Arbovirus, herpesvirus, and enterovirus associated with neurological syndromes in adult patients of a university hospital, 2017-2018.

INTRODUCTION: Herpesviruses, enteroviruses, and arboviruses are important because of their clinical relevance and ability to cause meningitis, encephalitis, meningoencephalitis, and other diseases. The clinical virology associated with diagnostic technologies can reduce the morbidity and mortality of such neurological manifestations. Here we aimed to identify the genomes of agents that cause neurological syndromes in cerebrospinal fluid (CSF) samples from patients with suspected nervous system infections admitted to the University Hospital of the University of Campinas, São Paulo, Brazil, in 2017-2018. METHODS: CSF samples collected from adult patients with neurological syndrome symptoms and negative CSF culture results were analyzed using polymerase chain reaction (PCR), reverse transcriptase-PCR, and real-time PCR, and their results were compared with their clinical symptoms. One CSF sample was obtained from each patient. RESULTS: Viral genomes were detected in 148/420 (35.2%) CSF samples: one of 148 (0.2%) was positive for herpes simplex virus-1; two (0.5%) for herpes simplex virus-2; eight (1.9%) for varicella-zoster virus; four (1%) for Epstein-Barr virus; one (0.2%) for cytomegalovirus; 32 (7.6%) for human herpesvirus-6; 30 (7.1%) for non-polio enterovirus; 67 (16.0%) for dengue virus, three (0.7%) for yellow fever virus, and 21 (5%) for Zika virus. CONCLUSIONS: The viral genomes were found in 35.2% of all analyzed samples, showing the high prevalence of viruses in the nervous system and the importance of using a nucleic acid amplification test to detect viral agents in CSF samples.

Arbovirus, herpesvirus, and enterovirus associated with neurological syndromes in adult patients of a university hospital, 2017-2018

Abstract INTRODUCTION: Herpesviruses, enteroviruses, and arboviruses are important because of their clinical relevance and ability to cause meningitis, encephalitis, meningoencephalitis, and other diseases. The clinical virology associated with diagnostic technologies can reduce the morbidity and mortality of such neurological manifestations. Here we aimed to identify the genomes of agents that cause neurological syndromes in cerebrospinal fluid (CSF) samples from patients with suspected nervous system infections admitted to the University Hospital of the University of Campinas, São Paulo, Brazil, in 2017-2018. METHODS: CSF samples collected from adult patients with neurological syndrome symptoms and negative CSF culture results were analyzed using polymerase chain reaction (PCR), reverse transcriptase-PCR, and real-time PCR, and their results were compared with their clinical symptoms. One CSF sample was obtained from each patient. RESULTS: Viral genomes were detected in 148/420 (35.2%) CSF samples: one of 148 (0.2%) was positive for herpes simplex virus-1; two (0.5%) for herpes simplex virus-2; eight (1.9%) for varicella-zoster virus; four (1%) for Epstein-Barr virus; one (0.2%) for cytomegalovirus; 32 (7.6%) for human herpesvirus-6; 30 (7.1%) for non-polio enterovirus; 67 (16.0%) for dengue virus, three (0.7%) for yellow fever virus, and 21 (5%) for Zika virus. CONCLUSIONS: The viral genomes were found in 35.2% of all analyzed samples, showing the high prevalence of viruses in the nervous system and the importance of using a nucleic acid amplification test to detect viral agents in CSF samples.

Correction to: Active human herpesvirus infections in adults with systemic lupus erythematosus and correlation with the SLEDAI score.

An amendment to this paper has been published and can be accessed via the original article.

Active human herpesvirus infections in adults with systemic lupus erythematosus and correlation with the SLEDAI score.

