Does gender or mode of HIV acquisition affect virological response to modern antiretroviral therapy (ART)?

OBJECTIVES: Previous UK studies have reported disparities in HIV treatment outcomes for women. We investigated whether these differences persist in the modern antiretroviral treatment (ART) era. METHODS: A single-centre cohort analysis was carried out. We included in the study all previously ART-naïve individuals at our clinic starting triple ART from 1 January 2006 onwards with at least one follow-up viral load (VL). Time to viral suppression (VS; first viral load < 50 HIV-1 RNA copies/mL), virological failure (VF; first of two consecutive VLs > 200 copies/mL more than 6 months post-ART) and treatment modification were estimated using standard survival methods. RESULTS: Of 1086 individuals, 563 (52%) were men whose risk for HIV acquisition was sex with other men (MSM), 207 (19%) were men whose risk for HIV acquisition was sex with women (MSW) and 316 (29%) were women. Median pre-ART CD4 count and time since HIV diagnosis in these groups were 298, 215 and 219 cells/µL, and 2.3, 0.3 and 0.3 years, respectively. Time to VS was comparable between groups, but women [adjusted hazard ratio (aHR) 2.32; 95% confidence interval (CI) 1.28-4.22] and MSW (aHR 3.28; 95% CI 1.91-5.64) were at considerably higher risk of VF than MSM. Treatment switches and complete discontinuation were also more common among MSW [aHR 1.38 (95% CI 1.04-1.81) and aHR 1.73 (95% CI 0.97-3.16), respectively] and women [aHR 1.87 (95% CI 1.43-2.46) and aHR 3.20 (95% CI 2.03-5.03), respectively] than MSM. CONCLUSIONS: Although response rates were good in all groups, poorer virological outcomes for women and MSW have persisted into the modern ART era. Factors that might influence the differences include socioeconomic status and mental health disorders. Further interventions to ensure excellent response rates in women and MSW are required.

A simple self-reported adherence tool as a predictor of viral rebound in people with viral suppression on antiretroviral therapy.

OBJECTIVES: The aim of the study was to investigate the relationship between self-reported antiretroviral therapy (ART) adherence and virological outcomes in the multinational Strategies for Management of Antiretroviral Therapy (SMART) study. METHODS: Eligible participants were from the continuous ART arm and had at least one viral load (VL) ≤ 50 HIV-1 RNA copies/mL and a subsequent VL value (VL pair). Self-reported adherence was measured at each visit using a five-point Likert scale which employed a 7-day recall. High adherence was defined as taking 'all pills every day' (level 1) for every regimen component; all others had suboptimal adherence (levels 2 - 5). In individuals with VL suppression (≤ 50 copies/mL), the association between adherence (at the time of VL suppression) and VL rebound (> 200 copies/mL at next visit) was assessed using multivariable logistic regression with generalized estimating equations. RESULTS: A total of 10 761 sets of VL pairs from 1986 participants were included in the study. For 1220 (11%) VL pairs, adherence was suboptimal. For 507 VL pairs (5%), VL rebound occurred. The risk of rebound generally increased as adherence decreased: 4.2% for level 1, 7.7% for level 2, 16.3% for level 3, 9.4% for level 4 and 12.9% for level 5. In multivariable analysis, suboptimal adherence at the time of suppression was associated with a 50% increased odds of experiencing subsequent VL rebound [odds ratio (OR) 1.51; 95% confidence interval (CI) 1.19-1.92; P = 0.0023], compared with high adherence. CONCLUSIONS: Self-reported suboptimal adherence in people with VL suppression is associated with an increased risk of VL rebound. Our findings highlight the importance of continued adherence counselling, even in people with VL suppression, and to ensure that people with HIV infection maintain excellent adherence in order to minimize the risk of VL rebound.

Survey of the prevalence of Salmonella species on commercial laying farms in the United Kingdom.

