Evidence Of HIV Infection Research Articles

Mortuary and hospital-based HIV mortality surveillance among decedents in a low-resource setting: lessons from Western Kenya

BackgroundLack of dependable morbidity and mortality data complicates efforts to measure the demographic or population-level impact of the global HIV/AIDS epidemic. Mortuary-based mortality surveillance can address gaps in vital statistics in low-resource settings by improving accuracy of measuring HIV-associated mortality and indicators of access to treatment services among decedents. This paper describes the process and considerations taken in conducting mortuary and hospital-based HIV mortality surveillance among decedents in Kenya.Main textWe conducted HIV mortuary and hospital-based mortality surveillance at two of the largest mortuaries in Kisumu County, Kenya (April 16–July 12, 2019). Medical charts were reviewed for documentation of HIV status among eligible decedents. HIV testing was done on blood and oral fluid samples from decedents with undocumented HIV status and those whose medical records indicated HIV-negative test results > 3 months before death. A panel of experts established the cause of death according to the International Classification of Diseases, 10th Revision rules. Civil registry data for the year 2017 were abstracted and coded to corresponding ICD-10 codes.Of the 1004 decedents admitted to the two mortuaries during the study period, 49 (4.9%) were unavailable because they had been transferred to other facilities or dispatched for burial before enrolment. Of the 955 available decedents, 104 (10.9%) were ineligible for the study. Blood samples were collected from 659 (77.4%) decedents, and 654 (99.2%) were tested for HIV. Of the 564 decedents eligible for the OraQuick® validation sub-study, 154 were eligible for oral sample collection, and 132 (85.7%) matched pre- and post-embalming oral samples were collected and tested. Of the 851 eligible decedents, 241 (28.3%) had evidence of HIV infection: 119 had a diagnosis of HIV infection recorded in their patient files, and 122 had serological evidence of HIV infection.ConclusionThis study shows that in low-resource settings, conducting hospital and mortuary-based surveillance is feasible and can be an alternative source of mortality data when civil registry data are inadequate.

The Use of Density-Based Spatial Clustering of Application With Noise (DBSCAN) for Record Linkage in An Observational HIV Cohort

IntroductionThe South African HIV Cancer Match (SAM) study is a probabilistic record linkage study involving creation of an HIV cohort from laboratory records from the National Health Laboratory Service (NHLS). This cohort was linked to the pathology based South African National Cancer Registry to establish cancer incidences among HIV positive population in South Africa. As the number of HIV records increases, there is need for more efficient ways of de-duplicating this big-data. In this work, we used clustering to perform big-data deduplication.
 Objectives and ApproachOur objective was to use DBSCAN as clustering algorithm together with bi-gram word analyser to perform big-data deduplication in resource-limited settings. We used HIV related laboratory records from entire South Africa collated in the NHLS Corporate Data Warehouse for period 2004-2014. This involved data pre-processing, deterministic deduplication, ngrams generation, features generation using Term Frequency Inverse Document Frequency vectorizer, clustering using DBSCAN and assigning cluster labels for records that potentially belonged to the same person. We used records with national identification numbers to assess quality of deduplication by calculating precision, recall and f-measure.
 ResultsWe had 51,563,127 HIV related laboratory records. Deterministic deduplication resulted in 20,387,819 patient record deduplicates. With DBSCAN clustering we further reduced this to 14,849,524 patient record clusters. In this final dataset, 3,355,544 (22.60%) patients had negative HIV test, 11,316,937 (76.21%) had evidence for HIV infection, and for 177,043 (1.19%) the HIV status could not be determined. The precision, recall and f-measure based on 1,865,445 records with national identification numbers were 0.96, 0.94 and 0.95, respectively.
 Conclusion / ImplicationsOur study demonstrated that DBSCAN clustering is an effective way of deduplicating big datasets in resource-limited settings. This enabled refining of an HIV observational database by accurately linking test records that potentially belonged to the same person. The methodology creates opportunities for easy data profiling to inform public health decision making.