BACKGROUND: Human herpesviruses (HHVs) are responsible for a significant number of clinical manifestations in systemic lupus erythematous (SLE) patients. The aim of this study was to determine the frequency of active HHV infections in SLE patients and correlating them with disease activity. METHODS: Serum samples were collected from 71 SLE patients and their DNAs were extracted and analyzed to detect HHV-DNA viruses using the nucleic acid amplification technique. RESULTS: Fifteen out of the 71 (21.1%) patients tested positive for the HHV-DNA virus. Of them, 11/15 HHV-DNA-positive patients (73.3%) had SLE activity index (SLEDAI - Systemic Lupus Erythematosus Disease Activity Index) ≥8 (p = 0.0001). Active HCMV infection was the mostly frequently observed infection, occurring in 6/15 patients (40%). The frequencies of other active viral infections were 22% for HSV-1, 16.7% for HHV-7, and 5.5% for HSV-2. Viral coinfection (two or more viruses detected in the same sample) occurred in three patients (16.7%). Active HHV infections in SLE patients are more frequent in those with active SLE (≥8), who is at high risk of HHV reactivation and HCMV disease. CONCLUSION: Viral surveillance is important to identify active HHV infections that can cause clinical symptoms and other complication in SLE patients.

Active human herpesvirus infections in adults with systemic lupus erythematosus and correlation with the SLEDAI score

Abstract Background: Human herpesviruses (HHVs) are responsible for a significant number of clinical manifestations in systemic lupus erythematous (SLE) patients. The aim of this study was to determine the frequency of active HHV infections in SLE patients and correlating them with disease activity. Methods: Serum samples were collected from 71 SLE patients and their DNAs were extracted and analyzed to detect HHV-DNA viruses using the nucleic acid amplification technique. Results: Fifteen out of the 71 (21.1%) patients tested positive for the HHV-DNA virus. Of them, 11/15 HHV-DNA-positive patients (73.3%) had SLE activity index (SLEDAI - Systemic Lupus Erythematosus Disease Activity Index) ≥8 (p = 0.0001). Active HCMV infection was the mostly frequently observed infection, occurring in 6/15 patients (40%). The frequencies of other active viral infections were 22% for HSV-1, 16.7% for HHV-7, and 5.5% for HSV-2. Viral coinfection (two or more viruses detected in the same sample) occurred in three patients (16.7%). Active HHV infections in SLE patients are more frequent in those with active SLE (≥8), who is at high risk of HHV reactivation and HCMV disease. Conclusion: Viral surveillance is important to identify active HHV infections that can cause clinical symptoms and other complication in SLE patients.

Synergistic effect of KIR ligands missing and cytomegalovirus reactivation in improving outcomes of haematopoietic stem cell transplantation from HLA-matched sibling donor for treatment of myeloid malignancies.

The goal of this study was to evaluate the influence of KIR-HLA genotypes on the outcome of patients undergoing treatment for haematological malignancies by non-T-depleted lymphocyte haematopoietic stem cell transplantation (HSCT) from HLA-matched sibling donors. The prospective study was conducted at the Center of Hematology, University of Campinas, and 50 patients and their donors were followed up from 2008 to 2014. KIR and HLA class I genes were genotyped and patients grouped based on the presence of KIR ligands combined with KIR genotype of their respective donors. Patients with all KIR ligands present (n=13) had a significantly higher (p=0.04) incidence of acute graft-versus-host-disease (GVHD) than patients with one or more KIR ligands missing (n=37). The overall survival following transplantation of patients with myeloid malignancies (n=27) was significantly higher (p=0.035) in the group with one or more KIR ligands missing (n=18) than in the group with all ligands present (n=9). Presence of KIR2DS2 was associated with a worsening of HSCT outcome while reactivation of cytomegalovirus (CMV) infection improved the outcome of patients with one or more KIR ligands missing. Our results indicate that KIR-HLA interactions affect the outcome of the HLA-matched transplantation, particularly in patients with myeloid malignancies.

The prevalence of adenoviral conjunctivitis at the Clinical Hospital of the State University of Campinas, Brazil.

OBJECTIVES: Viral conjunctivitis is a common, highly contagious disease that is often caused by an adenovirus. The aim of this study was to evaluate the prevalence of adenoviral conjunctivitis by analyzing data from a prospective clinical study of 122 consecutively enrolled patients who were treated at the Clinical Hospital of the State University of Campinas (UNICAMP) after a clinical diagnosis of infectious conjunctivitis between November 2011 and June 2012. METHODS: Polymerase chain reaction was used to evaluate all cases of clinically diagnosed infectious conjunctivitis and based on the laboratory findings, the prevalence of adenoviral infections was determined. The incidence of subepithelial corneal infiltrates was also investigated. RESULTS: Of the 122 patients with acute infectious conjunctivitis included, 72 had positive polymerase chain reaction results for adenoviruses and 17 patients developed subepithelial corneal infiltrates (13.93%). CONCLUSIONS: The polymerase chain reaction revealed that the prevalence of adenoviral conjunctivitis was 59% in all patients who presented with a clinical diagnosis of infectious conjunctivitis from November 2011 to June 2012. The prevalence of adenoviral conjunctivitis in the study population was similar to its prevalence in other regions of the world.

