Characteristics associated with antenatally unidentified small-for-gestational-age fetuses: prospective cohort study nested within DESiGN randomized controlled trial.

OBJECTIVE: To identify the clinical characteristics and patterns of ultrasound use amongst pregnancies with an antenatally unidentified small-for-gestational-age (SGA) fetus, compared with those in which SGA is identified, to understand how to design interventions that improve antenatal SGA identification. METHODS: This was a prospective cohort study of singleton, non-anomalous SGA (birth weight < 10th centile) neonates born after 24 + 0 gestational weeks at 13 UK sites, recruited for the baseline period and control arm of the DESiGN trial. Pregnancy with antenatally unidentified SGA was defined if there was no scan or if the final scan showed estimated fetal weight (EFW) at the 10th centile or above. Identified SGA was defined if EFW was below the 10th centile at the last scan. Maternal and fetal sociodemographic and clinical characteristics were studied for associations with unidentified SGA using unadjusted and adjusted logistic regression models. Ultrasound parameters (gestational age at first growth scan, number and frequency of ultrasound scans) were described, stratified by presence of indication for serial ultrasound. Associations of unidentified SGA with absolute centile and percentage weight difference between the last scan and birth were also studied on unadjusted and adjusted logistic regression, according to time between the last scan and birth. RESULTS: Of the 15 784 SGA babies included, SGA was not identified antenatally in 78.7% of cases. Of pregnancies with unidentified SGA, 47.1% had no recorded growth scan. Amongst 9410 pregnancies with complete data on key maternal comorbidities and antenatal complications, the risk of unidentified SGA was lower for women with any indication for serial scans (adjusted odds ratio (aOR), 0.56 (95% CI, 0.49-0.64)), for Asian compared with white women (aOR, 0.80 (95% CI, 0.69-0.93)) and for those with non-cephalic presentation at birth (aOR, 0.58 (95% CI, 0.46-0.73)). The risk of unidentified SGA was highest among women with a body mass index (BMI) of 25.0-29.9 kg/m2 (aOR, 1.15 (95% CI, 1.01-1.32)) and lowest in those with underweight BMI (aOR, 0.61 (95% CI, 0.48-0.76)) compared to women with BMI of 18.5-24.9 kg/m2 . Compared to women with identified SGA, those with unidentified SGA had fetuses of higher SGA birth-weight centile (adjusted odds for unidentified SGA increased by 1.21 (95% CI, 1.18-1.23) per one-centile increase between the 0th and 10th centiles). Duration between the last scan and birth increased with advancing gestation in pregnancies with unidentified SGA. SGA babies born within a week of the last growth scan had a mean difference between EFW and birth-weight centiles of 19.5 (SD, 13.8) centiles for the unidentified-SGA group and 0.2 (SD, 3.3) centiles for the identified-SGA group (adjusted mean difference between groups, 19.0 (95% CI, 17.8-20.1) centiles). CONCLUSIONS: Unidentified SGA was more common amongst women without an indication for serial ultrasound, and in those with cephalic presentation at birth, BMI of 25.0-29.9 kg/m2 and less severe SGA. Ultrasound EFW was overestimated in women with unidentified SGA. This demonstrates the importance of improving the accuracy of SGA screening strategies in low-risk populations and continuing performance of ultrasound scans for term pregnancies. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Improving antenatal detection of small-for-gestational-age fetus: economic evaluation of Growth Assessment Protocol.

OBJECTIVE: To determine whether the Growth Assessment Protocol (GAP), as implemented in the DESiGN trial, is cost-effective in terms of antenatal detection of small-for-gestational-age (SGA) neonate, when compared with standard care. METHODS: This was an incremental cost-effectiveness analysis undertaken from the perspective of a UK National Health Service hospital provider. Thirteen maternity units from England, UK, were recruited to the DESiGN (DEtection of Small for GestatioNal age fetus) trial, a cluster randomized controlled trial. Singleton, non-anomalous pregnancies which delivered after 24 + 0 gestational weeks between November 2015 and February 2019 were analyzed. Probabilistic decision modeling using clinical trial data was undertaken. The main outcomes of the study were the expected incremental cost, the additional number of SGA neonates identified antenatally and the incremental cost-effectiveness ratio (ICER) (cost per additional SGA neonate identified) of implementing GAP. Secondary analysis focused on the ICER per infant quality-adjusted life year (QALY) gained. RESULTS: The expected incremental cost (including hospital care and implementation costs) of GAP over standard care was £34 559 per 1000 births, with a 68% probability that implementation of GAP would be associated with increased costs to sustain program delivery. GAP identified an additional 1.77 SGA neonates per 1000 births (55% probability of it being more clinically effective). The ICER for GAP was £19 525 per additional SGA neonate identified, with a 44% probability that GAP would both increase cost and identify more SGA neonates compared with standard care. The probability of GAP being the dominant clinical strategy was low (11%). The expected incremental cost per infant QALY gained ranged from £68 242 to £545 940, depending on assumptions regarding the QALY value of detection of SGA. CONCLUSION: The economic case for replacing standard care with GAP is weak based on the analysis reported in our study. However, this conclusion should be viewed taking into account that cost-effectiveness analyses are always limited by the assumptions made. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Trends and predictors of linkage to HIV outpatient care following diagnosis in the era of expanded testing in England, Wales and Northern Ireland: Results of a national cohort study.

