The follow-up of a cohort of anti-hiv seropositive haemophiliacs for up to 15 years from seroconversion

111 men with haemophilia registered at the Royal Free Hospital Haemophilia Centre became infected with HIV between 1979 and 1985 after treatment with infected blood products. These men have been followed for up to 15 years since HIV seroconversion. This thesis presents an epidemiologic follow-up of this cohort of patients. By the end of 1994, 47 men had developed AIDS and 45 had died, Kaplan-Meier progression rates of 56.5[percent] (9570 confidence interval 39.5-73.6) and 46.9[percent] (9570 confidence interval 35.6-582) by 14 years after seroconversion respectively. Prior to the development of AIDS, 82 of the men had developed at least one more minor condition indicative of their HIV infection. Older individuals and those who seroconverted prior to 1981 and from 1983 onwards appear to have a more rapid progression of disease. The CD4 lymphocyte count, which drops throughout infection, is a strong prognostic marker for disease progression. The rate of CD4 decline, the Immunoglobulin A level and the development of p24 antigenaemia all add some additional prognostic information to that provided by the most recent CD4 count alone. In contrast, the CD8 lymphocyte count simply identifies those individuals with the lowest and most rapidly declining CD4 counts. Whilst the beta-2 microglobulin level appears to provide additional prognostic information to the CD4 count at high CD4 levels, it is of less value at lower counts. The development of a bacterial infection prior to AIDS suggests that a patient's condition is likely to deteriorate, irrespective of their immune status. Despite being the best marker of progression, the CD4 count is, unfortunately, measured imperfectly. This has the effect of reducing the apparent relationship with disease progression and may lead to erroneous conclusions about the value of other covariates in a proportional hazards model

Defining multimorbidity in people with HIV - what matters most?

PURPOSE OF REVIEW: Although multimorbidity (defined as the coexistence of multiple conditions) presents significant health challenges to people with HIV, there is currently no consensus on how it should be defined among this population. This review aimed to examine the definition of multimorbidity in existing studies among people with HIV (n = 22). RECENT FINDINGS: Variation in the definition of multimorbidity (in terms of the number and nature of conditions included) across studies among people with HIV was observed, with less than half (45%) reporting a selection criteria for conditions. The number of conditions considered ranged from 4 to 65. Certain conditions (e.g. stroke, myocardial infarction and chronic kidney disease) and risk factors (e.g. hypertension) were more frequently included, while other symptoms (e.g. joint pain, peripheral neuropathy and sleeping problems) and mental health conditions (e.g. anxiety and panic attacks) were rarely included in the definition of multimorbidity. SUMMARY: The definition of multimorbidity among people with HIV is highly variable, with certain conditions overlooked. We propose recommendations that researchers should consider when defining multimorbidity among this population to not only enable comparisons between studies/settings but also to ensure studies consider a person-centred approach that can accurately capture multimorbidity among people with HIV

Understanding the conditions included in data-driven patterns of multimorbidity: a scoping review

BACKGROUND: Despite the growing utilization of data-driven methods to investigate multimorbidity patterns, there is currently no consensus or guidance on the conditions to include when identifying patterns. This scoping review aims to systematically examine the nature of conditions included in existing studies using data-driven techniques. METHODS: A comprehensive search of three electronic databases (MEDLINE, Web of Science and Scopus) was conducted to identify relevant publications from inception to 28 February 2022 using predefined search terms and inclusion/exclusion criteria. The reference lists and citations of relevant papers were also searched. RESULTS: Among 7326 search results, 5444 relevant articles were identified. After screening against the eligibility criteria, 60 articles were included in the review. Half of the reviewed studies reported selection criteria for conditions, with prevalence in the population of interest being the most common criterion (40%). Most studies included at least one neurological [59 (98.3%)], musculoskeletal [58 (96.7%)], respiratory [57 (95.0%)] or mental health [56 (93.3%)] condition. In contrast, only a small proportion of studies included skin [17 (28.3%)], infections [14 (23.3%)] or autoimmune conditions [10 (16.7%)]. Nine conditions (hypertension, diabetes, cancer, arthritis, COPD, asthma, depression, stroke and osteoporosis) were included by more than half of the studies. CONCLUSIONS: This review highlights the considerable heterogeneity among the conditions included in analyses of multimorbidity patterns. Researchers should provide a clear rationale for the selection of conditions to facilitate comparisons across studies and ensure reproducibility, as well as consider selecting a diverse range of conditions to capture the complexity of multimorbidity

Cardiovascular risks associated with protease inhibitors for the treatment of HIV

