Evolution of CD4 T-Cell Count With Age in a Cohort of Young People Growing Up With Perinatally Acquired Human Immunodeficiency Virus.

BACKGROUND: Recent studies have shown a decrease in CD4 count during adolescence in young people with perinatally acquired human immunodeficiency virus (HIV, PHIV). METHODS: Young people with PHIV in the United Kingdom, followed in the Collaborative HIV Paediatric Study who started antiretroviral therapy (ART) from 2000 onward were included. Changes in CD4 count over time from age 10 to 20 years were analyzed using mixed-effects models, and were compared to published CD4 data for the gerneral population. Potential predictors were examined and included demographics, age at ART start, nadir CD4 z score (age-adjusted) in childhood, and time-updated viral load. RESULTS: Of 1258 young people with PHIV included, 669 (53%) were female, median age at ART initiation was 8.3 years, and the median nadir CD4 z score was -4.0. Mean CD4 count was higher in young people with PHIV who started ART before age 10 years and had a nadir CD4 z score ≥-4; these young people with PHIV had a decline in CD4 count after age 10 that was comparable to that of the general population. Mean CD4 count was lower in young people with PHIV who had started ART before age 10 and had a nadir CD4 z score <-4; for this group, the decline in CD4 count after age 10 was steeper over time. CONCLUSIONS: In children, in addition to starting ART at an early age, optimizing ART to maintain a higher CD4 z score during childhood may be important to maximizing immune reconstitution later in life.

A comparison of transient elastography with acoustic radiation force impulse elastography for the assessment of liver health in patients with chronic hepatitis C: Baseline results from the TRACER study.

Background: Liver stiffness measurements can be used to assess liver fibrosis and can be acquired by transient elastography using FibroScan® and with Acoustic Radiation Force Impulse imaging. The study aimed to establish liver stiffness measurement scores using FibroScan® and Acoustic Radiation Force Impulse in a chronic hepatitis C cohort and to explore the correlation and agreement between the scores and the factors influencing agreement. Methods: Patients had liver stiffness measurements acquired with FibroScan® (right lobe of liver) and Acoustic Radiation Force Impulse (right and left lobe of liver). We used Spearman's correlation to explore the relationship between FibroScan® and Acoustic Radiation Force Impulse scores. A Bland-Altman plot was used to evaluate bias between the mean percentage differences of FibroScan® and Acoustic Radiation Force Impulse scores. Univariable and multivariable analyses were used to assess how factors such as body mass index, age and gender influenced the agreement between liver stiffness measurements. Results: Bland-Altman showed the average (95% CI) percentage difference between FibroScan® and Acoustic Radiation Force Impulse scores was 27.5% (17.8, 37.2), p < 0.001. There was a negative correlation between the average and percentage difference of the FibroScan® and Acoustic Radiation Force Impulse scores ( r (95% CI) = -0.41 (-0.57, -0.21), p < 0.001), thus showing that percentage difference gets smaller for greater FibroScan® and Acoustic Radiation Force Impulse scores. Body mass index was the biggest influencing factor on differences between FibroScan® and Acoustic Radiation Force Impulse (r = 0.12 (0.01, 0.23), p = 0.05). Acoustic Radiation Force Impulse scores at segment 5/8 and the left lobe showed good correlation (r (95% CI) = 0.83 (0.75, 0.89), p < 0.001). Conclusion: FibroScan® and Acoustic Radiation Force Impulse had similar predictive values for the assessment of liver stiffness in patients with chronic hepatitis C infection; however, the level of agreement varied across lower and higher scores.

Prevalence of pain in women living with HIV aged 45-60: associated factors and impact on patient-reported outcomes.

As the population of women with HIV ages, an increasing proportion are experiencing the menopause, with potential associated pain. Among 844 participants in the Positive Transitions Through the Menopause (PRIME) study (72.3% black African; median age 49 (interquartile-range 47-53) years; 20.9%, 44.0% and 35.1% pre-, peri- and post-menopausal), 376 (44.6%) and 73 (8.7%) reported moderate or extreme pain. Women had been diagnosed with HIV for 14 (9-18) years, 97.7% were receiving antiretroviral therapy and 88.4% had a suppressed viral load. In adjusted ordinal logistic regression, peri-menopausal status (adjusted odds ratio (1.80) [95% confidence interval 1.22-2.67]), current smoking (1.85 [1.11-3.09]), number of comorbid conditions (1.95 [1.64-2.33] /condition) and longer duration of HIV (1.12 [1.00-1.24]/5 years) were independently associated with increased reported pain, whereas being in full-time work (0.61 [0.45-0.83]) and having enough money for basic needs (0.47 [0.34-0.64]) were associated with decreased pain reporting. Increasing pain was independently related to insomnia symptoms (moderate: 2.76 [1.96-3.90]; extreme: 8.09 [4.03-16.24]) and severe depressive symptoms (PHQ4 ≥ 6; moderate: 3.96 [2.50-6.28]; extreme: 9.13 [4.45-18.72]). Whilst our analyses cannot determine the direction of any associations, our findings point to the importance of eliciting a history of pain and addressing symptoms in order to improve wellbeing.

