Impaired humoral responses to subgenus D adenovirusenovirus infections in HIV-positive patients

HIV-positive patients are at increased risk of developing adenovirus infection, particularly of the gastrointestinal tract and with unusual subgenus D strains. To investigate humoral immunity to these strains of adenoviruses, the humoral immune response was examined in longitudinal samples of serum against isolates collected from a prospective study of HIV-positive patients with subgenus D adenovirus infection. Of 10 HIV-positive patients developing adenovirus infection, 3 had chronic infection (8->27 months) with one serotype, 3 had chronic infection (>/=10 months) with changing serotypes and 4 had acute and self-limiting adenovirus infection (<1 month). Fifty-one sera were tested, and samples collected before adenovirus infection were available in 8 patients. Neutralising assays were performed against the patient's own isolate (adenoviruses 9, 17, 19, 19/23, 19/37, 23, 26, 23/26, 43 and 46) and common circulating strains of adenovirus 1-5. Indirect immunofluorescence tests were carried out against the autologous isolate and complement-fixation tests were undertaken using a standard assay. Immunofluorescence test antibodies were detected (titre >/=160) in all patients, and present to high titre (>/=320) in 8/10 patients. Complement-fixing antibodies were not detected in significant titre. Of particular note, there was no significant neutralising antibody response to the patient's own isolate after acute infection. Neutralising antibody to adenovirus 3 (titre 20) was transiently detected in two patients. In the remaining patients neutralising antibody directed against adenoviruses 1-5 was not detected. Persistent carriage of subgenus D adenoviruses in HIV-positive patients is probably the result of failure of cell-mediated immune responses to clear primary infection. Nevertheless, there is marked impairment of B cell responses resulting in poor neutralising and complement-fixing antibody production even though immunofluorescence test determined antibodies are produced in high titre. These possibly reflect impairment of effective B cell priming mechanisms within the germinal centres of lymph nodes, or the polyclonal activation of B cells driven by HIV infection.     

CD4/CD8 ratio,comorbidities, and aging in treated HIV infected individuals on viral suppression

The progression of the human immunodeficiency virus (HIV) infection to acquired immunodeficiency syndrome (AIDS) can be efficiently interrupted by antiretroviral therapy (ART). However, even successfully treated HIV-infected individuals are prone to develop non-AIDS-related diseases that affect the metabolism and several organs and systems. Biomarkers that predict the occurrence of comorbidities may help develop preventive measures. Current research shows that CD4⁺ T cell counts and viral load do not predict the development of non-AIDS-related diseases. The CD4/CD8 ratio has been indicated as a suitable marker of persistent immune dysfunction and the occurrence of non-AIDS-related events in treated HIV-positive patients. In this study, we explored the relationship between CD4/CD8 ratios, comorbidities, and aging in ART-treated HIV patients on viral suppression. We collected and evaluated data from 352 HIV-positive adults who were virologically suppressed (<40 copies/mL) on ART and with CD4 counts above 350 cells/mm³. The median age for participants was 46 years, 218 individuals had at least one comorbidity, and 239 had inverted CD4/CD8 ratios (<1). Current CD4/CD8 ratios were predicted by baseline CD4/CD8 ratios and nadir CD4 counts. Despite the high rates of inverted CD4/CD8 ratios and prevalence of comorbidities, no association between them was observed. The prevalence of comorbidities was significantly higher in older individuals, though aging alone did not explain the rate of all individual comorbidities. Low CD4/CD8 ratios were linked to neurocognitive disorders, suggesting that persistent T cell dysfunction contributes to neurocognitive decline.     

A correlation analysis of HHV infection and its predictive factors in an HIV-seropositive population in Yunnan,China

