Presence Of Opportunistic Infections Research Articles

Management of Antiretroviral Therapy for HIV Infection: Modelling when to Change Therapy

To evaluate four strategies for monitoring plasma HIV RNA levels and/or resistance genotypes to decide when to change antiretroviral therapy. The strategies include: (i) 1997 guidelines recommending a therapy switch when plasma RNA exceeds a threshold level; (ii) a viral load policy, using a fixed increase in viral load as the trigger; (iii) a genotype policy, requiring a smaller viral rebound than (ii) and detection of genotypic resistance before switching; and (iv) a proactive policy, switching drug regimens at a predetermined time if viral load has not rebounded. A Monte Carlo simulation tracks patients' viral loads and presence of opportunistic infection during therapy. The model uses clinical and virological data and statistical variation in patient parameters for the evaluation of therapeutic strategies. To determine which strategies minimize viral rebound detection delay while maintaining a low (prespecified) probability of switching therapy before rebound. 1997 Guidelines and the viral load policy create lengthy delays in detection of rebound, particularly when patients are drug-naive and the detection limit of the viral load assay is 500 copies/ml. A detection limit of 20 copies/ml decreases this delay substantially. Genotyping achieves only minor additional delay reductions. Of the strategies tested, the proactive policy leads to the shortest delays. This model indicates that prolonged periods may be required for viral load to rebound to detectable levels following prolonged suppression. Proactive switching produces the best outcome in our model because it may reduce the duration of viral replication under pressure of a failing regimen before detection of viral rebound. This strategy should be evaluated in clinical trials.

Autoantibodies directed against phospholipids or human beta 2-glycoprotein I in HIV-seropositive patients: relationship with endothelial activation and antimalonic dialdehyde antibodies.

We investigated the possible role of antiphospholipid (APA) and anti-human 2-glycoprotein I (beta2-GPI) antibodies (Ab) in thrombosis and atherosclerosis in human immunodeficiency (HIV)-positive patients, in whom they seem to be more frequent. We measured APA and anti-beta2-GPI Ab in 58 HIV-positive patients together with markers of disease progression, circulating beta2-GPI, plasma lipids, biological markers of endothelial activation and integrity (plasma thrombomodulin, von Willebrand factor, vascular cell adhesion molecule 1) and with antimalonic dialdehyde antibodies (anti-MDA Ab). We found a 41% frequency of IgG APA in the HIV-positive patients. APA IgMs were rarely positive (7%), and anti-beta2-GPI IgGs were positive in 3-4% patients. There was no correlation between APA or anti-beta2-GPI Ab and the presence of opportunistic infections. Although plasma thrombomodulin, von Willebrand factor and vascular cell adhesion molecule 1 were significantly increased in the HIV-positive patients, APA was correlated only with vascular cell adhesion molecule 1, suggesting that APAs are correlated with endothelial activation but not with vascular endothelial lesions. A correlation between APA and anti-MDA IgG was demonstrated using multivariate analysis (r=0.542, P < 0.0001), suggesting a relationship between the targets of these antibodies. Finally, IgG APAs are frequent in HIV infection but are not correlated with biological markers of endothelial injury. Our results do not support a role for APA or anti-beta2-GPI in HIV-associated silent vascular endothelial damage. However, the role of these autoantibodies in clinically relevant thrombotic events should be investigated in HIV-positive patients.

Serum Pancreatic Enzymes in Human Immunodeficiency Virus-Infected Children: A Collaborative Study of the Italian Society of Pediatric Gastroenterology and Hepatology

Background: Numerous studies have shown pancreatic disease in adult human immunodeficiency virus (HIV)-infected patients, but there are very few reports on pediatric patients. Our aim was to determine the prevalence of increased serum pancreatic enzyme levels and their relationship to clinical manifestations of acute pancreatitis in HIV-infected children. Methods: Forty-seven consecutive, symptomatic HIV-infected children (24 male; median age, 7.3 years; range, 1-17 years) and 45 sex- and age-matched controls without gastroenterologic disease were enrolled. In all subjects serum total amylase, pancreatic amylase, and lipase were assayed with commercial kits. The following were recorded: disease progression (CDC class), nutritional status (weight Z-score), CD4 lymphocyte count, drug treatment during the previous 12 months, presence of opportunistic infections, clinical evidence of acute pancreatitis (increased serum pancreatic enzymes associated with vomiting, abdominal distention, and intolerance when eating). Results: Ten of 47 HIV patients had increased serum total amylase values; however fewer patients had increased specific pancreatic enzymes: 6 of 47 for pancreatic amylase (range, 1.8- to 19.8-fold normal limit) and 7 of 47 for lipase (range, 1.4- to 4-fold normal limit). Values were normal in all controls. Two HIV patients with increased total amylase had clinically evident parotid inflammation. None of the patients with increased serum pancreatic amylase and/or lipase had clinical symptoms of acute pancreatitis. Regression analysis showed no correlation between increased serum pancreatic enzyme levels and disease progression (CDC class), immunologic status (CD4 count), nutritional status, drug administration, or opportunistic infections. Conclusions: Fifteen per cent of HIV-infected children had biochemical evidence of pancreatic involvement; however, this condition was unrelated to clinical signs of pancreatitis. Neither drug administration nor opportunistic infections seem to determine the increased serum pancreatic enzyme levels.