Lung cancer chemotherapy and radiotherapy toxicity in patients with HIV.

e13616 Background: Lung cancer is the leading cause of cancer death for people living with HIV (PWH), and this group experiences lung cancer outcome disparities for unclear reasons. To better understand these disparities, we explored potential differences in adverse events since the start of chemotherapy, or radiation therapy (RT), among PWH with stage I-IIIA non-small cell lung cancer (NSCLC). Methods: Our matched case-cohort study used data from SEER-Medicare data on stage I-IIIA NSCLC diagnosed between 2000 and 2013. We identified 809 early stage NSCLC patients with HIV; 40 were treated with chemotherapy and 60 with RT. For each therapy type, a PWH case was matched, by age, sex, and cancer stage to 10 controls with no evidence of HIV infection. Outcome Measures: Acute severe chemotherapy or RT toxicity ascertained by a relevant inpatient diagnosis within 6 months of chemotherapy initiation or chronic toxicities from outpatient diagnostic codes within 24 months. We also evaluated overall (all-cause) and lung cancer-specific survival. Results: Among hematologic toxicities, PWH treated with chemotherapy were more than twice as likely to develop severe anemia [odds ratio [OR] = 2.3 (95% confidence interval [95% CI]: 1.2-4.6)]; but not neutropenia or thrombocytopenia (both p > 0.06). Among patients receiving chemotherapy, HIV was not associated with any other severe acute toxicities including fever, infection, nausea, renal dysfunction, and septicemia. For chronic complications, PWH had increased risk of neuropathy (OR 4.2; 95% CI: 1.3-13.6). Overall, HIV was associated with an increased count of chemotherapy complications seen per patient [p = 0.02]. PWH receiving chemotherapy had worse all-cause mortality (hazard ratio (HR) = 1.7; 95% CI: 1.2-2.4) and higher lung cancer-specific mortality (HR 1.8; 95% CI: 1.2-2.7) compared to uninfected persons after adjusting for treatment with surgery. In contrast, HIV was not significantly associated with severe RT complications (esophagitis, pneumonitis or hemoptysis), although all-cause mortality (HR 1.5; 95% CI: 1.1-2.0) and lung-cancer specific mortality (HR 1.5; 95% CI: 1.1-2.0) were higher among PWH receiving RT after adjusting for treatment with surgery. Conclusions: Antiretroviral-era PWH with early stage lung cancer experienced more frequent complications after chemotherapy but not radiotherapy compared to matched uninfected persons. These toxicities may have led to treatment alterations potentially contributing to outcome disparities seen in this high-risk group.

Frequency of Type 8 Human Herpes Virus in Patients with Pemphigus Vulgaris in Tabriz Sina Hospital since 2016-2017

Background: Pemphigus vulgaris is the most common form of autoimmune vesiculobullous skin disease. Human herpesvirus-8 (HHV-8) has a well-known association with Kaposi's sarcoma. Considering the reports about the incidence of Kaposi's sarcoma in patients with pemphigus and bolus pemphigoid without evidence of HIV infection, this study was designed to investigate the presence of HHV-8 in patients with pemphigus. Methods: In this cross-sectional and descriptive-analytic study, 27 patients with newly diagnosed pemphigus vulgaris were selected. The control group included 27 patients with benign non- vesiculobullous skin lesions. IHC (Immunohistochemistry) staining was performed to detect HHV-8 in tissue samples taken from skin lesions or mucosal lesions in both groups. Results: IHC showed HHV-8 in 12 patients in case group with pemphigus vulgaris (44.4%) and 9 patients in control group (33.3%) (P=0.402). Conclusion: Although HHV-8 prevalence was higher in Pemphigus vulgaris patients, this difference was not statistically significant, and there is unlikely to be a causal relationship between HHV-8 and Pemphigus.

