Disease In HIV-infected Patients Research Articles

Enhancement of HIV-specific cytotoxic T lymphocyte responses by zidovudine (AZT) treatment

Zidovudine or 3'-azido-2'-3'-dideoxy-thymidine (AZT) is an antiviral drug widely used to treat HIV-infected patients. Because cytotoxic T lymphocytes (CTL) are thought to contribute actively to resistance against HIV-induced disease, we studied sequentially 10 HIV-infected individuals under zidovudine treatment for a period of 6-12 months. For a given patient all lymphocyte suspensions corresponding to the complete zidovudine therapy period were tested on the same day and on the same target cells. Patients were selected for expression of HLA-A2 and/or HLA-A3 class I transplantation antigen. HLA-restricted cytotoxicity specific for env, gag and nef HIV proteins was quantified for each patient at 6 week intervals. The data clearly indicated that zidovudine has a beneficial effect on the CTL response during the first 6-12 weeks of treatment, inducing cytotoxicity levels up to 100-fold stronger than base line. This effect was usually short lived. However, patients who maintained strong levels of cytotoxicity had better clinical and survival outlook than patients who had lost all detectable cytotoxic lymphocytes. It is proposed that AZT, among other effects, delays the onset of disease in HIV-infected patients by contributing to the stimulation of the HIV-specific CTL response.

Prevention Strategies for Cardiovascular Disease in HIV-Infected Patients

Effective antiretroviral therapy (ART) improves the survival of patients with human immunodeficiency virus (HIV) infection.1 With increased life expectancy, HIV-infected patients increasingly are experiencing complications of illnesses that are not directly related to HIV infection.2 Cardiovascular disease (CVD), the leading cause of death in the United States,3 recently has been recognized as an important cause of morbidity and mortality among patients with HIV (see Working Group 2, Epidemiological Evidence for Cardiovascular Disease in HIV-Infected Patients and Relationship to Highly Active Antiretroviral Therapy).2,4–6 Among these patients, traditional CVD risk factors predict CVD events; however, certain components of ART appear to be associated with increased CVD risk.5 Much of the increased CVD risk observed in patients undergoing ART is related primarily to the effects of ART on traditional CVD risk factors; however, direct effects of ART on the vasculature and other inflammatory, immune, and viral factors associated with HIV infection may also contribute to increased CVD risk.5,7,8 A central tenet of preventing CVD is that the intensity of risk-reducing interventions should be based on the level of CVD risk.9 Patients with established CVD are at the highest risk and qualify for the most aggressive risk factor management, with special focus on interventions that have been proven to prevent cardiovascular death, myocardial infarction, and stroke. For patients without established CVD, management is based on the presence of risk factors for developing complications of CVD, such as death, myocardial infarction, and stroke9–12 (see Working Group 4, Screening and Assessment of Coronary Heart Disease in HIV-Infected Patients). The intensity of CVD risk-reducing therapy, however, must be modified by the context of the patient’s overall health. This is an especially important consideration in patients with HIV infection, who often have competing morbidities that may be as likely to …

Screening and Assessment of Coronary Heart Disease in HIV-Infected Patients

Human immunodeficiency virus (HIV)–infected individuals are living longer in the era of antiretroviral therapy. As a result, they are increasingly prone to the development of concomitant chronic disease. Coronary heart disease (CHD) is the leading cause of death in the United States and Europe. Recent studies suggest that CHD rates may be increasing among HIV-infected patients (see Epidemiological Evidence for Cardiovascular Disease in HIV-Infected Patients and Relationship to Highly Active Antiretroviral Therapy, Working Group 2), and thus appropriate screening strategies for CHD in this population are needed. Recently, approaches to screening and assessment of cardiovascular disease (CVD) in HIV-infected individuals were discussed at a State of the Science Conference. Although insufficient evidence now exists to recommend a screening strategy for CHD in HIV that differs from that recommended in the non-HIV population, emerging risk factors and surrogate markers for atherosclerosis unique to the HIV population suggest specific strategies that may be useful in this population. Two broad screening categories are discussed here. The first screening strategy seeks to define the pretest likelihood of disease by identifying the presence of predisposing risk factors such as hypertension, elevated serum cholesterol, cigarette smoking, and physical inactivity. The second screening strategy aims at the detection of established CHD, even in its earliest stages. The currently available recommendations and guidelines for screening for the presence of cardiovascular risk factors in the general, non–HIV-infected population are detailed in Table 1.1–7 View this table: Table 1. Recommendations and Guidelines for Screening for Cardiovascular Risk Factors in the General Population The currently available recommendations and guidelines for screening for the presence of CVD risk factors in persons with HIV infection are detailed in Table 2. These recommendations take into account the evidence for dyslipidemia, insulin resistance, and changes in body fat distribution that have been shown to occur …