OBJECTIVES: We explore trends in linkage to HIV care following diagnosis and investigate the impact of diagnosis setting on linkage in the era of expanded testing. METHODS: All adults (aged ≥ 15 years) diagnosed with HIV between 2005 and 2014 in England, Wales and Northern Ireland (EW&NI) were followed up until the end of 2017. People who died within 1 month of diagnosis were excluded (n = 1009). Trends in linkage to outpatient care (time to first CD4 count) were examined by sub-population and diagnosis setting. Logistic regression identified predictors of delayed linkage of > 1 month, > 3 months and > 1 year post-diagnosis (2012-2014). RESULTS: Overall, 97% (60 250/62 079) of people linked to care; linkage ≤ 1 month was 75% (44 291/59 312), ≤ 3 months was 88% (52 460) and ≤ 1 year was 95% (56 319). Median time to link declined from 15 days [interquartile range (IQR): 4-43] in 2005 to 6 (IQR: 0-20) days in 2014 (similar across sub-populations/diagnosis settings). In multivariable analysis, delayed linkage to care was associated with acquiring HIV through injecting drug use, heterosexual contact or other routes compared with sex between men (> 1 month/3 months/1 year), being diagnosed in earlier years (> 1 month/3 months/1 year) and having a first CD4 ≥ 200 cells/µL (> 3 months/1 year). Diagnosis outside of sexual health clinics, antenatal services and infectious disease units predicted delays of > 1 month. By 3 months, only diagnosis in 'other' settings (prisons, drug services, community and other medical settings) was significant. CONCLUSIONS: Linkage to care following HIV diagnosis is relatively timely in EW&NI. However, non-traditional testing venues should have well-defined referral pathways established to facilitate access to care and treatment.

Protocol for a cluster randomised control trial evaluating the efficacy and safety of treatment for latent tuberculosis infection in recent migrants within primary care: the CATAPuLT trial.

BACKGROUND: The identification and treatment of LTBI is a key component of the WHO's strategy to eliminate TB. Recent migrants from high TB-incidence countries are recognised to be at risk TB reactivation, and many high-income countries have focused on LTBI screening and treatment programmes for this group. However, migrants are the group least likely to complete the LTBI cascade-of-care. This pragmatic cluster-randomised, parallel group, superiority trial investigates whether a model of care based entirely within a community setting (primary care) will improve treatment completion compared with treatment in specialist TB services (secondary care). METHODS: The CATAPuLT trial (Completion and Acceptability of Treatment Across Primary Care and the community for Latent Tuberculosis) randomised 34 general practices in London, England, to evaluate the efficacy and safety of treatment for LBTI in recent migrants within primary care. GP practices were randomised to either provide management for LTBI entirely within primary care (GPs and community pharmacists) or to refer patients to secondary care. The target recruitment number for individuals is 576. The primary outcome is treatment completion (defined as taking at least 90% of antibiotic doses). The secondary outcomes assess adherence, acceptance of treatment, the incidence of adverse effects including drug-induced liver injury, the rates of active TB, patient satisfaction and cost-effectiveness of LTBI treatment. This protocol adheres to the SPIRIT Checklist. DISCUSSION: The CATAPuLT trial seeks to provide implementation research evidence for a patient-centred intervention to improve treatment completion for LTBI amongst recent migrants to the UK. TRIAL REGISTRATION: NCT03069807, March 2017, registered retrospectively.

Factors associated with delayed linkage to care following HIV diagnosis in the WHO European Region.