The prevalence of adenoviral conjunctivitis at the Clinical Hospital of the State University of Campinas, Brazil

OBJECTIVES: Viral conjunctivitis is a common, highly contagious disease that is often caused by an adenovirus. The aim of this study was to evaluate the prevalence of adenoviral conjunctivitis by analyzing data from a prospective clinical study of 122 consecutively enrolled patients who were treated at the Clinical Hospital of the State University of Campinas (UNICAMP) after a clinical diagnosis of infectious conjunctivitis between November 2011 and June 2012. METHODS: Polymerase chain reaction was used to evaluate all cases of clinically diagnosed infectious conjunctivitis and based on the laboratory findings, the prevalence of adenoviral infections was determined. The incidence of subepithelial corneal infiltrates was also investigated. RESULTS: Of the 122 patients with acute infectious conjunctivitis included, 72 had positive polymerase chain reaction results for adenoviruses and 17 patients developed subepithelial corneal infiltrates (13.93%). CONCLUSIONS: The polymerase chain reaction revealed that the prevalence of adenoviral conjunctivitis was 59% in all patients who presented with a clinical diagnosis of infectious conjunctivitis from November 2011 to June 2012. The prevalence of adenoviral conjunctivitis in the study population was similar to its prevalence in other regions of the world.

Human herpesvirus infections of the central nervous system: laboratory diagnosis based on DNA detection by nested PCR in plasma and cerebrospinal fluid samples.

Infections of the central nervous systems (CNS) present a diagnostic problem for which an accurate laboratory diagnosis is essential. Invasive practices, such as cerebral biopsy, have been replaced by obtaining a polymerase chain reaction (PCR) diagnosis using cerebral spinal fluid (CSF) as a reference method. Tests on DNA extracted from plasma are noninvasive, thus avoiding all of the collateral effects and patient risks associated with CSF collection. This study aimed to determine whether plasma can replace CSF in nested PCR analysis for the detection of CNS human herpesvirus (HHV) diseases by analysing the proportion of patients whose CSF nested PCR results were positive for CNS HHV who also had the same organism identified by plasma nested PCR. In this study, CSF DNA was used as the "gold standard," and nested PCR was performed on both types of samples. Fifty-two patients with symptoms of nervous system infection were submitted to CSF and blood collection. For the eight HHV, one positive DNA result-in plasma and/or CSF nested PCR-was considered an active HHV infection, whereas the occurrence of two or more HHVs in the same sample was considered a coinfection. HHV infections were positively detected in 27/52 (51.9%) of the CSF and in 32/52 (61.5%) of the plasma, difference not significant, thus nested PCR can be performed on plasma instead of CSF. In conclusion, this findings suggest that plasma as a useful material for the diagnosis of cases where there is any difficulty to perform a CSF puncture.

Dexamethasone/Povidone Eye Drops versus Artificial Tears for Treatment of Presumed Viral Conjunctivitis: A Randomized Clinical Trial.

PURPOSE: To determine whether topical dexamethasone 0.1%/povidone-iodine 0.4% reduces the duration of presumed viral conjunctivitis better than artificial tears and whether the treatment relieves the symptoms of this disease. METHODS: Randomized, masked and controlled trial. One-hundred twenty-two patients with a clinical diagnosis of presumed viral conjunctivitis were randomized to either the treatment group or the control group. Physicians and patients were masked to the treatment. Swabs were taken from the conjunctival fornix for adenovirus PCR analyses. Patients in the treatment group received topical dexamethasone 0.1%/povidone-iodine 0.4% eye drops four times daily, and patients in the placebo group received artificial tears four times daily, both for seven days. Symptoms were recorded on the day of recruitment and at the time of a follow-up examination 5, 10 and 30 d later. The main outcome was duration of the disease. The others outcomes were overall discomfort, itching, foreign body sensation, tearing, redness, eyelid swelling, side effects of the eye drops, intraocular pressure and the incidence of subepithelial corneal infiltrates. RESULTS: There was no statistically significant difference between the treatment group and the control group in terms of the patients' symptoms, intraocular pressure and incidence of subepithelial cornea infiltrates during the entire follow-up period. Patients of the treatment group reported more stinging (p < 0.001) and a shorter conjunctivitis duration (9.4 ± 4.6 d in the dexamethasone 0.1%/povidone-iodine 0.4% group versus 11.8 ± 4.9 d in the artificial tears group, p = 0.009). CONCLUSIONS: The use of topical dexamethasone 0.1%/povidone-iodine 0.4% eye drops four times daily appears to reduce the duration of conjunctivitis, although it causes more stinging than artificial tears.