A survey of salmonella infection on 454 commercial layer flock holdings in the uk was carried out between October 2004 and September 2005. Fifty-four (11.7 per cent, 95 per cent confidence interval 9.3 to 14.0 per cent) were salmonella positive. The most common serovar identified was Salmonella Enteritidis at a prevalence of 5.8 per cent, and 70 per cent of these isolates were phage types 4, 6, 7 and 35. Salmonella Typhimurium was the second most prevalent serovar, found in 1.8 per cent of the farms. Of the three other serovars given top priority by the eu because of their public health significance, Salmonella Virchow and Salmonella Infantis were each isolated from one holding, but Salmonella Hadar was not isolated from any of the holdings. Analysis of antimicrobial resistance patterns revealed that over 76 per cent of the isolates were sensitive to all of the 16 drugs tested, and all the isolates were sensitive to ciprofloxacin, gentamicin, ceftazidime, apramycin, amikacin, amoxicillin/clavulanic acid, neomycin and cefotaxime.

Removal of methylene blue from plasma via an adsorbent filter.

OBJECTIVE: To evaluate adsorbent filtration of methylene blue (MB) and leukocytes from plasma. METHODS: Plasma (750 ml) from apheresis of 10 normal subjects was split into three aliquots: control (A), filtration (B) and MB addition (to 1 microM), phototreatment and filtration (C). Biochemical and coagulation tests were performed: units A and B were reinfused. RESULTS: Filtration reduced MB to undetectable (< 0.05 microM) levels and leukocytes by 3 log10. Biochemical analytes were unchanged. The partial thromboplastin time was prolonged with MB addition (11 +/- 13%) or filtration (26 +/- 12%, p < 0.05), but the effects were not additive. Autologous transfusion was well tolerated. CONCLUSION: Adsorbent filtration can reduce residual MB to undetectable levels and yields a component suitable for transfusion.

Evaluation of a new prestorage leukoreduction filter for red blood cell units.

BACKGROUND AND OBJECTIVES: Prestorage leukoreduction offers a variety of potential benefits and is becoming more commonly practiced. The LeukoNet prestorage leukoreduction filtration system is intended for leukoreduction of red blood cells and uses a vent to allow automatic drainage of red cells from the filter. MATERIALS AND METHODS: We studied the functional characteristics and the in-vivo and in-vitro properties of leukoreduced AS-1 Red Blood Cells prepared with this new system. Units of AS-1 Red Blood Cells were filtered at 4 degrees C through the LeukoNet filter 24-48 h after collection and stored under usual conditions for 42 days. Residual leukocytes were enumerated using a Nageotte chamber or with a polymerase chain reaction (PCR) technique. In the clinical trial (phase one), 21 donors had units stored with and without leukoreduction for 42 days; biochemical assays were done before and after storage, and 51Cr/99mTc red cell recovery studies at the end of the storage period. RESULTS: Leukocyte content after filtration was 3.2 +/- 2.6 x 10(4)/unit (n = 21), and all units had < 1 x 10(5) leukocytes (median: 3.8 x 10(4)). In-vivo paired studies showed no difference in 24-hour recovery (control: 82.1 +/- 5.8%; test: 82.9 +/- 6.0%). Hemolysis was halved with leuko-reduction (0.59 +/- 0.30 vs. 0.29 +/- 0.11%; p < 0.05), and glucose consumption was reduced by 5% compared to control units (p = < 0.05). Other biochemical parameters showed no differences. In the practical trial (phase two), filtration time was 41 +/- 23 min. With a residual leukocyte content of 6.6 +/- 4.9 x 10(4)/unit and 14 +/- 3% red cell loss (n = 84). Six additional units underwent leukocyte enumeration by PCR and had 2.6 +/- 1.1 x 10(4) residual leukocytes. CONCLUSIONS: Under the conditions studied, the LeukoNet leukoreduction filtration system produces about 4-5 log10 leukocyte content reduction.

William T. Bovie and electrosurgery.

For thousands of years human beings have used heat in the form of cautery to treat trauma and disease. By the late nineteenth century, as technology advanced, heat could be produced by electric current. In 1920 William T. Bovie, an eccentric inventor with a doctorate in plant physiology, developed an innovative electrosurgical unit that Harvey Cushing, the founder of modern neurosurgery, introduced to clinical practice. The Bovine unit passes high frequency alternating current into the body allowing the current to cut or coagulate. After 75 years this basic device remains a fundamental tool in the practice of surgery.

