High number of CD56(bright) NK-cells and persistently low CD4+ T-cells in a hemophiliac HIV/HCV co-infected patient without opportunistic infections.

BACKGROUND: Both the human immunodeficiency virus (HIV) and hepatitis C virus (HCV), either alone or as coinfections, persist in their hosts by destroying and/or escaping immune defenses, with high morbidity as consequence. In some cases, however, a balance between infection and immunity is reached, leading to prolonged asymptomatic periods. We report a case of such an indolent co-infection, which could be explained by the development of a peculiar subset of Natural Killer (NK) cells. RESULTS: Persistently high peripheral levels of CD56+ NK cells were observed in a peculiar hemophiliac HIV/HCV co-infected patient with low CD4 counts, almost undetectable HIV viral load and no opportunistic infections. Thorough analysis of NK-subsets allowed to identify a marked increase in the CD56bright/dim cell ratio and low numbers of CD16+/CD56- cells. These cells have high levels of natural cytotoxicity receptors but low NCR2 and CD69, and lack both CD57 and CD25 expression. The degranulation potential of NK-cells which correlates with target cytolysis was atypically mainly performed by CD56bright NK-cells, whereas no production of interferon γ (IFN-γ) was observed following NK activation by K562 cells. CONCLUSIONS: These data suggest that the expansion and lytic capacity of the CD56bright NK subset may be involved in the protection of this « rare » HIV/HCV co-infected hemophiliac A patient from opportunistic infections and virus-related cancers despite very low CD4+ cell counts.

Tuberculosis in HIV-negative and HIV-infected patients in a low-incidence country: clinical characteristics and treatment outcomes.

BACKGROUND: In Switzerland and other developed countries, the number of tuberculosis (TB) cases has been decreasing for decades, but HIV-infected patients and migrants remain risk groups. The aim of this study was to compare characteristics of TB in HIV-negative and HIV-infected patients diagnosed in Switzerland, and between coinfected patients enrolled and not enrolled in the national Swiss HIV Cohort Study (SHCS). METHODS AND FINDINGS: All patients diagnosed with culture-confirmed TB in the SHCS and a random sample of culture-confirmed cases reported to the national TB registry 2000-2008 were included. Outcomes were assessed in HIV-infected patients and considered successful in case of cure or treatment completion. Ninety-three SHCS patients and 288 patients selected randomly from 4221 registered patients were analyzed. The registry sample included 10 (3.5%) coinfected patients not enrolled in the SHCS: the estimated number of HIV-infected patients not enrolled in the SHCS but reported to the registry 2000-2008 was 146 (95% CI 122-173). Coinfected patients were more likely to be from sub-Saharan Africa (51.5% versus 15.8%, P<0.0001) and to present disseminated disease (23.9% vs. 3.4%, P<0.0001) than HIV-negative patients. Coinfected patients not enrolled in the SHCS were asylum seekers or migrant workers, with lower CD4 cell counts at TB diagnosis (median CD4 count 79 cells/µL compared to 149 cells/µL among SHCS patients, P = 0.07). There were 6 patients (60.0%) with successful outcomes compared to 82 (88.2%) patients in the SHCS (P = 0.023). CONCLUSIONS: The clinical presentation of coinfected patients differed from HIV-negative TB patients. The number of HIV-infected patients diagnosed with TB outside the SHCS is similar to the number diagnosed within the cohort but outcomes are poorer in patients not followed up in the national cohort. Special efforts are required to address the needs of this vulnerable population.

Adénopathies et fièvre chez une patiente VIH positive [Immunocompromised HIV patient with lymphadenopathy and fever].

The case of a immunocompromised HIV patient with fever and lymphadenopathy discussed in an anatomo-pathological round. This complex clinical case was used as an opportunity to discuss the broad differential diagnosis of fever in an immunocompromized individual with multiples lymphadenopathies. Clinical reasoning leading to the probable diagnosis based on clinical, biological and radiological informations is not only a difficult task for the speaker but also a rich source of learning opportunities for our medical community.