Prevalence of Viremia in Human Immunodeficiency Virus-Infected Patients With Renal Disease

The prevalence of viremia and its relationship to the pathogenesis of nephropathy in human immunodeficiency virus (HIV)-infected patients with renal disease is unknown. To assess the prevalence of plasma viremia in HIV-infected patients with chronic renal disease, we performed a cohort study in two urban university medical centers. Samples of blood from 11 HIV-infected patients with renal failure who were treated with hemodialysis were analyzed concurrently with control samples from three non-HIV-positive patients receiving hemodialysis treatment. Samples from four HIV-infected patients with chronic renal insufficiency were evaluated concurrently. Thirty-three HIV-infected patients with serum creatinine levels of less than 132 mumol/L (1.5 mg/dL), and trace or absent dipstick proteinuria served as controls for the population with renal disease. The patients infected with HIV were staged by CD4 cell counts and the presence of opportunistic infections. Blood samples were analyzed for plasma HIV p24 antigenemia by antigen capture enzyme-linked immunosorbent assay. Blood samples were analyzed for the presence of viremia by infection of normal stimulated peripheral blood mononuclear cell cultures with plasma samples and detection of HIV p24 antigen in culture supernatants. Two of the 11 patients treated with hemodialysis had evidence of HIV p24 antigenemia, while seven of the 11 had evidence of plasma viremia. The proportion of hemodialysis patients with detectable antigenemia and viremia was similar to that in patients with chronic renal insufficiency. A significantly greater proportion of HIV-infected patients with renal disease had plasma viremia and antigenemia, compared with HIV-infected patients without renal disease. In logistic regression analysis, race, CD4 cell count (either on a continuous scale or dichotomized at 0.2 x 10(9)/L), and treatment with zidovudine were not significantly associated with the presence of plasma viremia, but patient age and the presence of renal disease were factors independently associated with viremia. The similar proportions of HIV-infected patients with viremia in groups of patients with chronic renal insufficiency and with renal disease treated with hemodialysis suggest that dialysis treatment does not increase the prevalence of plasma viremia in HIV-infected patients with renal disease. The similar proportions of HIV-infected hemodialyzed patients and patients with chronic renal insufficiency with plasma viremia, and the greater prevalence of viremia in patients with renal disease compared with HIV-infected patients without clinical renal disease suggest that plasma viremia and renal dysfunction are related. Whether this represents a cause and effect relationship is unknown. The greater prevalence of viremia in HIV-infected patients with renal disease has implications for the pathogenesis of HIV-related renal diseases and for caregivers in clinical settings and dialysis units.

The efficacy of erythropoietin in human immunodeficiency virus—infected end-stage renal disease patients treated by maintenance hemodialysis

The superimposition of human immunodeficiency virus (HIV) infection, associated opportunistic infections, and anti-retroviral therapy further worsens the severity of anemia in patients also suffering from end-stage renal disease. A major cause of anemia in renal failure is a deficiency of erythropoietin. The causes of anemia in HIV disease include direct and indirect stem cell inhibition by the virus, increased peripheral destruction of red blood cells, and bone marrow suppression by various opportunistic infections and therapeutic drugs, particularly zidovudine. We compared the efficacy of recombinant human erythropoietin (rHuEPO) therapy in improving the anemia in HIV-infected end-stage renal disease patients (group I) with that in nondiabetic (group II) and diabetic (group III) hemodialysis patients without HIV infection. All three groups of patients were comparable in dialysis prescription and serum iron studies. Iron supplementation was prescribed to all patients, and none received blood transfusions. After 8 weeks of rHuEPO therapy (administered intravenously in a dose of 100 U/kg body weight thrice weekly), the mean increase in hematocrit was similar in all responders (5.8% increase in hematocrit in 23 of 30 HIV patients and 6.7% increase in 24 of 30 non-HIV patients). Response in hematocrit was noted in HIV patients despite the presence of opportunistic infections in 15 and zidovudine administration in 11. Seven HIV-positive patients and six non-HIV patients failed to respond to rHuEPO. Irrespective of the HIV status, the baseline serum EPO levels in patients responding to rHuEPO were significantly lower than those in nonresponders. We conclude that HIV-infected end-stage renal disease patients respond well to rHuEPO therapy despite further bone marrow suppression by opportunistic infections and zidovudine, and that the responses correlate with low baseline serum EPO levels.

