Abstract Objective: We aimed to describe the prevalence of various mental health symptoms according to menopausal status (pre, peri, post) among women living with HIV ages 45-60 in England, and to identify groups of women with similar general and menopause-related mental health symptoms. We then investigated demographic predictors of group-membership and group differences in HIV-related care outcomes (antiretroviral therapy adherence, HIV clinic attendance, CD4-count, and last HIV viral load). Methods: An analysis of cross-sectional data from the Positive Transitions through Menopause study, an observational study of the health and well-being impacts of menopause on 869 women with HIV aged 45-60 years. Self-reported data on eight mental health indicators were collected from women in pre-, peri- and post-menopausal state using validated measures. Groups (termed “classes”) of women with similar mental health symptoms were derived via latent class analysis. Class membership was linked to demographic factors using nominal logistic regression, and to clinical outcomes using Wald tests. Results: We identified five classes: 1) few mental health symptoms ( n = 501, 57.8%); 2) high current anxiety/depression ( n = 120, 13.8%); 3) history of depression, with elevated current substance use ( n = 40, 4.6%); 4) history of depression with current psychological menopause symptoms ( n = 81, 9.3%); and 5) high previous and concurrent mental health problems ( n = 125, 14.4%). University attendance, ethnicity, and longer time since HIV diagnosis predicted class membership. Antiretroviral therapy adherence was lower in classes 3 (11%), 4 (19%) and 5 (24%) compared to class 1 (4%; all P <0.001). Members of class 5 were more likely to have missed ≥1 HIV clinic appointment in the past year than those in class 1 (34% vs 17%, P = 0.005). Conclusions: Women with a history of depression, current anxiety/depression, and current menopause-related mental health symptoms were more likely to have poorer clinical outcomes. Although we cannot comment on causality, our findings highlight the importance of assessing and managing menopausal symptoms and mental health to improve well-being and engagement in HIV care.
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/m 2 ), 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.
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.
Recent studies have shown a decrease in CD4 count during adolescence in young people with perinatally acquired human immunodeficiency virus (HIV, PHIV).
We identify factors associated with the normalization of the CD4+:CD8+ T cell ratio among UK Collaborative HIV Cohort study participants, and describe the association of the CD4+ and CD8+ T cell counts and the CD4+:CD8+ T cell ratio, with the risk of new AIDS events among individuals who achieve a suppressed viral load. Participants initiating combination antiretroviral therapy (cART) after 2006 with a CD4+:CD8+ T cell ratio <1, and viral suppression within 6 months were included. Cox proportional hazard models were used to examine associations with ratio normalization (ratio ≥1). Poisson regression models were used to investigate factors associated with the development of AIDS after viral load suppression. A total of 13,178 participants [median age: 37 (interquartile range: 31-44)] were followed for 75,336 person-years. Of the 4,042 (32.9%) who experienced ratio normalization, individuals with a high CD4+ T cell count [>500 vs. ≤200 cells/mm3, adjusted hazard ratio (95% confidence interval): 7.93 (6.97-9.01)], low CD8+ T cell count [>1,150 vs. ≤500 cells/mm3: 0.18 (0.16-0.21)], and low CD4+:CD8+ T cell ratio [>0.8 vs. <0.2: 12.36 (10.41-14.68)] at cART initiation were more likely to experience ratio normalization. Four hundred and nineteen people developed a new AIDS event. Most recent CD4+ T cell count [>500 vs. ≤200 cells/mm3: adjusted rate ratio 0.24 (0.16-0.34)] and CD4+:CD8+ T cell ratio [>0.8 vs. <0.2: 0.33 (0.21-0.52)] were independently associated with a new AIDS event. One third of study participants experienced ratio normalization after starting cART. CD4+ T cell count and CD4+:CD8+ T cell ratio are both individually associated with ratio normalization and the development of new AIDS events after cART.
Abstract Aim To characterize the longitudinal variability of estimated glomerular filtration rate (eGFR) in people with type 2 diabetes mellitus (T2DM), including variation between categories and individuals. Methods People with T2DM and sufficient recorded serum creatinine measurements were identified from the Clinical Practice Research Datalink (T2DM diagnosis from 1 January 2009 to 1 January 2011 with 5 years follow‐up); eGFR was calculated using the CKD‐EPI equation. Results In total, 7766 individuals were included; 32.8%, 50.2%, 12.4%, 4.0% and 0.6% were in glomerular filtration rate (GFR) categories G1, G2, G3a, G3b and G4, respectively. Overall, eGFR decreased by 0.44 mL/min/1.73 m 2 per year; eGFR increased by 0.80 mL/min/1.73 m 2 between index and year 1, then decreased by 0.75 mL/min/1.73 m 2 annually up to year 5. Category G1 showed a steady decline in eGFR over time; G2, G3a and G3b showed an increase between index and year 1, followed by a decline. Category G4 showed a mean eGFR increase of 1.85 mL/min/1.73 m 2 annually. People in categories G3‐G4 moved across a greater number of GFR categories than those in G1 and G2. Individual patients' eGFR showed a wide range of values (change from baseline at year 5 varied from −80 to +59 mL/min/1.73 m 2 ). Conclusion Overall, eGFR declined over time, although there was considerable variation between GFR categories and individuals. This highlights the difficulty in prescribing many glucose‐lowering therapies, which require dose adjustment for renal function. The study also emphasizes the importance of regular monitoring of renal impairment in people with T2DM.
