The influence of immunodeficiency, disease features, and patient characteristics on survival in plasmablastic lymphoma.

ABSTRACT: Plasmablastic lymphoma (PBL) is a rare and aggressive non-Hodgkin lymphoma associated with immunodeficiency, characterized by uncertain treatment approaches and an unfavorable prognosis. We conducted a multicenter, international, retrospective cohort study, aiming to characterize the clinical features, risk factors, and outcomes of patients with PBL. Data were collected from 22 institutions across 4 countries regarding patients diagnosed with PBL between 1 January 1999 and 31 December 2020. Survival risk factors were analyzed using both univariate and multivariate regression models. Overall survival (OS) was calculated using Kaplan-Meier statistics. First-line treatment regimens were stratified into standard- and higher-intensity regimens, and based on whether they incorporated a proteasome inhibitor (PI). A total of 281 patients (median age, 55 years) were included. Immunodeficiency of any kind was identified in 144 patients (51%), and 99 patients (35%) had HIV-positive results. The 5-year OS for the entire cohort was 36% (95% confidence interval, 30%-42%). In multivariate analysis, inferior OS was associated with Epstein-Barr virus-negative lymphoma, poor performance status, advanced stage, and bone marrow involvement. In an independent univariate analysis, the international prognostic index was associated with OS outcomes. Neither immunosuppression nor HIV infection, specifically, influenced OS. Among patients treated with curative intent (n = 234), the overall response rate was 72%. Neither the intensity of the treatment regimen nor the inclusion of PIs in first-line therapy was associated with OS. In this large retrospective study of patients with PBL, we identified novel risk factors for survival. PBL remains a challenging disease with poor long-term outcomes.

Factors associated with bacterial sexually transmitted infections among people of South Asian ethnicity in England.

OBJECTIVES: Despite being the largest ethnic minority group in England, South Asians have historically had low levels of utilisation of sexual health services (SHS) and sexually transmitted infection (STI) diagnoses, although recent data suggests this may be changing. This study aimed to investigate factors associated with a bacterial STI diagnosis among South Asians attending SHS in England. METHODS: Using data from the GUMCAD STI Surveillance system, a descriptive analysis of South Asians attending SHS in England in 2019 was carried out. Factors associated with a bacterial STI diagnosis were examined using univariate and multivariable logistic regression models adjusted for age, Asian ethnic subgroup, HIV status, patient's region of residence and Index of Multiple Deprivation quintile. Analyses were stratified by gender and sexual orientation (heterosexual male versus gay, bisexual and other men who have sex with men (GBMSM) versus women of any sexual orientation). Crude and adjusted associations were derived using binary logistic regression. RESULTS: There were 121 842 attendances by South Asians to SHS in England in 2019. Compared with heterosexual South Asian men, GBMSM had a higher odds of being diagnosed with a bacterial STI (adjusted odds ratio (aOR) 2.32, 95% CI 2.19 to 2.44) and South Asian women had a lower odds (aOR 0.83, 95% CI 0.78 to 0.87). For women and heterosexual South Asian men, a diagnosis was associated with younger age, being of any other Asian background other than Bangladeshi, Indian or Pakistani and not being HIV positive. For heterosexual South Asian men, there was an association with increasing socioeconomic deprivation. For GBMSM, a bacterial STI diagnosis was associated with known HIV-positive status and living in London. CONCLUSION: People of South Asian ethnicity in England are heterogeneous with regard to their sexual health needs, which should be explored further through focused research and policy.

Confronting the consequences of racism, xenophobia, and discrimination on health and health-care systems.

Racism, xenophobia, and discrimination are key determinants of health and equity and must be addressed for improved health outcomes. We conclude that far broader, deeper, transformative action is needed compared with current measures to tackle adverse effects of racism on health. To challenge the structural drivers of racism and xenophobia, anti-racist action and other wider measures that target determinants should implement an intersectional approach to effectively address the causes and consequences of racism within a population. Structurally, legal instruments and human rights law provide a robust framework to challenge the pervasive drivers of disadvantage linked to caste, ethnicity, Indigeneity, migratory status, race, religion, and skin colour. Actions need to consider the historical, economic, and political contexts in which the effects of racism, xenophobia, and discrimination affect health. We propose several specific actions: a commission that explores how we action the approaches laid out in this paper; building a conversation and a series of events with international multilateral agency stakeholders to raise the issue and profile of racism, xenophobia, and discrimination within health; and using our multiple platforms to build coalitions, expand knowledge, highlight inequities, and advocate for change across the world.