Elevation of IgE in HIV-infected children and its correlation with the progression of disease

Background: According to recent data, a switch from a TH1 to a TH2 pattern of cytokines might be a critical step in the progression of human immunodeficiency virus (HIV) infection. Previous studies have demonstrated a disturbance in IgE synthesis in HIV-infected adults. Methods: Fifty-eight children infected vertically with HIV and 35 children with seroreversion, aged 4 months to 11 years, were evaluated for IgE serum level, CD4+ cell count, skin prick test responses to common airborne and food allergens, individual and family history of atopy, and presence of opportunistic infections. In thirty of the 58 HIV-infected children serum interleukin-4 and interferon-γ levels were assessed. Thirty-three of the 58 HIV-infected children had a follow-up of 1 year for IgE levels, CD4+ cell count, and occurrence of opportunistic infections and recurrent bacterial infections. Results: Both IgE concentration and the percentage of children with IgE elevation were markedly increased (with no correlation to skin prick test responses or opportunistic infections) in the group of 58 HIV-infected children as compared with the 35 children with seroreversion (p < 0.05). The same parameters were higher in children with acquired immunodeficiency syndrome as compared with children with asymptomatic or mildly symptomatic disease (p < 0.05). Serum interleukin-4 and interferon-γ levels do not account for IgE hyperproduction. There was a significant association between persistent IgE elevation and severe decline (≥30% over 1 year) in CD4+ counts, as well as increased susceptibility to bacterial infections. Conclusions: Our study demonstrates a spectrum of IgE dysfunction in children, which is similar to that observed in adults. A persistent IgE hyperproduction appears to be associated with a severe decline in CD4+ cell count, suggesting that this clinical test is a useful marker of disease progression. (J ALLERGY CLIN IMMUNOL 1995;95:627-32.)

Cryptosporidiosis of liver and pancreas in rhesus monkeys with experimental SIV infection.

Following an experimental SIV infection, 11 rhesus monkeys were evaluated to determine the presence of opportunistic infections. Five animals had severe alterations of the hepatobiliary tree, three of which were associated with the presence of numerous Cryptosporidium spp. Subacute to chronic inflammatory changes were observed in the pancreatic ducts of four animals, one without histologic evidence of parasites. In one animal, the inflamed ducts were associated with a chronic interstitial pancreatitis. The rate of Cryptosporidium infection together with hepatic and pancreatic involvement (36%) supports the hypothesis that systemic cryptosporidiosis is the result of a loss of protective mucosal immunity.

Nuclear medicine and AIDS.

The human immunodeficiency virus (HIV) infection and its associated illnesses in a relatively young population of patients provides an expanding role for nuclear medicine. The disease enforces a review of each department's infection control procedures. It also necessitates a widening of the differential diagnosis in high risk patients. It has also resulted in an increase in the number of patients presenting with diseases such as Pneumocystis carinii pneumonia, Kaposi's sarcoma etc. which prior to the HIV epidemic were extremely rare. Thus in high risk patients the interpretation of abnormalities in nuclear medicine scans needs to include the spectrum of opportunistic infections and unusual tumours. The presence of opportunistic infections in the severely immunocompromised patient has lead to the development of techniques not normally used, i.e. lung 99Tcm-diethylenetriamine pentaacetate (DTPA) transfer/clearance, donor leukocyte scanning to allow rapid diagnosis of an abnormality. Radionuclide techniques are also used to monitor the effect of therapy directed at the HIV itself or against opportunistic infections. This review covers aspects of infection control as well as the use of radionuclides to investigate specific problems related to HIV infection and therapy of the associated disease processes.

Etude du profil protéique au cours de l'infection par le virus de l'immunodéficience humaine

The aim of this study was to evaluate the inflammatory response during HIV infection, using plasma acute phase proteins determination. Despite the presence of opportunistic infections and cancers, the levels of inflammatory response would be impaired in HIV infection.

