Immunogenicity of a meningococcal serogroup C conjugate vaccine in HIV-infected children, adolescents, and young adults

Children and adolescents infected with HIV typically have a lower response to immunization than do those in the general population. In most developed countries, meningococcal serogroup C conjugate vaccine is one of the recommended vaccines for such individuals. However, there have been no studies evaluating the antibody response to this vaccine in HIV-infected children, adolescents or young adults. In this study, we evaluated that response using serum bactericidal antibody (SBA) and enzyme-linked immunosorbent assay, comparing HIV-infected with non-HIV-infected patients, as well as analysing the occurrence of side effects. In non-responders, we assessed the antibody response to revaccination. This clinical trial involved 92 patients between 10 and 20 years of age: 43 HIV-infected patients (HIV+ group) and 49 non-HIV-infected patients (HIV- group). After one dose of the vaccine, 72.1% of the HIV+ group patients and 100% of the HIV- group patients were considered protected. Of the HIV+ group patients who received a second dose of the vaccine, only 40% acquired protection. Overall, 81.4% of the HIV+ group patients acquired protection (after one or two doses of the vaccine). Side effects occurred in 16.3% and 44% of the HIV+ group and HIV- group patients, respectively. Therefore, the meningococcal serogroup C conjugate vaccine proved to be safe and effective for use in HIV-infected children, adolescents, and young adults, although their antibody response was weaker than that shown by non-HIV-infected patients. This indicates the need to discuss changes to the immunization schedule for children, adolescents, and young adults infected with HIV, in order to ensure more effective protection against meningococcal disease. (c) 2012 Elsevier Ltd. All rights reserved.

Expanding the Clinical and Genetic Spectrum of Human CD40L Deficiency: The Occurrence of Paracoccidioidomycosis and Other Unusual Infections in Brazilian Patients

CD40 ligand (CD40L) deficiency or X-linked hyper-IgM syndrome (X-HIGM) is a well-described primary immunodeficiency in which Pneumocystis jiroveci pneumonia is a common clinical feature. We have identified an unusual high incidence of fungal infections and other not yet described infections in a cohort of 11 X-HIGM patients from nine unrelated Brazilian families. Among these, we describe the first case of paracoccidioidomycosis (PCM) in X-HIGM. The molecular genetic analysis of CD40L was performed by gene sequencing and evaluation of CD40L protein expression. Nine of these 11 patients (82%) had fungal infections. These included fungal species common to CD40L deficiency (P. jiroveci and Candida albicans) as well as Paracoccidioides brasiliensis. One patient presented with PCM at age 11 years and is now doing well at 18 years of age. Additionally, one patient presented with a simultaneous infection with Klebsiella and Acinetobacter, and one with condyloma caused by human papilloma virus. Molecular analysis revealed four previously described CD40L mutations, two novel missense mutations (c.433 T>G and c.476 G>C) resulting in the absence of CD40L protein expression by activated CD4(+) cells and one novel insertion (c.484_485insAA) within the TNFH domain leading to a frame shift and premature stop codon. These observations demonstrated that the susceptibility to fungal infections in X-HIGM extends beyond those typically associated with X-HIGM (P. jiroveci and C. albicans) and that these patients need to be monitored for those pathogens.

Evaluation of inadequate anti-retroviral treatment in patients with HIV/AIDS

Introduction: Since the emergence of antiretroviral therapy, the survival of patients infected with human immunodeficiency virus has increased. Non-adherence to this therapy is directly related to treatment failure, which allows the emergence of resistant viral strains. Methods: A retrospective descriptive study of the antiretroviral dispensing records of 229 patients from the Center for Health Care, University Hospital, Federal University of Juiz de Fora, Brazil, was conducted between January and December 2009. Results: The study aimed to evaluate patient compliance and determine if there was an association between non-adherence and the therapy. Among these patients, 63.8% were men with an average age of 44.0 +/- 9.9 years. The most used treatment was a combination of 2 nucleoside reverse transcriptase inhibitors with 1 non-nucleoside reverse transcriptase inhibitor (55.5%) or with 2 protease inhibitors (28.8%). It was found that patients taking lopinavir/ritonavir with zidovudine and lamivudine had a greater frequency of inadequate treatment than those taking atazanavir with zidovudine and lamivudine (85% and 83.3%, respectively). Moreover, when the combination of zidovudine/lamivudine was used, the patients were less compliant (chi(2) = 4.468, 1 degree of freedom, p = 0.035). Conclusions: The majority of patients failed to correctly adhere to their treatment; therefore, it is necessary to implement strategies that lead to improved compliance, thus ensuring therapeutic efficacy and increased patient survival.