Experiences of initiating rapid antiretroviral therapy among people newly diagnosed with HIV in East London: a qualitative study.

OBJECTIVES: We aimed to explore the experiences of people who initiated rapid antiretroviral therapy (ART) within 7 days of HIV diagnosis, as part of routine care in London. METHODS: Using purposive sampling, 18 in-depth, semistructured interviews were conducted between December 2020 and September 2021 with people who started rapid ART at Barts Health NHS Trust. Participants aged 22-69 years included 15 cisgender men and three cisgender women. Five identified as heterosexual and 13 as gay and bisexual and other men who have sex with men. Ethnic identities: six White Non-UK, five White UK, three Black Caribbean, two South Asian and two East Asian. Interviews explored feelings about the new HIV diagnosis, attitudes to rapid ART including barriers to and facilitators of starting. Thematic analysis of transcribed interviews was undertaken. RESULTS: Four themes were identified: (1) being offered rapid ART is acceptable; (2) it is a way of taking control of their health; (3) the need for information and support and (4) an individualised approach to care. Reasons for starting included getting well, staying well and reducing the likelihood of passing on HIV. Facilitators included being given comprehensive information about treatment and managing potential side-effects and a supportive clinical team. Support specified included a non-judgemental attitude, approachability, reassurance, encouragement and information about peer support. Most participants expressed they could not understand why people would not begin treatment, but suggested needing more time to decide and denial of diagnosis as possible barriers. CONCLUSIONS: To our knowledge, this is the first qualitative study exploring the experiences of people initiating rapid ART in the UK. It was deemed acceptable to an ethnically diverse, predominantly male sample of people newly diagnosed with HIV. Future research should include strategies to recruit a more gender diverse sample and those who declined or stopped rapid ART.

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.

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.

Ethnic inequalities in mental health and socioeconomic status among older women living with HIV: results from the PRIME Study.

OBJECTIVES: Women living with HIV in the UK are an ethnically diverse group with significant psychosocial challenges. Increasing numbers are reaching older age. We describe psychological and socioeconomic factors among women with HIV in England aged 45-60 and explore associations with ethnicity. METHODS: Analysis of cross-sectional data on 724 women recruited to the PRIME Study. Psychological symptoms were measured using the Patient Health Questionnaire 4 and social isolation with a modified Duke-UNC Functional Social Support Scale. RESULTS: Black African (BA) women were more likely than Black Caribbean or White British (WB) women to have a university education (48.3%, 27.0%, 25.7%, respectively, p<0.001), but were not more likely to be employed (68.4%, 61.4%, 65.2%, p=0.56) and were less likely to have enough money to meet their basic needs (56.4%, 63.0%, 82.9%, p<0.001). BA women were less likely to report being diagnosed with depression than WB women (adjusted odds ratio (aOR) 0.40, p<0.001) but more likely to report current psychological distress (aOR 3.34, p<0.05). CONCLUSIONS: We report high levels of poverty, psychological distress and social isolation in this ethnically diverse group of midlife women with HIV, especially among those who were BA. Despite being more likely to experience psychological distress, BA women were less likely to have been diagnosed with depression suggesting a possible inequity in access to mental health services. Holistic HIV care requires awareness of the psychosocial needs of older women living with HIV, which may be more pronounced in racially minoritised communities, and prompt referral for support including psychology, peer support and advice about benefits.

Decline in Hepatitis C Virus (HCV) Incidence in Men Who Have Sex With Men Living With Human Immunodeficiency Virus: Progress to HCV Microelimination in the United Kingdom?