Disseminated Coccidioidomycosis Refractory to Multi-Drug Therapies in an Immunocompetent Patient

Coccidioidomycosis is a fungal infection caused by Coccidioides immitis which thrives in dry desert climates such as the southwestern United States. Disseminated coccidioidomycosis is often seen in patients with an underlying immunodeficiency. Historically there have been few reported cases of opportunistic infections in the setting of low CD4+ count and no evidence of HIV infection. Coccidioidomycosis typically presents asymptomatically or as a minor respiratory illness in immunocompetent individuals. We report a case of disseminated coccidioidomycosis in a patient who is otherwise immunocompetent. Patient is a 24-year-old Hispanic male who presented with severe headache, fever, body pain, vomiting, and diarrhea for approximately 14 days. On admission, patient’s CD4+ count was 91 and CSF culture grew Coccidioides immitis, for which patient was started on fluconazole. Patient’s hospital stay was complicated by multiple bouts of altered mental status, fevers, hyponatremia, hydrocephalus, neurogenic bladder, new-onset Mobitz II heart arrhythmia, urinary tract infection, and sepsis. MRI studies revealed abnormal enhancement of leptomeninges, bilateral basal ganglia, thecal sac and cauda equina fibers, signifying disseminated disease. Patient’s serum Coccidioides complement fixation (IgG) titers remained elevated despite aggressive therapy with IV amphotericin B. After a total of six months of hospitalization, including treatment with intrathecal amphotericin B, patient’s last CD4+ count was 549, CSF IgG titers achieved

HIV risk associated with serum medroxyprogesterone acetate levels among women in East and southern Africa.

Some observational studies have found increased HIV risk associated with self-reported use of injectable depot medroxyprogesterone acetate. Testing blood samples for medroxyprogesterone acetate (MPA), the progestin in depot medroxyprogesterone acetate, permits validation of self-reported data, and exploration of whether potential HIV risk is correlated with MPA levels, which are highest soon after injection. We conducted a case-control study testing archived serum from women who participated in three longitudinal studies of HIV prevention in East and southern Africa. Case samples, from women who acquired HIV, were from visits that occurred at or immediately prior to the first evidence of HIV infection. Secondary analyses restricted to case samples collected within 15 and 30 days of the estimated date of HIV infection. Matched control samples were from women who remained HIV uninfected. We used multivariable conditional logistic regression to compare exogenous hormone levels, quantified through mass spectrometry, among cases and controls. When restricted to cases with samples collected within 15 days or less of estimated date of HIV infection, MPA detection was more frequent among women who acquired HIV (adjusted odds ratio = 2.75, 95% confidence interval 1.22-6.19). In this subset, the increase in HIV risk was only among samples with MPA detected at a low level of 0.02-0.50 ng/ml: 36.7% of cases and 9.4% of controls, adjusted odds ratio = 6.03, 95% confidence interval 2.50-14.54. Detection of MPA at low levels close to the estimated time of HIV acquisition was significantly more frequent among women who acquired HIV. Studies are needed that explore biological mechanisms elicited by any MPA level and HIV risk.

Cryptococcal meningitis in an immunocompetent patient with obstructive hydrocephalus: A case report

BackgroundCryptococcal infections of the central nervous system are very rare in immunocompetent patients. They usually present as meningitis or as fungal cysts with or without hydrocephalus. Rapid diagnosis and treatment is crucial to the prognosis. Case reportWe report the case of an immunocompetent 40-year-old male patient with no medical or surgical history and no recent travel, who was hospitalized in our neurosurgery department because of a rapidly worsening headache. The neurological examination revealed no focal deficit but worrying signs of increased intracranial pressure. Magnetic resonance imaging (MRI) with contrast showed thick and large-scale cortico-pial cerebellar enhancements, associated with severe obstructive hydrocephalus. This required emergency endoscopic ventriculocisternostomy during which we observed cottony tissues along the ventricular walls. Biopsied tissues and cerebrospinal fluid samples (CSF) were not contributive. A CT scan of the chest and abdomen and blood markers of common primary tumors were all negative. No evidence of HIV infection or any cause of immunosuppression was identified. Symptoms and a second MRI slightly improved with intravenous corticosteroid therapy. The hypothesis of a lymphoma or granulomatous disease was made initially for which direct surgical biopsies were scheduled. The diagnosis of cryptococcal meningitis was obtained later on by simultaneous plasma and CSF Cryptococcus antigen detection. Cryptococcus neoformans (formerly C. neoformans var. grubii [serotype A]) was then identified by PCR. Clinical improvement was obtained with antifungal therapy. ConclusionCryptococcal meningitis is a well-known condition in immunocompromised patients, often causing hydrocephalus requiring neurosurgical management. The diagnosis is more difficult in patients with no history of HIV or organ transplant. Neurologists and neurosurgeons must consider this possibility in case of diffuse, thick leptomeningeal enhancement on MRI.