The Treatment of AIDS-Related Lymphoma

To the Editor. —Levine et al 1 have recently reported in JAMA that low-dose chemotherapy with central nervous system (CNS) prophylaxis and zidovudine maintenance did not compromise the therapeutic outcome of 42 patients with non-Hodgkin's lymphoma (NHL) related to the acquired immunodeficiency syndrome (AIDS). However, patients with poor prognosis, ie, those with low performance status and presence of opportunistic infections (OIs), were not eligible for entry into this study. We in the French-Italian Cooperative Study Group have recently performed a prospective study in patients with poor-prognosis AIDS-related NHL, defined as those with performance status greater than 3 and/or presence of OIs. We used a low-dose chemotherapeutic regimen with CNS prophylaxis in combination with antiretroviral therapy, the aim being to reduce both the toxic effects on the bone marrow and the occurrence of OIs. The chemotherapeutic regimen employed was that used by the European Organization on Research and Treatment of

Immunologic aspects of HIV infection

Infection of Human organism by Human Immunodeficiency viruses induces, after a shorter or a longer period, a complex immune Deficiency (ID) that has been named Acquired Immune Deficiency Syndrome (AIDS). Although the designation is not correct, it has been accepted by the scientific community. AIDS includes multiple clinical situations that have in common HIV infection and an almost constant ID, that at the end of natural course of infection manifestated by the presence of opportunistic infections and malignant tumors. HIV-1 and HIV-2 are slow RNA viruses with a common architecture and well known genomic organization. The characteristics that made HIV infectious agent n. 1 in XXth Century are their remarkable heterogeneity, close AA sequence homology between some of their proteins and relevant molecules in human beings: MHC molecules, IL-2, VIP, etc. and a strong affinity of gp 120 to CD4 receptor of T helper lymphocytes (T4), mononuclear phagocytes, natural killer cells, etc. all of them sharing a relevant role in normal immune response (IR). Affected in its cornerstones of cellular defense, human organism starts an immune defense through antibodies, cytotoxic T Lymphocytes (CTL) Natural Killer Cells (NK) antibody dependent cell cytotoxicity (ADCC), that fails. Activating immune system HIV turn that defense strategy to their own profit and enhanced replication. After an apparent latency period--in which the balance seems to favor the host--new viral variants arise due to high rate of HIV mutagenesis, that in turn stimulate immune system, induce new cycles of viral replication and new high virulent mutants, leading to the final collapse of Immune System.(ABSTRACT TRUNCATED AT 250 WORDS)

Surgical pathology of the liver in HIV infection.

In the 6-year period 1984-1989, 101 liver biopsies or 'needle necropsies' from human immunodeficiency virus positive patients were examined histologically. Of these, only nine showed no abnormality whatsoever. The commonest histological findings were either fatty change or changes related to co-existent chronic viral hepatitis. Granulomas were seen in 15 cases, four of which were positive for acid-fast bacilli. A range of organisms were recorded: cytomegalovirus (4); Histoplasma capsulatum (1); Pneumocystis carinii (2); Cryptococcus neoformans (1); and Leishmania donovani (1). There were two cases of non-Hodgkin's lymphoma, but no cases of Kaposi's sarcoma. Marked iron deposition, which correlated with multiple blood transfusions was seen in nine biopsies. We were unable to identify any histological feature in the liver as being specific for HIV infection. The high incidence of liver abnormalities reflects: (i) the coincident exposure to hepatotropic viruses; (ii) the presence of opportunistic infections and neoplasms, usually part of a disseminated multi-organ process arising in the setting of profound immune depression; (iii) iatrogenic causes, in particular iron overload related to multiple blood transfusions received for treatment of zidovudine-induced anaemia; and (iv) non-specific changes associated with chronic debilitating disease.

Hodgkin's Disease in 50 Intravenous Drug Users with HIV-Infection.

