Intestinal parasitic infections in HIV/AIDS patients: epidemiological, nutritional and immunological aspects

This study applied a socioeconomic questionnaire designed to evaluate the frequency of intestinal parasites and characterize epidemiological, nutritional, and immunological variables in 105 HIV/AIDS patients - with and without parasitic infections, attending the Day Hospital in Botucatu, UNESP, from 2007 to 2008. Body mass index was calculated and the following tests performed: parasitological stool examinations; eosinophil, IgE, CD4(+) T and CD8(+) T lymphocyte cell counts; albumin test; viral load measure; and TNF-alpha, IFN-gamma, IL-2, IL-5 and IL-10 cytokine levels. Results were positive for parasitic intestinal infections in 12.4% of individuals. Most patients had good socioeconomic conditions with basic sanitation, urban dwellings, treated water supply and sewage, good nutritional and immunological status and were undergoing HAART. Parasites were found at the following frequencies: Entamoeba - five patients (38.5%), Giardia lamblia-four (30.7%), Blastocystis hominis-three (23.0%), Endolimax nana-two (15.4%), and Ascaris lumbricoides - one (7.7%). There were no significant differences between the two groups for eosinophils, albumin, IgE, CD4(+) T and CD8(+) T lymphocytes, INF-gamma, IL-2, or IL-10. Most patients also showed undetectable viral load levels. Significant differences were found for TNF-alpha and IL-5. These results show the importance of new studies on immunodeficient individuals to increase understanding of such variables.

Cryptococcus gattii VGIII isolates causing infections in HIV/AIDS patients in Southern California: identification of the local environmental source as arboreal.

Ongoing Cryptococcus gattii outbreaks in the Western United States and Canada illustrate the impact of environmental reservoirs and both clonal and recombining propagation in driving emergence and expansion of microbial pathogens. C. gattii comprises four distinct molecular types: VGI, VGII, VGIII, and VGIV, with no evidence of nuclear genetic exchange, indicating these represent distinct species. C. gattii VGII isolates are causing the Pacific Northwest outbreak, whereas VGIII isolates frequently infect HIV/AIDS patients in Southern California. VGI, VGII, and VGIII have been isolated from patients and animals in the Western US, suggesting these molecular types occur in the environment. However, only two environmental isolates of C. gattii have ever been reported from California: CBS7750 (VGII) and WM161 (VGIII). The incongruence of frequent clinical presence and uncommon environmental isolation suggests an unknown C. gattii reservoir in California. Here we report frequent isolation of C. gattii VGIII MATα and MATa isolates and infrequent isolation of VGI MATα from environmental sources in Southern California. VGIII isolates were obtained from soil debris associated with tree species not previously reported as hosts from sites near residences of infected patients. These isolates are fertile under laboratory conditions, produce abundant spores, and are part of both locally and more distantly recombining populations. MLST and whole genome sequence analysis provide compelling evidence that these environmental isolates are the source of human infections. Isolates displayed wide-ranging virulence in macrophage and animal models. When clinical and environmental isolates with indistinguishable MLST profiles were compared, environmental isolates were less virulent. Taken together, our studies reveal an environmental source and risk of C. gattii to HIV/AIDS patients with implications for the >1,000,000 cryptococcal infections occurring annually for which the causative isolate is rarely assigned species status. Thus, the C. gattii global health burden could be more substantial than currently appreciated.

Tuberculosis and the risk of opportunistic infections and cancers in HIV-infected patients starting ART in Southern Africa

To investigate the incidence of selected opportunistic infections (OIs) and cancers and the role of a history of tuberculosis (TB) as a risk factor for developing these conditions in HIV-infected patients starting antiretroviral treatment (ART) in Southern Africa.

Cerebro-meningeal infections in HIV-infected patients: a study of 116 cases in Libreville, Gabon.

Background: Cerebro-meningeal pathology is common in human immunodeficiency virus (HIV) infection and the aetiology is often difficult to ascertain with certainty. Objective: To describe the major suspected and identified causes of meningeal or encephalitic syndromes in HIV infection in Libreville, Gabon. Methods: A descriptive study using clinical records of patients hospitalised in the Department of Medicine in the Military Hospital of Libreville (Gabon) between January 2006 and May 2010. Clinical features were evaluated using multivariable logistic regression to evaluate association with the outcome of a clinical improvement or death. Results: The most frequent neurological symptoms were reduced level of consciousness (54.3%), headache (55.2%), motor deficit (38.7%), and convulsions (36.2%). Cerebral toxoplasmosis represented 64.7% of diagnoses, followed by cryptococcal neuromeningitis in 12.9% of cases. Tuberculoma was diagnosed in 4 cases and lymphoma in 2 cases. In 9.5% of cases, no aetiology was determined. Toxoplasmosis treatment led to clinical improvement in 69.3% of cases with suspected cerebral toxoplasmosis. Overall mortality was 39.7%. Conclusion: The diagnosis of neurological conditions in HIV positive patients is difficult, particularly in a low-resource setting. A trial of treatment for toxoplasmosis should be initiated first line with all signs of neurological pathology in a patient infected with HIV.