BACKGROUND: Modeling of the London hepatitis C virus (HCV) epidemic in men who have sex with men (MSM) and are living with human immunodeficiency virus (HIV) suggested that early access to direct-acting antiviral (DAA) treatment may reduce incidence. With high rates of linkage to care, microelimination of HCV within MSM living with HIV may be realistic ahead of 2030 World Health Organization targets. We examined trends in HCV incidence in the pre- and post-DAA eras for MSM living with HIV in London and Brighton, United Kingdom. METHODS: A retrospective cohort study was conducted at 5 HIV clinics in London and Brighton between 2013 and 2018. Each site reported all acute HCV episodes during the study period. Treatment timing data were collected. Incidence rates and reinfection proportion were calculated. RESULTS: A total of.378 acute HCV infections were identified, comprising 292 first infections and 86 reinfections. Incidence rates of acute HCV in MSM living with HIV peaked at 14.57/1000 person-years of follow-up (PYFU; 95% confidence interval [CI], 10.95-18.20) in 2015. Rates fell to 4.63/1000 PYFU (95% CI, 2.60 to 6.67) by 2018. Time from diagnosis to starting treatment declined from 29.8 (2013) to 3.7 months (2018). CONCLUSIONS: We observed a 78% reduction in the incidence of first HCV episode and a 68% reduction in overall HCV incidence since the epidemic peak in 2015, which coincides with wider access to DAAs in England. Further interventions to reduce transmission, including earlier access to treatment and for reinfection, are likely needed for microelimination to be achieved in this population.

Menopausal status, age and management among women living with HIV in the UK.

BACKGROUND: There is currently little evidence exploring menopausal status, age at last menstrual period (LMP) and management of menopause among women living with HIV aged 45-60 years in England. METHODS: Socio-demographic, lifestyle and clinical data were collected through a self-completed cross-sectional survey. Longitudinal CD4 count and viral load data were available from linkage to clinical records, if consent was provided. Women were categorised as pre-, peri- or post-menopausal. Factors associated with menopausal stage were examined using ordinal logistic regression adjusting for age. Age at LMP was estimated using Kaplan-Meier survival analysis. RESULTS: The 847 women had a median age of 49 [interquartile range (IQR): 47-52] years. Most were of black ethnicity (81.3%), were born outside the UK (85.0%) and had completed secondary education (88.7%); 177 (20.4%), 373 (43.0%) and 297 (34.2%) were pre-, peri- or post-menopausal, respectively. After adjusting for age, associations of menopausal status with non-cohabiting relationship [adjusted odds ratio = 0.63 (95% confidence interval: 0.43-0.91)], baseline viral load ≥ 100 000 copies/mL [2.67 (1.20-5.94)] and unemployment [1.34 (0.97-1.84)] remained significant. Median (IQR) age at LMP was 54 (51-55) years in the group. In total, 27.9% (233/836) of women reported severe menopausal symptoms; 45.6% of those with somatic symptoms had heard of hormone replacement therapy and 8.7% had used it. Only 5.6% of women with urogenital symptoms had used topical oestrogen. CONCLUSIONS: Our findings highlight the importance of educating both women and their healthcare providers about menopausal symptoms and management options.

The association between severe menopausal symptoms and engagement with HIV care and treatment in women living with HIV.

Using data from the PRIME Study, an observational study of the menopause in women living with HIV in England, we explored the association between menopausal symptoms and: (i) antiretroviral therapy (ART) adherence and (ii) HIV clinic attendance. We measured menopausal symptom severity with the Menopause Rating Scale (MRS, score ≥17 indicating severe symptoms), adherence with the CPCRA Antiretroviral Medication Adherence Self-Report Form, and ascertained HIV clinic attendance via self-report. Odds ratios were obtained using logistic regression. Women who reported severe menopausal symptoms had greater odds of suboptimal ART adherence (adjusted odds ratio (AOR) 2.22; 95% CI 1.13, 4.35) and suboptimal clinic attendance (AOR 1.52; 95% CI 1.01, 2.29). When psychological, somatic and urogenital domains of the MRS were analysed individually there was no association between adherence and severe symptoms (all p > 0.1), however there was an association between suboptimal HIV clinic attendance and severe somatic (AOR 1.98; 95% CI 1.24, 3.16) and psychological (AOR 1.76; 95% CI 1.17, 2.65) symptoms. Severe menopausal symptoms were significantly associated with sub-optimal ART adherence and HIV clinic attendance, however we cannot infer causality, highlighting the need for longitudinal data.