OBJECTIVES: To describe linkage to HIV care following diagnosis in Europe and to identify factors associated with delayed linkage. METHODS: We analysed data of adults (aged ≥ 15 years) diagnosed with HIV from 2010 to 2014 in 31 European countries. Linkage to care was calculated using the time between HIV diagnosis and first CD4 count. Linkage was considered delayed if the CD4 count was taken more than 3 months after diagnosis. Logistic regression was used to determine factors for delayed linkage. RESULTS: Of the 120 129 adults diagnosed from 2010 to 2014, 4560 were previously diagnosed elsewhere, 808 died within 3 months of diagnosis and 54 731 people were missing CD4 count and/or date information. Among the 60 030 people included, linkage to care within 3 months was 96%. A lower bound (LB) for this was 55%, when those missing CD4 data were assumed not to be linked. Prompt linkage varied significantly by region [Western: 97% (LB: 65%); Central: 90% (LB: 65%); Eastern: 91% (LB: 11%)] and risk group. In multivariable analysis, delayed linkage to care was associated with: acquiring HIV through injecting drug use/heterosexual contact, being diagnosed in Central/Eastern Europe and having a first CD4 count > 200 cells/µL. People of older age at diagnosis and those diagnosed after 2011 were more likely to be linked promptly. Associations differed by region. CONCLUSIONS: Among those with CD4 data available, linkage to care is prompt. However, HIV surveillance must be strengthened and data quality improved, particularly in Eastern Europe. Our findings highlight disparities in care access and significant differences between regions.

Where do we diagnose HIV infection? Monitoring new diagnoses made in nontraditional settings in England, Wales and Northern Ireland.

OBJECTIVES: The objectives of the study were to describe 10-year trends in HIV diagnosis setting and to explore predictors of being diagnosed outside a sexual health clinic (SHC). METHODS: Analyses of national HIV surveillance data were restricted to adults (aged ≥ 15 years) diagnosed in 2005-2014 in England, Wales and Northern Ireland. Logistic regression identified factors associated with diagnosis outside an SHC (2011-2014). RESULTS: Between 2005 and 2014, 63 599 adults were newly diagnosed with HIV infection; 83% had a diagnosis setting reported. Most people were diagnosed in SHCs (69%) followed by: medical admissions/accident and emergency (A&E; 8.6%), general practice (6.4%), antenatal services (5.5%), out-patient services (3.6%), infectious disease units (2.7%) and other settings (4.0%). The proportion of people diagnosed outside SHCs increased from 2005 to 2014, overall (from 27% to 32%, respectively) and among men who have sex with men (MSM) (from 14% to 21%) and black African men (from 25% to 37%) and women (from 39% to 52%) (all trend P < 0.001). Median CD4 increased across all settings, but was highest in SHCs (384 cells/µL) and lowest in medical admissions/A&E (94 cells/µL). Predictors of being diagnosed outside SHCs included: acquiring HIV through heterosexual contact [adjusted odds ratio (aOR) 1.99; 95% confidence interval (CI) 1.81-2.18] or injecting drug use (aOR: 3.28; 95% CI: 2.56-4.19; reference: MSM), being diagnosed late (< 350 cells/µL) (aOR: 2.55; 95% CI: 2.36-2.74; reference: diagnosed promptly) and being of older age at diagnosis (35-49 years: aOR: 1.60; 95% CI: 1.39-1.83; ≥ 50 years: aOR: 2.48; 95% CI: 2.13-2.88; reference: 15-24 years). CONCLUSIONS: The proportion of HIV diagnoses made outside SHCs has increased over the past decade in line with evolving HIV testing guidelines. However, the rate of late diagnosis remains high, indicating that further expansion of testing is necessary, as many people may have had missed opportunities for earlier diagnosis.

Predictors of CD4 cell recovery following initiation of antiretroviral therapy among HIV-1 positive patients with well-estimated dates of seroconversion.

OBJECTIVES: To investigate factors that predict speed of recovery and long-term CD4 cell count in HIV-1 seroconverters initiating combination antiretroviral therapy (cART), and to quantify the influence of very early treatment initiation. We make use of all pre-treatment CD4 counts, because analyses using only a single observation at initiation may be subject to biases. METHODS: We used data from the CASCADE (Concerted Action on SeroConversion to AIDS and Death in Europe) multinational cohort collaboration of HIV-1 seroconverters. We analysed pre- and post-treatment data of patients with seroconversion dates estimated January 2003-March 2014 (n = 7600 for primary analysis) using a statistical model in which the characteristics of recovery in CD4 counts are determined by multiple predictive factors. Secondary analyses were performed incorporating uncertainty in the exact timing of seroconversion to allow more precise estimation of the benefit of very early treatment initiation. RESULTS: 'True' CD4 count at cART initiation was the strongest predictor of CD4 count beyond 3 years on cART. Allowing for lack of complete certainty in the date of seroconversion, CD4 recovery was more rapid for patients in whom treatment was initiated within 4 months. For a given CD4 count, higher viral load (VL) at initiation was strongly associated with higher post-treatment CD4 recovery. For other patient and drug characteristics, associations with recovery were statistically significant but small in magnitude. CONCLUSIONS: CD4 count at cART initiation is the most important factor in predicting post-treatment recovery, but VL provides substantial additional information. If cART is initiated in the first 4 months following seroconversion, recovery of CD4 counts appears to be more rapid.