In vitro antifungal susceptibility of Candida spp. oral isolates from HIV-positive patients and control individuals

Oropharyngeal candidiasis is the most common fungal infection among HIV-positive patients. This condition can be treated with either systemic or topical antifungal agents; treatments are usually indicated empirically on the basis of clinical data. The knowledge of in vitro antifungal susceptibility is important to determine correct therapeutic guides for the treatment of fungal infections. Therefore, the objective of this study was to determine the antifungal susceptibility profile of oral Candida isolates from HIV-positive patients and control individuals. Amphotericin B, fluconazole, flucytosine, nystatin and ketoconazole were tested according to the methodology of microdilution proposed by the Clinical and Laboratory Standards Institute (CLSI); results were recorded in values of minimal inhibitory concentration (MIC). A total of 71 Candida isolates from HIV-positive patients were examined with the following species represented: C. albicans (59), C. tropicalis (9), C. glabrata (1), C. guilliermondii (1) and C. krusei (1). A total of 15 Candida isolates were evaluated from control individuals comprised of 11 C. albicans and 4 C. tropicalis samples. Our results demonstrated that the tested antifungal agents showed good activity for most isolates from both groups; however, variability in MIC values among isolates was observed.

Human gammaherpesviruses viraemia in HIV infected patients

The Epstein-Barr virus (EBV) and Kaposi's sarcoma associated herpesvirus (KSHV) are consistently associated with lymphoproliferative diseases and cancers in humans, notably in patients with HIV. Our aim was to evaluate whether EBV and/or KSHV viral loads regularly assessed in peripheral blood mononuclear cells (PBMC) correlate with clinical or laboratorial parameters retrieved for patients living with HIV. This was a longitudinal study with a cohort of 157 HIV positive patients attending an academic HIV outpatient clinic in São Paulo State, Brazil. For each patient, up to four blood samples were collected over a 1 year clinical follow-up: on enrolment into the study, and after 4, 8 and 12 months. Total DNA was extracted from PBMC, and EBV and KSHV viral loads were assessed by real time quantitative PCR. Higher viral loads for EBV were significantly associated with high HIV viraemia, a greater number of circulating T CD8+ cells and lack of virological response to the antiretroviral treatment. KSHV viral load was undetectable in virtually all samples. EBV viral load in PBMC correlated with the number of circulating T CD8+ lymphocytes and the response to the antiretroviral therapy in HIV infected patients. In contrast, KSHV was undetectable in PBMC, presumably an effect of the antiretroviral treatment. Therefore, either KSHV infection in the population studied was absent or viral load in PBMC was beyond the analytical limit of the assay.

Antimicrobial Photodynamic Therapy in the Treatment of Oral Candidiasis in HIV-Infected Patients

Objective: Antimicrobial photodynamic therapy (aPDT) has been used to combat local infections, and it consists of the combination of a photosensitizer, a light source, and reactive oxygen species (ROS) to kill microbial cells. In this study, we evaluated the effectiveness of aPDT in the treatment of candidiasis in HIV-infected patients. Methods: Twenty-one patients were divided into three groups. Control group (CG) was treated with the conventional medication for candidiasis (fluconazole 100 mg/day during 14 days). Laser group (LG) was subjected to low-level laser therapy (LLLT), wavelength 660 nm, power of 30 mW, and fluence of 7.5 J/cm(2), in contact with mucosa during 10 sec on the affected point. An aPDT group (aPDTG) was treated with aPDT, that is, combination of a low-power laser and methylene blue 450 mu g/mL. Pre-irradiation time was 1 min. Parameters of irradiation were the same ones as for the LG, and patients were single irradiated. Patients were clinically evaluated and culture analysis was performed before, immediately after, and 7, 15, and 30 days after the treatment. Results: Our results showed that fluconazole was effective; however, it did not prevent the return of the candidiasis in short-term. LLLT per se did not show any reduction on Candida spp. aPDT eradicated 100% of the colonies of this fungus and the patients did not show recurrence of candidiasis up to 30 days after the irradiation. Conclusions: These findings suggest that aPDT is a potential approach to oral candidiasis treatment in HIV-infected patients.

