Analysis of primary care electronic health record data of people living with hepatitis B virus: infection and hepatocellular carcinoma risk associated with socio-economic deprivation.

OBJECTIVES: We set out to characterise chronic hepatitis B (CHB) in the primary care population in England and investigate risk factors for progression to hepatocellular carcinoma (HCC). STUDY DESIGN: Retrospective cohort study. METHODS: We identified 8039 individuals with CHB in individuals aged ≥18 years between 1999 and 2019 in the English primary care database QResearch. HCC risk factors were investigated using Cox proportional hazards modelling. RESULTS: Most of those with a record of CHB were males (60%) of non-White ethnicity (>70%), and a high proportion were in the most deprived Townsend deprivation quintile (44%). Among 7029 individuals with longitudinal data, 161 HCC cases occurred. Increased HCC hazards were significantly associated with male sex (adjusted hazards ratio [aHR] 3.17, 95% confidence interval [95% CI] 1.92-5.23), in the fifth deprivation quintile as compared to the third quintile (aHR 1.69, 95% CI 1.01-2.84), with older age (for age groups 56-65 and ≥66 years, compared to 26-35 years, aHRs 2.82 [95% CI 1.45-5.46] and 3.76 [95% CI 1.79-7.9], respectively), Caribbean ethnicity (aHR 3.32, 95% CI 1.43-7.71, compared to White ethnicity), ascites (aHR 3.15, 95% CI 1.30-7.67), cirrhosis (aHR 6.55, 95% CI 4.57-9.38) and peptic ulcer disease (aHR 2.26, 95% CI 1.45-3.51). CONCLUSIONS: Targeting interventions and HCC surveillance at vulnerable groups is essential to improve CHB outcomes and to support progress towards international goals for the elimination of hepatitis infection as a public health threat.

Characteristics, management and outcome of a large necrotising otitis externa case series: need for standardised case definition.

BACKGROUND: Necrotising otitis externa is a severe ear infection for which there are no established diagnostic or treatment guidelines. METHOD: This study described clinical characteristics, management and outcomes for patients managed as necrotising otitis externa cases at a UK tertiary referral centre. RESULTS: A total of 58 (63 per cent) patients were classified as definite necrotising otitis externa cases, 31 (34 per cent) as probable cases and 3 (3 per cent) as possible cases. Median duration of intravenous and oral antimicrobial therapy was 6.0 weeks (0.49-44.9 weeks). Six per cent of patients relapsed a median of 16.4 weeks (interquartile range, 23-121) after stopping antimicrobials. Twenty-eight per cent of cases had complex disease. These patients were older (p = 0.042), had a longer duration of symptoms prior to imaging (p < 0.0001) and higher C-reactive protein at diagnosis (p = 0.005). Despite longer courses of intravenous antimicrobials (23 vs 14 days; p = 0.032), complex cases were more likely to relapse (p = 0.016). CONCLUSION: A standardised case-definition of necrotising otitis externa is needed to optimise diagnosis, management and research.

Parenchymal involvement on CT pulmonary angiography in SARS-CoV-2 Alpha variant infection and correlation of COVID-19 CT severity score with clinical disease severity and short-term prognosis in a UK cohort.

AIM: To determine if there is a difference in radiological, biochemical, or clinical severity between patients infected with Alpha-variant SARS-CoV-2 compared with those infected with pre-existing strains, and to determine if the computed tomography (CT) severity score (CTSS) for COVID-19 pneumonitis correlates with clinical severity and can prognosticate outcomes. MATERIALS AND METHODS: Blinded CTSS scoring was applied to 137 hospital patients who had undergone both CT pulmonary angiography (CTPA) and whole-genome sequencing of SARS-CoV-2 within 14 days of CTPA between 1/12/20-5/1/21. RESULTS: There was no evidence of a difference in imaging severity on CTPA, viral load, clinical parameters of severity, or outcomes between Alpha and preceding variants. CTSS on CTPA strongly correlates with clinical and biochemical severity at the time of CTPA, and with patient outcomes. Classifying CTSS into a binary value of "high" and "low", with a cut-off score of 14, patients with a high score have a significantly increased risk of deterioration, as defined by subsequent admission to critical care or death (multivariate hazard ratio [HR] 2.76, p<0.001), and hospital length of stay (17.4 versus 7.9 days, p<0.0001). CONCLUSION: There was no evidence of a difference in radiological severity of Alpha variant infection compared with pre-existing strains. High CTSS applied to CTPA is associated with increased risk of COVID-19 severity and poorer clinical outcomes and may be of use particularly in settings where CT is not performed for diagnosis of COVID-19 but rather is used following clinical deterioration.