Study of Reversible CD4/CD8+ve T Cell Counts in Patients with HIV Negative Pulmonary Tuberculosis after Effective Treatment with Antitubercular Therapy (ATT)

Background/Purpose: Tuberculosis (T.B) an infectious disease caused by Mycobacterium tuberculosis is still one of the biggest killers among the infectious diseases. Immunological deficiencies of various magnitudes have been reported in TB which include CD4 + T and CD8 + T cells. The aim of the study was investigating the at the occurrence of CD4+ T cell lymphopenia in patients with active pulmonary tuberculosis and the response of this abnormality to ATT in HIV negative patients. Methods: The study subjects included three groups in which 30 patients were with sputum positive pulmonary tuberculosis without any evidence of HIV infection and second group of10 healthy controls. Third group included10 patients with pulmonary tuberculosis co-infected HIV sero-positivity. Zeil Nelson (ZN) method was used to diagnose pulmonary tuberculosis, ELISA method was adopted to confirm the HIV status and CD4 and CD8 count was done by flow cytometry. Results: The CD­4 + T cell lymphopenia was observed significantly associated (p=0.000) in Non-HIV pulmonary tuberculosis cases as compared to controls (370.87 ± 209.00 cells/μl v/s 673.60 ± 120.30 cells/μl).CD4 + T cell lymphopenia was significantin HIV positive pulmonary TB patients compared to healthy controls (p=0.000). CD4 + T cell lymphopenia was more severe in HIV co-infected pulmonary tuberculosis patients compared to Non-HIV pulmonary TB cases (p=0.029). Conclusion: We conclude that the pulmonary tuberculosis is an important cause of non HIV CD4, CD8 lymphopenia, with reversal of CD4/CD8 ratio, and this is reversible with effective treatment with antitubercular therapy (ATT).

Administration of interleukin-7 increases CD4 T cells in idiopathic CD4 lymphocytopenia

AbstractIdiopathic CD4 lymphopenia (ICL) is a rare syndrome defined by low CD4 T-cell counts (<300/µL) without evidence of HIV infection or other known cause of immunodeficiency. ICL confers an increased risk of opportunistic infections and has no established treatment. Interleukin-7 (IL-7) is fundamental for thymopoiesis, T-cell homeostasis, and survival of mature T cells, which provides a rationale for its potential use as an immunotherapeutic agent for ICL. We performed an open-label phase 1/2A dose-escalation trial of 3 subcutaneous doses of recombinant human IL-7 (rhIL-7) per week in patients with ICL who were at risk of disease progression. The primary objectives of the study were to assess safety and the immunomodulatory effects of rhIL-7 in ICL patients. Injection site reactions were the most frequently reported adverse events. One patient experienced a hypersensitivity reaction and developed non-neutralizing anti-IL-7 antibodies. Patients with autoimmune diseases that required systemic therapy at screening were excluded from the study; however, 1 participant developed systemic lupus erythematosus while on study and was excluded from further rhIL-7 dosing. Quantitatively, rhIL-7 led to an increase in the number of circulating CD4 and CD8 T cells and tissue-resident CD3 T cells in the gut mucosa and bone marrow. Functionally, these T cells were capable of producing cytokines after mitogenic stimulation. rhIL-7 was well tolerated at biologically active doses and may represent a promising therapeutic intervention in ICL. This trial was registered at www.clinicaltrials.gov as #NCT00839436.

A fatal case of pulmonary infection by Mycobacterium colombiense in Para State, Amazon Region, Brazil

Mycobacterium avium complex (MAC) is a heterogeneous group of species found in several environmental sources and that exhibit variable degrees of pathogenicity. Among the MAC members, Mycobacterium colombiense has been related to pulmonary disease and disseminated infection in HIV-infected patients in Colombia. Lymphadenopathy cases have also been reported. We have described a fatal case of M. colombiense pulmonary disease in a Brazilian patient without evidence of HIV infection or other known causes of immunosuppression.