Human herpesviruses (HHVs) have a particularly high prevalence in certain high-risk populations and cause increased morbidity and mortality in patients with acquired immunodeficiency syndrome (AIDS). Screening and treating subclinical HHV infections reduce human immunodeficiency virus (HIV) infection incidence, disease progression, and transmission. However, there are few studies on HHVs, HIV coinfection rates, and their related risk factors. We aimed to clarify the prevalence of all eight HHVs in peripheral blood samples collected from HIV-positive patients, and explore the association of HHV infection in HIV-positive patients in an HIV-seropositive population in Yunnan. We recruited 121 HIV-positive patients with highly active antiretroviral therapy (HAART) and 45 healthy individuals. All the eight HHVs were detected using polymerase chain reaction and their epidemiological information and clinical data were collected and statistically analyzed. A high prevalence of HHVs (89.3%) was observed in individuals with HIV infections and with herpes simplex virus (HSV)-2 (65.3%), and HSV-1 (59.5%) being the most common. Coinfection with more than two different HHVs was more common in patients with HIV infections receiving HAART (72.7%) than in healthy controls. Older age, being married, higher HIV-1 plasma viral loads, and use of antiviral protease inhibitors were independently correlated with an increased frequency of HHVs, but we found no association with CD4 count, WHO HIV clinical stage, and HIV infection duration. Our findings are of great significance for the prevention of HHV opportunistic infection in patients with AIDS and their clinical treatment.     

Field Evaluation of the Determine Rapid Human Immunodeficiency Virus Diagnostic Test in Honduras and the Dominican Republic

Rapid detection of human immunodeficiency virus (HIV) infection can result in improved patient care and/or faster implementation of public health preventive measures. A new rapid test, Determine (Abbott, Abbott Park, Ill.), detects HIV type 1 (HIV-1) and HIV-2 antibodies within 15 min by using 50 microl of serum or plasma. No specialized equipment or ancillary supplies are required, and results are read visually. A positive result is noted by the appearance of a red line. An operational control (red line) indicates proper test performance. We evaluated the Determine rapid HIV detection test with a group of well-characterized serum samples (CD4 counts and viral loads were known) and serum samples from HIV-positive individuals at field sites in Honduras and the Dominican Republic. In the field evaluations, the results obtained by the Determine assay were compared to those obtained by local in-country HIV screening procedures. We evaluated serum from 100 HIV-positive patients and 66 HIV-negative patients. All samples gave the expected results. In a companion study, 42 HIV-positive samples from a Miami, Fla., serum bank were tested by the Determine assay. The samples had been characterized in terms of CD4 counts and viral loads. Fifteen patients had CD4 counts <200 cells/mm(3), while 27 patients had CD4 counts >200 cells/mm(3). Viral loads ranged from 630 to 873,746 log(10) copies/ml. All samples from the Miami serum bank were positive by the Determine test. Combined results from the multicenter studies indicated that the correct results were obtained by the Determine assay for 100% (142 of 142) of the HIV-positive serum samples and 100% (66 of 66) of the HIV-negative serum samples. The Determine test was simple to perform and the results were easy to interpret. The Determine test provides a valuable new method for the rapid identification of HIV-positive individuals, especially in developing countries with limited laboratory infrastructures.     

Chronic diarrhoea in HIV patients: prevalence of coccidian parasites

The purpose of this study was to determine the prevalence of intestinal parasites in HIV patients with or without diarrhoea and to see an association between diarrhoea and the coccidian parasites in our setting. Stool samples from 113 HIV patients, 34 chronic diarrhoea and 79 without any history of diarrhoea were collected and examined for enteric parasites by microscopy. One hundred and thirteen control samples from HIV negative patients complaining of prolonged diarrhoea were also collected and analysed. Prevalence of coccidian parasites in HIV and non-HIV patients; with and without diarrhoea was compared using chi-square tests. Enteric parasites were detected in 55.8% HIV patients with diarrhoea compared to 16.4% in patients without diarrhoea (P<0.001). Isospora belli was found in 41.1% (14/34) of chronic diarrhoea and 6.3% (5/79) in non-diarrhoeal cases (P<0.001). Cryptosporidium was detected in 20.6% (7/34) of chronic diarrhoea and 2.5% (2/79) in non-diarrhoeal cases (P<0.001). Cyclospora cayetanensis associated diarrhoea was detected in only one case of chronic diarrhoea (2.9%). CD4+ T-cell count was lower (180 cells/microL) in diarrhoeal HIV patients as compared to non-diarrhoeal patients. Coccidian parasites were seen at a mean CD4+ T-cell count of 186.3 cells/microL. This study concluded that Isospora belli was the predominant parasite followed by Cryptosporidium spp. and both were strongly associated with diarrhoea among HIV patients.     

Adenovirus infection of the large bowel in HIV positive patients.