Artificial Intelligence: Guidance for clinical imaging and therapeutic radiography professionals, a summary by the Society of Radiographers AI working group.

INTRODUCTION: Artificial intelligence (AI) has started to be increasingly adopted in medical imaging and radiotherapy clinical practice, however research, education and partnerships have not really caught up yet to facilitate a safe and effective transition. The aim of the document is to provide baseline guidance for radiographers working in the field of AI in education, research, clinical practice and stakeholder partnerships. The guideline is intended for use by the multi-professional clinical imaging and radiotherapy teams, including all staff, volunteers, students and learners. METHODS: The format mirrored similar publications from other SCoR working groups in the past. The recommendations have been subject to a rapid period of peer, professional and patient assessment and review. Feedback was sought from a range of SoR members and advisory groups, as well as from the SoR director of professional policy, as well as from external experts. Amendments were then made in line with feedback received and a final consensus was reached. RESULTS: AI is an innovative tool radiographers will need to engage with to ensure a safe and efficient clinical service in imaging and radiotherapy. Educational provisions will need to be proportionately adjusted by Higher Education Institutions (HEIs) to offer the necessary knowledge, skills and competences for diagnostic and therapeutic radiographers, to enable them to navigate a future where AI will be central to patient diagnosis and treatment pathways. Radiography-led research in AI should address key clinical challenges and enable radiographers co-design, implement and validate AI solutions. Partnerships are key in ensuring the contribution of radiographers is integrated into healthcare AI ecosystems for the benefit of the patients and service users. CONCLUSION: Radiography is starting to work towards a future with AI-enabled healthcare. This guidance offers some recommendations for different areas of radiography practice. There is a need to update our educational curricula, rethink our research priorities, forge new strong clinical-academic-industry partnerships to optimise clinical practice. Specific recommendations in relation to clinical practice, education, research and the forging of partnerships with key stakeholders are discussed, with potential impact on policy and practice in all these domains. These recommendations aim to serve as baseline guidance for UK radiographers. IMPLICATIONS FOR PRACTICE: This review offers the most up-to-date recommendations for clinical practitioners, researchers, academics and service users of clinical imaging and therapeutic radiography services. Radiography practice, education and research must gradually adjust to AI-enabled healthcare systems to ensure gains of AI technologies are maximised and challenges and risks are minimised. This guidance will need to be updated regularly given the fast-changing pace of AI development and innovation.

Findings from home-based HIV testing and facilitated linkage after scale-up of test and treat in rural South Africa: young people still missing.

OBJECTIVES: The aim of the study was to estimate rates of linkage to HIV care and antiretroviral treatment (ART) initiation after the introduction of home-based HIV counselling and testing (HBHCT) and telephone-facilitated support for linkage in rural South Africa. METHODS: A population-based prospective cohort study was carried out in KwaZulu Natal, South Africa. All residents aged ≥ 15 years were eligible for HBHCT. Those who tested positive and were not in care were referred for ART at one of 11 public-sector clinics. Individuals who did not attend the clinic within 2 weeks were sent a short message service (SMS) reminder; those who had not attended after a further 2 weeks were telephoned by a nurse counsellor, to discuss concerns and encourage linkage. Kaplan-Meier methods were used to estimate the proportion of newly diagnosed individuals linking to care and initiating ART. RESULTS: Among 38 827 individuals visited, 26% accepted HBHCT. Uptake was higher in women than in men (30% versus 20%, respectively), but similar in people aged < 30 years and ≥ 30 years (28% versus 26%, respectively). A total of 784 (8%) tested HIV positive, of whom 427 (54%) were newly diagnosed. Within 6 months, 31% of women and 18% of men < 30 years old had linked to care, and 29% and 16%, respectively, had started ART. Among those ≥ 30 years, 41% of women and 38% of men had linked to care within 6 months, and 41% and 35%, respectively, had started ART. CONCLUSIONS: Despite facilitated linkage, rates of timely linkage to care and ART initiation after HBHCT were very low, particularly among young men. Innovations are needed to provide effective HIV care and prevention interventions to young people, and thus maximize the benefits of universal test and treat.