Hypermetabolism and altered substrate oxidation in HIV-infected patients with lipodystrophy

Objective: Human immunodeficiency virus type 1 (HIV)-associated lipodystrophy syndrome compromises body composition and produces metabolic alterations, such as dyslipidemia and insulin resistance. This study aims to determine whether energy expenditure and substrate oxidation are altered due to human HIV-associated lipodystrophy syndrome. Methods: We compared energy expenditure and substrate oxidation in 10 HIV-infected men with lipodystrophy syndrome (HIV+LIPO+), 22 HIV-infected men without lipodystrophy syndrome (HIV+LIPO-), and 12 healthy controls. Energy expenditure and substrate oxidation were assessed by indirect calorimetry, and body composition was assessed by dual-energy X-ray absorptiometry. The substrate oxidation assessments were performed during fasting and 30 min after eucaloric breakfast consumption (300 kcal). Results: The resting energy expenditure adjusted for lean body mass was significantly higher in the HIV+LIPO+ group than in the healthy controls (P = 0.02). HIV-infected patients had increased carbohydrate oxidation and lower lipid oxidation when compared to the control group (P < 0.05) during fasting conditions. After the consumption of a eucaloric breakfast, there was a significant increase in carbohydrate oxidation only in the HIV+LIPO- and control groups (P < 0.05), but there was no increase in the HIV+LIPO+ group. Conclusion: Hypermetabolism and alteration in substrate oxidation were observed in the HIV+LIPO+ group. (C)2012 Elsevier Inc. All rights reserved.

Estimated mortality of adult HIV-infected patients starting treatment with combination antiretroviral therapy

To provide estimates of mortality among HIV-infected patients starting combination antiretroviral therapy.

The IFNL3/4 ΔG variant increases susceptibility to cytomegalovirus retinitis among HIV-infected patients.

BACKGROUND Cytomegalovirus (CMV) retinitis is a major cause of visual impairment and blindness among patients with uncontrolled HIV infections. Whereas polymorphisms in interferon-lambda 3 (IFNL3, previously named IL28B) strongly influence the clinical course of hepatitis C, few studies examined the role of such polymorphisms in infections due to viruses other than hepatitis C virus. OBJECTIVES To analyze the association of newly identified IFNL3/4 variant rs368234815 with susceptibility to CMV-associated retinitis in a cohort of HIV-infected patients. DESIGN AND METHODS This retrospective longitudinal study included 4884 white patients from the Swiss HIV Cohort Study, among whom 1134 were at risk to develop CMV retinitis (CD4 nadir <100 /μl and positive CMV serology). The association of CMV-associated retinitis with rs368234815 was assessed by cumulative incidence curves and multivariate Cox regression models, using the estimated date of HIV infection as a starting point, with censoring at death and/or lost follow-up. RESULTS A total of 40 individuals among 1134 patients at risk developed CMV retinitis. The minor allele of rs368234815 was associated with a higher risk of CMV retinitis (log-rank test P = 0.007, recessive mode of inheritance). The association was still significant in a multivariate Cox regression model (hazard ratio 2.31, 95% confidence interval 1.09-4.92, P = 0.03), after adjustment for CD4 nadir and slope, HAART and HIV-risk groups. CONCLUSION We reported for the first time an association between an IFNL3/4 polymorphism and susceptibility to AIDS-related CMV retinitis. IFNL3/4 may influence immunity against viruses other than HCV.

CURB-65 and Other Markers of Illness Severity in Community-Acquired Pneumonia Among HIV-Positive Patients

As the relative burden of community-acquired bacterial pneumonia among HIV-positive patients increases, adequate prediction of case severity on presentation is crucial. We sought to determine what characteristics measurable on presentation are predictive of worse outcomes. We studied all admissions for community-acquired bacterial pneumonia over one year at a tertiary centre. Patient demographics, comorbidities, HIV-specific markers and CURB-65 scores on Emergency Department presentation were reviewed. Outcomes of interest included mortality, bacteraemia, intensive care unit admission and orotracheal intubation. A total of 396 patients were included: 49 HIV-positive and 347 HIV-negative. Mean CURB-65 score was 1.3 for HIV-positive and 2.2 for HIV-negative patients (p < 0.0001), its predictive value for mortality being maintained in both groups (p = 0.03 and p < 0.001, respectively). Adjusting for CURB-65 scores, HIV infection by itself was only associated with bacteraemia (adjusted odds ratio [AOR] 7.1, 95% CI [2.6-19.5]). Patients with < 200 CD4 cells/µL presented similar CURB-65 adjusted mortality (aOR 1.7, 95% CI [0.2-15.2]), but higher risk of intensive care unit admission (aOR 5.7, 95% CI [1.5-22.0]) and orotracheal intubation (aOR 9.1, 95% CI [2.2-37.1]), compared to HIV-negative patients. These two associations were not observed in the > 200 CD4 cells/µL subgroup (aOR 2.2, 95% CI [0.7-7.6] and aOR 0.8, 95% CI [0.1-6.5], respectively). Antiretroviral therapy and viral load suppression were not associated with different outcomes (p > 0.05). High CURB-65 scores and CD4 counts < 200 cells/µL were both associated with worse outcomes. Severity assessment scales and CD4 counts may both be helpful in predicting severity in HIV-positive patients presenting with community-acquired bacterial pneumonia.