PCR-Based Detection and Genotyping of Helicobacter pylori in Endoscopic Biopsy Samples from Brazilian Patients.

Helicobacter pylori (H. pylori) is considered the second most prevalent infection in man. A precise diagnosis is important for treating patients with the indicative gastrointestinal symptoms. The present study analyzes the effectiveness of a molecular biology method (PCR) comparing the results obtained with the histology and with the rapid urease tests. PCR was used in the detection and genotyping of the H. pylori urease-C gene and the patterns which were obtained from the patients studied. 141 biopsy samples from 131 patients were evaluated. 59 paraffin biopsies samples were positive for H. pylori according to the histological examination. Of those, 59/12 (20.3%) were amplified using PCR. Of the 82 samples from the fresh biopsies, 64 were positive for H. pylori according to the rapid urease test (78%); there was an agreement of 100% with PCR. Sixty positive H. pylori samples were genotyped (58 samples of fresh biopsies and 2 samples of paraffin biopsies) using two restriction enzymes. The patterns observed were analyzed with the computational program BIO 1D; 11 patterns with the enzyme HhaI and 12 patterns with the enzyme MboI were found. However, it was not possible to find a statistically significant correlation between the specific genotypes and digestive pathologies. Accordingly, future research should be performed to confirm a statistically significant relationship between genotyping and gastrointestinal symptoms.

Simultaneous monitoring of CMV and human herpesvirus 6 infections and diseases in liver transplant patients: one-year follow-up.

OBJECTIVE: The aim of this study was to simultaneously monitoring cytomegalovirus and human herpesvirus 6 active infections using nested-polymerase chain reaction and, together with clinical findings, follow the clinical status of patients undergoing liver transplant. INTRODUCTION: The human ß-herpesviruses, including cytomegalovirus and human herpesvirus 6, are ubiquitous among human populations. Active infections of human herpesvirus 6 and cytomegalovirus are common after liver transplantation, possibly induced and facilitated by allograft rejection and immunosuppressive therapy. Both viruses affect the success of the transplant procedure. METHODS: Thirty patients submitted to liver transplant at the Liver Transplant Unit, at the Gastro Center, State University of Campinas, SP, Brazil, were studied prospectively from six months to one year, nested-polymerase chain reaction for cytomegalovirus and human herpesvirus 6 DNA detections. Two or more consecutive positive nested-polymerase chain reaction were considered indicative of active infection. RESULTS: Active infection by cytomegalovirus was detected in 13/30 (43.3%) patients, median time to first cytomegalovirus detection was 29 days after transplantation (range: 0-99 days). Active infection by human herpesvirus 6 was detected in 12/30 (40%) patients, median time to first human herpesvirus 6 detection was 23.5 days after transplantation (range: 0-273 days). The time-related appearance of each virus was not statistically different (p = 0.49). Rejection of the transplanted liver was observed in 16.7% (5/30) of the patients. The present analysis showed that human herpesvirus 6 and/or cytomegalovirus active infections were frequent in liver transplant recipients at our center. CONCLUSIONS: Few patients remain free of betaherpesviruses after liver transplantation. Most patients presenting active infection with more than one virus were infected sequentially and not concurrently. Nested-polymerase chain reaction can be considered of limited value for clinically monitoring cytomegalovirus and human herpesvirus 6.