Home-based intervention to test and start (HITS) protocol: a cluster-randomized controlled trial to reduce HIV-related mortality in men and HIV incidence in women through increased coverage of HIV treatment.

BACKGROUND: To realize the full benefits of treatment as prevention in many hyperendemic African contexts, there is an urgent need to increase uptake of HIV testing and HIV treatment among men to reduce the rate of HIV transmission to (particularly young) women. This trial aims to evaluate the effect of two interventions - micro-incentives and a tablet-based male-targeted HIV decision support application - on increasing home-based HIV testing and linkage to HIV care among men with the ultimate aim of reducing HIV-related mortality in men and HIV incidence in young women. METHODS/DESIGN: This is a cluster randomized trial of 45 communities (clusters) in a rural area in the uMkhanyakude district of KwaZulu Natal, South Africa (2018-2021). The study is built upon the Africa Health Research Institute (AHRI)'s HIV testing platform, which offers annual home-based rapid HIV testing to individuals aged 15 years and above. In a 2 × 2 factorial design, individuals aged ≥15 years living in the 45 clusters are randomly assigned to one of four arms: i) a financial micro-incentive (food voucher) (n = 8); ii) male-targeted HIV specific decision support (EPIC-HIV) (n = 8); iii) both the micro incentives and male-targeted decision support (n = 8); and iv) standard of care (n = 21). The EPIC-HIV application is developed and delivered via a tablet to encourage HIV testing and linkage to care among men. A mixed method approach is adopted to supplement the randomized control trial and meet the study aims. DISCUSSION: The findings of this trial will provide evidence on the feasibility and causal impact of two interventions - micro-incentives and a male-targeted HIV specific decision support - on uptake of home-based HIV testing, linkage to care, as well as population health outcomes including population viral load, HIV related mortality in men, and HIV incidence in young women (15-30 years of age). TRIAL REGISTRATION: This trial was registered on 28 November 2018 on, identifier https://clinicaltrials.gov/ .

Lipoprotein markers associated with disability from multiple sclerosis.

Altered lipid metabolism is a feature of chronic inflammatory disorders. Increased plasma lipids and lipoproteins have been associated with multiple sclerosis (MS) disease activity. Our objective was to characterise the specific lipids and associated plasma lipoproteins increased in MS and to test for an association with disability. Plasma samples were collected from 27 RRMS patients (median EDSS, 1.5, range 1-7) and 31 healthy controls. Concentrations of lipids within lipoprotein sub-classes were determined from NMR spectra. Plasma cytokines were measured using the MesoScale Discovery V-PLEX kit. Associations were tested using multivariate linear regression. Differences between the patient and volunteer groups were found for lipids within VLDL and HDL lipoprotein sub-fractions (p < 0.05). Multivariate regression demonstrated a high correlation between lipids within VLDL sub-classes and the Expanded Disability Status Scale (EDSS) (p < 0.05). An optimal model for EDSS included free cholesterol carried by VLDL-2, gender and age (R2 = 0.38, p < 0.05). Free cholesterol carried by VLDL-2 was highly correlated with plasma cytokines CCL-17 and IL-7 (R2 = 0.78, p < 0.0001). These results highlight relationships between disability, inflammatory responses and systemic lipid metabolism in RRMS. Altered lipid metabolism with systemic inflammation may contribute to immune activation.

Improving access to ART in low-income settings through knowledge transfer: a case study from Zimbabwe.

It may be assumed that infertility is not a problem in resource-poor areas where fertility rates are high. However, evidence overwhelmingly shows that childlessness is highly stigmatized in these settings and that women who are unable to bear children suffer significant social and psychological consequences. The World Health Organization has recommended that infertility be considered a global health problem and stated the need for ART to be adapted to low-resource settings. This paper describes a model for improving access to ART in low-resource settings. Experienced ART health professionals from Australia and Italy representing medical science, embryology, nursing and counselling used knowledge transfer to support a clinician, a laboratory scientist and a nurse to establish an ART service in Harare, Zimbabwe. Support and mentorship provided between October 2016 and December 2017 included: hosting the clinician and the embryologist for the new service in established ART clinics for short periods and providing them with dedicated mentorship and training during their stay; funding an experienced embryologist to travel to Zimbabwe (three times) to oversee the setting up of the lab and provide hands-on embryology training; funding a scientist and a nurse to travel to Zimbabwe to troubleshoot and establish protocols for record keeping and psychosocial care; and contributing approximately AUD $15,000 to the purchase of some equipment. By 31 March 2018, the team at IVF Zimbabwe had performed 166 ART procedures, which at time of writing had resulted in 16 births and 4 ongoing pregnancies. This case study demonstrates that with mentorship and modest financial support from ART experts from high-income settings, health professionals in low-income settings can deliver affordable ART with successful outcomes.