Markers, Cofactors and Staging Systems in the Study of HIV Disease Progression: A Review

This paper is aimed at providing a comprehensive review of markers, cofactors and staging systems used for HIV disease, focusing on some aspects that nowadays could even be considered historical, and advancing in current issues such as the prognostic value of viral load measurements, viral genotypic and phenotypic characterization, and new HIV disease treatment protocols. CD4+ cell values, combined with the new viral markers mentioned are promising as a parsimonious predictor set for defining both severity and progression. An adequate predictor of patient resource use for planning purposes still needs to be defined

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

BACKGROUND: 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. METHODS: Self-reported information on sexual preference, sexual partners, and condom use was collected at semi-annual visits in all participants of the prospective Swiss HIV Cohort Study from April 2007 through March 2009. Multivariable logistic regression models were fit using generalized estimating equations to investigate associations between characteristics of cohort participants and condom use. FINDINGS: A total of 7309 participants contributed to 21,978 visits. A total of 4291 persons (80%) reported sexual contacts with stable partners, 1646 (30%) with occasional partners, and 557 (10%) with stable and occasional partners. Of the study participants, 5838 (79.9%) of 7309 were receiving antiretroviral therapy, and of these, 4816 patients (82%) had a suppressed viral load. Condom use varied widely and differed by type of partner (visits with stable partners, 10,368 [80%] of 12,983; visits with occasional partners, 4300 [88%] of 4880) and by serostatus of stable partner (visits with HIV-negative partners, 7105 [89%] of 8174; visits with HIV-positive partners, 1453 [48%] of 2999). Participants were more likely to report unprotected sex with stable partners if they were receiving antiretroviral therapy, if HIV replication was suppressed, and after the publication of the "Swiss statement." Noninjection drug use and moderate or severe alcohol use were associated with unprotected sex. CONCLUSIONS: Antiretroviral treatment and plasma HIV RNA titers influence sexual behavior of HIV-positive persons. Noninjection illicit drug and alcohol use are important risk factors for unprotected sexual contacts.

The debate over the effector function of eosinophils in helminth infection: new evidence from studies on the regulation of vaccine immunity by IL-12

The production of Th1-type cytokines is associated with strong cell-mediated immunity while Th2-type cytokines are typically involved in the generation of humoral immune responses. In mice vaccinated a single time (1X) with attenuated cercariae of Schistosoma mansoni, the immunity induced is highly dependent on CD4+ T cells and IFN-gamma. In contrast, mice vaccinated multiple times (3X) have decreased IFN-gamma expression, develop a more dominant Th2-type cytokine response as well as protective antibodies which can passively transfer immunity to naive recipients. Previously, we demonstrated the ability of IL-12, a potent IFN-gamma-inducing cytokine to enhance (1X) schistosome cell-mediated immunity when administered during the period of immunization. More recently, we asked what effects IL-12 would have on the development humoral-based immunity. While multiply-immunized/saline-treated mice demonstrated a 70-80% reduction in parasite burden, 3X/IL-12-vaccinated animals displayed an even more striking >90% reduction in challenge infection, with many mice in the later group demonstrating complete protection. Analysis of pulmonary cytokine mRNA responses demonstrated that control challenged mice elicited a dominant Th2-type response, 3X/saline-vaccinated produced a mixed Th1/Th2-type cytokine response, while 3X/IL-12-immunized animals displayed a dominant Th1-type response. The IL-12-treated group also showed a marked reduction in total serum IgE and tissue eosinophilia while SWAP-specific IgG2a and IgG2b Abs were elevated. Interestingly, animals vaccinated with IL-12 also showed a highly significant increase in total Ig titers specific for IrV-5, a known protective antigen. More importantly, 3X/IL-12 serum alone, when transferred to naive mice reduced worm burdens by over 60% while 3X/saline serum transferred significantly less protection. Nevertheless, animals vaccinated in the presence of IL-12 also develop macrophages with enhanced nitric oxide dependent killing activity against the parasites. Together, these observations suggest that IL-12, initially described as an adjuvant for cell-mediated immunity, may also be used as an adjuvant for promoting both humoral and cell-mediated protective responses.