Contribution of metabolic and anthropometric abnormalities to cardiovascular disease risk factors.

Patients with human immunodeficiency virus (HIV) infection have sustained alterations in metabolism (lipids and insulin/glucose homeostasis) and body composition (fat distribution) that are proatherogenic (the Figure). HIV infection itself and/or its therapies may contribute to these alterations (the Table); although most effects are reversible, there are some possibly irreversible consequences of treatment. With the relative restoration to health seen in the era of highly active antiretroviral therapy (HAART), many traditional risk factors and promoters of dyslipidemia and diabetes also are present; they interact with HIV-specific inducers to worsen dyslipidemia and to increase the prevalence of insulin resistance and diabetes. Figure. Overview of the effects of HIV and its therapies on CVD risk. The contribution of traditional risk factors must be kept in mind, and they may occur with increased prevalence in people with HIV infection (eg, smoking). HIV, likely through the inflammatory response, and antiretroviral therapies independently affect many of the mediators of CVD risk. The effects on lipids are a prominent but complex example; HIV infection lowers LDL levels, but antiretroviral therapy raises LDL back up to normal levels. The bidirectional arrows indicate associations, but there is not yet adequate proof of causality. The dotted arrow between body composition and CVD indicates that body fat is known to affect the mediators such as dyslipidemia and insulin resistance but may also have a direct effect. FFA indicates free fatty acids; ARV, antiretroviral. View this table: Table. Effects of HIV Treatment These disturbances in lipid and glucose metabolism and renal disease may contribute, at least in part, to the excess cardiovascular disease (CVD) morbidity and mortality observed in HIV-infected individuals (the Figure). However, the relative contribution to excess CVD risk of traditional CVD risk factors, especially smoking, compared with these infection- and treatment-specific complications requires clarification. More prospective data with multivariable modeling are needed. …

Epidemiological evidence for cardiovascular disease in HIV-infected patients and relationship to highly active antiretroviral therapy.

In the mid-1990s, case reports of myocardial infarction (MI) in young patients infected with human immunodeficiency virus (HIV) sparked interest in the relationship between HIV infection and cardiovascular disease (CVD).1,2 Although the initial focus was primarily on the relationship between dyslipidemia associated with antiretroviral therapy (ART) and cardiovascular risk, a broader appreciation of the complex interplay between traditional risk factors for CVD and HIV infection has emerged more recently. Several groups of investigators have designed studies to examine various aspects of the relationship between HIV infection, traditional cardiovascular risk factors, ART, and short- and longer-term cardiovascular risk3–11 (see also Working Group 1). Studies have included both clinical end points (MI, hospitalization for MI or angina, and revascularization) and surrogate markers of atherosclerosis (endothelial function or carotid intima-media thickness). Successive studies have generally improved in quality, with inclusion of data on traditional risk factors, longer follow-up, and more diverse patient populations. HIV and ART can contribute to an altered risk of CVD in 3 principal ways: (1) HIV may serve as a marker to identify a subgroup of the general population with an altered prevalence of traditional cardiovascular risk factors, unrelated to HIV or ART (eg, HIV-infected patients may have higher smoking rates); (2) HIV or ART may affect the risk of developing a traditional cardiovascular risk factor (eg, HIV or ART may worsen dyslipidemia); and (3) HIV or ART may affect the pathogenetic process that leads to CVD in ways other than via an effect on traditional risk factors (eg, through effects on inflammation or endothelial function). Importantly, there is substantial evidence to suggest that all 3 mechanisms are in operation and affect the risk of CVD in patients infected with HIV. All 3 factors should be considered in epidemiological studies assessing the relationship between CVD and HIV …