AIMS: To describe the microscopic appearance of adenovirus infection in the large bowel of human immunodeficiency virus (HIV) positive patients with diarrhoea. METHODS: Large bowel biopsy specimens from 10 HIV positive patients, eight of whom were also infected with other gastrointestinal pathogens, with diarrhoea were examined, together with six small bowel biopsy specimens from the same group of patients. Eight of the patients had AIDS. The biopsy specimens were examined by light microscopy performed on haematoxylin and eosin stained and immunoperoxidase preparations, the latter using a commercially available antibody (Serotec MCA 489). Confirmation was obtained with electron microscopy. RESULTS: The morphological appearance of cells infected with adenovirus showed characteristic nuclear and cellular changes, although the inflammatory reaction was non-specific. Immunoperoxidase staining for adenovirus was sensitive and specific, and the presence of viral inclusions consistent with adenovirus was confirmed by electron microscopy. CONCLUSIONS: The light microscopic features of adenovirus infection are distinctive and immunocytochemistry with a commercially available antibody is a sensitive and specific means of confirming the diagnosis. Further studies of the role of adenovirus in causing diarrhoea in these patients are indicated.     

Role of C-reactive protein in HIV infection: a pilot study

Limited data on acute phase C-reactive protein (CRP) levels in human immunodeficiency virus (HIV) infection exist. The relationship of CRP with HIV was assessed in 119 HIV-positive patients and correlated with CD4 counts and mortality at 1 y. CRP was negatively correlated with CD4 counts with levels of CRP being highest in the group with CD4 counts below 200 cells/microL. It was an indicator of mortality and hence may serve as a useful and inexpensive predictor of HIV disease progression.     

Cryptosporidium and other enteric parasitic infections in HIV-seropositive individuals with and without diarrhoea in Osogbo, Nigeria

The primary objective of this cross-sectional study is to correlate the presence of Cryptosporidium and other gastrointestinal parasites with the presence of diarrhoea in human immunodeficiency virus (HIV)-infected patients. Stool samples from 96 HIV-seropositive cases were examined for non-opportunistic parasites using the direct and formol-ether concentration methods, while the modified Ziehl-Neelsen technique was used to detect Cryptosporidium spp. The overall prevalence of Cryptosporidium spp. was 54.2%. Other intestinal parasites detected included Ascaris lumbricoides (59.4%), hookworm (5.2%), Entamoeba histolytica (3.1%), Strongyloides stercoralis (1%) and Taenia spp. (1%). Infection inmales was more common (68.2%) than in females (55.4%) but the difference was not statistically significant. Therewas a significant association between Cryptosporidium infection and CD4+ count (P=0.0001), with the highest parasite prevalence (90%) observed among patients who had the lowest CD4+ count (<200 cells/mm3). Forty-five (86.5%) patients with Cryptosporidium infection presented with diarrhoea and the difference between those with and without diarrhoea was statistically significant (P=0.0001). There was a statistically significant difference (P=0.0001) among the age groups, with the 41-50 group showing the highest prevalence (84.6%) of infection. Co-infection was observed in 13.5% of the patients. As no drug is currently available for the treatment of cryptosporidiosis, emphasis should be placed on educating HIV-infected individuals about prevention.     

SEN virus seroprevalence in HIV positive patients: association with immunosuppression and HIV-replication.

BACKGROUND: Patients infected with HIV are often co-infected with other viruses. SEN virus (SENV) was isolated from a HIV positive patient with intravenous drug use and post-transfusion hepatitis. SENV strains D and H seem to be relevant for the development of post-transfusion hepatitis. We compared the prevalence of SENV strains D and H and the viral load of SENV H in HIV-infected patients with healthy blood donors. The results were correlated with clinical markers such as HIV stage, CD4 cell count, HIV-RNA positivity, HAART or the transmission mode in HIV infected individuals. OBJECTIVES: Blood samples of 143 HIV-positive patients were analysed and compared with a control group of 122 healthy blood donors. SENV D and -H was detected by PCR. RESULTS: SENV was detectable in 15.4% (22/143) of HIV-positive patients compared to 10.4% (12/122) in the control group (P=0.18). SENV H DNA-levels were significantly higher in HIV-positive patients (P=0.01). The prevalence in patients with CD4 cells less than 200/mm(3) was 31% (13/42), compared to 12.3% (8/65) in cases with CD4 cells between 200 and 500/mm(3), and 2.8% in cases with CD4 cells above 500/mm(3) (P=0.002 for CD4 cells <200 versus CD4 cells >200, P=0.031 for CD4 cells <500 versus CD4 cells >500). Prevalence of these strains was not significantly influenced by CDC stages. SENV was detected significantly more frequent in patients with detectable HIV-RNA (P=0.005). Patients undergoing HAART were significantly less frequent positive for SENV D or -H (P=0.029) than patients without HAART. In a multivariate analysis using a logistic regression model HIV-RNA positivity and CD4 cell count were identified as independent factors for SENV prevalence. CONCLUSION: SENV (D and H) prevalence is not significantly higher in HIV-positive patients in comparison to healthy blood donors. SENV prevalence depends on CD4 cell count and HIV-RNA.     