Fifty cases of Hodgkin's disease in intravenous drug users (IVDU) have been collected by the Italian Cooperative Group on AIDS-Related Tumors (G.I.C.A.T.). Ninety-two per cent of the patients were males; the median age was 26 years. Persistent generalized lymphadenopathy (PGL) at onset was present in 54% of patients, AIDS in 9%, ARC in 9% while 28% were simply HIV-positive. The initial median absolute number of CD4 lymphocytes was 264/mmc. Opportunistic infections were diagnosed in 20% of patients. In most patients the histological pattern was that of mixed cellularity and lymphocytic depletion (76%). In almost half the initial symptom was a persistent lymph node enlargement due to PGL. In the majority of patients (58%) only a clinical staging and bone marrow biopsy could be performed due to the presence of opportunistic infections, rapid disease progression or refusal of pathologic staging procedures. One patient presented with a Waldeyer's ring involvement, but no other unusual presentations were observed. After MOPP alternated or followed by ABVD or MOPP alone, 15/29 CR (52%) and 14/29 PR (48%) were observed. The median duration of CR was 14 months, while the median survival of CR has not been reached; the median survival of patients treated with chemotherapy with CD4 values at presentation {geq}400/mmc was significantly superior to that in those with CD4 < 400/mmc. The overall median survival was 16 months. Twenty-eight per cent of patients receiving chemotherapy + radiotherapy developed opportunistic as well as non-opportunistic infections (21%). Lethal hepatic toxicity was observed in 2 patients. In conclusion, Hodgkin's disease in IVDU was not found to be associated with unusual presentations, as previously reported for homosexuals. Complete remissions could be achieved in over 50% of patients, but in IVDU non-opportunistic infections in addition to opportunistic infections may also limit treatment administration. The presence of parenchymal functional impairment due to drug abuse, or drug abuse-related infections, such as pneumonia, endocarditis and hepatitis, should lead to the choice of antitumour agents with no or only minor potential liver, lung and cardiac toxicity.

Fetal AIDS Syndrome Score

To objectively evaluate the fetal acquired immunodeficiency syndrome, we have developed a scoring system based on the presence of the characteristic features that we have previously reported. Using this scoring system, 37 children seropositive for the human immunodeficiency virus were classified into three groups: dysmorphologically severely affected (12 children); moderately affected (15 children); and mildly affected (ten children). There was a statistically significant correlation between the severity of the dysmorphic features and both the presence of opportunistic infections within the first year of life and the age at onset of symptoms associated with immune dysfunction, with the more severely stigmatized children manifesting symptoms at a younger age. There was no correlation, however, between severity of the dysmorphic features and presence of opportunistic infections at the time of our examination. We conclude that this scoring system may be useful in presymptomatic identification of severely dysmorphic human immunodeficiency virus-infected infants.

DEVELOPMENTAL ABNORMALITIES IN INFANTS AND CHILDREN WITH ACQUIRED IMMUNE DEFICIENCY SYNDROME (AIDS) AND AIDS‐RELATED COMPLEX

Children with acquired immune deficiency syndrome (AIDS) display two types of clinical picture: a full-blown AIDS characterized by the presence of opportunistic infections and/or Kaposi's sarcoma and a prodromal stage now identified as AIDS-related complex (ARC). Neurological complications have been identified in infants and children with the disease. This paper discusses the developmental abnormalities in 16 pediatric patients, seven with AIDS and nine with ARC, ranging in age from six months to six years. In all cases, the mothers of these children either had ARC, AIDS and/or used intravenous drugs. Developmental histories showed delayed acquisition of milestones in most children following the diagnosis of AIDS or ARC, with delayed motor milestones consistently noted in both groups. Several children with AIDS actually lost milestones as their illness progressed; this has not occurred in the ARC group. Psychometric testing revealed more severe cognitive dysfunction in the group with AIDS. Involvement of the central nervous system was documented clinically, radiologically, and/or electrophysiologically in all patients with AIDS. In the ARC group the course of the illness has shown greater variability. Medical and social factors that may contribute to the developmental abnormalities are discussed.

The economic crisis of 1837–1839 in Upper Canada: Case study of a temporary suspension of specie payments

As HIV steps into the third decade, there are more number of patients living on lifelong (antiretroviral therapy) ART and facing the threat of drug resistance with subsequent treatment failure. The aim of this study was to determine predictors of first-line ART failure with the objectives to estimate the burden of 2nd line ART.A retrospective 5-year cohort of HIV patients who were initiated on first line ART in 2008–09 was studied. Patients were followed from the time of ART initiation. Kaplan–Meier methods and Cox proportional hazards regression models were used to estimate probabilities and predictors of first line ART failure.Of the total of 195 patients initiated on first line ART, 15 patients were switched to second line ART yielding 7.69% failure rate. During the 7178 person-years of follow-up, the incidence of first line ART failure was 2.09 per 1000 person-years. The Kaplan–Meier survival analysis gave a mean survival time of 55.6 months. BMI, CD4 count at ART initiation and presence of opportunistic infections were significant predictors of first line ART failure. The burden of second line ART patients by the end of 5 years of first line ART is expected to be 151 patients.Though the first line ART failure is quite low in this study, we still need to be vigilant for lower BMI, low baseline CD4 count and occurrence of opportunistic infections to efficiently manage failures on first line ART.