Simultaneous monitoring of CMV and human herpesvirus 6 infections and diseases in liver transplant patients: one-year follow-up

OBJECTIVE: The aim of this study was to simultaneously monitoring cytomegalovirus and human herpesvirus 6 active infections using nested-polymerase chain reaction and, together with clinical findings, follow the clinical status of patients undergoing liver transplant. INTRODUCTION: The human β-herpesviruses, including cytomegalovirus and human herpesvirus 6, are ubiquitous among human populations. Active infections of human herpesvirus 6 and cytomegalovirus are common after liver transplantation, possibly induced and facilitated by allograft rejection and immunosuppressive therapy. Both viruses affect the success of the transplant procedure. METHODS: Thirty patients submitted to liver transplant at the Liver Transplant Unit, at the Gastro Center, State University of Campinas, SP, Brazil, were studied prospectively from six months to one year, nested-polymerase chain reaction for cytomegalovirus and human herpesvirus 6 DNA detections. Two or more consecutive positive nested-polymerase chain reaction were considered indicative of active infection. RESULTS: Active infection by cytomegalovirus was detected in 13/30 (43.3 percent) patients, median time to first cytomegalovirus detection was 29 days after transplantation (range: 0-99 days). Active infection by human herpesvirus 6 was detected in 12/30 (40 percent) patients, median time to first human herpesvirus 6 detection was 23.5 days after transplantation (range: 0-273 days). The time-related appearance of each virus was not statistically different (p = 0.49). Rejection of the transplanted liver was observed in 16.7 percent (5/30) of the patients. The present analysis showed that human herpesvirus 6 and/or cytomegalovirus active infections were frequent in liver transplant recipients at our center. CONCLUSIONS: Few patients remain free of betaherpesviruses after liver transplantation. Most patients presenting active infection with more than one virus were infected sequentially and not concurrently. Nested-polymerase chain reaction can be considered of limited value for clinically monitoring cytomegalovirus and human herpesvirus 6.

Active human Cytomegalovirus infection and Glycoprotein B genotypes in Brazilian pediatric renal or hematopoietic stem cell transplantation patients

A prospective analysis of active Human Cytomegalovirus infection (HCMV) was conducted on 33 pediatric renal or hematopoietic stem cell post-transplant patients. The HCMV-DNA positive samples were evaluated for the prevalence of different gB subtypes and their subsequent correlation with clinical signs. The surveillance of HCMV active infection was based on the monitoring of antigenemia (AGM) and on a nested polymerase chain reaction (N-PCR) for the detection of HCMV in the patients studied. Using restriction analysis of the gB gene sequence by PCR-RFLP (Restriction Fragment Length Polymorphism), different HCMV strains could be detected and classified in at least four HCMV genotypes. Thirty-three pediatric recipients of renal or bone marrow transplantation were monitored. Twenty out of thirty-three (60.6 percent) patients demonstrated active HCMV infection. gB1 and gB2 genotypes were more frequent in this population. In this study, we observed that gB2 had correlation with reactivation of HCMV infection and that patients with mixture of genotypes did not show any symptoms of HCMV disease. Future studies has been made to confirm this.

Active human cytomegalovirus infection and glycoprotein b genotypes in brazilian pediatric renal or hematopoietic stem cell transplantation patients.

A prospective analysis of active Human Cytomegalovirus infection (HCMV) was conducted on 33 pediatric renal or hematopoietic stem cell post-transplant patients. The HCMV-DNA positive samples were evaluated for the prevalence of different gB subtypes and their subsequent correlation with clinical signs. The surveillance of HCMV active infection was based on the monitoring of antigenemia (AGM) and on a nested polymerase chain reaction (N-PCR) for the detection of HCMV in the patients studied. Using restriction analysis of the gB gene sequence by PCR-RFLP (Restriction Fragment Length Polymorphism), different HCMV strains could be detected and classified in at least four HCMV genotypes. Thirty-three pediatric recipients of renal or bone marrow transplantation were monitored. Twenty out of thirty-three (60.6%) patients demonstrated active HCMV infection. gB1 and gB2 genotypes were more frequent in this population. In this study, we observed that gB2 had correlation with reactivation of HCMV infection and that patients with mixture of genotypes did not show any symptoms of HCMV disease. Future studies has been made to confirm this.

Restriction fragment length polymorphism of urease C and urease B genes of Helicobacter pylori strains isolated from Brazilian patients with peptic ulcer and chronic gastritis.