Factors associated with CD4 lymphocyte counts in HIV-negative Senegalese individuals

CD4+ lymphocytes are a primary target of the human immunodeficiency virus (HIV), and CD4 counts are one of the factors used to measure disease progression in HIV-positive individuals. CD4 counts vary in uninfected individuals and across populations due to a variety of demographic, environmental, immunological and genetic factors that probably persist throughout the course of HIV infection. This study sought to determine reference levels and identify factors that influence lymphocyte counts in 681 HIV-uninfected adults in Senegal, where residents are exposed to a variety of infectious diseases and other conditions that may affect CD4 counts. Lymphocyte counts were assessed in commercial sex workers, symptomatic men and women presenting to the University of Dakar infectious disease clinic for out-patient care and women seeking family planning services. CD4 and CD3 lymphocyte counts differed between the four study groups (P < 0.01). Men had the lowest mean CD4 count (711.6 cells/microl), while commercial sex workers had the highest levels (966.0 cells/microl). After adjustment for age and other behavioural and clinical factors, the difference in CD4 counts between the three groups of women did not remain. However, both gender and smoking were associated independently with CD4 counts, as men maintained lower mean CD4 counts (beta = -156.4 cells/microl, P < 0.01) and smokers had higher mean CD4 counts (beta = 124.0 cells/microl, P < 0.01) than non-smokers in multivariable analyses. This study is the first to explore factors that may influence CD4 levels in Senegal and to estimate baseline CD4 levels among HIV-negatives, information that may guide clinicians in interpreting CD4 counts.     

DETECTION OF OPPORTUNISTIC DNA VIRAL INFECTIONS BY MULTIPLEX PCR AMONG HIV INFECTED INDIVIDUALS RECEIVING CARE AT A TERTIARY CARE HOSPITAL IN SOUTH INDIA

Purpose: Opportunistic viral infections cause increased morbidity and mortality among human immunodeficiency virus (HIV) infected individuals, especially those who are not on antiretroviral treatment. Early diagnosis of these opportunistic viruses will be able to reduce the risk of disease progression with appropriate intervention. Materials and Methods: Multiplex PCR was attempted to detect the opportunistic herpes viruses (HSV-1, HSV-2, VZV, EBV, and CMV), adenovirus and polyoma viruses (JC and BK) in three cocktails of PCR reactions. Subsequently, all the viruses detected were quantitated by testing using monoplex real time PCR. Whole blood samples collected between 2006 and 2007 from 68 treatment naïve HIV-1 infected and 30 normal healthy individuals were tested for these eight viruses. Among the 68 HIV -1 infected individuals 35 had CD4+ T cell count less than or equal to 200 while the other 33 had greater than 200 CD4+ T cells. Results: Among the 68 HIV-1 infected individuals, 49 (72%) were positive for EBV, 5 (7%) samples were positive for CMV. All the five CMV positive individuals had CD4+ T cell count of less than or equal to 200 cells/µL. The mean EBV load among the individuals with a CD4+ T cells of less than or equal to 200 cells/µL was 3.88 log₁₀ while among those with greater than 200 CD4+ T cells it was 3.75 log₁₀. The mean CMV load was 6.98 log_10. Three samples were positive for both CMV & EBV. None of the samples was positive for HSV-1, HSV-2, VZV, Adenovirus, JC and BK viruses. Conclusions: In our study, multiplex PCR based detection system was found useful in detecting opportunistic viruses in HIV infected individuals. Though EBV is the most prevalent opportunistic viral infection among HIV infected individuals, there was no significant association between EBV load, CD4+ T cell counts and HIV-1 virus load. CMV was seen in HIV infected individuals with low CD4+ T cell counts (less than 200 cells/μL).     