Introduction: Cumulative use of some first-generation protease inhibitors has been associated with higher rates of dyslipidemia and increased risk of cardiovascular disease. The protease inhibitors most commonly in use are atazanavir and darunavir, which have fewer detrimental lipid effects and greater tolerability. This paper aims to review the evidence of a potential association of these contemporary protease inhibitors with the risk of ischemic CVD and atherosclerotic markers.Areas covered: We searched for publications of randomized trials and observational studies on PubMed from 1st January 2000 onwards, using search terms including: protease inhibitors; darunavir; atazanavir; cardiovascular disease; cardiovascular events; dyslipidemia; mortality; carotid intima media thickness; arterial elasticity; arterial stiffness and drug discontinuation. Ongoing studies registered on clinicaltrials.gov as well as conference abstracts from major HIV conferences from 2015-2020 were also searched.Expert opinion: Atazanavir and darunavir are no longer part of first-line HIV treatment, but continue to be recommended as alternative first line, second- and third-line regimens, as part of two drug regimens, and darunavir is used as salvage therapy. Although these drugs will likely remain in use globally for several years to come, baseline CVD risk should be considered when considering their use, especially as the population with HIV ages

The global burden of cognitive impairment in people living with HIV: a systematic review and meta-analysis

OBJECTIVE: Whilst life expectancies of people living with HIV (PLWH) have increased through the successes of antiretroviral treatment, cognitive impairment remains a pressing concern. Prevalence estimates vary worldwide as different definitions for cognitive impairment are used and resource availability differs across geographical settings. We aim to explore this heterogeneity and estimate the global cognitive impairment burden in PLWH. DESIGN: Systematic literature review & meta-analysis. METHODS: We searched PubMed, Embase, SCOPUS and Web of Science for studies reporting on cognitive impairment prevalence in PLWH. Nine factors were investigated for their potential association with the prevalence using univariate meta-analysis and a meta-regression: assessment method, geographical region, country income, exclusion criteria, study quality, age, gender, publication year, and sample size. RESULTS: The literature search identified 8539 records, of which 225 were included. The adjusted prevalence was significantly lower in males than females. Across 44 countries, twelve assessment methods were used; the HAND/Frascati criteria, known for high false-positive rates, was employed in 44.4% of studies. The pooled cognitive impairment prevalence estimate in PLWH, including asymptomatic cases, is 39.6% [95% CI: 37.2-42.1%; range: 7-87%]. The meta-regression explained 13.3% of between-study variation, with substantial residual heterogeneity (I2 = 97.7%). CONCLUSION: Lack of data from >70% of the world's countries, cohorts being unselected for symptoms in most research studies, and limitations of the HAND/Frascati criteria restrict the ability to accurately determine the global burden of cognitive impairment in PLWH. More studies in low-resource settings and a standardised approach to assessing cognitive impairment, bridging research and clinical realms, are needed

Incidence and risk factors for tuberculosis among people with HIV on antiretroviral therapy in the UK

Objective: The United Kingdom has a low tuberculosis incidence and earlier combination antiretroviral therapy (cART) is expected to have reduced incidence among people with HIV. Epidemiological patterns and risk factors for active tuberculosis were analysed over a 20-year period among people accessing HIV care at sites participating in the UK CHIC observational study. Design: Cohort analysis. Methods: Data were included for individuals over 15 years old attending for HIV care between 1996 and 2017 inclusive, with at least 3 months follow-up recorded. Incidence rates of new tuberculosis events were calculated and stratified by ethnicity (white/Black/other) as a proxy for tuberculosis exposure. Poisson regression models were used to determine the associations of calendar year, ethnicity and other potential risk factors after cART initiation. Results: Fifty-eight thousand seven hundred and seventy-six participants (26.3% women; 54.5% white, 32.0% Black, 13.5% other/unknown ethnicity; median (interquartile range) age 34 (29–42) years) were followed for 546 617 person-years. Seven hundred and four were treated for active tuberculosis [rate 1.3; 95% confidence interval (CI) 1.2–1.4/1000 person-years). Tuberculosis incidence decreased from 1.3 (1.2–1.5) to 0.6 (0.4–0.9)/1000 person-years from pre-2004 to 2011–2017. The decline among people of Black ethnicity was less steep than among those of white/other ethnicities, with incidence remaining high among Black participants in the latest period [2.1 (1.4–3.1)/1000 person-years]. Two hundred and eighty-three participants [191 (67%) Black African] had tuberculosis with viral load less than 50 copies/ml. Conclusion: Despite the known protective effect of cART against tuberculosis, a continuing disproportionately high incidence is seen among Black African people. Results support further interventions to prevent tuberculosis in this group

A scoping review of media campaign strategies used to reach populations living with or at high risk for Hepatitis C in high income countries to inform future national campaigns in the United Kingdom