Effectiveness of lipid-lowering therapy in HIV patients

The aim of this article is to analyse the effectiveness of lipid-lowering therapy in HIV-infected patients. Although data on prevention of cardiovascular disease in HIV-infected patients are limited, available evidence suggests that intervention guidelines should be similar to those that are recommended for the general population. The main target of lipid-lowering therapy is LDL cholesterol; therefore statins are the drugs of choice. The efficacy of statins in HIV-infected persons appears to be lower than expected, although adherence to statin therapy has not been well assessed. Statins combining high potency and little clinically meaningful interactions with antiretroviral therapy (pravastatin, fluvastatin, atorvastatin and rosuvastatin) should be preferred as initial therapy, though comparative studies in HIV-infected persons are scarce. A combination of a statin at medium doses with either ezetimibe or a fibrate other than gemfibrozil may result in more satisfactory results than higher doses of statin monotherapy when LDL cholesterol goals are difficult to achieve or there persist elevated triglycerides and low HDL cholesterol, respectively. Adequate choice and dosing of lipid-lowering drugs, given as isolated agents or in combination therapy, and care for good drug compliance in HIV-infected patients at moderate or high cardiovascular risk should help maximize their long-term health.

Cardiovascular disease in HIV-infected patients: does HIV infection in and of itself increase cardiovascular risk?

Cardiovascular disease is increasingly recognized to be a significant cause of morbidity and mortality among patients with chronic HIV infection in the current era of effective antiretroviral therapy. HIV-infected patients treated with antiretroviral therapy have increased traditional cardiovascular risk factors, but whether HIV infection in and of itself confers a significant increase in cardiovascular risk is largely unknown. This review summarizes recent data investigating cardiovascular risk in HIV patients and the evidence for an effect of HIV per se. The potential physiological mechanisms by which HIV might contribute to coronary artery disease are reviewed. Several interesting studies in the last year have evaluated cardiovascular endpoints and surrogate measures such as carotid intima-media thickness and endothelial function in HIV-infected patients compared with uninfected control groups. Several studies to date using surrogate measurements such as carotid intima-media thickness and endothelial dysfunction suggest a possible independent HIV effect on cardiovascular risk, but some studies have yielded conflicting results. Numerous potential mechanisms by which HIV might contribute to coronary artery disease exist. These mechanisms include effects of HIV proteins to attract monocytes to the intimal wall, and impair cholesterol efflux, and effects of activated monocytes to induce an inflammatory response. More definitive prospective studies are needed to fully answer whether HIV infection per se promotes cardiovascular disease, but ample evidence suggests that HIV and related inflammatory responses could contribute to increased cardiovascular disease.

Cryptogenic liver disease in hiv infected patients treated with anti-retroviral drugs

Cryptogenic liver disease in hiv infected patients treated with anti-retroviral drugs

Intérêt de l’imagerie nucléaire pour l’infectiologue

Nuclear imaging could be helpful for infections diseases specialists in search for bone or joint and endovascular septic foci (with or without foreign body) but also for various metastatic infectious locations and for exploring fever of unknown origin (FUO), especially in HIV-infected patients. In this paper, the interest of “conventional” scintigraphic methods (labeled leukocyte and gallium scintigraphy) and positron emission tomography coupled with fluorodeoxyglucose (FDG–PET) for the diagnosis of endovascular infections (especially those associated with foreign body) and some opportunistic diseases in HIV-infected patients (especially those presenting central nervous system involvement and FUO) will be discussed. Then other potential areas of isotopic investigations will be briefly listed; some of them, including bone and joint infections and FUO in the general population, will be presented in details in other papers in this issue.