Association of HIV status with sexual function in women aged 45-60 in England: results from two national surveys.

Increasing numbers of women living with HIV are reaching their midlife. We explore the association of HIV status with sexual function (SF) in women aged 45-60 using two national cross-sectional surveys: the third British National Survey of Sexual Attitudes and Lifestyles ("Natsal-3") and "PRIME", a survey of women living with HIV attending HIV clinics across England. Both studies asked the same questions about SF that take account not only sexual difficulties but also the relationship context and overall level of satisfaction, which collectively allowed an overall SF score to be derived. We undertook analyses of sexually-active women aged 45-60 from Natsal-3 (N = 1228, presumed HIV-negative given the low estimated prevalence of HIV in Britain) and PRIME (N = 386 women living with HIV). Women living with HIV were compared to Natsal-3 participants using multivariable logistic regression (adjusting for key confounders identified a priori: ethnicity, ongoing relationship status, depression and number of chronic conditions) and propensity scoring. Relative to Natsal-3 participants, women living with HIV were more likely to: have low overall SF (adjusted odds ratio (AOR) 3.75 [2.15-6.56]), report ≥1 sexual problem(s) lasting ≥3 months (AOR 2.44 [1.49-4.00]), and report almost all 8 sexual problems asked about (AORs all ≥2.30). The association between HIV status and low SF remained statistically significant when using propensity scoring (AOR 2.43 [1.68-3.51]). Among women living with HIV (only), low SF was more common in those who were postmenopausal vs. Premenopausal (55.6% vs. 40.4%). This study suggests a negative association between HIV status and sexual function in women aged 45-60. We recommend routine assessment of SF in women living with HIV.

Associations of depression and anxiety symptoms with sexual behaviour in women and heterosexual men attending sexual health clinics: a cross-sectional study.

OBJECTIVE: To assess the association of symptoms of depression and anxiety with sexual risk behaviour and history, among women and heterosexual men attending genitourinary medicine (GUM) clinics. METHODS: Attitudes to and Understanding of Risk of Acquisition of HIV (AURAH) was a cross-sectional, self-administered questionnaire study recruited from 20 GUM clinics in England, 2013-2014. This analysis included women and heterosexual men. The prevalence of depression and anxiety symptoms was assessed. Modified Poisson regression was used to produce adjusted prevalence ratios (aPR) for the association of t demographic, socioeconomic and lifestyle factors with depression and anxiety, adjusted for gender, age, ethnicity, education level and study region. Among individuals reporting sex in the past 3 months, associations of depression and anxiety with sexual risk behaviour and history were assessed separately by gender, adjusted for age, ethnicity, study region, education and relationship status. RESULTS: Questionnaires were completed by 676 women and 470 heterosexual men. Depression symptoms were reported by 100 (14.8%) women and 33 men (7.0%). Anxiety symptoms were reported by 79 women (11.7%) and 21 men (4.5%). Among women reporting recent sex, those with depression symptoms were more likely to report condomless sex with a non-regular partner, aPR 1.38 (1.07-1.77) and recent condomless sex with two or more partners, 1.80 (1.25-2.59). Women with anxiety symptoms more likely to report recent condomless sex with two or more partners, 1.68 (1.13-2.50), low self-efficacy for condom use, 1.54 (1.02-2.31) and STI diagnosis in the last year 1.51 (1.04-2.20). Among heterosexual men reporting recent sex, depression and anxiety symptoms were associated with low self-efficacy with condom use, 2.32 (1.29-4.19) for depression and 2.23 (1.26-3.94) for anxiety, but not with measures of condomless sex. DISCUSSION: The associations between psychological symptoms and sexual risk behaviours highlight the importance of holistic assessment of need by both general and sexual health clinicians. We highlight the challenge in delivering holistic care associated with fragmentation of sexual health services.

Shame and HIV: Strategies for addressing the negative impact shame has on public health and diagnosis and treatment of HIV.