The impact, effectiveness and outcomes of targeted screening thresholds for programmatic latent tuberculosis infection testing in HIV.

BACKGROUND: Screening and treatment for latent tuberculosis infection (LTBI) are key for TB control. In the UK, the National Institute for Health and Care Excellence (NICE) and the British HIV Association (BHIVA) give conflicting guidance on which groups of people with HIV (PWH) should be screened, and previous national analysis demonstrated heterogeneity in how guidance is applied. There is an urgent need for a firmer clinical effectiveness evidence base on which to build screening policy. METHODS: We conducted a systematic, programmatic LTBI-screening intervention for all PWH receiving care in Leicester, UK. We compared yields (percentage IGRA positive) and number of tests required when applying the NICE and BHIVA testing strategies, as well as strategies targeting screening by TB incidence in patients' countries of birth. RESULTS: Of 1053 PWH tested, 118 were IGRA-positive (11.2%). Positivity was associated with higher TB incidence in country-of-birth [adjusted odds ratio, 50-149 cases compared with <50 cases/100 000: 11.6; 95% confidence interval (CI) 4.79-28.10)]. There was high testing uptake (1053/1069, 98.5%). Appropriate chemoprophylaxis was commenced in 100 of 117 (85.5%) patients diagnosed with LTBI, of whom 96 of 100 (96.0%) completed treatment. Delivering targeted testing to PWH from countries with TB incidence greater than 150 per 100 000 population or any sub-Saharan African country, would have correctly identified 89.8% of all LTBI cases while cutting tests required by 46.1% compared with NICE guidance, performing as well as BHIVA 2018 guidance. CONCLUSION: Targeting screening to higher risk PWH increases yield and reduces the number requiring testing. Our proposed 'PWH-LTBI streamlined guidance' offers a simplified approach, with the potential to improve national LTBI-screening implementation.

Obesity in women living with HIV aged 45-60 in England: An analysis of the PRIME study.

OBJECTIVES: Menopause contributes to weight gain in women. We explored factors associated with obesity in women with HIV aged 45-60 years. METHODS: The present study is an analysis of cross-sectional questionnaire and clinic data from the Positive Transitions Through the Menopause (PRIME) Study. We categorized body mass index (BMI) as normal/underweight (< 25 kg/m2 ), overweight (25-29.9 kg/m2 ) and obese (> 30 kg/m2 ). We used logistic regression to explore demographic, social, lifestyle and clinical factors associated with BMI. RESULTS: We included 396 women in this analysis. Median age was 49 years [interquartile range (IQR): 47-52]. Most (83.6%) were not UK-born; the majority (69.4%) were black African (BA). Median (IQR) BMI was 28.6 (24.6-32.6) kg/m2 ; and 110 (27.8%), 127 (32.1%) and 159 (40.1%) of the women were normal/underweight, overweight and obese, respectively. Median (IQR) BMI did not differ in pre-, peri- and post-menopausal women (p = 0.90). In univariable analysis, being non-UK-born was associated with BMI > 30 kg/m2 [odds ratio (OR) = 1.94, 95% confidence interval (CI): 1.07-3.53]. Compared with BA women, women of other black ethnicities were more likely to be obese (OR = 2.37, 95% CI: 1.02-5.50) whereas white British women were less likely to be obese (OR = 0.34, 95% CI: 0.17-0.68). Current smoking and increasing number of comorbid conditions were associated with increased BMI. We found no association between obesity and socioeconomic status. On multivariable analysis, only ethnicity remained associated with obesity (compared with BA: white British, OR = 0.34, 95% CI: 0.17-0.68; other black, OR = 2.50, 95% CI: 1.07-5.82). CONCLUSIONS: Nearly two-fifths of women had BMI > 30 kg/m2 . Obesity was associated with black ethnicities but not with menopausal status. The combination of obesity and HIV may place women at increased risk of co-morbidities, requiring tailored and culturally appropriate interventions.