BACKGROUND: With the advent of direct acting antivirals, the World Health Organisation proposed eliminating Hepatitis C as a public health threat by 2030. To achieve this, countries need to diagnose, engage in care and treat their undiagnosed populations. This will require sensitisation campaigns. However previous media campaigns have had mixed impact. We conducted a scoping review to identify and understand the impact of previous Hepatitis C media campaigns. These findings could inform the delivery of future campaigns. METHODS: We searched five electronic databases for published literature on media campaigns conducted for Hepatitis C awareness, testing, and treatment in Organisation for Economic Co-operation and Development (OECD) countries since 2010. Two independent reviewers screened citations for inclusion. Additionally, we spoke to stakeholders in the Hepatitis C field in the UK and conducted a Google search to identify any unpublished literature. A quantitative synthesis was conducted to identify targeted populations, strategies and media used, aims and impact of the campaigns. RESULTS: A title and year of publication screening of 3815 citations resulted in 113 papers that had a full abstract screen. This left 50 full-text papers, 18 were included of which 9 (50%) were from Europe. 5 (27.8%) of campaigns targeted minority ethnicities, and 9 (50%) aimed to increase testing. A Google search identified 6 grey literature sources. Most campaigns were not evaluated for impact. Discussions with stakeholders identified several barriers to successful campaigns including lack of targeted messaging, stigmatising or accusatory messaging, and short-lived or intermittent campaign strategies. CONCLUSION: Future campaigns will likely need to be multifaceted and have multiple tailored interventions. Campaigns will need to be sizeable and robust, integrated into health systems and viewed as an ongoing service rather than one-offs

Treatment of mild-to-moderate pelvic inflammatory disease with a short-course azithromycin-based regimen versus ofloxacin plus metronidazole: results of a multicentre, randomised controlled trial

OBJECTIVE: A multicentre, randomised non-inferiority trial compared the efficacy and safety of 14 days of ofloxacin and metronidazole (standard-of-care (SoC)) versus a single dose of intramuscular ceftriaxone followed by 5 days of azithromycin and metronidazole (intervention arm (IA)) in women with mild-to-moderate pelvic inflammatory disease (PID). METHODS: Women with a clinical diagnosis of PID presenting at sexual health services were randomised to the SoC or IA arms. Treating clinicians and participants were not blinded to treatment allocation but the clinician performing the assessment of primary outcome was blinded. The primary outcome was clinical cure defined as ≥70% reduction in the modified McCormack pain score at day 14-21 after starting treatment. Secondary outcomes included adherence, tolerability and microbiological cure. RESULTS: Of the randomised population 72/153 (47.1%) reached the primary end point in the SoC arm, compared with 68/160 (42.5%) in the IA (difference in cure 4.6% (95% CI -15.6% to 6.5%). Following exclusion of 86 women who were lost to follow-up, attended outside the day 14-21 follow-up period, or withdrew consent, 72/107 (67.3%) had clinical cure in the SoC arm compared with 68/120 (56.7%) in the IA, giving a difference in cure rate of 10.6% (95% CI -23.2% to 1.9%). We were unable to demonstrate non-inferiority of the IA compared with SoC arm. Women in the IA took more treatment doses compared with the SoC group (113/124 (91%) vs 75/117 (64%), p=0.0001), but were more likely to experience diarrhoea (61% vs 24%, p<0.0001). Of 288 samples available for analysis, Mycoplasma genitalium was identified in 10% (28/288), 58% (11/19) of which had baseline antimicrobial resistance-associated mutations. CONCLUSION: A short-course azithromycin-based regimen is likely to be less effective than the standard treatment with ofloxacin plus metronidazole. The high rate of baseline antimicrobial resistance supports resistance testing in those with M. genitalium infection to guide appropriate therapy. TRIAL REGISTRATION NUMBER: 2010-023254-36

Self-management Interventions for Pain and Physical Symptoms Among People Living With HIV:A Systematic Review of the Evidence

Introduction: Pain and symptoms still persist among people living with HIV/AIDS. Evidence-based self-management interventions have the potential to help people with HIV/AIDS to successfully manage pain and symptoms. We aimed to identify and appraise the evidence regarding the effectiveness of self-management interventions for pain and/or physical symptoms in people living with HIV/AIDS. Methods: We searched for controlled intervention studies in Amed, Assian, CINAHL, Cochrane Library, Embase, Medline, PsycInfo, Scopus, and Web of Science data bases, from 1984 to February 2017. Two reviewers screened and extracted data, assessed risk of bias (using Joanna Briggs Institute Critical Appraisal checklist for randomized and nonrandomized trials), and rated the quality of evidence (GRADE tool). Results: We identified 22 original papers reporting 19 different studies. Of these, 17 used randomized controlled trial designs. Three studies reported data on pain severity, and 2 studies reported data on pain interference outcomes with one study reporting positive effect on both outcomes. Outcomes for physical symptoms were reported in 13 studies with 6 studies reporting positive effect. The quality of evidence was moderate for pain outcomes. For physical symptoms, one study was rated as moderate; the rest were rated as low n = 8 and very low n = 4 quality. Conclusions: There is some evidence to suggest that self-management interventions delivered either online, face-to-face, or group-based consisting of booklet, leaflet, or manuals are effective in improving pain and physical symptoms. Findings suggest the need for theoretically plausible high-quality clinical trials of pain and physical symptom self-management among culturally diverse people with HIV