Background Cofactors associated with persistently abnormal CD4 + :CD8 + T-cell ratio in people with HIV (PWH) on antiretroviral treatment (ART) might change over time as the population of people with HIV ages or as new ART drugs become available. The main objective of our study was to determine the long-term associations of baseline factors, including the CD4 + T-cell count and ratio, with ratio normalization (≥1). In addition to this, we explored whether the ratio remained associated with the risk of both AIDS and non-AIDS events among individuals on suppressive ART. Methods Clinic-based study in a tertiary, university hospital in Madrid. People with HIV starting a first-line ART regimen (January 2006–June 2017) were included in a prospective national multicentre cohort (CoRIS). People with controlled HIV-infection within the first year of ART initiation and complete CD4 + and CD8 + T-cell records were selected. Cox proportional hazard (PH) regression models were used to estimate the cumulative incidence of ratio normalization and to examine associations with socio-demographic and clinical variables. To investigate factors independently associated with the development of AIDS and non-AIDS events we used a time updated Poisson regression model. Results The study included 557 subjects. During follow-up (median 5.24 years), 44% of participants achieved a ratio of 1 within a median of 1.49 years. In a multivariate PH model, pre-ART factors negatively associated with ratio normalization were the pre-ART CD4 + :CD8 + T-cell ratio and mode of HIV acquisition. For the secondary analysis, 1.3 events/100 person years of follow-up were observed. After adjustment, older age, HIV RNA >200 copies/ml and CD4 + :CD8 + T-cell ratios over follow-up, remained significantly associated with the development of AIDS and non-AIDS events. In contrast, pre-ART ratio was not associated with the risk of AIDS and non-AIDS events. Conclusions In summary, our study showed that higher pre-ART CD4 + :CD8 + T-cell ratio is associated with rates of ratio normalization ≥1. In addition, the risk of AIDS and non-AIDS events seems to be predicted by the time updated CD4 + :CD8 + T-cell ratio not by the pre-ART CD4 + :CD8 + T-cell ratio. Therefore, CD4 + :CD8 + T-cell ratio should be considered as a dynamic marker for translation into clinical practice.
Background: Screening and treatment for latent tuberculosis infection (LTBI) are recognised as key for tuberculosis control, being central to WHO’s End TB Strategy. In the UK, the National Institute for Health and Care Excellence (NICE) and British HIV Association (BHIVA) give conflicting guidance on which groups of people living with HIV (PLWH) 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 using interferon gamma release assay (IGRA) tests for all PLWH 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 tuberculosis incidence in patients’ countries of birth.Findings: Of 1175 PLWH tested, 142 were IGRA-positive (12·1%), with IGRA-positivity associated with higher tuberculosis incidence in country-of-birth (adjusted odds ratio, incidence 150-249/100,000: 7·25 (95%CI 4·06–12·95)). There was high uptake of testing (1175/1191, 98·7%), LTBI chemoprophylaxis commencement (121/141, 85·8%) and completion (116/121, 95·9%). Proposed ‘PLWH-LTBI streamlined guidance’, targeting testing to PLWH born in countries with TB incidence >150/100,000 or any sub-Saharan African country, would have correctly identified 88·7% of all LTBI cases while cutting tests required by 42·6% compared to NICE guidance (screening all PLWH), performing as well as BHIVA 2018 guidance.Interpretation: LTBI screening and treatment is feasible and achievable for PLWH in the UK. Targeting screening to higher-risk PLWH increases yield and reduces screening costs, at the expense of missing some LTBI cases. Our proposed ‘PLWH-LTBI streamlined guidance’ based on country-of-birth performs as well as current BHIVA guidance and offers a simplified approach, with the hope of improving national screening uptake.Funding: NIHR, MRC, Wellcome TrustDeclaration of Interest: MP received grants and personal fees from Gilead Sciences and personal fees from QIAGEN, outside the submitted work. All other authors have nothing to declare.
The widespread use of the integrase strand transfer inhibitor (INSTI) dolutegravir (DTG) in first- and second-line antiretroviral therapy (ART) may facilitate emerging resistance. We combined data from HIV cohorts to examine patterns of drug resistance mutations (DRMs) and identify risk factors for DTG resistance.
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