Decreased hippocampal translocator protein (18 kDa) expression in alcohol dependence: a [11C]PBR28 PET study.

Repeated withdrawal from alcohol is clinically associated with progressive cognitive impairment. Microglial activation occurring during pre-clinical models of alcohol withdrawal is associated with learning deficits. We investigated whether there was microglial activation in recently detoxified alcohol-dependent patients (ADP), using [11C]PBR28 positron emission tomography (PET), selective for the 18kDa translocator protein (TSPO) highly expressed in activated microglia and astrocytes. We investigated the relationship between microglial activation and cognitive performance. Twenty healthy control (HC) subjects (45±13; M:F 14:6) and nine ADP (45±6, M:F 9:0) were evaluated. Dynamic PET data were acquired for 90 min following an injection of 331±15 MBq [11C]PBR28. Regional volumes of distribution (VT) for regions of interest (ROIs) identified a priori were estimated using a two-tissue compartmental model with metabolite-corrected arterial plasma input function. ADP had an ~20% lower [11C]PBR28 VT, in the hippocampus (F(1,24) 5.694; P=0.025), but no difference in VT in other ROIs. Hippocampal [11C]PBR28 VT was positively correlated with verbal memory performance in a combined group of HC and ADP (r=0.720, P<0.001), an effect seen in HC alone (r=0.738; P=0.001) but not in ADP. We did not find evidence for increased microglial activation in ADP, as seen pre-clinically. Instead, our findings suggest lower glial density or an altered activation state with lower TSPO expression. The correlation between verbal memory and [11C]PBR28 VT, raises the possibility that abnormalities of glial function may contribute to cognitive impairment in ADP.

Abnormal frontostriatal connectivity in adolescent-onset schizophrenia and its relationship to cognitive functioning.

BACKGROUND: Adolescent-onset schizophrenia (AOS) is associated with cognitive impairment and poor clinical outcome. Cognitive dysfunction is hypothesised, in part, to reflect functional dysconnectivity between the frontal cortex and the striatum, although structural abnormalities consistent with this hypothesis have not yet been demonstrated in adolescence. OBJECTIVE: To characterise frontostriatal white matter (WM) tracts in relation to cognition in AOS. DESIGN: A MRI volumetric and diffusion tensor imaging study. PARTICIPANTS: Thirty-seven AOS subjects and 24 age and sex-matched healthy subjects. OUTCOME MEASURES: Using probabilistic tractography, cortical regions with the highest connection probability for each striatal voxel were determined, and correlated with IQ and specific cognitive functions after co-varying for age and sex. Fractional anisotropy (FA) from individual tracts was a secondary measure. RESULTS: Bayesian Structural Equation modeling of FA from 12 frontostriatal tracts showed processing speed to be an intermediary variable for cognition. AOS patients demonstrated generalised cognitive impairment with specific deficits in verbal learning and memory and in processing speed after correction for IQ. Dorsolateral prefrontal cortex connectivity with the striatum correlated positively with these measures and with IQ. DTI voxel-wise comparisons showed lower connectivity between striatum and the motor and lateral orbitofrontal cortices bilaterally, the left amygdalohippocampal complex, right anterior cingulate cortex, left medial orbitofrontal cortex and right dorsolateral prefrontal cortex. CONCLUSIONS: Frontostriatal dysconnectivity in large WM tracts that can explain core cognitive deficits are evident during adolescence. Processing speed, which is affected by alterations in WM connectivity, appears an intermediary variable in the cognitive deficits seen in schizophrenia.

Body fat differences by self-reported race/ethnicity in healthy term newborns.