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.

HIV-1 tropism and CD4 T lymphocyte recovery in a prospective cohort of patients initiating HAART in Ribeirão Preto, Brazil

While human immunodeficiency virus (HIV)-1 chemokine co-receptors 5 tropism and the GWGR motif in the envelope third variable region (V3 loop) have been associated with a slower disease progression, their influence on antiretroviral response remains unclear. The impact of baseline V3 characteristics on treatment response was evaluated in a randomised, double blind, prospective cohort study with patients initiating highly active antiretroviral therapy with lopinavir or efavirenz plus azithothymidine/3TC (1:1) over 48 weeks. Similar virological and immunological responses were observed for both treatment regimens. The 43 individuals had a mean baseline CD4 T cell count of 119 cells/mm³ [standard deviation (SD) = 99] and a mean viral load of 5.09 log10 copies/mL (SD = 0.49). The GWGR motif was not associated with a CD4 T cell response, but predicted R5 tropism by the geno2pheno[clinical20%] algorithm correlated with higher CD4 T cell levels at all monitoring points (p < 0.05). Moreover, higher false-positive rates (FPR) values from this analysis revealed a strong correlation with CD4 T cell recovery (p < 0.0001). Transmitted drug resistance mutations, documented in 3/41 (7.3%) cases, were unrelated to the assigned antiretroviral regimen and had no impact on patient outcomes. In conclusion, naÏve HIV-1 R5 infected patients exhibited higher CD4 T cell counts at baseline; this difference was sustained throughout therapy. The geno2pheno[clinical] option FPR positively correlated with CD4 T cell gain and may be useful in predicting CD4 T cell recovery.

Avaliação do acesso ao tratamento de tuberculose por coinfectados ou não pelo vírus da imunodeficiência humana

Este estudo objetivou avaliar o acesso ao tratamento das pessoas com tuberculose tanto coinfectadas ou não pelo Vírus da Imunodeficiência Humana (HIV). Trata-se de estudo transversal - com utilização do instrumento Primary Care Assessment Tool aplicado a 95 pessoas - que abordou questões sobre o acesso ao tratamento em município do interior paulista. Para avaliação do acesso ao tratamento, utilizou-se o teste t de Student. Os escores médios das variáveis foram analisados individualmente e comparados entre os dois grupos (pessoas com TB e coinfectadas com HIV e pessoas com TB não coinfectadas pelo HIV). Os escores médios mostraram que as coinfectadas pelo HIV apresentaram maiores dificuldades na obtenção do acesso do que as não coinfectadas. Os profissionais visitavam mais vezes as coinfectadas quando comparadas às não coinfectadas; as coinfectadas quase nunca realizavam o tratamento da doença em posto de saúde perto de sua residência. Há, portanto, necessidade de maior integração e comunicação entre os Programas de Tuberculose e DST/aids.

Outcome of HIV-infected patients with hepatocellular carcinoma: a comparison with HIV negative controls

Background and rationale for the study. This study investigated whether human immunodeficiency virus (HIV) infection adversely affects the prognosis of patients diagnosed with hepatocellular carcinoma (HCC).Thirty-four HIV-positive patients with chronic liver disease, consecutively diagnosed with HCC from 1998 to 2007 were one-to-one matched with 34 HIV negative controls for: sex, liver function (Child-Turcotte-Pugh class [CTP]), cancer stage (BCLC model) and, whenever possible, age, etiology of liver disease and modality of cancer diagnosis. Survival in the two groups and independent prognostic predictors were assessed. Results. Among HIV patients 88% were receiving HAART. HIV-RNA was undetectable in 65% of cases; median lymphocyte CD4+ count was 368.5/mmc. Etiology of liver disease was mostly related to HCV infection. CTP class was: A in 38%, B in 41%, C in 21% of cases. BCLC cancer stage was: early in 50%, intermediate in 23.5%, advanced in 5.9%, end-stage in 20.6% of cases. HCC treatments and death causes did not differ between the two groups. Median survival did not differ, being 16 months (95% CI: 6-26) in HIV positive and 23 months (95% CI: 5-41) in HIV negative patients (P=0.391). BCLC cancer stage and HCC treatment proved to be independent predictors of survival both in the whole population and in HIV patients. Conclusions. Survival of HIV infected patients receiving antiretroviral therapy and diagnosed with HCC is similar to that of HIV negative patients bearing this tumor. Prognosis is determined by the cancer bulk and its treatment.

