Cognitive impairment is frequent among symptomatic carriers of human T-cell lymphotropic virus type 1 (HTLV-1), regardless of their clinical status.

The main goal of this study was to investigate the presence of cognitive impairment in patients infected with HTLV-1 presenting or not TSP/HAM. METHODS: Cross-sectional study including 104 participants: 37 asymptomatic HTLV-1 carriers, 37 patients diagnosed with TSP/HAM and 30 HTLV-1 negative control patients. Within the HTLV-1 positive group, 53 were female and 21 were male, the average age was 46 (SD=13.5) and the average schooling time was 7.7years (SD=3.3).The sociodemographic variables (genre, age and education) were compared between the three groups. The assessment tools used were: Beck Depression Inventory, Lawton's Activities of Daily Life Scale and a complete neuropsychological battery. The application of these assessment tools was carried out in blind. Both HTLV-1 asymptomatic subjects and HAM/TSP patients showed a lower performance on neuropsychological tests and higher depression scores when compared to the control group. HTLV-1 patients performed poorly in several cognitive domains, but only fluid intelligence, estimated intellectual functioning, immediate and delayed recall of visual memory and information processing speed (in the specific case of patients with TSP/HAM) reached statistical significance when compared with controls. Depression was not associated with cognitive impairment. HTLV-1 carriers presented a higher frequency of cognitive impairment than normal controls.

High frequency of dolutegravir resistance in patients failing a raltegravir-containing salvage regimen

OBJECTIVES: Dolutegravir is a second-generation integrase strand transfer inhibitor (InSTI) that has been recently approved by the FDA to treat antiretroviral therapy-naive as well as treatment-experienced HIV-infected individuals, including those already exposed to the first-generation InSTI. Despite having a different mutational profile, some cross-resistance mutations may influence its susceptibility. The aim of this study was to evaluate the impact of a raltegravir-containing salvage regimen on dolutegravir activity. PATIENTS AND METHODS: Blood samples of 92 HIV-infected individuals with virological failure (two or more viral loads >50 copies/mL after 6 months of treatment) using raltegravir with optimized background therapy were sequenced and evaluated according to the Stanford University HIV Drug Resistance Database algorithm. RESULTS: Among the 92 patients analysed, 32 (35%) showed resistance to dolutegravir, in most cases associated with the combination of Q148H/R/K with G140S/A mutations. At genotyping, patients with resistance to dolutegravir had viral load values closer to the highest previously documented viral load. CONCLUSIONS: Changes in viraemia during virological failure may indicate the evolution of raltegravir resistance and may predict the emergence of secondary mutations that are associated with a decrease in dolutegravir susceptibility. Early discontinuation of raltegravir from failing regimens might favour subsequent salvage with dolutegravir, but further studies are necessary to evaluate this issue.

Cerebral and ocular toxoplasmosis related with IFN-y, TNF-a, and IL-10

This study analyzed the synthesis of Interferon gamma (IFN-γ), Tumor Necrosis Factor alpha (TNF-α), and Interleukin 10 (IL-10) in chronically infected patients which developed the symptomatic disease as cerebral or ocular toxoplasmosis. Blood from 61 individuals were divided into four groups: Cerebral toxoplasmosis/AIDS patients (CT/AIDS group) (n = 15), ocular toxoplasmosis patients (OT group) (n = 23), chronic toxoplasmosis individuals (CHR group) (n = 13) and healthy individuals (HI group) (n = 10). OT, CHR, and HI groups were human immunodeficiency virus (HIV) seronegative. The diagnosis was made by laboratorial (PCR and ELISA) and clinical subjects. For cytokine determination, peripheral blood mononuclear cells (PBMC) of each patient were isolated and stimulated in vitro with T. gondii antigen. IFN-γ, TNF-α, and IL-10 activities were determined by ELISA. Patients from CT/AIDS and OT groups had low levels of IFN-γ when were compared with those from CHR group. These data suggest the low resistance to develop ocular lesions by the low ability to produce IFN-γ against the parasite. The same patients, which developed ocular or cerebral toxoplasmosis had higher TNF-α levels than CHR individuals. High TNF-α synthesis contribute to the inflammatory response and damage of the choroid and retina in OT patients and in AIDS patients caused a high inflammatory response as the TNF-α synthesis is not affected since monocytes are the major source this cytokine in response to soluble T. gondii antigens. IL-10 levels were almost similar in CT/AIDS and OT patients but low when compared with CHR individuals. The deviation to Th2 immune response including the production of anti-inflammatory cytokines, such as IL-10 may promote the parasite's survival causing the tissue immune destruction. IL-10 production in T. gondii-infected brains may support the persistence of parasites as down-regulating the intracerebral immune response. All these indicate that OT and CT/AIDS patients produced low levels of IL-10 (Th2 response) and IFN-γ (Th1 response). They produced high TNF-α suggesting a high inflammatory response triggered by the parasite.

JC virus DNA in cerebrospinal fluid samples from Brazilian AIDS patients with focal brain lesions without mass effect.

OBJECTIVE: To evaluate the presence of JC virus DNA in CSF samples from Brazilian AIDS patients with focal lesions of CNS white matter without mass effect compatible with progressive multifocal leukoencephalopathy (PML). METHODS: CSF samples from AIDS patients with neurological symptoms and a CT scan showing focal lesions of CNS white matter without mass effect suggestive of PML, and from AIDS and non-AIDS patients with non-PML neurological diseases were tested for JC virus DNA by PCR. The primers used to amplify the T antigen region of the JC virus resulted in a 173-bp fragment. The presence of the JC virus was confirmed by digestion of the PCR product using BamH1. RESULTS: The PCR for JCV DNA was negative in 119/120 non-PML CSF samples (specificity =99.2%). Of 56 CSF samples from AIDS patients with focal lesions of CNS white matter without mass effect, JCV DNA was positive in 48.2% (27/56). In 23/29 (79.3%) JCV DNA-negative cases, other causes for the encephalitic lesions were found. No JCV DNA-positive cases showed other diagnoses. CONCLUSIONS: The prevalence of JCV DNA by PCR in CSF samples from Brazilian AIDS patients with focal brain lesions, without mass effect was 48.2%. In these patients, a negative JCV PCR is highly suggestive of other neurological conditions.

Tuberculous brain abscess in AIDS patients: report of three cases and literature review.

OBJECTIVE: Clinical description of tuberculous brain abscess in patients with acquired immunodeficiency syndrome (AIDS). METHODS: Clinical case report and review of the literature from January 1981 to January 2003 using the MEDLINE database. RESULTS: The authors report three cases of tuberculous brain abscess in AIDS patients and review nine similar cases. The mean age was 30 years (range: 18-56 years) with seven patients being male. Five (42%) were intravenous drug users, had prior history of extra-cerebral tuberculosis, and presented alterations on chest radiograph. Tuberculin skin test was anergic in six (75%) of eight patients. Three patients of nine had a CD4+ cell count higher than 200 cells/microL, and three had a CD4+ cell count lower than 100 cells/microl. All but one patient had a brain computerized tomography scan with a single lesion. All patients received anti-tuberculous treatment and underwent surgical procedures. Most patients (75%) showed appropriate clinical responses. CONCLUSION: Tuberculous brain abscess must be considered in the differential diagnosis of intracranial mass in AIDS patients. A careful epidemiological, clinical and laboratory evaluation may guide a diagnostic suspicion. Surgery combined with specific anti-tuberculosis treatment seems to determine a good outcome.