Fas (CD95) expression on CD4+ T cells from HIV-infected patients increases with disease progression

Active T cell suicide (apoptosis) is supposed to be involved in the CD4⁺ T cell depletion in the course of HIV infection. We investigated the expression of the apoptosis-related antigen Fas on CD4⁺ T cells from 25 HIV-positive individuals (CDC I-III) and 8 HIV-negative controls by two-colour flowcytometry. In addition, we evaluated: total CD4 count, HIV p24 antigen concentration in serum after immune complex dissociation, and clinical course of infection in HIV-positive individuals. We found a significant increase in mean Fas expression on CD4⁺ T cells from HIV-positive individuals compared to HIV-negative individuals (85.84±14.92% vs. 64.28±7.59%, P<0.001). Within the HIV-positive group the increase in Fas expression was correlated with the decline in CD4 count (r=–0.76, P<0.001), p24 antigen concentration in serum after immune complex dissociation (r=0.67, P<0.001), and CDC stage (r=0.73, P<0.001). The upregulation of Fas antigen on CD4 cells is associated with CD4 depletion and other virological and clinical marker of disease progression in HIV infection.Abbreviations AIDS Acquired immunodeficiency syndrome - CDC Center of disease control - CTL Cytotoxic T lymphocyte - FasL Fas ligand - HIV Human immunodeficiency virus - MFI Mean fluorescence intensity     

One-year prospective cross-sectional study to assess the importance of group F adenovirus infections in children under 2 years admitted to hospital

A 1-year prospective cross-sectional study of 363 children under 2 years of age admitted to hospital was undertaken to assess the importance of group F adenovirus infections. Faeces obtained within 48 hours of admission from 97 patients with and 266 patients without diarrhoea were screened by electron microscopy. Viruses were identified by morphological criteria, and all adenoviruses seen were retested by immune electron microscopy to identify group F serotypes. Group F adenoviruses (4 infections) were second in frequency to rotaviruses (16 infections), and both viruses were significantly associated with diarrhoea (P = 0.005 and 0.00001 respectively, chi-squared test). All four group F infections occurred in children with diarrhoeal disease aged between 1 and 6 months and were numerically as important as rotavirus (three infections) in this group. Rotavirus infections occurred significantly more frequently in the 7-24-month age group with diarrhoea (11 v.0 infections, P = 0.001, chi-squared test). Nosocomial infection occurred with group F adenovirus as well as rotavirus. The finding that group F adenoviruses occur as frequently as rotaviruses in diarrhoeal disease that results in hospital admission in children between 1 and 6 months of age could have important implications for preventative strategies.     

Carriage frequency, intensity of carriage, and strains of oral yeast species vary in the progression to oral candidiasis in human immunodeficiency virus-positive individuals

Candida samples were taken over a period of 2 years from 54 human immunodeficiency virus (HIV)-positive asymptomatic subjects to evaluate changes in yeast carriage, intensity of carriage, and genotype over time. Overall, we found that HIV-positive patients with CD4(+)-cell counts of between 200 and 400/microl had significantly more yeast colonization than healthy control subjects. Of the 54 patients, 11 developed thrush. We found that intensity of carriage in these 11 patients increased significantly in the progression from asymptomatic yeast carrier to an episode of oral thrush. Also, the most common yeast species isolated was Candida albicans; however, we did see a number of patients harboring multiple species at the same time. Using the C. albicans-specific probe Ca3, we found that 54% (n = 6) of the 11 patients who developed thrush maintained genetically similar strains throughout the study period, with minor genetic variations in all patients except one. Forty-six percent of these patients had either multiple strains throughout the study period (n = 2), strain replacement (n = 1), or species replacement (n = 2). Of the patients who had multiple strains, one (I4) was infected by two different strains of Candida dubliniensis distinguished by a recently developed species-specific probe. These results suggest that commensal strains colonizing HIV-positive individuals can undergo alterations prior to producing an episode of thrush.     