The triple threat of pregnancy, HIV infection and malaria: reported causes of maternal mortality in two nationwide health facility assessments in Mozambique, 2007 and 2012.

BackgroundThe paper’s primary purpose is to determine changes in magnitude and causes of institutional maternal mortality in Mozambique. We also describe shifts in the location of institutional deaths and changes in availability of prevention and treatment measures for malaria and HIV infection.MethodsTwo national cross-sectional assessments of health facilities with childbirth services were conducted in 2007 and 2012. Each collected retrospective data on deliveries and maternal deaths and their causes. In 2007, 2,199 cases of maternal deaths were documented over a 12 month period; in 2012, 459 cases were identified over a three month period. In 2007, data collection also included reviews of maternal deaths when records were available (n = 712).ResultsInstitutional maternal mortality declined from 541 to 284/100,000 births from 2007 to 2012. The rate of decline among women dying of direct causes was 66 % compared to 26 % among women dying of indirect causes. Cause-specific mortality ratios fell for all direct causes. Patterns among indirect causes were less conclusive given differences in cause-of-death recording. In absolute numbers, the combination of antepartum and postpartum hemorrhage was the leading direct cause of death each year and HIV and malaria the main non-obstetric causes. Based on maternal death reviews, evidence of HIV infection, malaria or anemia was found in more than 40 % of maternal deaths due to abortion, ectopic pregnancy and sepsis. Almost half (49 %) of all institutional maternal deaths took place in the largest hospitals in 2007 while in 2012, only 24 % occurred in these hospitals. The availability of antiretrovirals and antimalarials increased in all types of facilities, but increases were most dramatic in health centers.ConclusionsThe rate at which women died of direct causes in Mozambique’s health facilities appears to have declined significantly. Despite a clear improvement in access to antiretrovirals and antimalarials, especially at lower levels of health care, malaria, HIV, and anemia continue to exact a heavy toll on child-bearing women. Going forward, efforts to end preventable maternal and newborn deaths must maximize the use of antenatal care that includes integrated preventive/treatment options for HIV infection, malaria and anemia.

A Case Report of an Atypical Presentation of IgG4-Related Disease and Idiopathic CD4 Lymphocytopenia.

The IgG4-related disease is a fibroinflammatory disease characterized by tumefactive lesions, a dense lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, storiform fibrosis, and, often but not always, elevated serum levels of IgG4. Idiopathic CD4 lymphocytopenia is a heterogenic and rare syndrome characterized by the detection of a persistent absolute CD4 T cells count <300 cells/mm3 (or <20% of total T cells) in more than one occasion and no evidence of HIV infection in absence of immunodeficiency or therapy associated with depressed levels of CD4 T cells. We report the case of a 50-year-old man with a multiorgan IgG4-related disease presenting in a temporal association with a profound and symptomatic idiopathic CD4 lymphocytopenia. Both clinical pictures improved after steroid treatment. Idiopathic CD4 lymphocytopenia has been associated with a number of autoimmune conditions but, to the best of our knowledge, this is the first case in which an association with the IgG4-related disease is reported.

Pooled nucleic acid testing increases the diagnostic yield of acute HIV infections in a high-risk population compared to 3rd and 4th generation HIV enzyme immunoassays

