV-infected patients receiving highly active antiretroviral therapy (HAART) who were coinfected with one of three common opportunistic pathogens. DESIGN: A retrospective cohort identified through a city-wide prospective surveillance program. METHODS: A retrospective chart review was performed for 180 HIV-infected patients who received HAART and were coinfected with Mycobacterium tuberculosis, Mycobacterium avium complex, or Cryptococcus neoformans between 1997 and 2000. Medical records were reviewed for baseline demographics, receipt and type of HAART, response to antiretroviral therapy, development of IRIS, and long-term outcome. RESULTS: In this cohort, 31.7% of patients who received HAART developed IRIS. Patients with IRIS were more likely to have initiated HAART nearer to the time of diagnosis of their opportunistic infection (P < 0.001), to have been antiretroviral naive at time of diagnosis of their opportunistic infection (P < 0.001), and to have a more rapid initial fall in HIV-1 RNA level in response to HAART (P < 0.001). CONCLUSIONS: IRIS is common among HIV-infected persons coinfected with M. tuberculosis, M. avium complex, or C. neoformans. Antiretroviral drug-naive patients who start HAART in close proximity to the diagnosis of an opportunistic infection and have a rapid decline in HIV-1 RNA level should be monitored for development of this disorder.     

CMV retinitis and the controversies associated with highly active antiretroviral therapy and the immune recovery hypothesis

The aggressive multidrug regimen of highly active antiretroviral therapy (HAART) has offered some degree of promise of immune reconstitution in AIDS patients, a phenomenon that theoretically would impact positively on the incidence and severity of opportunistic infections. Some studies already have noted complete regression of cytomegalovirus (CMV) retinitis without specific use of anti-CMV agents in patients undergoing HAART. However, the role of HAART in CMV retinitis remains controversial among investigators. This review of the salient details regarding the controversies associated with CMV retinitis and the immune recovery hypothesis is meant to shed light on current and future therapeutic issues concerns. Early data seem to predict a decline in CMV retinitis. However, some investigators have noted that increased CD4 T-lymphocyte counts may not protect against CMV retinitis; therefore, the diagnosis cannot be excluded based on count alone. There is also the question of whether CMV retinitis progression in any way represents failure of HAART in those patients receiving this type of combination therapy. HAART is seen as an encouraging development in the treatment of AIDS and opportunistic infection, but its more specific therapeutic effect on CMV retinitis requires further research with controlled prospective clinical trials.     

Can chemoprophylaxis against opportunistic infections be discontinued after an increase in CD4 cells induced by highly active antiretroviral therapy?

BACKGROUND: In the 'USPHS/IDSA Guidelines for Prevention of Opportunistic Infections in Persons Infected with Human Immunodeficiency Virus', the indications for chemoprophylaxis are based on nadir CD4 cell count. Many patients have, however, experienced an increase in CD4 cell count after the introduction of highly active antiretroviral therapy (HAART). OBJECTIVES: To assess incidences of opportunistic infections after discontinuation of chemoprophylaxis in HIV-infected patients, who have experienced a HAART-induced increase in CD4 cell count. METHODS: The Danish guidelines for chemoprophylaxis against opportunistic infections in HIV-infected patients were revised in late 1997, allowing discontinuation of chemoprophylaxis after initiation of HAART if the CD4 cell count remained above a specified limit for more than 6 months. Consecutive patients were followed, and incidences of opportunistic infections after discontinuation of chemoprophylaxis were assessed. RESULTS: A total of 219 patients discontinued Pneumocystis carinii pneumonia (PCP)-chemoprophylaxis (12% maintenance therapy). One case of PCP was diagnosed within 174 person-years (PY) of follow-up, resulting in an incidence of 0.6 cases/100 PY follow-up (95% confidence interval, 0.0-3.2). No cases of cerebral toxoplasmosis, cytomegalovirus chorioretinitis, or disseminated Mycobacterium avium infection were observed. Follow-up time for these was, however, limited. CONCLUSION: PCP-chemoprophylaxis can be safely discontinued after HAART-induced increase in CD4 cell count to more than 200 x 10(6) cells/l. Among consecutive patients who discontinue chemoprophylaxis according to well-defined guidelines, the observed incidence of PCP is below those reported earlier in patients with similar CD4 cell count.     

53-j?hriger Patient mit Fieber und Husten

We describe a patient with late HIV presentation, opportunistic infections and an immune reconstitution syndrome (IRIS) after starting a combination antiretroviral therapy (ART)occurring in this severely immunodeficient patient. In the beginning, a miliary tuberculosis was diagnoses, followed by a second opportunistic infection, i.e. pneumocystis jiroveci pneumonia. After start of ART, further organ manifestations developed, interpreted as immune reconstitution syndrome. The decision about the optimal time point for starting ART in the presence of an opportunistic infection is essential.     

Acute respiratory failure following HAART introduction in patients treated for Pneumocystis carinii pneumonia.