There are five ways in which shame might negatively impact upon our attempts to combat and treat HIV. Shame can prevent an individual from disclosing all the relevant facts about their sexual history to the clinician. Shame can be a motivational factor in people living with HIV not engaging with or being retained in care. Shame can prevent individuals from presenting at clinics for STI and HIV testing. Shame can prevent an individual from disclosing their HIV (or STI) status to new sexual partners. Shame can serve to psychologically imprison people, it makes the task of living with HIV a far more negative experience than it should, or needs to, be. Drawing on recent philosophical work on shame, and more broadly on work in the philosophy and psychology of emotion, we (a.) propose a framework for understanding how shame operates upon those who experience the emotion, (b.) propose a strategy for combatting the negative role shame plays in the fight against HIV, and (c) suggest further study so as to identify the tactics that might be employed in pursuing the strategy here proposed.

Shame, stigma, HIV: philosophical reflections.

It is a distinctive feature of HIV that its pathology cannot be adequately grasped separate from a number of psychosocial factors, and stigma is widely seen as the most prominent. We argue that it is equally important to have an adequate understanding of shame, as the emotional response to stigma. We have identified five ways shame might negatively impact upon attempts to combat and treat HIV, which emerge from the stigma HIV carries and STI-stigma in general. In this paper, we draw out four insights from philosophical work on emotions and shame which we propose will improve understanding of shame and stigma. We conclude by briefly discussing how these insights might shed light on the negative role shame can play for a person living with HIV engaging with, or being retained in, care. We conclude by proposing further study.

Antenatal atazanavir: a retrospective analysis of pregnancies exposed to atazanavir.

INTRODUCTION: There are few data regarding the tolerability, safety, or efficacy of antenatal atazanavir. We report our clinical experience of atazanavir use in pregnancy. METHODS: A retrospective medical records review of atazanavir-exposed pregnancies in 12 London centres between 2004 and 2010. RESULTS: There were 145 pregnancies in 135 women: 89 conceived whilst taking atazanavir-based combination antiretroviral therapy (cART), "preconception" atazanavir exposure; 27 started atazanavir-based cART as "first-line" during the pregnancy; and 29 "switched" to an atazanavir-based regimen from another cART regimen during pregnancy. Gastrointestinal intolerance requiring atazanavir cessation occurred in five pregnancies. Self-limiting, new-onset transaminitis was most common in first-line use, occurring in 11.0%. Atazanavir was commenced in five switch pregnancies in the presence of transaminitis, two of which discontinued atazanavir with persistent transaminitis. HIV-VL < 50 copies/mL was achieved in 89.3% preconception, 56.5% first-line, and 72.0% switch exposures. Singleton preterm delivery (<37 weeks) occurred in 11.7% preconception, 9.1% first-line, and 7.7% switch exposures. Four infants required phototherapy. There was one mother-to-child transmission in a poorly adherent woman. CONCLUSIONS: These data suggest that atazanavir is well tolerated and can be safely prescribed as a component of combination antiretroviral therapy in pregnancy.

Gender and ethnicity intersect to reduce participation at a large European hybrid HIV conference.

OBJECTIVE: To evaluate how gender and ethnicity of panel members intersect to effect audience participation at a large European hybrid conference. DESIGN: An observational cross-sectional study design was used to collect data at the conference and descriptive survey was used to collect data retrospectively from the participants. SETTING: European AIDS Clinical Society 18th Conference; a 3223-delegate, hybrid conference held online and in London over 4 days in October 2021. MAIN OUTCOME MEASURES: We observed the number and type of questions asked at 12 of 69 sessions and described characteristics of the panel composition by ethnicity, gender and seniority. A postconference survey of conference attendees collated demographic information, number of questions asked during the conference and the reasons for not asking questions. RESULTS: Men asked the most questions and were more likely to ask multiple questions in the observed sessions (61.5%). People from white ethnic groups asked >95% of the questions in the observed sessions. The fewest questions were asked in the sessions with the least diverse panels in terms of both ethnicity and gender. Barriers to asking questions differed between genders and ethnicities. CONCLUSIONS: Our study aims to provide evidence to help conference organisers improve leadership, equality, diversity and inclusion in the professional medical conference setting. This will support equitable dissemination of knowledge and improve education and engagement of delegates. To our knowledge, this is the first study describing conference participation by both ethnicity and gender in panellists and delegates within a hybrid conference setting.