The "3 in 1" Study: Pooling Self-Taken Pharyngeal, Urethral, and Rectal Samples into a Single Sample for Analysis for Detection of Neisseria gonorrhoeae and Chlamydia trachomatis in Men Who Have Sex with Men.

Triple-site testing (using pharyngeal, rectal, and urethral/first-void urine samples) for Neisseria gonorrhoeae and Chlamydia trachomatis using nucleic acid amplification tests detects greater numbers of infections among men who have sex with men (MSM). However, triple-site testing represents a cost pressure for services. MSM over 18 years of age were eligible if they requested testing for sexually transmitted infections (STIs), reported recent sexual contact with either C. trachomatis or N. gonorrhoeae, or had symptoms of an STI. Each patient underwent standard-of-care (SOC) triple-site testing, and swabs were taken to form a pooled sample (PS) (pharyngeal, rectal, and urine specimens). The PS was created using two methods during different periods at one clinic, but we analyzed the data in combination because the sensitivity of the two methods did not differ significantly for C. trachomatis (P = 0.774) or N. gonorrhoeae (P = 0.163). The sensitivity of PS testing (92%) was slightly lower than that of SOC testing (96%) for detecting C. trachomatis (P = 0.167). For N. gonorrhoeae, the sensitivity of PS testing (90%) was significantly lower than that of SOC testing (99%) (P < 0.001). When pharynx-only infections were excluded, the sensitivity of PS testing to detect N. gonorrhoeae infections increased to 94%. Our findings show that pooling of self-taken samples could be an effective and cost-saving method, with high negative predictive values. (Interim results of this study were presented at the BASHH 2013 summer meeting.).

Patterns of sexual mixing with respect to social, health and sexual characteristics among heterosexual couples in England: analyses of probability sample survey data.

Patterns of sexual mixing are major determinants of sexually transmitted infection (STI) transmission, in particular the extent to which high-risk populations mix with low-risk populations. However, patterns of mixing in the general population are poorly understood. We analysed data from a national probability sample survey of households, the Health Survey for England 2010. A total of 943 heterosexual couples living together, where at least one partner was aged between 16-44 years, were included. We used correlation coefficients to measure the strength of similarities between partners with respect to demographic characteristics, general health, health behaviours and sexual history. Males were on average 2 years older than their female partners, although this age difference ranged from a median of 0 years in men aged 16-24 years to a median of 2 years in men aged 35-44 years. A positive correlation between partners was found for all demographic characteristics. With respect to general health and health behaviours, a strongly positive correlation was found between men and women in reporting alcohol consumption at ⩾3 days a week and smoking. Men typically reported greater numbers of sexual partners than their female partner, although men and women with more partners were more likely to mix with each other. We have been able to elucidate the patterns of sexual mixing between men and women living together in England. Mixing based on demographic characteristics was more assortative than sexual characteristics. These data can better inform mathematical models of STI transmission.

COVID-19-related mortality and hospital admissions in the VIVALDI study cohort: October 2020 to March 2023.

BACKGROUND: Long-term-care facilities (LTCFs) were heavily affected by COVID-19 early in the pandemic, but the impact of the virus has reduced over time with vaccination campaigns and build-up of immunity from prior infection. OBJECTIVES: To evaluate the mortality and hospital admissions associated with SARS-CoV-2 in LTCFs in England over the course of the VIVALDI study, from October 2020 to March 2023. METHODS: We included residents aged ≥65 years from participating LTCFs who had available follow-up time within the analysis period. We calculated incidence rates (IRs) of COVID-19-linked mortality and hospital admissions per calendar quarter, along with infection fatality ratios (IFRs, within 28 days) and infection hospitalization ratios (IHRs, within 14 days) following positive SARS-CoV-2 test. RESULTS: A total of 26,286 residents were included, with at least one positive test for SARS-CoV-2 in 8513 (32.4%). The IR of COVID-19-related mortality peaked in the first quarter (Q1) of 2021 at 0.47 per 1000 person-days (1 kpd) (around a third of all deaths), in comparison with 0.10 per 1 kpd for Q1 2023 which had a similar IR of SARS-CoV-2 infections. There was a fall in observed IFR for SARS-CoV-2 infections from 24.9% to 6.7% between these periods, with a fall in IHR from 12.1% to 8.8%. The population had high overall IRs for mortality for each quarter evaluated, corresponding to annual mortality probability of 28.8-41.3%. CONCLUSIONS: Standardized real-time monitoring of hospitalization and mortality following infection in LTCFs could inform policy on the need for non-pharmaceutical interventions to prevent transmission.