Frequency and determinants of unprotected sex among HIV-infected persons: the Swiss HIV cohort study

Access to antiretroviral therapy may have changed condom use behavior. In January 2008, recommendations on condom use for human immunodeficiency virus (HIV)-positive persons were published in Switzerland, which allowed for unprotected sex under well-defined circumstances ("Swiss statement"). We studied the frequency, changes over time, and determinants of unprotected sex among HIV-positive persons.

Tuberculosis in HIV programmes in lower-income countries: practices and risk factors

BACKGROUND: Tuberculosis (TB) is a common diagnosis in human immunodeficiency virus (HIV) infected patients on antiretroviral treatment (ART). OBJECTIVE: To describe TB-related practices in ART programmes in lower-income countries and identify risk factors for TB in the first year of ART. METHODS: Programme characteristics were assessed using standardised electronic questionnaire. Patient data from 2003 to 2008 were analysed and incidence rate ratios (IRRs) calculated using Poisson regression models. RESULTS: Fifteen ART programmes in 12 countries in Africa, South America and Asia were included. Chest X-ray, sputum microscopy and culture were available free of charge in respectively 13 (86.7%), 14 (93.3%) and eight (53.3%) programmes. Eight sites (53.3%) used directly observed treatment and five (33.3%) routinely administered isoniazid preventive treatment (IPT). A total of 19 413 patients aged ≥16 years contributed 13 227 person-years of follow-up; 1081 new TB events were diagnosed. Risk factors included CD4 cell count (>350 cells/μl vs. <25 cells/μl, adjusted IRR 0.46, 95%CI 0.33–0.64, P < 0.0001), sex (women vs. men, adjusted IRR 0.77, 95%CI 0.68–0.88, P = 0.0001) and use of IPT (IRR 0.24, 95%CI 0.19–0.31, P < 0.0001). CONCLUSIONS: Diagnostic capacity and practices vary widely across ART programmes. IPT prevented TB, but was used in few programmes. More efforts are needed to reduce the burden of TB in HIV co-infected patients in lower income countries.

Morbidity and aging in HIV-infected persons: the Swiss HIV cohort study

Patterns of morbidity and mortality among human immunodeficiency virus (HIV)-infected individuals taking antiretroviral therapy are changing as a result of immune reconstitution and improved survival. We studied the influence of aging on the epidemiology of non-AIDS diseases in the Swiss HIV Cohort Study.

No longitudinal mitochondrial DNA sequence changes in HIV-infected individuals with and without lipoatrophy

The potential for mitochondrial (mt) DNA mutation accumulation during antiretroviral therapy (ART), and preferential accumulation in patients with lipoatrophy compared with control participants, remains controversial. We sequenced the entire mitochondrial genome, both before ART and after ART exposure, in 29 human immunodeficiency virus (HIV)-infected Swiss HIV Cohort Study participants initiating a first-line thymidine analogue-containing ART regimen. No accumulation of mtDNA mutations or deletions was detected in 13 participants who developed lipoatrophy or in 16 control participants after significant and comparable ART exposure (median duration, 3.3 and 3.7 years, respectively). In HIV-infected persons, the development of lipoatrophy is unlikely to be associated with accumulation of mtDNA mutations detectable in peripheral blood.

Improved virological outcome in White patients infected with HIV-1 non-B subtypes compared to subtype B

Antiretroviral compounds have been predominantly studied in human immunodeficiency virus type 1 (HIV-1) subtype B, but only ~10% of infections worldwide are caused by this subtype. The analysis of the impact of different HIV subtypes on treatment outcome is important.

