The meaning of caring touch for healthcare professionals in an intensive care unit: A qualitative interview study.

BACKGROUND: The way health care professionals touch patients and relatives in the intensive care unit plays a significant role. A negative feeling can be caused by being touched in the wrong way, this is why a holistic approach with respect for the patient is important for the ability to make the patient and their relatives feel secure, avoiding unnecessary suffering. AIM: The aim of the study was to describe the meaning of caring touch that is given in the ICU from the health care professionals perspective. METHOD: Qualitative interview study with health care professionals in the intensive care unit, analysed using inductive content analysis, resulting in two themes and four main categories. FINDINGS: Two themes emerged: Imperative touch and emotional touch and four main categories: touch as a natural tool, create a prerequisite for touch, empathetic touch and conversant touch. CONCLUSION: Caring touch can be used as a natural tool in the daily work in order to bring comfort and calm to the patient in the intensive care unit.

Genotype at the PMEL17 locus affects social and explorative behaviour in chickens.

1. We studied behaviour and brain gene expression in homozygous PMEL17 genotypes, using chickens originating from an advanced White Leghorn x red junglefowl intercross. The behavioural studies consisted of three social and one explorative behaviour test. There were significant differences between the genotypes in both social and explorative behaviour. 2. Gene expression studies showed no PMEL17 expression in brain, so the genotype differences must depend on extra-neural gene expression or expression during embryonic development. However, linkage or spurious family effects (genetic drift) can not be excluded. 3. The study strongly suggests a correlated effect between plumage colour and behaviour, and we conclude that PMEL17 may have a pleiotropic effect on social and explorative behaviour in chickens.

Prevalence of drug resistance and importance of viral load measurements in Honduran HIV-infected patients failing antiretroviral treatment.

OBJECTIVE: The Honduran HIV/AIDS Program began to scale up access to HIV therapy in 2002. Up to May 2008, more than 6000 patients received combination antiretroviral therapy (cART). As HIV drug resistance is the major obstacle for effective treatment, the purpose of this study was to assess the prevalence of antiretroviral drug resistance in Honduran HIV-1-infected individuals. METHODS: We collected samples from 138 individuals (97 adults and 41 children) on cART with virological, immunological or clinical signs of treatment failure. HIV-1 pol sequences were obtained using an in-house method. Resistance mutations were identified according to the 2007 International AIDS Society (IAS)-USA list and predicted susceptibility to cART was scored using the ANRS algorithm. RESULTS: Resistance mutations were detected in 112 patients (81%), 74% in adults and 98% in children. Triple-, dual- and single-class drug resistance was documented in 27%, 43% and 11% of the study subjects, respectively. Multiple logistic regression showed that resistance was independently associated with type of treatment failure [virological failure (odds ratio (OR) = 1) vs. immunological failure (OR = 0.11; 95% confidence interval (CI) 0.030-0.43) vs. clinical failure (OR = 0.037; 95% CI 0.0063-0.22)], route of transmission (OR = 42.8; 95% CI 3.73-491), and years on therapy (OR = 1.81; 95% CI 1.11-2.93). CONCLUSION: The prevalence of antiretroviral resistance was high in Honduran HIV-infected patients with signs of treatment failure. A majority of study subjects showed dual- or triple-class resistance to nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors and protease inhibitors. Virologically defined treatment failure was a strong predictor of resistance, indicating that viral load testing is needed to correctly identify patients with treatment failure attributable to resistance.

Antiretroviral drug therapy alters the profile of human immunodeficiency virus type 1-specific T-cell responses and shifts the immunodominant cytotoxic T-lymphocyte response from Gag to Pol.

Antiretroviral drug therapy and cytotoxic T lymphocytes (CTL) both exert selective pressures on human immunodeficiency virus type 1, which influence viral evolution. Compared to chronically infected, antiretroviral-untreated patients, most chronically infected, treated patients with detectable viremia lack a cellular immune response against the Gag 77-85(SL9) epitope but show a new immunodominant response against an epitope in protease PR 76-84. Hence, mutations induced by antiretroviral therapy likely alter the profile of epitopes presented to T cells and thus the direction of the response. The consequences of dual pressures from treatment and CTL need to be considered in monitoring of drug therapy.