A pilot cross-sectional study of non-communicable diseases in TB household contacts.

BACKGROUND: Data on the prevalence of non-communicable diseases (NCDs) in TB household contacts (HHCs) are limited, yet important to inform integrated screening and care for NCD within contact investigations. It is also unclear if screening these contacts reveals more people with NCDs than individuals in the same neighbourhood. METHOD: We conducted a pilot cross-sectional study in South Africa and Tanzania, enrolling adult HHCs of TB and individuals in neighbourhood households (controls). We inquired about known NCD and systematically measured blood pressure, and tested for spot blood glucose and haemoglobin A1c. RESULTS: We enrolled 203 adult contacts of 111 persons with TB and 160 controls. Among contacts, respectively 12.2% (95% CI 8.3-17.6) and 39.7% (95% CI 33.1-46.7) had diabetes and hypertension, compared to 14.1% (95% CI 9.2-21.0) and 44.7% (95% CI 36.9-52.7) among controls. More than half of NCDs were newly identified. We did not find a significant difference in the prevalence of at least one NCD between the two groups (OR 0.85, 95% CI 0.50-1.45, adjusted for age and sex). CONCLUSIONS: We found a high prevalence of undiagnosed NCDs among contacts, suggesting a potential benefit of integrating NCD screening and care within contact investigations. Screening in the same community might similarly find undiagnosed NCDs.

CONTEXTE: Les données sur la prévalence des maladies non transmissibles (NCD, pour l'anglais « non-communicable diseases ¼) chez les contacts familiaux (HHC, pour l'anglais « household contacts ¼) de personnes atteintes de TB sont restreintes, mais elles revêtent une grande importance pour le dépistage et la prise en charge intégrée des NCD dans le cadre des enquêtes sur les contacts. De plus, on ignore si le dépistage de ces contacts permet de détecter davantage de personnes atteintes de NCD par rapport aux les individus résidant dans le même quartier. MÉTHODE: Nous avons réalisé une étude pilote transversale en Afrique du Sud et en Tanzanie, au cours de laquelle nous avons recruté des adultes HHC de personnes atteintes de TB et des individus vivant dans les ménages voisins (témoins). Nous les avons interrogés sur les NCD connues et avons systématiquement mesuré la pression artérielle, ainsi que réalisé des tests de de glycémie et d'hémoglobine glyquée. RÉSULTATS: Un total de 203 contacts adultes de 111 personnes atteintes de TB et 160 témoins ont été répertoriés. Parmi ces contacts, respectivement 12,2% (IC à 95% 8,3­17,6) et 39,7% (IC à 95% 33,1­46,7) souffraient de diabète et d'hypertension, contre 14,1% (IC à 95% 9,2­21,0) et 44,7% (IC à 95% 36,9­52,7) chez les témoins. Plus de la moitié des NCD ont été récemment découvertes. Aucune disparité significative n'a été observée dans la prévalence d'au moins une NCD entre les deux groupes (OR 0,85 ; 95% CI 0,50­1,45, ajusté pour l'âge et le sexe). CONCLUSIONS: Nous avons observé une fréquence élevée de NCDs non diagnostiquées parmi les contacts, ce qui indique qu'il pourrait être potentiellement bénéfique d'inclure le dépistage et les soins des NCD dans les enquêtes sur les contacts. Le dépistage au sein de la même communauté pourrait également révéler des NCD non diagnostiquées.

Hepatitis C in men who have sex with men in London--a community survey.