Hepatitis C virus infections in the Swiss HIV Cohort Study: a rapidly evolving epidemic

Hepatitis C virus (HCV) infection has a growing impact on morbidity and mortality in patients infected with human immunodeficiency virus (HIV). We assessed trends in HCV incidence in the different HIV transmission groups in the Swiss HIV Cohort Study (SHCS).

Choice of Initial Combination Antiretroviral Therapy in Individuals With HIV Infection: Determinants and Outcomes

BACKGROUND Current guidelines give recommendations for preferred combination antiretroviral therapy (cART). We investigated factors influencing the choice of initial cART in clinical practice and its outcome. METHODS We analyzed treatment-naive adults with human immunodeficiency virus (HIV) infection participating in the Swiss HIV Cohort Study and starting cART from January 1, 2005, through December 31, 2009. The primary end point was the choice of the initial antiretroviral regimen. Secondary end points were virologic suppression, the increase in CD4 cell counts from baseline, and treatment modification within 12 months after starting treatment. RESULTS A total of 1957 patients were analyzed. Tenofovir-emtricitabine (TDF-FTC)-efavirenz was the most frequently prescribed cART (29.9%), followed by TDF-FTC-lopinavir/r (16.9%), TDF-FTC-atazanavir/r (12.9%), zidovudine-lamivudine (ZDV-3TC)-lopinavir/r (12.8%), and abacavir/lamivudine (ABC-3TC)-efavirenz (5.7%). Differences in prescription were noted among different Swiss HIV Cohort Study sites (P < .001). In multivariate analysis, compared with TDF-FTC-efavirenz, starting TDF-FTC-lopinavir/r was associated with prior AIDS (relative risk ratio, 2.78; 95% CI, 1.78-4.35), HIV-RNA greater than 100 000 copies/mL (1.53; 1.07-2.18), and CD4 greater than 350 cells/μL (1.67; 1.04-2.70); TDF-FTC-atazanavir/r with a depressive disorder (1.77; 1.04-3.01), HIV-RNA greater than 100 000 copies/mL (1.54; 1.05-2.25), and an opiate substitution program (2.76; 1.09-7.00); and ZDV-3TC-lopinavir/r with female sex (3.89; 2.39-6.31) and CD4 cell counts greater than 350 cells/μL (4.50; 2.58-7.86). At 12 months, 1715 patients (87.6%) achieved viral load less than 50 copies/mL and CD4 cell counts increased by a median (interquartile range) of 173 (89-269) cells/μL. Virologic suppression was more likely with TDF-FTC-efavirenz, and CD4 increase was higher with ZDV-3TC-lopinavir/r. No differences in outcome were observed among Swiss HIV Cohort Study sites. CONCLUSIONS Large differences in prescription but not in outcome were observed among study sites. A trend toward individualized cART was noted suggesting that initial cART is significantly influenced by physician's preference and patient characteristics. Our study highlights the need for evidence-based data for determining the best initial regimen for different HIV-infected persons.

Discontinuation of maintenance therapy against toxoplasma encephalitis in AIDS patients with sustained response to anti-retroviral therapy

Discontinuation of maintenance therapy against toxoplasma encephalitis (TE) for individuals infected with human immunodeficiency virus (HIV) who are receiving successful anti-retroviral therapy is considered safe. Nevertheless, there are few published studies concerning this issue. Within the setting of the Swiss HIV Cohort Study, this report describes a prospective study of discontinuation of maintenance therapy against TE in patients with a sustained increase of CD4 counts to > 200 cells/microL and 14% of total lymphocytes, and no active lesions on cerebral magnetic resonance imaging (MRI). In addition to clinical evaluation, cerebral MRI was performed at baseline, and 1 and 6 months following discontinuation. Twenty-six AIDS patients with a history of TE agreed to participate, but three patients (11%) could not be enrolled because they still showed enhancing cerebral lesions without a clinical correlate. One patient refused MRI after 6 months while clinically asymptomatic. Among the remaining 22 patients who discontinued maintenance therapy, one relapsed after 3 months. During a total follow-up of 58 patient-years, there was no TE relapse among the patients who had remained clinically and radiologically free of relapse during the study. Thus, discontinuation of maintenance therapy against TE was generally safe, but may fail in a minority of patients. Patients who remain clinically and radiologically free of relapse at 6 months after discontinuation are unlikely to experience a relapse of TE.