Incidence and clinical and immunological characteristics of primary Toxoplasma gondii infection in HIV-infected patients

SummaryObjectivesTo determine the incidence and laboratory characteristics of primary Toxoplasma gondii infection in HIV-infected individuals.MethodsThis retrospective study was conducted between 1988 and 2012 on a cohort of 1130 HIV-infected patients at the AIDS Center Prague. Toxoplasma serology, standard laboratory parameters, and health status were evaluated at 3–6-month intervals for all patients.ResultsThe total person-time of follow-up of patients at risk of Toxoplasma seroconversion was 3046.3 years; there were 14 primary T. gondii infections, yielding an incidence rate of 0.0046 (95% confidence interval 0.0027–0.0078). Most of the subjects were clinically asymptomatic, but in one case seroconversion was accompanied by transient cervical lymphadenopathy. The CD4+ T-lymphocyte count geometric mean increased from 418 (95% confidence interval 303–579) cells/μl before seroconversion to 501 (95% confidence interval 363–691) cells/μl after seroconversion (p = 0.004), while other parameters (CD8+ T-lymphocytes, natural killer cells, viral load, beta2-microglobulin, total immunoglobulins) remained unchanged. As compared to the control group, patients with primary toxoplasmosis had higher initial levels of total immunoglobulins IgA and IgG and a tendency to higher CD8+ T lymphocyte counts.ConclusionsNeither the incidence nor the course of the primary Toxoplasma infection was influenced by the immune status of the patients. Immune parameters of patients with primary Toxoplasma infection did not differ from those of the controls

O331 Patterns of viral suppression on cART as predictors of uncontrolled viremia after starting a new antiretroviral after 1 January 2003

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Immuno-virological discordance and the risk of non-AIDS and AIDS events in a large observational cohort of HIV-patients in Europe

The impact of immunosuppression despite virological suppression (immuno-virological discordance, ID) on the risk of developing fatal and non-fatal AIDS/non-AIDS events is unclear and remains to be elucidated. METHODS: Patients in EuroSIDA starting at least 1 new antiretroviral drug with CD4500 copies/mL were followed-up from the first day of VLgrade 3), cardio- and cerebrovascular events, and end-stage renal disease. Patients were classified over time according to whether current CD4 count was above (non-ID) or below (ID) baseline level. Relative rates (RR) of events were calculated for ID vs. non-ID using adjusted Poisson regression models. RESULTS: 2,913 patients contributed 11,491 person-years for the analysis of non-AIDS. 241 pre-specified non-AIDS events (including 84 deaths) and 89 AIDS events (including 10 deaths) occurred. The RR of developing pre-specified non-AIDS events for ID vs. non-ID was 1.96 (95% CI 1.37-2.81, p<0.001) in unadjusted analysis and 1.43 (0.94-2.17, p = 0.095) after controlling for current CD4 count. ID was not associated with the risk of AIDS events (aRR 0.76, 95% CI 0.41-1.38, p = 0.361). CONCLUSION: Compared to CD4 responders, patients with immuno-virological discordance may be at increased risk of developing non-AIDS events. Further studies are warranted to establish whether in patients with ID, strategies to directly modify CD4 count response may be needed besides the use of ART

Current and Novel Inhibitors of HIV Protease

The design, development and clinical success of HIV protease inhibitors represent one of the most remarkable achievements of molecular medicine. This review describes all nine currently available FDA-approved protease inhibitors, discusses their pharmacokinetic properties, off-target activities, side-effects, and resistance profiles. The compounds in the various stages of clinical development are also introduced, as well as alternative approaches, aiming at other functional domains of HIV PR. The potential of these novel compounds to open new way to the rational drug design of human viruses is critically assessed

Expression of TIM-3 on Plasmacytoid Dendritic Cells as a Predictive Biomarker of Decline in HIV-1 RNA Level during ART

Depletion and functional impairment of circulating plasmacytoid dendritic cells (pDCs) are characteristic attributes of HIV-1-infection. The mechanism of dysfunction of pDCs is unclear. Here, we studied the development of phenotype of pDCs in a cohort of HIV-1-infected individuals monitored before the initiation and during a 9-month follow up with antiretroviral therapy (ART). Using polychromatic flow cytometry, we detected significantly higher pDC-surface expression of the HIV-1 receptor CD4, regulatory receptor BDCA-2, Fc&gamma; receptor CD32, pDC dysfunction marker TIM-3, and the marker of killer pDC, TRAIL, in treatment-na&iuml;ve HIV-1-infected individuals before initiation of ART when compared to healthy donors. After 9 months of ART, all of these markers approached but did not reach the expression levels observed in healthy donors. We found that the rate of decline in HIV-1 RNA level over the first 3 months of ART negatively correlated with the expression of TIM-3 on pDCs. We conclude that immunogenic phenotype of pDCs is not significantly restored after sustained suppression of HIV-1 RNA level in ART-treated patients and that the level of the TIM-3 expressed on pDCs in treatment na&iuml;ve patients could be a predictive marker of the rate of decline in the HIV-1 RNA level during ART

Region specifický přístup v analýze ekologických rizik - metodika hodnoceni ve vztahu k přírodním katastrofám:Projekt IDRIS II. Hodnocení ekologických rizik

Region specifický přístup jako metodika využívající data dostupná z biomonitoringu pro hodnocení vlivu plošně působících ekologických katastrof. Praktické možnosti bioindikace pro hodnocení vlivu přírodních katastrof v různých ekosystémech. Možnosti vypracování "krizových" plánů pro hodnocení ekologických rizik pro území potenciálně zasažitelná povodněmi a vypracování region specifické strategie bioindikace a hodnocení rizik. Vypracování strategie pro indikaci expozice a účinku známých i dosud málo sledovaných skupin polutantů v průběhu katastrof typu povodní - současná aplikace chemických, toxikologických a molekulárně biologických metod. Koncepční dopracování metodiky hodnocení ekologických rizik postihující vliv na biologické systémy od molekulární a buněčné úrovně až po úroveň ekosystémů. Prezentace EcoRA

Current hemoglobin levels are more predictive of disease progression than hemoglobin measured at baseline in patients receiving antiretroviral treatment for HIV type 1 infection

The role of hemoglobin levels as an independent prognostic marker of progression to AIDS and/or death in HIV-infected patients starting combination antiretroviral therapy (cART) was investigated. A total of 2579 patients from the EuroSIDA cohort with hemoglobin, CD4 cell count, and HIV RNA viral load measured 6 months prior to starting cART was included in the analyses. Anemia was defined as mild (<= 14 g/dl males, <= 12 g/dl females) and severe (<8 g/dl both genders). Poisson regression was used to determine factors related to clinical progression (new AIDS/death). Hemoglobin levels increased by a median of +0.48 g/dl (IQR -0.4 to +1.3) in the first year of cART. During 14,272 person years of follow-up (PYFU) there were 505 new AIDS/deaths. Of the patients 304 (11.8%) developed mild and 19 severe anemia (0.7%). In multivariate analysis baseline hemoglobin was significantly associated with progression to AIDS/death after starting cART with an IRR of 1.07 per 1 g/dl lower (95% CI 1.01-1.13; p = 0.023). When hemoglobin was fitted as a time-updated variable the IRR increased to 1.36 per 1 g/dl lower (95% CI 1.30-1.42; p < 0.001). Starting cART was associated with an increase in hemoglobin levels. Lower hemoglobin values, particularly the latest measured, were associated with an increased risk of disease progression