OBJECTIVES: For the last 10 years there has been an epidemic of hepatitis C virus (HCV) infection in men who have sex with men (MSM) in Europe, North America and Australia. The majority of those infected are also HIV-positive and it is unclear to what extent HIV-negative MSM are also at increased risk of infection with HCV. This study provides the first examination of the association between HIV and hepatitis C serostatus in a sample of MSM recruited in community settings. METHODS: A total of 1121 participants completed a short questionnaire in 2008/2009 giving demographic and behavioural data, and donated a sample of oral fluid that was subsequently tested for antibodies to selected pathogens (HIV, syphilis and HCV). RESULTS: The seroprevalence of hepatitis C antibody was 2.1% [95% confidence interval (CI) 1.4-3.2%]. It was more common in those with HIV infection [7.7% (95% CI 4.2-12.9%) vs. 1.2% (95% CI 0.6-2.1%) in those without HIV infection; P < 0.001], those with a history of syphilis [12.2% (95% CI 4.6-24.8%) vs. 1.7% (95% CI 1.0-2.6%) in those without such a history; P < 0.001] and those who reported casual unprotected anal intercourse in the previous year [4.1% (95% CI 2.0-7.4%) vs. 1.2% (95% CI 0.5-2.2%) in those who did not report such intercourse; P = 0.01]. There was no relationship between hepatitis C antibody (anti-HCV) status and other demographic variables (age, ethnicity, employment status or education). CONCLUSIONS: The seroprevalence of anti-HCV in HIV-negative MSM (1.2%) was higher, but not significantly higher, than that in the general population (0.67%). The prevalence was significantly higher in those infected with HIV or with previous syphilis infection and in those reporting unprotected anal intercourse. Our findings support current British Association for Sexual Health and HIV guidelines recommending the provision of selective HCV testing in MSM according to individual risk profile.

Salivary Testosterone and Sexual Function and Behavior in Men and Women: Findings from the Third British National Survey of Sexual Attitudes and Lifestyles (Natsal-3).

Using data from the third British National Survey of Sexual Attitudes and Lifestyles (Natsal-3) we examined associations between salivary testosterone (Sal-T) and sexual function and behavior. Single morning saliva samples were self-collected from a subsample of participants aged 18-74 years and analyzed using mass spectrometry. 1,599 men and 2,123 women were included in the analysis (40.6% of those invited to provide a sample). We adjusted for confounders in a stepwise manner: in model 1 we adjusted for age only; model 2 for age, season and relationship status, and model 3 we added BMI and self-reported health. In the fully adjusted models, among men, Sal-T was positively associated with both partnered sex (vaginal sex and concurrent partners) and masturbation. Among women, Sal-T was positively associated with masturbation, the only association with partnered sex was with ever experience of same-sex sex. We found no clear association between Sal-T and sexual function. Our study contributes toward addressing the sparsity of data outside the laboratory on the differences between men and women in the relationship between T and sexual function and behavior. To our knowledge, this is the first population study, among men and women, using a mass spectrometry Sal-T assay to do so.

Immunosuppression among HIV-1-positive patients attending for care: experience from two large HIV centres in the United Kingdom.

OBJECTIVES: The aim of the study was to describe the prevalence of and examine the factors associated with immunosuppression (CD4 < 200 cells/microL) among HIV-infected patients attending two large inner London treatment centres. METHODS: Patients attending for care who had a CD4 count < 200 cells/microL during a 6-month period (1 January to 30 June 2007) were identified from the UK national CD4 surveillance database. Corresponding case notes were reviewed and factors associated with the most recent immunosuppressive episode examined. Patients either previously had a CD4 count > 200 cells/microL at any time under follow-up which had decreased (group A) or never had a CD4 count > 200 cells/microL (group B; late presenters). RESULTS: Of 4589 patients, 10.2% (467) had at least one CD4 count < 200 cells/microL. In group A (60.1% of patients), 70.4% were not receiving antiretroviral therapy (ART) at the time at which the CD4 count fell to < 200 cells/microL. Reasons included: treatment interruption (TI; 32.6%), patient declined ART (20.2%), infrequent attendance (19.1%), physician delay in offer (23.1%) and transient CD4 cell count decrease (3.9%). Among those receiving ART, one in three had poor adherence. In group B, 92.3% had started ART after presentation: most had recently started and were responding virologically. AIDS-defining diagnoses occurred in the year preceding the decrease in CD4 cell count in 12.6% of patients in group A and 33.3% of those in group B. CONCLUSION: The majority of patients became immunosuppressed while under care. Our findings suggest that, in addition to strategies aimed at earlier diagnosis, there are further opportunities to reduce severe immunosuppression in patients already attending for HIV care.

Discordant responses on starting highly active antiretroviral therapy: suboptimal CD4 increases despite early viral suppression in the UK Collaborative HIV Cohort (UK CHIC) Study.