Occult hepatitis B virus infection in HIV-infected Lebanese patients with isolated antibodies to hepatitis B core antigen

The presence of hepatitis B virus (HBV) serological markers have been investigated in 101 Lebanese patients (69 men, 32 women; mean age 32.7 +/- 1.7 years) infected with human immunodeficiency virus type 1 (HIV-1). Seven patients (6.9%) were HBsAg carriers compared with 54 patients (53.5%) who had no evidence of exposure to HBV infection. Twenty-four patients (23.8%) had anti-HBc alone as a serological marker compared with four patients who were positive for anti-HBs alone and 12 patients (11.9%) who were anti-HBc and anti-HBs-positive. Occult HBV infection (presence of HBV DNA in the absence of HBsAg) is found to be relatively high (28.7%) in HIV-infected Lebanese patients and the overwhelming majority (83.3%) of those who were positive for anti-HBc alone had a detectable HBV DNA in their serum. However, none of our HIV-positive patients with occult HBV infection had abnormal alanine aminotransferase level, which also raises the question as to whether occult HBV plays a role in the aetiology of liver disease in HIV-infected patients. Further, studies on the association between HBV DNA levels and markers of liver function in addition to data on liver biopsy would help in answering this question.

Immune Reconstitution and “Unmasking” of Tuberculosis during Antiretroviral Therapy

Tuberculosis (TB) is the most common opportunistic disease in HIV-infected patients during the initial months of antiretroviral therapy (ART) and presents a great challenge to ART programs in resource-limited settings. The mechanisms underlying development of TB in this period are complex. Some cases may represent progression of undiagnosed subclinical disease present before starting ART, emphasizing the importance of careful screening strategies for TB. It has been suggested that progression in such cases is due to immune reconstitution disease-a phenomenon in which dysregulated restoration of pathogen-specific immune responses triggers the presentation of subclinical disease. However, whereas some cases have exaggerated or overtly inflammatory manifestations consistent with existing case definitions for IRD, many others do not. Moreover, since ART-induced immune recovery is a time-dependent process, active TB may develop as a consequence of persisting immunodeficiency. All these mechanisms are likely to be important, representing a spectrum of complex interactions between mycobacterial burden and changing host immune response. We propose that the potential range of effects of ART includes (1) shortening of the time for subclinical TB to become symptomatic (a phenomenon often referred to as "unmasking"), (2) increased rapidity of initial onset of TB symptoms, and (3) heightened intensity of clinical manifestations. We suggest that the term "ART-associated TB" be used to refer collectively to all cases of TB presenting during ART and that "immune reconstitution disease" be used to refer to the subset of ART-associated TB cases in which the effect on disease severity results in exaggerated and overtly inflammatory disease.

Observations on a Cohort of HIV-Infected Patients Undergoing Native Renal Biopsy

Aims: This study aims to explore the spectrum of renal disease in HIV-infected patients, identify clinical predictors of HIV-associated nephropathy (HIVAN), and investigate the performance of renal biopsy in HIV-infected patients. Method: Of 263 HIV-infected patients with renal disease evaluated between 1995 and 2004, 152 had a renal biopsy, while 111 had not. A group comparison was performed. Results: The leading biopsy diagnoses were HIVAN (35%), noncollapsing focal segmental glomerulosclerosis (22%), and acute interstitial nephritis (7.9%), amongst over a dozen others. There was a trend of decreasing yearly incidence of HIVAN diagnoses, paralleling the use of antiretroviral therapy. By multivariate logistic regression, CD4 counts >200 cells/mm³ and higher estimated glomerular filtration rate were strong negative predictors of HIVAN. HIVAN patients were more likely to require dialysis (p < 0.0001) and had worse overall survival (p = 0.02). Younger age and lower estimated glomerular filtration rate were significant predictors of renal biopsy in multivariate regression analysis. More biopsied patients progressed to dialysis (51 vs. 25%, p = 0.001) and death (15 vs. 5.4%, p = 0.001), despite more frequent corticosteroid treatment (29 vs. 3.6%, p = 0.001). Conclusion: These findings may reflect more severe acute and/or chronic disease at the time of biopsy and suggests that earlier renal biopsy may be warranted in HIV-infected patients, especially in light of the changing spectrum of renal disease in this group.