ObjectivesWe compared a 3rd generation (gen) and two 4th gen HIV enzyme immunoassays (EIA) to pooled nucleic acid testing (PNAT) for the identification of pre- and early seroconversion acute HIV infection (AHI). Study Design9550 specimens from males >18 year from clinics attended by men who have sex with men were tested by Siemens ADVIA Centaur® HIV 1/O/2 (3rd gen) and HIV Combo (4th gen), as well as by Abbott ARCHITECT® HIV Ag/Ab Combo (4th gen). Third gen non-reactive specimens were also tested by Roche COBAS® Ampliprep/COBAS® TaqMan HIV-1 Test v.2 in pools of 24 samples. Sensitivity and specificity of the three EIAs for AHI detection were compared. Results7348 persons contributed 9435 specimens and had no evidence of HIV infection, 79 (94 specimens) had established HIV infection, 6 (9 specimens) had pre-seroconversion AHI and 9 (12 specimens) had early seroconversion AHI. Pre-seroconversion AHI cases were not detected by 3rd gen EIA, whereas 2/6 (33.3%) were detected by Siemens 4th gen, 4/6 (66.7%) by Abbott 4th gen and 6/6 (100%) by PNAT. All three EIAs and PNAT detected all individuals with early seroconversion AHI. Overall sensitivity/specificity for the EIAs relative to WB or NAT resolved infection status was 93.6%/99.9% for Siemens 3rd gen, 95.7%/99.7% for Siemens 4th gen and 97.9%/99.2% for Abbott 4th gen. ConclusionsWhile both 4th gen EIAs demonstrated improved sensitivity for AHI compared to 3rd gen EIA, PNAT identified more AHI cases than either 4th gen assay. PNAT is likely to remain a useful strategy to identify AHI in high-risk populations.

Contribution of HIV infection to mortality among cancer patients in Uganda

HIV infection is associated with cancer risk. This relationship has resulted in a growing cancer burden, especially in resource-limited countries where HIV is highly prevalent. Little is known, however, about how HIV affects cancer survival in these settings. We therefore investigated the role of HIV in cancer survival in Uganda. Retrospective cohort (N = 802). Eligible cancer patients were residents of Kyadondo County, at least 18 years of age at cancer diagnosis, and diagnosed between 2003 and 2010 with one of the following: breast cancer, cervical cancer, non-Hodgkin's lymphoma, Hodgkin's lymphoma, or esophageal cancer. Patients were classified as HIV-infected at cancer diagnosis based on a documented positive HIV antibody test, medical history indicating HIV infection, or an HIV clinic referral letter. The primary outcome, vital status at 1 year following cancer diagnosis, was abstracted from the medical record or determined through linkage to the national hospice database. The risk of death during the year after cancer diagnosis was compared between cancer patients with and without evidence of HIV infection using Cox proportional hazards regression. HIV-infected cancer patients in Uganda experienced a more than two-fold increased risk of death during the year following cancer diagnosis compared to HIV-uninfected cancer patients [hazard ratio 2.28; 95% confidence interval (CI) 1.61-3.23]. This association between HIV and 1-year cancer survival was observed for both cancers with (hazard ratio 1.56; 95% CI 1.04-2.34) and without (hazard ratio 2.68; 95% CI 1.20-5.99) an infectious cause. This study demonstrates the role of HIV in cancer survival for both cancers with and without an infectious cause in a resource-limited, HIV-endemic setting.

Idiopathic CD4 lymphocytopenia: a case of missing, wandering or ineffective T cells

Idiopathic CD4 lymphocytopenia (ICL) is a presumed heterogenous syndrome with key element low CD4 T-cell counts (below 300/mm3) without evidence of HIV infection or other known immunodeficiency. The etiology, pathogenesis, and management of ICL remain poorly understood and inadequately defined. The clinical presentation can range from serious opportunistic infections to incidentally diagnosed asymptomatic individuals. Cryptococcal and non-tuberculous mycobacterial infections and progressive multifocal leukoencephalopathy are the most significant presenting infections, although the spectrum of opportunistic diseases can be similar to that in patients with lymphopenia and HIV infection. Malignancy is common and related to opportunistic pathogens with an oncogenic potential. Autoimmune diseases are also seen in ICL with an increased incidence. The etiology of ICL is unknown. Mechanisms implicated in CD4 reduction may include decreased production, increased destruction, and tissue sequestration. New distinct genetic defects have been identified in certain patients with ICL, supporting the hypothesis of the lack of a common etiology in this syndrome. The management of ICL is focused on the treatment of opportunistic infections, appropriate prophylactic antibiotics, and close monitoring. In selected patients with life-threatening infections or profound immunodeficiency, strategies to increase T-cell counts or enhance immune function could be considered and have included interleukin-2, interferon-gamma, interleukin-7, and hematopoietic stem cell transplantation. The prognosis is influenced by the accompanying opportunistic infections and may be affected by publication bias of severe cases with unfavorable outcomes. As newer laboratory investigation techniques are being developed and targeted experimental treatments become available, our comprehension and prognosis of this rare syndrome could be significantly improved.