Impact of human immunodeficiency virus infection on the histological features of chronic hepatitis C: a case-control study. The MULTIVIRC group

Hepatitis C virus (HCV) is frequently encountered in human immunodeficiency virus (HIV)-infected patients because of common routes of transmission. Previous studies suggested that HIV infection impaired the natural course of chronic hepatitis C, with a more rapid progression to cirrhosis. However, these studies did not assess the HIV infection impact on chronic hepatitis C by taking into account the risk factors for liver fibrosis progression: alcohol, sex, age at the contamination, and duration of HCV infection. We studied liver biopsy specimens of 2 groups of 58 patients that were infected by both HCV and HIV or by HCV alone. The 2 groups were matched according those risk factors, and liver biopsy responses were evaluated with the METAVIR items. The METAVIR activity was higher in HIV-positive than HIV-negative patients. Cirrhosis was more frequent: (1) in HIV-positive patients with CD4 < or = 200 cells/microL (45%) than in HIV-negative patients (10%) (P = .003), (2) in HIV-positive patients with CD4 < or = 200 cells/microL (45%) than in HIV-positive patients with CD4 > 200 cells/microL (17%) (P = .04). These differences, which were linked to HIV status, might be related to the enhanced HCV replication during HIV infection or other immune mechanisms that need further studies.     

Seroprevalence of HHV 8 antibodies among the general population and HIV positive persons in the Czech Republic.

BACKGROUND: The seroprevalence rates of herpesvirus 8 (HHV 8) antibodies were determined for the general Czech population and HIV-positive individuals. OBJECTIVES: Six hundred and sixty six serum samples from the general Czech population and 129 serum samples from HIV-positive persons were tested for the presence of antibodies to the HHV 8 lytic and latent antigens. STUDY DESIGN: HHV 8 antibodies were detected by the indirect immunofluorescence test. RESULTS: In the general Czech population, only 2.4 and 0.3% of the serum samples tested positive for antibodies against the lytic and latent HHV 8 antigens, respectively. As many as 34.9 and 10.9% HIV positive individuals had antibodies to the HHV 8 antigens, respectively. Only three of them have developed Kaposi's sarcoma (KS) to date. At the time of KS diagnosis, the three patients had antibodies to both HHV 8 antigens. HIV-positive homo/bisexuals were at significantly higher risk of acquiring HHV 8 infection compared with HIV-positive heterosexuals. The increase in HHV 8 seroprevalence was associated with progression of the HIV infection from stage A to stage B. No correlation was found between the HHV 8 seroprevalence and CD 4+T-lymphocytes counts or the HIV viral load. CONCLUSIONS: Among the general Czech population, the HHV 8 seroprevalence is as low as in the West European countries. The mean HHV 8 seroprevalence rate in HIV-positive individuals was 34.9% and was comparable with those reported in other low seroprevalence countries.     

Dynamics of CD4 cell count among HIV-infected individuals in Lagos,Nigeria

Human immunodeficiency virus (HIV) infection leads to progressive loss of CD4 T cells. Antiretroviral therapy has been able to inhibit this process, resulting in significant level of immune recovery and function. Our aim is to investigate the dynamics of CD4 recovery among HIV patients in Lagos, Nigeria. A total of 213 HIV-positive individuals were enrolled between October 2007 and May 2008, and followed up for 9 months based on CD4 count. CD4 analysis was done by flow cytometry at enrollment and after every 3 months. Data were grouped according to age range, antiretroviral treatment (ART), and time between infection and diagnosis. Kaplan–Meier survival analysis was used for data analysis. There was a significant difference in CD4 count between antiretroviral (ART) naïve and ART experienced subjects (P < 0.001). About 50% of the ART experienced population was identified to show poor CD4 reconstitution unable to achieve a CD4 of 500 cells/µl after 9 months of therapy. Time interval between infection and therapy was also identified to contribute to poor CD4 restoration. Further studies need to be done to classify immunological nonresponders among HIV patients in Nigeria. We also recommend introduction of programs that will facilitate early detection of HIV infection.     