OBJECTIVES: Patients starting highly active antiretroviral therapy (HAART) may have a suboptimal CD4 increase despite rapid virological suppression. The frequency and the significance for patient care of this discordant response are uncertain. This study was designed to determine the incidence of a discordant response at two time-points, soon after 6 months and at 12 months, and to determine the relationship with clinical outcomes. METHODS: Data obtained in the UK Collaborative HIV Cohort Study were analysed. A total of 2584 treatment-naïve patients starting HAART with HIV viral load (VL) > 1000 HIV-1 RNA copies/mL at baseline and < 50 copies/mL within 6 months were included in the analysis. Patients were classified at either 6-10 (midpoint 8) months or 10-14 (midpoint 12) months as having a discordant (CD4 count increase < 100 cells/microL from baseline) or concordant response (CD4 count increase >or= 100 cells/microL). RESULTS: Discordant responses occurred in 32.1% of patients at 8 months and in 24.2% at 12 months; 35% of those discordant at 8 months were concordant at 12 months. A discordant response was associated with older age, lower baseline VL, and (at 12 months) higher baseline CD4 cell count. In a multivariate analysis it was associated with an increased risk of death, more strongly at 12 months [incidence rate ratio (IRR) 3.35, 95% confidence interval (CI) 1.73-6.47, P < 0.001] than at 8 months (IRR 2.08, 95% CI 1.19-3.64, P = 0.010), but not with new AIDS events. CONCLUSIONS: Discordant responders have a worse outcome, but assessment at 12 months may be preferred, given the number of 'slow' responders. Management strategies to improve outcomes for discordant responders need to be investigated.

Prognostic value of C-reactive protein in HIV-infected patients with Pneumocystis jirovecii pneumonia.

C-reactive protein (CRP) is a sensitive marker of inflammation and tissue damage. We aimed to describe CRP responses in HIV-infected patients presenting with Pneumocystis pneumonia (PCP), bacterial pneumonia (BP) and pulmonary tuberculosis (TB) and, in patients with PCP, to identify if elevated CRP has prognostic significance. Data obtained by case-note review of consecutive HIV-infected adults with acute respiratory episodes included admission CRP (elevated >5 mg/L), haemoglobin, white blood count, CD4 count and partial pressure of oxygen in the blood (PaO(2)), presence of pulmonary co-pathology/intercurrent infection and outcome (survival). Median (range) CRP in patients with BP = 120 mg/L (<5-620 mg/L), TB = 44 mg/L (<5-256.3 mg/L) and PCP = 35 mg/L (<5-254 mg/L). CRP was elevated in 93/103 (90.3%) patients with PCP; six patients died; and all had an elevated CRP. PaO(2) and CRP values were associated as follows: average CRP levels declined by 10% (95% confidence interval [CI] 0.20%) per kPa increase in PaO(2) = 0.002. Factors associated with death were higher CRP, odds ratio (OR) (95% CI) = 5.30 (1.61 to 17.51) per 100 mg/L increase, P = 0.006 and haemoglobin, OR (95% CI) = 0.52 (0.29 to 0.93) per g/dL, P = 0.033. CRP is elevated in the majority of HIV-infected patients with PCP, BP and TB. Admission CRP measurement lacks specificity, but in PCP elevations of CRP are associated with disease severity (PaO(2)) and poor outcome and might be used prognostically, together with other mortality risk factors; further prospective evaluation is needed.

Tenofovir-associated renal and bone toxicity.

OBJECTIVES: The aims of the study were to describe the clinical presentation and renal and bone abnormalities in a case series of HIV-infected patients receiving treatment with tenofovir (TDF), and to recommend appropriate screening for toxicity related to TDF. METHODS: Patients were identified from referrals to a specialist HIV renal clinic. Patients were included if treatment with TDF was assessed as the primary cause of the renal function impairment and clinical data were available prior to and following discontinuation of TDF treatment. Data were collected from case note review and clinic databases. RESULTS: Twenty-two patients (1.6% of all those who received TDF) were identified with TDF-associated renal toxicity. All had normal serum creatinine prior to TDF therapy. All presented with proteinuria. On stopping TDF, renal function improved. Eight patients had confirmed Fanconi syndrome. Twelve patients presented with bone pain and osteomalacia was confirmed on an isotope bone scan in seven of these patients. The findings (in those patients tested) of tubular proteinuria, reduced tubular transport maximum of phosphate (TmP), and glycosuria were all consistent with the proximal tubule being the site of toxicity. CONCLUSION: Renal toxicity remains a concern in patients treated with TDF. Clinical presentation may be with renal dysfunction, Fanconi syndrome or osteomalacia. Our investigations suggest proximal tubular toxicity as a common pathogenic mechanism.