BACKGROUND: Ethnic differences in total body fat (fat mass [FM]) have been reported in adults and children, but the timing of when these differences manifest and whether they are present at birth are unknown. OBJECTIVES: This study aimed to assess whether ethnic differences in body fat are present at birth in healthy infants born at term, where body fat is measured using air displacement plethysmography and fat distribution by skin-fold thickness. METHODS: Data were from a multiracial cross-sectional convenience sample of 332 term infants from four racial or ethnic groups based on maternal self-report (A, Asian; AA, non-Hispanic Black [African-American]; C, non-Hispanic White; and H, Hispanic). The main outcome measure was infant body fat at 1-3 days after birth, with age, birth weight, gestational age and maternal pre-pregnancy weight as covariates. RESULTS: Significant effects for race (P = 0.0011), sex (P = 0.0051) and a race by sex interaction (P = 0.0236) were found. C females had higher FM than C males (P = 0.0001), and AA females had higher FM than AA males (P = 0.0205). C males had less FM than A males (P = 0.0353) and H males (P = 0.0001). CONCLUSION: Race/ethnic and sex differences in FM are present in healthy term newborns. Although the implications of these differences are unclear, studies beginning in utero and birth set the stage for a life course approach to understanding disease later in life.

The interactions between temperature and activity levels in driving metabolic rate: theory, with empirical validation from contrasting ectotherms.

The rate of change in resting metabolic rate (RMR) as a result of a temperature increase of 10 °C is termed the temperature coefficient (Q10), which is often used to predict how an organism's total MR will change with temperature. However, this method neglects a potentially key component of MR; changes in activity level (and thus activity MR; AMR) with temperature may significantly alter the relationship between MR and temperature. The present study seeks to describe how thermal effects on total MR estimated from RMR-temperature measurements can be misleading when the contribution of activity to total MR is neglected. A simple conceptual framework illustrates that since the relationship between activity levels and temperature can be different to the relationship between RMR and temperature, a consistent relationship between RMR and total MR cannot be assumed. Thus the thermal effect on total MR can be considerably different to the thermal effect on RMR. Simultaneously measured MR and activity from three ectotherm species with differing behavioural and physiological ecologies were used to empirically examine how changes in temperature drive changes in RMR, activity level, AMR and the Q10 of MR. These species exhibited varied activity- and MR-temperature relationships, underlining the difficulty in predicting thermal influences on activity levels and total MR. These data support a model showing that thermal effects on total MR will deviate from predictions based solely on RMR; this deviation will depend upon the difference in Q10 between AMR and RMR, and the relative contribution of AMR to total MR. To develop mechanistic, predictive models for species' metabolic responses to temperature changes, empirical information about the relationships between activity levels, MR and temperature, such as reported here, is required. This will supersede predictions based on RMR alone.

Virologic suppression among HIV-infected US Air Force members in a highly-structured programme with free access to care.

SummaryThe United States Air Force HIV programme has several features that may enhance antiretroviral therapy outcomes, including free access to healthcare and mandatory clinical visits every six months at a single centre. We evaluated viral load suppression (<50 copies/ml) after 12 months of initial antiretroviral therapy, with extension to 18 and 24 months. Active duty Air Force members were categorised by year of antiretroviral therapy initiation: 2000-2005 (n = 95, 36.1%) and 2006-2011 (n = 168, 63.9%). The median months from HIV diagnosis to initial antiretroviral therapy were shorter in the 2000-2005 group (2.4, IQR 1.2-5.9) compared with the 2006-2011 group (12.6, IQR 2.6-29.0; p < 0.001). Viral load suppression was greater in the 2006-2011 group compared with the 2000-2005 group at 12 months (93.2% versus 78.6%, p = 0.002) and 18 months (91.8% versus 80.3%, p = 0.03), and trended higher at 24 months (90.8% versus 82.5%; p = 0.15). Factors associated with viral load suppression at 12 months in multivariate models included antiretroviral therapy initiation during 2006-2011 (OR 5.22, 95% CI 1.50-18.18) and CD4 count at antiretroviral therapy initiation (OR 2.29, 95% CI 1.19-14.43 per 100 cells/µl increase). Structured programmes that minimise traditional barriers to care combined with the use of contemporary antiretroviral therapy regimens can achieve clinic-wide viral load suppression in >90% of patients.

