Neurocognitive function in HIV infected patients on antiretroviral therapy

OBJECTIVE To describe factors associated with neurocognitive (NC) function in HIV-positive patients on stable combination antiretroviral therapy. DESIGN We undertook a cross-sectional analysis assessing NC data obtained at baseline in patients entering the Protease-Inhibitor-Monotherapy-Versus-Ongoing-Triple therapy (PIVOT) trial. MAIN OUTCOME MEASURE NC testing comprised of 5 domains. Raw results were z-transformed using standard and demographically adjusted normative datasets (ND). Global z-scores (NPZ-5) were derived from averaging the 5 domains and percentage of subjects with test scores >1 standard deviation (SD) below population means in at least two domains (abnormal Frascati score) calculated. Patient characteristics associated with NC results were assessed using multivariable linear regression. RESULTS Of the 587 patients in PIVOT, 557 had full NC results and were included. 77% were male, 68% Caucasian and 28% of Black ethnicity. Mean (SD) baseline and nadir CD4+ lymphocyte counts were 553(217) and 177(117) cells/µL, respectively, and HIV RNA was <50 copies/mL in all. Median (IQR) NPZ-5 score was -0.5 (-1.2/-0) overall, and -0.3 (-0.7/0.1) and -1.4 (-2/-0.8) in subjects of Caucasian and Black ethnicity, respectively. Abnormal Frascati scores using the standard-ND were observed in 51%, 38%, and 81%, respectively, of subjects overall, Caucasian and Black ethnicity (p<0.001), but in 62% and 69% of Caucasian and Black subjects using demographically adjusted-ND (p = 0.20). In the multivariate analysis, only Black ethnicity was associated with poorer NPZ-5 scores (P<0.001). CONCLUSIONS In this large group of HIV-infected subjects with viral load suppression, ethnicity but not HIV-disease factors is closely associated with NC results. The prevalence of abnormal results is highly dependent on control datasets utilised. TRIAL REGISTRY ClinicalTrials.gov, NCT01230580

Traumatic brain injury recorded in the UK Joint Theatre Trauma Registry among the UK Armed Forces

OBJECTIVES: To use the UK Joint Theatre Trauma Registry (UK-JTTR) to identify service personnel sustaining traumatic brain injury (TBI) in recent conflicts and to examine injury characteristics, outcomes, and severity measures predictive of survival. SETTING: Operations HERRICK (Afghanistan) and TELIC (Iraq). DESIGN: The UK-JTTR records data for every UK service person either killed on operations or treated by Defence Medical Services after a trauma call, including those evacuated for inpatient care following traumatic injury. UK-JTTR data were retrospectively analyzed to identify those who sustained TBI. MAIN MEASURES: The Mayo system was used to define TBI. Glasgow Coma Scale score, injury severity score, new injury severity score, trauma injury severity score, abbreviated injury scale, and a severity characterization of trauma were used to predict survival. RESULTS: In total, 464 UK service personnel sustained TBI, representing 19% of the 2440 casualties in Afghanistan and Iraq, recorded in the UK-JTTR. Most TBI casualties had moderate-severe TBI (402, 87%). There were 181 (39%) survivors, 56% of these received neurorehabilitation. Improvised explosive devices accounted for 55% of TBIs sustained in Afghanistan and 31% of TBIs in Iraq. Logistic regression analyses were performed using the 412 cases (149 survivors: 263 fatalities) with scores on all severity measures. The best-fitting model was based on trauma injury severity score. A trauma injury severity score more than 11.13 indicates a more than 95% probability of survival. CONCLUSION: This is the first study of UK combat TBIs between 2003 and 2011. Almost 1 in 5 UK service personnel recorded in the UK-JTTR had TBI; most were moderate-severe. However, mild TBI is likely to be underrepresented in the UK-JTTR. These findings may be used to plan future rehabilitation needs, as almost half the survivors did not receive neurorehabilitation

Subdominant Gag-specific anti-HIV efficacy in an HLA-B*57-positive elite controller

Despite the discovery of HIV over three decades ago, the 2008 ‘Berlin patient’ is the only case of sustained HIV remission. Other cases of apparent ‘cure’ eventually relapsed [1] and although early antiretroviral therapy (ART) has recently gained traction as a factor contributing to remission [2,3], most cases are likely to relapse [4]. In contrast, relapse in ‘elite controllers’ of HIV infection is less common. These are ART-naïve individuals who spontaneously suppress viremia to undetectable levels. Approximately 40% of elite controllers express HLA-B*57 [5], an example being the original 1999 ‘Berlin patient’, in whom virologic control has been maintained for &gt;15 years to date [6]

Does discordancy between the CD4 count and CD4 percentage in HIV-positive individuals influence outcomes on highly active antiretroviral therapy?

INTRODUCTION The CD4 count and CD4 percentage (CD4%) are both strong predictors of clinical disease progression in human immunodeficiency virus (HIV). Although individuals may show discordancy between their CD4 count and CD4%, the clinical relevance of this is unclear. METHODS Discordancy was defined where the CD4% was ≤10th percentile for a selected CD4 count range (referred to as low discordancy), within the central 80% range (concordant), or ≥90th percentile (high discordancy). Regression methods identified factors associated with low and high discordancy in untreated individuals and assessed the impact of discordancy on treatment responses to highly active antiretroviral therapy (HAART). RESULTS High discordancy was associated with female sex, low viral load, and white ethnicity; low discordancy was associated with black or nonwhite ethnicity, older age, and injection drug use. Clinical event rates were higher in individuals with high discordancy starting HAART, but there was no association with subsequent HIV progression by 6 months after starting HAART. CD4 count increases remained lower, by 20 cells/mm(3), in individuals with low discordancy, and higher, by 27 cells/mm(3), in those with high discordancy. CONCLUSIONS Overall discrepancies between the CD4/CD4% are small, confirming the use of absolute CD4 counts as a monitoring tool

Neurocognitive testing results.

<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0061949#pone-0061949-t002" target="_blank"><i>Table 2</i></a><i> legend</i>: ^§patients with complete neurocognitive data including patients of ethnicity other than Caucasian or Black (n = 20); IQR  =  interquartile range, SD  =  standard deviation; ^¶Excludes all patients of ethnicity other than Caucasian and Black, as well as 30 subjects of Black ethnicity who fell outside the age range covered by the adjusted normative data; NPZ-5 results using standard normative data in these 30 patients were similar to those of the other 126 patients. Data are number (%) or median (interquartile range).</p

Association between NPZ-5 score and Frascati score.

<p>Association between NPZ-5 score and Frascati score.</p