A review of the evidence concerning hepatic glutathione depletion and susceptibility to hepatotoxicity after paracetamol overdose.

Paracetamol (acetaminophen) poisoning is common throughout the world. The management of nonstaggered (acute) paracetamol overdose is based on the plasma paracetamol concentration plotted on a treatment nomogram. In the UK there are two treatment lines on this nomogram, with the lower treatment line used for individuals felt to be at ‘high risk’ of paracetamol-related hepatotoxicity either as a result of induction of cytochrome P450 isoenzymes or reduction of intrahepatic glutathione. In this article we review the risk factors that, in current guidelines, are felt to increase risk due to a reduction in intrahepatic glutathione concentrations. Based on our review of the published literature, we feel that cystic fibrosis, acute viral illness, malnutrition, and eating disorders such as anorexia nervosa are likely to be associated with reduction in intrahepatic glutathione concentrations, and that this risk is likely to be related to malnutrition secondary to the disease. Chronic hepatitis C infection is also associated with reduced glutathione concentrations, although this appears to be independent of any associated malnutrition. Ageing and acute fasting are not associated with an increased risk of paracetamol-related hepatotoxicity due to reductions in glutathione concentrations. Finally, the evidence for HIV infection is inconclusive, particularly as the majority of studies were conducted in the pre-anti-viral treatment (HAART) era; however it is likely that patients with symptomatic HIV/AIDS have reduced glutathione concentrations due to associated malnutrition. Although there have been few studies which have specifically investigated whether there is an association between reduced intrahepatic glutathione concentrations and increased risk of paracetamol-related hepatotoxicity, in our opinion, it is likely that the above conditions that are associated with reduced glutathione concentrations, will be associated with an increased risk of paracetamol-related hepatotoxicity.

Pandemic (H1N1) 2009 and HIV Co-infection

To the Editor: We report a case of pandemic (H1N1) 2009 infection in a man with serologic evidence of HIV-1 infection. The clinical course was complicated by lung and brain involvement (respiratory failure and lethargy), severe leukopenia, and thrombocytopenia, but complications resolved after treatment with oseltamivir (150 mg 2×/d). In November 2009, a 47-year-old man who had received a diagnosis of hepatitis C infection 8 months earlier sought treatment at Ospedale Santa Maria Nuova, Reggio Emilia, Italy. He had a 3-day history of fever, dry cough, and drowsiness. Eight days before being admitted, the man had resided in the hospital’s inpatient detoxification unit, in which at least 10 influenza-like cases had been recorded. While in the detoxification unit, he had received methadone, 50 mg 1×/d. Computed tomography images of the brain and radiographs of the chest were normal; ultrasound examination showed upper lobe consolidation of the left lung. Hematochemistry showed high creatine phosphokinase levels, leukocyte count of 1,380 cells/mm3 (reference range 4,000–10,000 cells/mm3), thrombocyte count of 34,000 cells/mm3 (reference range 150,000–450,000 cells/mm3), partial pressure of oxygen 56 mm Hg, and partial pressure of carbon dioxide 53 mm Hg. Urinalysis results were negative for heroin, cocaine, and alcohol; cerebrospinal fluid (CSF) analysis results were within normal limits. Thrombocyte count returned to reference range after 2 days, and leukocyte count improved but remained <3,500 cells/mm3 for 3 weeks. After admission to hospital, the man became lethargic and received noninvasive continuous positive airway pressure ventilation and treated with oseltamivir (150 mg 2×/d for 5 d), as well as with ceftriaxone, and levofloxacin. Reverse transcription–PCR on a throat swab confirmed influenza subtype H1N1 infection; blood cultures and urine were negative for pneumococcus, and Legionella spp. antigens. In addition, PCR of CSF for enterovirus and herpesvirus had negative results. The patient needed respiratory support for 4 days, after which his mental status and blood gases returned to reference levels. He was discharged from the hospital 2 weeks later. On day 3 after admission, a nurse was accidentally exposed to the patient’s urine through her eye. An ELISA was positive for HIV infection. Negative results for confirmatory Western blot tests on days 5, 15, and 23 showed the p24 and p41 bands; HIV RNA was >6 million copies/mL, CD4 lymphocytes 51% (reference range 29%–59%). Reverse transcription–PCR for influenza subtype H1N1 performed 2 months later on a stored CSF sample gave a negative result; PCR for HIV of the same sample indicated 25,000 copies/mL. In mid-December, because of a further drop in CD4 lymphocytes to 17% (214 cells/mm3) and blood HIV RNA of 2.8 million copies/mL, the patient started highly active antiretroviral therapy and is being followed up as an outpatient. Influenza (H1N1) and primary HIV infection share many signs and symptoms, such as fever, cough, sore throat, joint or limb pain, and diarrhea. The infections also share uncommon complications of the central nervous system (CNS); e.g., drowsiness, coma, and seizures. We cannot confirm that CNS involvement in the patient reported here was caused primarily by pandemic (H1N1) 2009, as suggested by influenza-like symptoms and the apparent effect of oseltamivir. Nor can we attribute CNS involvement to primary infection with HIV-1 (1); CSF results within normal limits and PCR negative for influenza subtype H1N1 do not rule out a causal relationship with pandemic (H1N1) 2009. In fact, the few cases of pandemic (H1N1) 2009 encephalopathy described show similar characteristics among children and adults (2–4). Alternatively, some authors have attributed HIV in CSF to brain inflammation and damage (5,6). The severe leukocytopenia and thrombocytopenia in our patient have not been described, even in complicated influenza subtype H1N1 infections (7). Because lymphopenia and mild thrombocytopenia are the usual findings, we believe that they probably resulted from HIV-1 or the effect of both viruses. HIV seroconversion may initially occur during an acute febrile illness resembling influenza, and CNS involvement can complicate both infections. During an epidemic, acute HIV infection should also be considered (8). Less frequently, as in the patient described above, the 2 infections can occur simultaneously. History of recent risk behavior for blood exposure and severe leukocytopenia and thrombocytopenia should alert clinicians to other causes and prompt them to offer an HIV test to the patient.