Follicle-stimulating hormone in postmenopausal women living with HIV: a prevalence study.

OBJECTIVES: We examined follicle-stimulating hormone (FSH) levels in women living with HIV aged > 45 reporting ≥ 12 months' amenorrhoea, and investigated correlation with menopausal symptoms. METHODS: A cross-sectional substudy of 85 women from the Positive Transitions through the Menopause (PRIME) Study who reported irregular periods at entry into the PRIME Study and ≥ 12 months' amenorrhoea at recruitment into this substudy. Serum FSH was supplemented with clinical data and menopausal symptom assessment. Serum FSH > 30 mIU/mL was defined as consistent with postmenopausal status. Associations between FSH and menopausal symptom severity were assessed using Pearson's correlation and the Kruskal-Wallis test. RESULTS: Median age was 53 years [interquartile range (IQR): 51-55]; all were on antiretroviral therapy, three-quarters (n = 65) had a CD4 T-cell count > 500 cells/µL and 91.8% (n = 78) had an HIV viral load (VL) < 50 copies/mL. Median FSH was 65.9 mIU/mL (IQR: 49.1-78.6). Only four women (4.7%) had FSH ≤ 30 mIU/mL; none reported smoking or drug use, all had CD4 T-cell count ≥ 200 cells/µL, and one had viral load (VL) ≥ 50 copies/mL. Median body mass index (BMI) was elevated compared with women with FSH > 30 mIU/mL (40.8 vs. 30.5 kg/m2 ). Over a quarter (28.2%) reported severe menopausal symptoms, with no correlation between FSH and severity of menopausal symptoms (p = 0.21), or hot flushes (p = 0.37). CONCLUSIONS: Four women in this small substudy had low FSH despite being amenorrhoeic; all had BMI ≥ 35 kg/m2 . We found that 95% of women with HIV aged > 45 years reporting ≥ 12 months' amenorrhoea had elevated FSH, suggesting that menopausal status can be ascertained from menstrual history alone in this group.

Risk Factors for Heart Failure: 20-Year Population-Based Trends by Sex, Socioeconomic Status, and Ethnicity.

BACKGROUND: There are multiple risk factors for heart failure, but contemporary temporal trends according to sex, socioeconomic status, and ethnicity are unknown. METHODS: Using a national UK general practice database linked to hospitalizations (1998-2017), 108 638 incident heart failure patients were identified. Differences in risk factors among patient groups adjusted for sociodemographic factors and age-adjusted temporal trends were investigated using logistic and linear regression. RESULTS: Over time, a 5.3 year (95% CI, 5.2-5.5) age difference between men and women remained. Women had higher blood pressure, body mass index, and cholesterol than men (P<0.0001). Ischemic heart disease prevalence increased for all to 2006 before reducing in women by 0.5% per annum, reaching 42.7% (95% CI, 41.7-43.6), but not in men, remaining at 57.7% (95% CI, 56.9-58.6; interaction P=0.002). Diabetes mellitus prevalence increased more in men than in women (interaction P<0.0001). Age between the most deprived (74.6 years [95% CI, 74.1-75.1]) and most affluent (79.9 [95% CI, 79.6-80.2]) diverged (interaction P<0.0001), generating a 5-year gap. The most deprived had significantly higher annual increases in comorbidity numbers (+0.14 versus +0.11), body mass index (+0.14 versus +0.11 kg/m2), and lower smoking reductions (-1.2% versus -1.7%) than the most affluent. Ethnicity trend differences were insignificant, but South Asians were overall 6 years and the black group 9 years younger than whites. South Asians had more ischemic heart disease (+16.5% [95% CI, 14.3-18.6]), hypertension (+12.5% [95% CI, 10.5-14.3]), and diabetes mellitus (+24.3% [95% CI, 22.0-26.6]), and the black group had more hypertension (+12.3% [95% CI, 9.7-14.8]) and diabetes mellitus (+13.1% [95% CI, 10.1-16.0]) but lower ischemic heart disease (-10.6% [95% CI, -13.6 to -7.6]) than the white group. CONCLUSIONS: Population groups show distinct risk factor trend differences, indicating the need for contemporary tailored prevention programs.