The aim of the present work is to identify the presence of Helicobacter pylori bacterium in samples of gastric mucosa fragments, obtained by gastric biopsy, from Brazilian patients with peptic ulcer and chronic gastritis and also to determine differences among the prevalent strains in these two diseases by urease C and urease B genes amplification utilizing nested polymerase chain reaction (PCR) and PCR. We encountered 17 genotyping patterns for urease C and 7 for urease B and, although no significant differences were found among the patterns encountered for both diseases, we found predominant groups for each disease. Typing methods of the products obtained by nested PCR and PCR show a functional scheme and are of great importance for epidemiologic studies and H. pylori strain characterization, in addition to allowing correlation among the several strains and their role in the diseases caused by this microorganism.

Detection of human herpesvirus-7 by qualitative nested-PCR: comparison between healthy individuals and liver transplant recipients / Detecção de herpesvirus humano-7 por nested-PCR qualitativo: comparação entre indivíduos sadios e receptores de transplante hepático

Diagnosis of human herpesvirus-7 active infection in transplant patients has proved difficult, because this virus is ubiquitous and can cause persistent infections in the host. The significance of viral DNA detected in leukocytes by PCR is unclear and cross-reaction in serological tests may occur. This study aimed to evaluate nested-PCR to detect human herpesvirus-7 active infection in liver transplant recipients compared to healthy individuals. human herpesvirus-7 nested-PCR was performed on leukocytes and sera of 53 healthy volunteers and sera of 29 liver transplant recipients. In healthy volunteers, human herpesvirus-7 was detected in 28.3 percent of leukocytes and 0 percent of serum. human herpesvirus-7 was detected in sera of 48.2 percent of the liver transplant recipients. Nested-PCR on DNA extracted from leukocytes detected latent infection and the study suggests that nested-PCR performed on serum could be useful to detect human herpesvirus-7 active infection in liver transplant recipients.

Diagnóstico da infecção ativa pelo herpesvirus humano-7 é difícil devido ao fato deste vírus ser ubíquo e poder causar infecção persistente no hospedeiro. O significado da detecção do DNA viral por reação em cadeia da polimerase não é claro e, reações cruzadas podem ocorrer em testes sorológicos. O objetivo deste estudo foi avaliar a nested-PCR para detectar infecção ativa pelo herpesvirus-7 em receptores hepáticos comparando com indivíduos sadios. Nested-PCR para herpesvirus-7 foi realizado em leucócitos e soro de 53 voluntários sadios e em soro de 29 receptores hepáticos. Nos voluntários sadios, herpesvirus-7 foi detectado em 28,3 por cento de leucócitos e 0 por cento de soro. herpesvirus-7 foi detectado em soro de 48,2 por cento de receptores hepáticos. Nested-PCR em DNA extraído de leucócitos detectou infecção latente e o estudo sugere que nested-PCR realizada em soro poderia ser útil para detectar infecção ativa por herpesvirus-7 em receptores de fígado.

Detection of human herpesvirus-7 by qualitative nested-PCR: comparison between healthy individuals and liver transplant recipients.

Diagnosis of human herpesvirus-7 active infection in transplant patients has proved difficult, because this virus is ubiquitous and can cause persistent infections in the host. The significance of viral DNA detected in leukocytes by PCR is unclear and cross-reaction in serological tests may occur. This study aimed to evaluate nested-PCR to detect human herpesvirus-7 active infection in liver transplant recipients compared to healthy individuals. human herpesvirus-7 nested-PCR was performed on leukocytes and sera of 53 healthy volunteers and sera of 29 liver transplant recipients. In healthy volunteers, human herpesvirus-7 was detected in 28.3% of leukocytes and 0% of serum. human herpesvirus-7 was detected in sera of 48.2% of the liver transplant recipients. Nested-PCR on DNA extracted from leukocytes detected latent infection and the study suggests that nested-PCR performed on serum could be useful to detect human herpesvirus-7 active infection in liver transplant recipients.

Withdrawal of maintenance therapy for cytomegalovirus retinitis in AIDS patients exhibiting immunological response to HAART.