Low Prevalence of Peripheral Arterial Disease in HIV-Infected Patients With Multiple Cardiovascular Risk Factors

To the Editor: There is an increasing awareness that cardiovascular disease (CVD) is augmented in HIV-infected patients.1 Lower-extremity peripheral arterial disease (PAD) is a powerful indicator of systemic atherosclerosis and a strong predictor of death from cardiovascular causes,2 equivalent to that of patients with coronary or cerebrovascular disease. However, to date, no studies have evaluated PAD in HIV-infected patients. To estimate the prevalence of PAD, we measured the ankle-brachial index (ABI) in a population of HIV-infected patients with 2 or more cardiovascular risk factors. A prospective cross-sectional study was performed at the HIV clinic of the University Hospital of Elche, Spain. HIV-infected patients with 2 or more traditional cardiovascular risk factors3 cared for in the clinic from January 2006 to January 2007 were invited to enroll in the study. The investigation was approved by the Ethics Committee for Clinical Research. Ninety-one (81.2%) of 112 patients with 2 or more traditional cardiovascular risk factors gave their informed consent to participate. Clinical and laboratory data were obtained at the visit. To calculate the ABI, systolic arterial pressure (SAP) in both arms and legs (posterior tibial and dorsalis pedis arteries) was taken with the blood pressure cuff and a Doppler probe (Smartdop 30; Hayashi Denki, Kawasaki, Japan) in supine. The highest readings were used to calculate the ABI of each leg, and the lowest ABI values were used to assess PAD. To define PAD, a cutpoint of <0.9 in either leg was used.4 Demographic and clinical characteristics of the patients are shown in Table 1. Thirty-three (36.3%) patients had 3 cardiovascular risk factors, and 26 (28.6%) had 4 or more. Low (<0.9) ABI was present in 4 (4.39%; 95% confidence interval [CI]: 1.41 to 11.49) patients. Patients with low ABI were males older than 45 years (median: 55.1; range: 48 to 73). Three patients were on antiretroviral therapy, 2 with protease inhibitor (PI)-based regimens and 1 with nonnucleoside reverse transcriptase inhibitors (NNRTIs), and all had previous exposure to PIs. Lipodystrophy was present in 3 patients and lipoatrophy in 2. Three patients had 3 or more cardiovascular risk factors, mainly dyslipidemia, smoking, hypertension, and family history of early coronary heart disease. Framingham score was moderate (10% to 20%) in 2 patients and high (>20%) in 1 patient. Two of the patients developed a heart attack a few months after this cross-sectional study was carried out.TABLE 1: Demographic and Clinical Characteristics of 91 HIV-Infected PatientsThis is the first study evaluating asymptomatic PAD in HIV-infected patients. We used the ABI, a validated, simple, and inexpensive diagnostic test, which is currently considered the method of choice to identify lower-extremity PAD.2 Our results show a low prevalence of peripheral artery damage in a cohort of HIV-infected patients with several cardiovascular risk factors. In the general population, the prevalence of PAD ranges from 5% to 30%, mainly depending on the age of the patients and the presence of cardiovascular risk factors,5,6 but most of the studies evaluated patients older than those included in the current investigation. A higher prevalence of PAD in HIV-infected patients is expected as patients get older. Despite the low prevalence found in the study, assessing PAD might be useful as an adjunct to estimate overall cardiovascular risk in HIV-infected patients with several risk factors. In addition to being a marker of systemic atherosclerosis, PAD is associated with a high frequency of fatal and nonfatal cardiovascular disease events.2 Awareness of PAD elevates asymptomatic patients to a higher risk category and justifies intense therapeutic intervention in primary prevention, equivalent to that of secondary prevention. Enrique Bernal, MD* Mar Masiá, MD* Sergio Padilla, MD* Ildefonso Hernández, MD† Félix Gutiérrez, MD* *Infectious Diseases Unit Hospital General Universitario de Elche Universidad Miguel Hernández Elche, Spain †Public Health Department Universidad Miguel Hernández Elche, Spain