The selection and evolution of viral quasispecies in HIV-1 infected children.

OBJECTIVES: To analyse the diversity and divergence of the viral populations in three mother-child pairs in longitudinally obtained samples for up to 7 years. METHODS: Peripheral blood mononuclear cells were obtained from three mothers at delivery and three to four samples were obtained from each of their children from 1.5 months up to 78 months of age. The V3 region of HIV-1 was amplified by polymerase chain reaction, cloned and sequenced. HIV-1 DNA sequence comparisons were performed by phylogenetic analysis. RESULTS: The viral population was initially homogenous in two children but highly heterogeneous in one child. Three patterns of vertical transmission seemed to have occurred: transmission of the most prevalent maternal strain, of a minor maternal strain and of multiple maternal strains. In one child, a possible reappearance of a maternal sequence was observed at 34 months of age. CONCLUSIONS: Children may become infected with the most prevalent maternal strain, a minor maternal variant or multiple maternal quasispecies. Maternal viral variants may reappear in children after several years of infection and could possibly be derived from a reservoir of founder quasispecies established during the children's primary HIV-1 infection.

Recent origin of human immunodeficiency virus type 1 variants in resting CD4+ T lymphocytes in untreated and suboptimally treated subjects.

Resting CD4(+) T lymphocytes are an important reservoir for human immunodeficiency virus type 1 (HIV-1) in treated patients with undetectable viremia. The knowledge of viral persistence in these cells is limited, however, for patients without treatment or patients for whom treatment is failing; therefore, this reservoir in such patients was characterized. Virus variants were characterized in 3 subjects who were followed-up from primary HIV-1 infection and 5 treatment-experienced subjects. No founder viral sequences and only a minority of the earlier identified drug-induced mutations were found in the resting T lymphocytes. Instead, the viral sequences were closely related to those detected simultaneously in plasma, except in 2 treatment-experienced subjects. Thus, a turnover and replenishment of this virus reservoir in peripheral blood is likely to occur in most persons with detectable viremia. However, infrequently the virus variants in plasma and resting T cells seem to be derived from independent sources.

Initiation of therapy during primary HIV type 1 infection results in a continuous decay of proviral DNA and a highly restricted viral evolution.

A latent pool of HIV-1 is established early in memory CD4+ T lymphocytes and persists during antiretroviral therapy. Also, viral replication may continue in subjects despite undetectable viremia. However, it remains unclear whether this residual replication results in any significant sequence evolution. We were therefore interested in studying the viral evolution and HIV-1 DNA dynamics in subjects with primary infection receiving or not receiving early potent antiretroviral therapy. In 16 subjects, HIV-1 DNA load was monitored from 1 to 23 days, up to 1253 days, after onset of symptoms. Extensive sequential cloning and sequence analysis of the V3 region was performed in four subjects. In the treated subjects a continuous decline in the proviral load was found, corresponding to a half-life of about 6 months. As expected in newly infected individuals the founder virus populations showed high intrasubject sequence similarity. Also, a limited increase in the viral divergence was detected during the first 6 months in three treated subjects. Thereafter, no significant sequence changes were found despite analysis of a large number of clones. Our data thus suggest that early and successful therapy in compliant subjects with primary HIV-1 infection results in a highly restricted viral evolution and a decline in the proviral load close to the decay rate of human memory T lymphocytes.

Viral dynamics in primary HIV-1 infection. Karolinska Institutet Primary HIV Infection Study Group.