Chagas' Disease and HIV Co-infection: Genotypic Characterization of the Trypanosoma cruzi Strain

In the past few years, new aspects of the immunopathology of Chagas' disease have been described in immunosuppressed patients, such as fatal central nervous system lesions related to the reactivation of the parasite. This article is the first description of the genotypic characterization, at the strain level, of Trypanosoma cruzi isolated from a patient with Chagas` disease/AIDS co-infection. The presence of four hypodense lesions was observed in the cranial compute tomographic scan. The diagnosis of AIDS was assessed by the detection of anti-HIV antibodies using enzyme-linked immunosorbent assay (ELISA) and Western blot techniques. The CD4+ lymphocyte counts were maintained under 200 cells/mm3 during one year demonstrating the severity of the state of immunosuppression. Chagas' disease was confirmed by serological and parasitological methods. Trypomastigote forms were visualized in a thick blood smear. The parasite isolated is genotypically similar to the CL strain. The paper reinforces that cerebral Chagas' disease can be considered as another potential opportunistic infection in AIDS resulting from the reactivation of a dormant T. cruzi infection acquired years earlier.

Phase 1 Study of an Inactivated Vaccine against American Tegumentary Leishmaniasis in Normal Volunteers in Brazil

A Phase 1 double-blind placebo-controlled study was performed to evaluate a vaccine against American tegumentary leishmaniasis in 61 healthy male volunteers. Side effects and the immune response to the vaccine were evaluated, with 1- and 2- dose schemes, with intervals of 7 or 21 days, each dose containing 1440 mg of protein N antigen of a single strain of Leishmania amazonensis (PH 8) diluted in merthiolated saline (1:10,000). Merthiolated saline and an inert substance were used as placebos. No significant clinical alterations were found following the respective injections in the vaccinated individuals as compared to the placebos, except for local pain, which was associated significantly with injection of the vaccine. The laboratory alterations we observed bore no association with the clinical findings and were unimportant. We observed no differences between the groups with regard to seroconversion or the Montenegro skin test. However, the group that received a single dose of the vaccine and the one that received two doses with a 21-day interval displayed cutaneous induration significantly larger than in the control group, with 100%, 100%, and 66% conversion in the skin test, respectively. We concluded that the vaccine does not present any major side effect that would contraindicate its use in healthy individuals.

Immunization of Persons with HIV Infection and other Secondary Immunodeficiencies

Patients with secondary immunodeficiencies are at a high risk of infection. Currently some of these infections are preventable through specific immunization. Prevention of these diseases can diminish morbidity and mortality amongst these patients. In this review we describe the use of vaccines in persons with secondary immunodeficiencies.

HIV Specific Humoral Immune Response in Rio de Janeiro, Brazil

Efforts to characterize HIV-1 polymorphism and anti-HIV immune response are being made in areas where anti-HIV/AIDS vaccines are to be employed. Anti-HIV-1 humoral immune response is being studied in infected individuals resident in Rio de Janeiro, in distinct cohorts involving recent seroconvertors, pregnant women or intravenous drug users (IDU). Comparative analyses of specificity of antibody response towards epitopes important for anti-HIV-1 immune response indicate quantitative differences between cohorts, with an exceptionally strong response in IDUs and weakest response in pregnant women. However, a comparative analysis between pregnant women cohorts from Rio de Janeiro and Rio Grande do Sul indicated an even lower response (with exception of the anti-V3-C clade peptide recognition) for the southern cohort. Studies analysing the immune function of the humoral response indicate a quite elevated occurrence of antibodies capable of neutralizing heterologous primary HIV-1 isolates from Rio de Janeiro. Attempts to correlate seroreactivity with HIV-1 neutralization with respect to HIV-1 polymorphism were not very successfull: while the Brazilian B clade B" variant could be recognized by binding assays, no significant distinction of HIV-1 clades/variants was observed in viral neutralization assays.