Cases of paradoxical worsening of opportunistic infections shortly after the beginning of highly active antiretroviral therapy (HAART) prompted questions on the optimal timing of introduction of HAART in patients with inaugural AIDS-related opportunistic infections. We describe three cases of acute respiratory failure after early introduction of HAART in patients treated for Pneumocystis carinii pneumonia (PCP). The three patients had severe PCP that initially improved with anti-PCP and adjunctive steroid therapy. HAART was introduced 1 to 16 d after diagnosis of PCP, and steroids were stopped on Day 15. Seven to 17 d after HAART introduction, the three patients developed a second episode of severe acute respiratory failure with high-grade fever and patchy alveolar opacities on the chest roentgenogram. PCP resistant to cotrimoxazole, pulmonary superinfection, and drug-related pneumonitis were suspected but subsequently ruled out. Bronchoalveolar lavage and lung pathologic findings showed severe nonspecific pulmonary inflammatory foci surrounding a few persistent P. carinii cysts. All three patients recovered after HAART interruption or steroid reintroduction. We conclude that acute respiratory failure can recur after initiation of antiretroviral therapy in patients being treated for severe PCP. This phenomenon could result from rapid pulmonary recruitment of fully competent immune and inflammatory cells responding to a few persistent P. carinii cysts. A short course of steroid therapy may suppress this reaction.     

Opportunistic infections as causes of death in HIV-infected patients in the HAART era in France

The objective of the study was to describe the underlying causes of death of HIV-infected patients in the HAART era and to focus on those related to opportunistic infection (OI), in a national multicentre study ('Mortalité 2000'). A total of 964 deaths were recorded and 924 cases were available for analysis. Underlying cause of death were AIDS-related (47%), viral hepatitis (11%), non-AIDS cancers (11%), cardiovascular diseases (7%) and others (11%). Among patients who died of AIDS events, 262 (27%) died of at least one OI. OIs reported at the time of death were Cytomegalovirus infection 67 times, Pneumocystis jiroveci pneumonia 56, disseminated Mycobacterium avium intracellulare infection 53 and cerebral toxoplasmosis 48. Compared to patients who died of other causes, patients who died of OIs were younger and more likely to be infected through heterosexual contact, in poor socioeconomic conditions, migrants, more recently diagnosed for HIV infection, and naive of antiretroviral therapy and OI prophylaxis. OIs are still a major cause of death in HIV-infected patient in the HAART era, especially among patients recently diagnosed for HIV infection and who do not have access to care, as well as in long term infected patients where prophylaxis should be revisited.     

Pulmonary manifestations of HIV infection in the era of highly active antiretroviral therapy.

STUDY OBJECTIVES: To determine whether the spectrum of HIV-related pulmonary disease seen by a university medical center Pulmonary and Critical Care Medicine Service has changed since the introduction of highly active antiretroviral therapy (HAART). DESIGN: Retrospective chart review. SETTING: A tertiary care university hospital. PATIENTS: All HIV-infected patients referred to the Pulmonary and Critical Care Medicine Service from January 1, 1993, through December 31, 1995 (era 1) and from July 1, 1997, through June 30, 2000 (era 2). INTERVENTIONS: Inpatient and outpatient charts were reviewed for data regarding patient demographics, CD4 cell counts, viral load levels, duration of HIV seropositivity, history of opportunistic infections, and final diagnosis. RESULTS: Pneumocystis carinii pneumonia (PCP) was less common in the HAART era than in the pre-HAART era, whereas bacterial pneumonia and non-Hodgkin's lymphoma (NHL) were more common in the HAART era than in the pre-HAART era. HAART was protective against PCP (odds ratio [OR], 0.37; confidence interval [CI], 0.16 to 0.89) in a manner dependent on the CD4 cell count. Patients receiving HAART were at increased risk for the development of bacterial pneumonia (OR, 2.41; CI, 1.12 to 5.17) and NHL (OR, 15.11; CI, 3.14 to 28.32). A history of PCP indicated a risk factor for bacterial pneumonia (OR, 2.14; CI, 1.13 to 4.04). A history of cytomegalovirus infection indicated a risk factor for NHL (OR, 6.0; CI, 1.27 to 28.32). CONCLUSIONS: There have been significant changes in the spectrum of HIV-related pulmonary complications seen by our Pulmonary and Critical Care Medicine Service in the HAART era.     

Recurrence of Pneumocystis carinii pneumonia in an HIV-infected patient: apparent selective immune reconstitution after initiation of antiretroviral therapy

Although several studies have reported that it is safe to discontinue secondary Pneumocystis carinii pneumonia (PCP) prophylaxis in patients infected with HIV who experience a sustained immune response as a result of antiretroviral therapy, we describe a patient who developed recurrent PCP <3 months after discontinuing trimethoprim-sulfamethoxazole prophylaxis. He developed disease despite a sustained CD4 T-cell count above 200 cells/microL for more than 3 years while on antiretroviral therapy, as well as an apparent immune reconstitution against disseminated Mycobacterium avium complex (MAC) and Histoplasma capsulatum, for which he also discontinued therapy but without adverse effects. Thus, although increasing evidence continues to indicate that HIV-infected patients receiving combinations of antiretroviral therapies may regain specific immunity against opportunistic infections, our patient's experience suggests that this immune recovery may be selective and incomplete.     