OBJECTIVES: To study the natural course of viremia during primary HIV infection (PHI). METHOD: Eight patients were followed from a median of 5 days from the onset of PHI illness. Plasma HIV-1 RNA levels were measured frequently and the results were fitted to mathematical models. HIV-1 RNA levels were also monitored in nine patients given two reverse transcriptase inhibitors and a protease inhibitor after a median of 7 days from the onset of PHI illness. RESULTS: HIV-1 RNA appeared in the blood during the week preceding onset of PHI illness and increased rapidly during the first viremic phase, reaching a peak at a mean of 7 days after onset of illness. This was followed by a phase of rapidly decreasing levels of HIV-1 RNA to an average of 21 days after onset. Viral density continued to decline thereafter but at a 5- to 50-fold lower rate; a steady-state level was reached at a median of 2 months after onset of PHI. Peak viral density levels correlated significantly with levels measured between days 50 and 600. Initiation of antiretroviral treatment during PHI resulted in rapidly declining levels to below 50 copies/mL. CONCLUSIONS: This study demonstrates the kinetic phases of viremia during PHI and indicates two new contributions to the natural history of HIV-1 infection: PHI peak levels correlate with steady-state levels and HIV-1 RNA declines biphasically; an initial rapid decay is usually followed by a slow decay, which is similar to the initial changes seen with antiviral treatment.

Diagnosis of primary HIV-1 infection and duration of follow-up after HIV exposure. Karolinska Institute Primary HIV Infection Study Group.

OBJECTIVE: To determine the sensitivity of 33 currently available and seven earlier tests for the detection of HIV or HIV antibody in primary HIV-1 infection, to estimate the duration of the 'window period' and the influence of early initiated antiretroviral treatment (ART). DESIGN: A prospective cohort study of 38 patients with primary HIV-1 infection. ART was initiated at a median time of 13 (range 0-23) days after the onset of symptoms in 10 patients. MAIN OUTCOME MEASURES: The time from infection to onset of symptoms and from onset of symptoms to the appearance of HIV antibody as measured by 36 different tests, and the start and duration of viraemia, as detected by four different tests. RESULTS: The illness appeared 13-15 days after infection in 12 of 15 determinable cases, and seroconversion was detected within 1-2 weeks after the onset of illness by 27 of 30 currently available tests for HIV antibody, in contrast to the 2-7 weeks or more needed by the old tests. HIV RNA appeared during the week preceding the onset of illness and was detected in all subsequent samples, except when ART had been initiated, which also induced a delay of the antibody response. CONCLUSION: Many tests for HIV or HIV antibody can now be employed for an early confirmation of primary HIV infection (PHI). Currently available screening tests proved much more sensitive than older tests, and seroconversion was usually detected within one month after infection. Consequently, in Sweden we now recommend only 3 months of follow-up after most cases of HIV exposure.

Reappearance of founder virus sequence in human immunodeficiency virus type 1-infected patients.

Different patterns of temporal evolution in human immunodeficiency virus type 1 V3 and p17 regions are described for eight patients studied during the first years following primary infection. In samples from three patients, a rapid replacement of the major sequence occurred but the original sequence reappeared later simultaneously with clinical deterioration and increased plasma viral load.

Characterization of the viral population during primary HIV-1 infection.

OBJECTIVE: To study viral heterogeneity at a very early phase of primary HIV-1 infection. DESIGN: Samples were drawn very early during primary HIV-1 infection. A virus population-based approach was used to study the viral heterogeneity in the C2-V3 and p17 regions. METHODS: Plasma samples (n = 33) were obtained before or shortly after onset of acute symptoms in 15 patients. In all subjects, the first sample was drawn within 10 days after onset of symptoms. Peripheral blood mononuclear cells (PBMC) were available in two patients. The number of polymorphic sites in the C2-V3 (15 patients) and p17 regions (eight patients) were determined by direct sequencing. RESULTS: The sequence heterogeneity was restricted in most patients, although only two out of 15 patients had a completely homogeneous C2-V3 sequence. However, pronounced individual differences were seen. Rapid sequence changes occurred during the first month in two patients. In one patient, the major DNA species at day 12 later became the major species in plasma. CONCLUSIONS: The viral population is seldom completely homogeneous during primary HIV-1 infection, although the heterogeneity is restricted in most, but not all, patients. These individual differences do not seem to be due to sex or viral subtype. Rapid changes of the virus population may occur during primary HIV-1 infection. The DNA species detected in PBMC do not only represent earlier viral quasispecies but are also a potential source of future viral RNA species.