Reliability of auditory brainstem responses from sequenced high-frequency (> or = 8 kHz) tonebursts.

An auditory brainstem response method is described for evoking responses to 4 high-frequency (8, 10, 12 and 14 kHz) tonebursts in the same amount of time normally required to obtain responses to single tonebursts. Reliability of responses to high-frequency toneburst stimuli presented in the conventional manner (one at a time) has been previously documented. In the present study, high-frequency tonebursts were presented to 20 normal-hearing subjects singly and in a 4-stimulus sequence. The reliability of resulting responses did not differ significantly between single- and multiple-stimulus test conditions. It is concluded that this sequenced-stimulus concept could be developed for use in serial monitoring of individuals receiving ototoxic agents as well as being broadly applicable to clinical situations in which patients cannot or will not respond voluntarily.

Multiple-stimulus method for rapid collection of auditory brainstem responses using high-frequency (> or = 8 kHz) tone bursts.

Auditory brainstem responses (ABR) to high-frequency (> or = 8 kHz) tone-burst stimuli have shown potential for objective early detection of ototoxicity. In the case of ill, unresponsive, or otherwise difficult-to-test individuals, the patient group for whom this test is targeted, a threshold-seeking process can be too lengthy. A new method is described for obtaining responses to several high-frequency tone bursts in the same amount of time as that used in obtaining a single responses. Using 10 normal-hearing subjects, four high-frequency tone-burst stimuli (14, 12, 10, and 8 kHz) were presented singly, then in a multiple-stimulus sequence with onsets separated by 10 msec. Wave V response latencies from the multiple-stimulus sequences are compared to those presented singly, with small but statistically significant longer latencies observed for all stimuli following the initial stimulus (14 kHz) in the multiple sequence. Test-retest reliability was comparable between multiple and single conditions. These findings support the development of this technique for clinical auditory monitoring.

Assessment of blood interactions with the Therapore Apheresis System.

Biocompatibility evaluations are a complex issue involving not only classical toxicity and animal testing but also the interactions of biological systems. The evaluations of the Therapore Primary System are reported for three model systems: (1) in vitro human blood, (2) a baboon (Papio anubis) animal model, and (3) normal human volunteer apheresis. Measurements of both complement (C3a) and platelet (BTG and TXB2) activation products during the apheresis procedures are given as a sensitive indicator of biocompatibility. No statistically significant elevations of these activation products were observed. Thus, the Therapore System was found to have negligible perturbations of the interacting biological systems evaluated even with the highly sensitive RIA procedures employed. These observations and methods establish a solid foundation for comprehensive biocompatibility evaluations of future extracorporeal devices.

Scintigraphic characteristics of experimental myocardial infarct extension.

Technetium-99m-stannous pyrophosphate scintiphotos were evaluated for diagnosing and quantitating myocardial infarct (MI) extension in sedated dogs. Infarction and extension were produced by serial left anterior descending coronary artery ligations at 0 and 48 hours. We compared serial scintiphoto data with regional myocardial blood flow (MBF) (microsphere technique) and infarct histopathology. In eight control dogs, the scintigraphic MI area was stable at 24, 48, and 72 hours. In each of 11 dogs undergoing extension, the MI area increased after the 48-hour occlusion, averaging a 48.9% increase (p less than 0.001). Grossly, most extensions were mixtures of confluent necrosis and moderate (patchy) necrosis. MBF to confluent infarct tissue decreased significantly, allowing the documentation of extension by totaling the grams of newly flow-deprived tissue, but patchy infarct tissue had little flow deprivation, making it difficult to quantitate this type of extension accurately by flow criteria alone. Rarely, extension could be diagnosed using conventional histologic criteria. We concluded that the scintiphoto MI area was related quantitatively to infarct weight in both control and extension. However, it was not possible to determine that an increase in the MI scintiphoto area was an accurate predictor of the degree of extension using independent flow or pathologic criteria.