Carotid intima media thickness with no cardiovascular disease in HIV-infected patients correlates with a hyperactivated/pro-apoptotic T-cell phenotype

Background HIV-infected patients may be at increased risk of cardiovascular disease (CVD), and present higher carotid intima media thickness (IMT) compared with healthy controls. Besides clinical and metabolic factors, atherosclerosis in HIV is influenced by immune and inflammatory parameters. Given that T-cell activation correlates with CVD and HIV accounts for heightened T-cell hyperactivation, we hypothesized that early IMT increases associate to T-cell hyperactivation.

Subclinical kidney disease in HIV-infected patients

Method A cross-sectional study was carried out in the HIV-Unit at a University Hospital in Barcelona, Spain. All patients were 20 years of age or older. A screening was made to detect the patients in stage I and II according to the K/ DOQI Clinical Practice for Guidelines Chronic Kidney [1]. Estimated glomerular filtration rate (EGFR) was ascertained according to the Modification of Diet in Renal Disease formula (MDRD-4). Glomerular damage (proteinuria and/or haematuria) was determined by dipstick, sequential urinalysis was made in 3 consecutive months, when proteinuria was detected to confirm the result the albumin/creatinine ratio (ACR) was determined, microalbuminuria was defined as ACR > 3 mg/ mmol.

Management of end-stage liver disease in HIV-infected patients

This review provides information on the natural history of end-stage liver disease in HIV/hepatitis C virus-coinfected patients from diagnosis to liver transplantation or death and summarizes recent developments in the epidemiology, management, and prognosis of end-stage liver disease and orthotopic liver transplantation in this population compared with the HIV-negative population. Many studies have described epidemiological aspects, including the increasing incidence of end-stage liver disease, as a cause of non-AIDS-related death in the co-infected population in developed countries, whereas other reports have focused on the clinical presentation and prognosis of end-stage liver disease in this specific clinical setting. The medical management of end-stage liver disease should be the same as for the HIV-negative population, and orthotopic liver transplantation is the only therapeutic option for HIV-infected patients who are eligible for this procedure. End-stage liver disease is becoming a major issue in the HIV/HCV-coinfected population because of its increasing frequency, especially now the prognosis of HIV infection has improved with combined antiretroviral therapy. Medical management is essential and should be considered a bridge to orthotopic liver transplantation. Nevertheless, many issues remain unclear and must be examined in further studies.

Association between sputum smear status and local immune responses at the site of disease in HIV-infected patients with pulmonary tuberculosis

Infection with human immunodeficiency virus (HIV) may affect the clinical presentation of pulmonary tuberculosis (TB). To investigate the association between sputum smear status at presentation and local pulmonary immune responses in HIV-infected patients with pulmonary TB, we compared the cellular and cytokine profiles in bronchoalveolar lavage (BAL) fluid obtained from the site of lung disease in 22 sputum smear- and culture-positive, and 17 sputum smear-negative but culture-positive pulmonary TB patients. Smear-positive patients had significantly higher BAL fluid concentrations of IL-6 (p=0.007), IL-8 (p=0.02), IL-10 (p=0.03) and IFN-gamma (p=0.008) than smear-negative patients. No significant differences in the proportions of examined BAL cells were found. We concluded that sputum smear-positive TB was associated with greater pro-inflammatory and immunomodulatory cytokine responses at the site of lung disease than sputum smear-negative disease. The local immune responses may affect the clinical presentation of active pulmonary TB in HIV-infected patients.

Hypertension portale chez un malade coinfecté par le virus de l’immunodéficience humaine et le virus de l’hépatite C

The case of a human immunodeficiency virus (HIV) and hepatitis C virus (HCV)-coinfected patient with a medical history of deep venous thrombosis is presented. A liver biopsy, performed for unexpected portal hypertension, showed vascular lesions presenting as nodular regenerative hyperplasia. Vascular liver diseases seem to be a new cause of chronic liver disease in HIV-infected patients receiving combined antiretroviral therapy. The syndrome of HIV-associated liver vasculopathy is discussed.