BACKGROUND: Before the introduction of highly active antiretroviral therapy (HAART), CMV retinitis was a common complication in patients with advanced HIV disease and the therapy was well established; it consisted of an induction phase to control the infection with ganciclovir, followed by a lifelong maintenance phase to avoid or delay relapses. METHODS: To determine the safety of CMV maintenance therapy withdrawal in patients with immune recovery after HAART, 35 patients with treated CMV retinitis, on maintenance therapy, with CD4+ cell count greater than 100 cells/mm(3) for at least three months, but almost all patients presented these values for more than six months and viral load < 30000 copies/mL, were prospectively evaluated for the recurrence of CMV disease. Maintenance therapy was withdrawal at inclusion, and patients were monitored for at least 48 weeks by clinical and ophthalmologic evaluations, and by determination of CMV viremia markers (antigenemia-pp65), CD4+/CD8+ counts and plasma HIV RNA levels. Lymphoproliferative assays were performed on 26/35 patients. RESULTS: From 35 patients included, only one had confirmed reactivation of CMV retinitis, at day 120 of follow-up. No patient returned positive antigenemia tests. No correlation between lymphoproliferative assays and CD4+ counts was observed. CONCLUSION: CMV retinitis maintenance therapy discontinuation is safe for those patients with quantitative immune recovery after HAART.

Withdrawal of maintenance therapy for cytomegalovirus retinitis in AIDS patients exhibiting immunological response to HAART

BACKGROUND: Before the introduction of highly active antiretroviral therapy (HAART), CMV retinitis was a common complication in patients with advanced HIV disease and the therapy was well established; it consisted of an induction phase to control the infection with ganciclovir, followed by a lifelong maintenance phase to avoid or delay relapses. METHODS: To determine the safety of CMV maintenance therapy withdrawal in patients with immune recovery after HAART, 35 patients with treated CMV retinitis, on maintenance therapy, with CD4+ cell count greater than 100 cells/mm³ for at least three months, but almost all patients presented these values for more than six months and viral load < 30000 copies/mL, were prospectively evaluated for the recurrence of CMV disease. Maintenance therapy was withdrawal at inclusion, and patients were monitored for at least 48 weeks by clinical and ophthalmologic evaluations, and by determination of CMV viremia markers (antigenemia-pp65), CD4+/CD8+ counts and plasma HIV RNA levels. Lymphoproliferative assays were performed on 26/35 patients. RESULTS: From 35 patients included, only one had confirmed reactivation of CMV retinitis, at day 120 of follow-up. No patient returned positive antigenemia tests. No correlation between lymphoproliferative assays and CD4+ counts was observed. CONCLUSION: CMV retinitis maintenance therapy discontinuation is safe for those patients with quantitative immune recovery after HAART.

Antes da introdução da terapia anti-retroviral altamente efetiva (HAART), a retinite por CMV era uma complicação comum em pacientes com doença por HIV avançada e a terapia era bem estabelecida e consistia em uma fase de indução com ganciclovir para controlar a infecção, seguida por uma manutenção por toda a vida, para evitar e retardar as recidivas. Para determinar a segurança da retirada da terapia de manutenção para retinite por citomegalovírus em pacientes com recuperação imunológica após o HAART, 35 pacientes com retinite por CMV tratados com terapia de manutenção, com contagem de células CD4+ maiores que 100 células/mm³ por no mínimo três meses, mas a maioria dos pacientes apresentava esses valores por mais de seis meses e carga viral < 30.000 cópias/mL, foram avaliados prospectivamente para a recorrência de doença por CMV. A terapia de manutenção foi retirada na inclusão e os pacientes foram monitorados no mínimo 48 semanas por avaliações clínicas e oftalmológicas e pela determinação de marcadores de viremia para CMV (antigenemia). Contagens de CD4+ e CD8+ e níveis de RNA de HIV no plasma. Métodos linfoproliferativos foram realizados em 26/35 pacientes. RESULTADOS: Dos 35 pacientes incluídos no estudo, somente um teve reativação da retinite por CMV confirmada, no dia 120 do seguimento. Nenhum paciente teve testes de antigenemia positivos. Nenhuma correlação entre os ensaios linfoproliferativos e contagens de CD4+ foi observada. CONCLUSÃO: Descontinuação da terapia de manutenção para retinite por CMV é segura para aqueles pacientes com recuperação imune quantitativa após HAART.