Concentrations of soluble Fas and soluble Fas ligand as indicators of programmed cell death among patients coinfected with Human Immunodeficiency Virus and Hepatitis C Virus

Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) coinfections can affect mechanisms of programmed cell death and therefore influence acquired immunodeficiency syndrome (AIDS) development as well as the course of chronic hepatitis C. The aim of the study was to assess soluble Fas (sFas) and soluble Fas ligand (sFasL) concentrations in HIV- and HCV-coinfected patients and, moreover, to establish their relationships with HIV viral load, CD4+ T lymphocyte count, as well as liver function tests. Seventy-eight patients were included in the study, among them 30 coinfected with HIV and HCV, 10 infected only with HIV, and 38 infected only with HCV. HIV infection was confirmed by means of Western blot analysis; HIV viral load was measured by RTPCR; and CD3+, CD4+, and CD8+ T lymphocyte counts were established by means of flow cytometry. HCV infection was confirmed through HCV RNA isolation, using RT-PCR. sFas and sFasL concentrations were measured in duplicate by ELISA. The mean CD4+ T lymphocyte count decreased in HIV- and HCV-coinfected patients versus HIV-infected individuals (429 versus 279/ml). sFasL protein was detectable principally in HIV-infected individuals without HCV infection (90%), whereas in those with HCV infection it occurred only in 11% of cases. The highest sFas concentration was observed in HCV-infected patients (25.9 ng/ml) as well as in HIV- and HCV-coinfected individuals (20.3 ng/ml). This concentration was negatively proportional to sFasL prevalence. The results of our study suggest that HCV infection in HIV-positive individuals may suppress processes of programmed cell death. There was no correlation between sFas, sFasL, and HIV-1 viral load. On the other hand, sFas concentration and the presence of sFasL were related to CD4+ T lymphocyte count.     

Enhanced accessory cell function by alveolar macrophages from patients infected with the human immunodeficiency virus: potential role for depletion of CD4+ cells in the lung

Mononuclear phagocytes, including alveolar macrophages (AM), can be infected by the human immunodeficiency virus (HIV). Acting as accessory cells (AC), AM could infect CD4 lymphocytes through cell-to-cell contact and by inducing T cell proliferation, which increases lymphocyte susceptibility to infection. Using normal allogeneic T cells as responders, AM from infected individuals demonstrated an enhanced ability to stimulate a Con A and pokeweed mitogen lymphocyte proliferation assay compared with normal AM. Exogenous IL 1 enhanced the stimulation of a mitogen response by normal AM, but not from HIV-positive individuals, suggesting increased levels of this cytokine may explain the observed enhancement. However, increased IL 1 secretion by AM from HIV-infected patients could not be demonstrated, either in a bioassay or antigenically using an ELISA for IL-1 beta. Syncytia formation was observed when AM from asymptomatic HIV-positive individuals were cultured with normal T cells, suggesting viral transmission was occurring. Finally, in individual patients the stimulation of a mitogen response was inversely correlated with the CD4/CD8 ratio and total CD4 count, suggesting that enhanced AC function and CD4 cell depletion may be related in vivo. These findings indicate that enhanced AM accessory cell function is seen in HIV-infected individuals and could be a potential mechanism for CD4 cell depletion in the lung.     

Immunoglobulin levels amongst persons with and without human immunodeficiency virus type 1 infection in Uganda and Norway

CD4+-cell count and viral load monitoring are expensive and unavailable to most human immunodeficiency virus (HIV)-infected people in Africa. In an attempt to evaluate alternative methods for monitoring antiretroviral (ARV) therapy, we measured concentrations of immunoglobulin (Ig)A, IgM, IgG and IgG1 amongst adults with and without HIV in Uganda and Norway. We adjusted for disease severity by stratifying HIV-positive subjects on CD4+-cell counts above and below 200 cells/ micro l. Median serum levels of IgG, IgG1 and IgA were significantly higher in HIV-positive persons compared with HIV-negative persons in both countries (P < 0.001 and P = 0.018 for IgA in Ugandan patients). Levels of IgA in Ugandan HIV-negative subjects were significantly lower than those in HIV-positive subjects with low CD4+ compared with those with high CD4+-cell counts (P < 0.001 and P = 0.069, respectively). IgM levels were different between the HIV-negative and the two HIV-positive groups in Norway (P < 0.001). The mean levels of IgM, IgG and IgG1 in HIV-negative and -positive African subjects were generally higher than those in comparable groups of Western subjects. Our results verify that levels of IgA, IgG and IgG1 vary between HIV-negative and -positive individuals in both study populations. Their determination may be useful in monitoring both disease progression and response to ARV therapy.