Can the Risk of Cardiovascular Disease in HIV-Infected Patients Be Estimated from Conventional Risk Prediction Tools?

Can the Risk of Cardiovascular Disease in HIV-Infected Patients Be Estimated from Conventional Risk Prediction Tools?

Aspergillus galactomannan antigenemia in penicilliosis marneffei

Penicillium marneffei usually causes pneumonia and other systemic diseases in HIV-infected patients, especially those who live in or travel to endemic areas [1]. In recent years, this organism has emerged in Taiwan among immunocompromised patients, particularly in HIV-infected patients in whom aspergillosis was rarely encountered [2]. The detection of galactomannan by the Platelia enzyme-linked immunosorbent assay (ELISA; Bio-Rad, Hercules, California, USA) has been widely used in diagnosing invasive aspergillosis [3]. False positives have been identified in patients receiving certain batches of piperacillin–tazobactam, amoxicillin–clavulanic acid [4,5]. In-vitro cross-reactivity of the Platelia ELISA with Penicillium galactomannan and Cryptococcus galactoxylomannan have been reported, and this cross-reactivity has also been reported in a human case with penicilliosis marneffei [6–8]. Patient A, a 47-year-old male heroin abuser with HIV infection, was referred with cough and fever lasting for one month. The blood culture at admission revealed Mycobacterium avium-intracellulare complex. A chest computed tomography scan revealed a cavitation over the left lower lung field. The serum galactomannan sent for suspicious Aspergillosis was positive [optical density (OD) index 4.419] and bronchial washing culture on the next day revealed P. marneffei. His blood culture (Bactec 9240 Myco/F Lytic bottle; Becton Dickinson, Sparks, Maryland, USA) was negative for P. marneffei and the serum galactomannan OD index remained positive 33 days after treatment (OD index 6.527; Fig. 1).Fig. 1: Serial optical density index of serum galactomannan for three patients with penicilliosis marneffei. ♦ Patient A; ▪ patient B; ▴ patient C.Patient B was a 34-year-old man with HIV infection suffering from fever and dry cough for half a month. A chest radiograph revealed a patchy lesion over the right upper lung region. Blood culture at admission revealed P. marneffei. The serum galactomannan test before initiating amphotericin B treatment was positive (OD index 7.752) and remained positive 27 days after treatment when the blood culture was sterile (OD index 1.586). Patient C was a 39-year-old man with HIV infection known for 2 years with poor drug compliance. He was admitted for fever and diarrhea lasting for one month. The chest radiograph showed a ground glass lesion over the left perihilar area. Blood culture at admission revealed P. marneffei. The serum galactomannan test before starting amphotericin B treatment was positive (OD index 10.48) and remained positive 15 days after treatment when the blood culture was sterile (OD index 7.356). The initial CD4 cell counts of these three AIDS patients were 9, 30 and 4 cells/μl for patients A, B, and C, respectively. None of the three patients received piperacillin–tazobactam or amoxicillin–clavunalic acid during their hospital stay. All three patients were not neutropenic and survived the episodes of penicilliosis marneffei. No Aspergillus species was ever isolated from their sputum or any clinical specimens. The results confirm the cross-reactivity of the Platelia ELISA kit with P. marneffei and with serum from patients with penicilliosis marneffei, which remained positive even after effective treatment. The length of galactomannan antigenemia might have been caused by the possibly lower clearance rate of Penicillium galactomannan compared with Aspergillus galactomannan or the presence of Penicillium in the lesion, with a continuous secretion of galactomannan, which enters the bloodstream. The cross-reactivity could be used as a rapid diagnosis for penicilliosis marneffei, although the test was not performed before positive cultures for P. marneffei were obtained. Effective treatment does not, however, decrease the titer but instead remains positive, indicating that this test may not be useful for monitoring treatment outcomes.