Cytomegalovirus infection: the point in 2001

The incidence of cytomegalovirus (CMV) disease, one of the most prevalent opportunistic infections in HIV‐infected persons in the early 1990s, has decreased by more than 80% since the introduction of highly active antiretroviral therapy (HAART). The rare cases of CMV disease still observed in Western countries occur mainly in profoundly immunosuppressed patients who have failed to respond to HAART. A new finding is the occasional occurrence of inflammatory retinitis in some patients on HAART with a history of healed retinitis. New tools for CMV detection have become available recently, including use of polymerase chain reaction (PCR) to detect CMV DNA from plasma. It has been possible to redefine, in the HAART period, patients at risk for CMV disease as those who have a low CD4 cell count as well as a blood marker of CMV blood dissemination (plasma CMV DNAaemia or high pp65 antigenaemia). Besides the classical therapeutic approach using ganciclovir (GCV), foscarnet and cidofovir, development of valganciclovir (VGCV), an orally administered prodrug of GCV, appears promising. There is evidence to suggest that it is as effective as intravenous GCV for the treatment of CMV retinitis, and it is currently being studied as a pre‐emptive therapy in patients at high risk for CMV disease. Finally, patients with inactive CMV retinitis receiving HAART and with stable immune reconstitution may be able to discontinue maintenance therapy provided a regular ophthalmological and virological surveillance is maintained.     

Opportunistic Diseases in HIV-Infected Patients in Gabon following the Administration of Highly Active Antiretroviral Therapy: A Retrospective Study

Opportunistic diseases cause substantial morbidity and mortality to human immunodeficiency virus (HIV)-infected patients. Highly active antiretroviral therapy (HAART) leading to immune reconstitution is the most effective treatment of preventing opportunistic diseases. This retrospective study established an epidemiologic profile of opportunistic diseases 10 years after the introduction of HAART. The HIV antiretroviral therapy-naive patients matching inclusion criteria were included. The primary outcome was the prevalence of opportunistic diseases. From January 1, 2002 to September 30, 2010, 654 opportunistic diseases were identified in 458 patients. Pulmonary tuberculosis, herpes zoster, cerebral toxoplasmosis, oral candidiasis, and severe pneumonia accounted for 22.05%, 15.94%, 14.19%, 14.19%, and 9.39%, respectively. Cryptococcal meningitis and pneumocystosis accounted for 0.44% and 0.21%, respectively. The prevalence of opportunistic diseases in Gabon remains high. New guidelines emphasize the importance of initiating antiretroviral therapy early to reconstitute the immune system, and reduce disease risk, and treat the primary opportunistic infection of pulmonary tuberculosis.     

Illness of immune reconstitution: Recognition and management

Some individuals who initiate highly active antiretroviral therapy (HAART) develop new or worsening opportunistic infections or malignancies despite improvements in surrogate markers of HIV-1 infection. These events of paradoxical clinical worsening, also known as immune reconstitution syndromes (IRS), are increased in individuals with prior opportunistic infections or low CD4+ T-cell nadirs. They are thought to result from reconstitution of the immune system’s ability to recognize pathogens or tumor antigens that were previously present, but clinically asymptomatic. There is no consensus regarding the diagnostic criteria or pathogenesis of IRS. Knowledge of their presentation and treatment is largely based on case reports. With the introduction of HAART into resource-limited settings, it is likely that significantly more and distinct forms of IRS will be observed. Prospective studies of the incidence and treatment of IRS in multiple settings are critical to better understand their pathogenesis and optimal management.     

Neurologic consequences of HIV infection in the era of HAART

In this brief review, we present a summary of the clinical presentation of HIV-associated dementia (HAD), HAD in the highly active antiretroviral therapy (HAART) era, the immunopathogenesis of HAD, and the possible role of a recently described novel macrophage-derived protein in HAD. Different aspects of the clinical presentation of HAD will be reviewed as well as the results of recent autopsy studies demonstrating that although HAART dramatically decreased the incidence of opportunistic infections and malignancies in the central nervous system, it has reduced but not eliminated HIV encephalopathy. This suggests a direct cytopathic effect of HIV on neuronal tissue. Consequently, the immunopathogenesis of HAD and the role of neurotoxins produced by brain macrophages and microglial cells will be reviewed including the possible role of a recently cloned macrophage-derived proapoptotic factor, soluble HIV apoptotic protein (SHIVA) identified in our laboratory. HAART therapy reduces the incidence of opportunistic infections, the direct pathogenic effect of HIV, especially on neuronal tissue, may become of increasing importance.     

Opportunistic infections in HIV disease: down but not out.

Despite the marked improvement in patient survival and reduction in the incidence of HIV-related opportunistic infections with the introduction of potent, combination antiretroviral therapy, these infections remain a significant challenge in the management of HIV-infected patients. Ongoing issues that will require further study include a better characterization of immune reconstitution illnesses, other potential alterations in the natural history of opportunistic infections with antiretroviral therapy, and to what degree patients who experience failure of antiviral treatment become susceptible to various opportunistic processes.