The burden and determinants of HIV and sexually transmitted infections in a population-based sample of female sex workers in Goa, India.

BACKGROUND: Interventions targeting sex workers are central to the National AIDS Control programme of India's third 5-year plan. Understanding the way in which societal and individual factors interact to shape sex workers' vulnerability would better inform interventions. METHODS: 326 female sex workers, recruited throughout Goa using respondent-driven sampling, completed interviewer-administered questionnaires. Biological samples were tested for Trichomonas vaginalis, Neisseria gonorrhoea, Chlamydia trachomatis and antibodies to herpes simplex virus type 2 (HSV-2) and HIV. Multivariate analysis was used to define the determinants of HIV infection and any bacterial sexually transmitted infection (STI). RESULTS: Infections were common, with 25.7% prevalence of HIV and 22.5% prevalence of bacterial STI; chlamydia 7.3%, gonorrhoea 8.9% and trichomonas 9.4%. Antibodies to HSV-2 were detected in 57.2% of women. STI were independently associated with factors reflecting gender disadvantage and disempowerment, namely young age, lack of schooling, no financial autonomy, deliberate self-harm, sexual abuse and sex work-related factors, such as having regular customers and working on the streets. Other factors associated with STI were Goan ethnicity, not having an intimate partner and being asymptomatic. Having knowledge about HIV and access to free STI services were associated with a lower likelihood of STI. HIV was independently associated with being Hindu, recent migration to Goa, lodge or brothel-based sex work and dysuria. CONCLUSION: Sex workers working in medium prevalence states of India are highly vulnerable to HIV and STI and need to be rapidly incorporated into existing interventions. Structural and gender-based determinants of HIV and STI are integral to HIV prevention strategies.

Modelling the association between patient characteristics and the change over time in a disease measure using observational cohort data.

In observational cohort studies we may wish to examine the associations between fixed patient characteristics and the longitudinal changes from baseline in a repeated outcome measure. Many biological and other outcome measures are known to be subject to measurement error and biological variation. In an initial analysis we may fit a regression model to all outcome measurements, accounting for all the identified sources of variability, and see how the characteristics are linked to the change for typical patients. However, the characteristics may also be linked to different distributions of the underlying outcome value at baseline, which itself may be correlated with the change over time. Therefore, if we wish to examine the change over time for patients of different characteristics but with the same underlying baseline value then the initial approach is confounded by the baseline values. Furthermore, if we attempt to remove this confounding by including the observed baseline measure as a covariate in a model for later measurements, then this may provide an approximate solution but is likely to introduce some bias. We propose a method based on first following the initial approach but then, applying a correction to the parameter estimates. This allows the predicted trajectories to be plotted and valid significance tests of association with characteristics. Our approach is compared with other methods and illustrated through a simulation study and an analysis of the association between HIV-1 subtype and immunological response after starting antiretroviral therapy.

How do UK medical graduates rate their knowledge and skills in sexual health and HIV medicine? A national survey.

The objectives of this study are to determine self-assessed knowledge and skills in sexual health and HIV medicine in preregistration house officers and to explore undergraduate experiences of teaching and assessment in these subjects prior to the launch of National Core Learning Outcomes in Sexual and Reproductive Health and HIV. The study was designed as a postal questionnaire survey. The participants were all UK medical graduates of August 2004. The response rate 1737/4746 (36%). The main outcome measures were Doctors' views on their preparedness to manage patients with sexual health and HIV-related problems. Since graduation, 90% of respondents had seen at least one patient with a sexually transmitted infection or HIV-related issue. Seventy-six percent felt confident to take a sexual history. In all, 63% and 53% felt competent in male and female genital examination, respectively. Forty-three percent felt they could conduct an appropriate HIV pretest discussion and 59% felt they could recognize clinical indicators suggestive of HIV. Seventy-eight percent had been formally assessed in sexual health and 55% in HIV medicine. Increased confidence in sexual history taking, HIV pretest discussion and recognition of HIV indicators was associated with a longer duration of teaching and formal examination. In conclusion, although the proportion of recent graduates confident in sexual history taking is encouraging, their lack of skill in discussing HIV testing, risk assessment and recognition of possible HIV presentations must be addressed. Integration of National Core Learning Outcomes into all undergraduate curricula is a key step in reducing inconsistencies in undergraduate training.