Seronegative HIV-1 infection: a review of the literature

HIV-1-specific antibodies can be detected in HIV-1-positive patients within weeks of primary infection. Rare cases have been reported of patients who are persistently seronegative despite evidence of HIV-1 infection. We present a retrospective review of the clinical, virologic and immunologic characteristics of 25 persistently seronegative patients whose cases have been published to date and postulate a biologic mechanism for this phenomenon.

Differences in NMDA Receptor Expression During Human Development Determine the Response of Neurons to HIV-Tat-mediated Neurotoxicity

HIV infection of the CNS can result in neurologic dysfunction in a significant number of infected individuals. NeuroAIDS is characterized by neuronal injury and loss, yet there is no evidence of HIV infection in neurons. Thus, neuronal damage and dropout are likely due to indirect effects of HIV infection of other CNS cells, through elaboration of inflammatory factors and neurotoxic viral proteins, including the viral transactivating protein tat. We and others demonstrated that tat induces apoptosis in differentiated mature human neurons. We now demonstrate that the high level of tat toxicity observed in human neurons involves specific developmental stages that correlate with N-methyl-D-aspartate receptor (NMDAR) expression, and that tat toxicity is also dependent upon the species being analyzed. Our results indicate that tat treatment of primary cultures of differentiated human neurons with significant amounts of NMDAR expression induces extensive apoptosis. In contrast, tat treatment induces only low levels of apoptosis in primary cultures of immature human neurons with low or minimal expression of NMDAR. In addition, tat treatment has minimal effect on rat hippocampal neurons in culture, despite their high expression of NMDAR. We propose that this difference may be due to low expression of the NR2A subunit. These findings are important for an understanding of the many differences among tissue culture systems and species used to study HIV-tat-mediated toxicity.

Idiopathic CD4+ T-lymphocytopenia with cryptococcal meningitis: first case report from Cambodia

We report on a patient with cryptococcal meningitis with CD4+ T-lymphocytopenia and no evidence of HIV infection.