Age independently affects myelin integrity as detected by magnetization transfer magnetic resonance imaging in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a heterogeneous disorder with a progressive course that is difficult to predict on a case-by-case basis. Natural history studies of MS have demonstrated that age influences clinical progression independent of disease duration. OBJECTIVE: To determine whether age would be associated with greater CNS injury as detected by magnetization transfer MRI. MATERIALS AND METHODS: Forty MS patients were recruited from out-patient clinics into two groups stratified by age but with similar clinical disease duration as well as thirteen controls age-matched to the older MS group. Images were segmented by automated programs and blinded readers into normal appearing white matter (NAWM), normal appearing gray matter (NAGM), and white matter lesions (WMLs) and gray matter lesions (GMLs) in the MS groups. WML and GML were delineated on T2-weighted 3D fluid-attenuated inversion recovery (FLAIR) and T1 weighted MRI volumes. Mean magnetization transfer ratio (MTR), region volume, as well as MTR histogram skew and kurtosis were calculated for each region. RESULTS: All MTR measures in NAGM and MTR histogram metrics in NAWM differed between MS subjects and controls, as expected and previously reported by several studies, but not between MS groups. However, MTR measures in the WML did significantly differ between the MS groups, in spite of no significant differences in lesion counts and volumes. CONCLUSIONS: Despite matching for clinical disease duration and recording no significant WML volume difference, we demonstrated strong MTR differences in WMLs between younger and older MS patients. These data suggest that aging-related processes modify the tissue response to inflammatory injury and its clinical outcome correlates in MS.

Cytoreductive nephrectomy for metastatic renal cell carcinoma: a review of the historical literature and its role in the era of targeted molecular therapy.

Renal cell carcinoma presents with metastatic disease in approximately 30% cases. While surgical intervention remains the standard of care for organ confined disease, its role is limited in the management of metastatic disease. Over the last decade, cytoreductive nephrectomy prior to immunotherapy has demonstrated significant improvement in overall survival for appropriately selected patients. This review summarizes the evidence for the role of cytoreductive nephrectomy in combination with immunotherapy and discusses its potential role in the current era of targeted molecular therapy.

Differential escape patterns within the dominant HLA-B*57:03-restricted HIV Gag epitope reflect distinct clade-specific functional constraints.

UNLABELLED: HLA-B*57:01 and HLA-B*57:03, the most prevalent HLA-B*57 subtypes in Caucasian and African populations, respectively, are the HLA alleles most protective against HIV disease progression. Understanding the mechanisms underlying this immune control is of critical importance, yet they remain unclear. Unexplained differences are observed in the impact of the dominant cytotoxic T lymphocyte (CTL) response restricted by HLA-B*57:01 and HLA-B*57:03 in chronic infection on the Gag epitope KAFSPEVIPMF (KF11; Gag 162 to 172). We previously showed that the HLA-B*57:03-KF11 response is associated with a >1-log-lower viral setpoint in C clade virus infection and that this response selects escape mutants within the epitope. We first examined the relationship of KF11 responses in B clade virus-infected subjects with HLA-B*57:01 to immune control and observed that a detectable KF11 response was associated with a >1-log-higher viral load (P = 0.02). No evidence of HLA-B*57:01-KF11-associated selection pressure was identified in previous comprehensive analyses of >1,800 B clade virus-infected subjects. We then studied a B clade virus-infected cohort in Barbados, where HLA-B*57:03 is highly prevalent. In contrast to findings for B clade virus-infected subjects expressing HLA-B*57:01, we observed strong selection pressure driven by the HLA-B*57:03-KF11 response for the escape mutation S173T. This mutation reduces recognition of virus-infected cells by HLA-B*57:03-KF11 CTLs and is associated with a >1-log increase in viral load in HLA-B*57:03-positive subjects (P = 0.009). We demonstrate functional constraints imposed by HIV clade relating to the residue at Gag 173 that explain the differential clade-specific escape patterns in HLA-B*57:03 subjects. Further studies are needed to evaluate the role of the KF11 response in HLA-B*57:01-associated HIV disease protection. IMPORTANCE: HLA-B*57 is the HLA class I molecule that affords the greatest protection against disease progression in HIV infection. Understanding the key mechanism(s) underlying immunosuppression of HIV is of importance in guiding therapeutic and vaccine-related approaches to improve the levels of HIV control occurring in nature. Numerous mechanisms have been proposed to explain the HLA associations with differential HIV disease outcome, but no consensus exists. These studies focus on two subtypes of HLA-B*57 prevalent in Caucasian and African populations, HLA-B*57:01 and HLA-B*57:03, respectively. These alleles appear equally protective against HIV disease progression. The CTL epitopes presented are in many cases identical, and the dominant response in chronic infection in each case is to the Gag epitope KF11. However, there the similarity ends. This study sought to better understand the reasons for these differences and what they teach us about which immune responses contribute to immune control of HIV infection.