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Showing papers in "Hiv Medicine in 2021"


Journal ArticleDOI
TL;DR: In this paper, a multicentre cohort study evaluated risk factors for morbidity and mortality of COVID-19 in people living with HIV (PLWH), infected with SARS-CoV-2 in three countries in different clinical settings.
Abstract: OBJECTIVES: A prior T cell depletion induced by HIV infection may carry deleterious consequences in the current COVID-19 pandemic. Clinical data on patients co-infected with HIV and SARS-CoV-2 are still scarce. METHODS: This multicentre cohort study evaluated risk factors for morbidity and mortality of COVID-19 in people living with HIV (PLWH), infected with SARS-CoV-2 in three countries in different clinical settings. COVID-19 was clinically classified as to be mild-to-moderate or severe. RESULTS: Of 175 patients, 49 (28%) had severe COVID-19 and 7 (4%) patients died. Almost all patients were on antiretroviral therapy (ART) and in 94%, HIV RNA was below 50 copies/mL prior to COVID-19 diagnosis. In the univariate analysis, an age 50 years or older, a CD4+ T cell nadir of < 200/µl, current CD4+ T cells < 350/µl and the presence of at least one comorbidity were significantly associated with severity of COVID-19. No significant association was found for gender, ethnicity, obesity, a detectable HIV RNA, a prior AIDS-defining illness, or tenofovir (which was mainly given as alafenamide) or protease inhibitor use in the current ART. In a multivariate analysis, the only factor associated with risk for severe COVID-19 was a current CD4+ T cell count of < 350/µl (adjusted odds ratio 2.85, 95% confidence interval 1.26-6.44, p=0.01). The only factor associated with mortality was a low CD4 T cell nadir. CONCLUSIONS: In PLWH, immune deficiency is a possible risk factor for severe COVID-19, even in the setting of virological suppression. There is no evidence for a protective effect of PIs or tenofovir alafenamide.

88 citations


Journal ArticleDOI
TL;DR: The electronic medical records of the Mount Sinai Health System, a medical network covering a wide area of New York City, comprised of eight hospitals and more than 400 ambulatory care units, were analysed using EPIC SLICER DICER software.
Abstract: Since coronavirus disease 2019 (COVID-19) emerged in China in late 2019, New York City has become an epicentre of the infection, experiencing 148 158 cases as of 1 May 2020 [1]. The impact of COVID-19 in patients with HIV infection is currently under active investigation in many countries; for example, Blanco et al. reported a clinical case series of patients with a coinfection of COVID-19 and HIV in Barcelona [2]. Herein, we sought to examine the prognosis of COVID-19 in patients with HIV infection in New York City, where the prevalence of HIV infection is 1.3% of the population [3]. We analysed the electronic medical records of the Mount Sinai Health System, a medical network covering a wide area of New York City, comprised of eight hospitals and more than 400 ambulatory care units, using EPIC SLICER DICER software (Epic,

47 citations


Journal ArticleDOI
TL;DR: In this article, the authors examined a cohort of PLHIV after prime (n = 88) and boost vaccination with BNT162b2 and found that the majority of patients mounted robust responses after complete vaccination but overall amounts of antibodies directed against the SARS-CoV-2 receptor-binding domain were variable.
Abstract: Objectives People living with HIV (PLWH) with low CD4 T-cell counts may be at a higher risk for severe coronavirus disease 2019 (COVID-19) outcomes and in need of efficient vaccination. The World Health Organization (WHO) now recommends prioritizing PLHIV for COVID-19 vaccination. Data on immune responses after messenger RNA (mRNA) vaccination in PLHIV in relation to CD4 counts are scarce. We aimed at assessing the humoral immune response in PLHIV after mRNA vaccination against COVID-19. Methods We examined a cohort of PLHIV after prime (n = 88) and boost (n = 52) vaccination with BNT162b2. We assessed levels of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein-specific immunoglobulin G (IgG)/IgA and circulating neutralizing antibodies in plasma and correlated results to the cellular immune status. BNT162b2-vaccinated health care workers served as controls. Results All PLWH had a viral load of ≤ 200 HIV-1 RNA copies/mL and 96.5% had a viral load of Conclusions The majority of PLWH mounted robust responses after complete BNT162b2 vaccination but overall amounts of antibodies directed against the SARS-CoV-2 receptor-binding domain were variable. The impact on clinical efficacy remains unclear.

40 citations


Journal ArticleDOI
TL;DR: In this paper, the authors describe the impact of the COVID-19 pandemic on HIV testing and treatment and describe strategies employed to mitigate the impact on HIV care, and suggest that providers and facilities should build on the lessons learned so far to further improve mitigation strategies and establish care priorities for both the pandemic and the post-pandemic periods.
Abstract: Objectives The coronavirus disease (COVID-19) pandemic has been associated with severe disruptions in health care services, and nonpharmacological measures such as social distancing also have an impact on access to screening tests and on the long-term care of patients with chronic conditions globally. We aimed to describe the impact of the COVID-19 pandemic on HIV testing and treatment and to describe strategies employed to mitigate the impact of COVID-19 on HIV care. Methods In this retrospective cohort study, we used secondary data from the AIDS Healthcare Foundation (AHF) Global Quality Program from 44 countries in four continents (Asia, Latin America and the Caribbean, Europe and Africa), and compared information on HIV testing, percentage of positive results, number of in-person appointments, and number of new enrolments in HIV care from 1 January 2020 to 31 August 2020 with the equivalent period in 2019. Results Despite marked inter-country heterogeneities, we found that COVID-19 was associated with a significant reduction in HIV testing, an increase in the percentage of positive tests, a reduction in the number of in-person consultations and a reduction in the number of new enrolments in care, despite the implementation of several mitigation strategies. The impact of COVID-19 differed across continents and key populations. Conclusions Our findings suggest that, in the years to come, health care services must be prepared to respond to the impact of COVID-19 on HIV testing and care. Providers and facilities should build on the lessons learned so far to further improve mitigation strategies and establish care priorities for both the pandemic and the post-pandemic periods.

35 citations


Journal ArticleDOI
TL;DR: In this article, the burden of non-communicable diseases (NCDs) and mortality among PLHIV in the pre-, early- and late-HAART (highly active antiretroviral therapy) era was estimated.
Abstract: Objectives To estimate the burden of non-communicable diseases (NCDs) and mortality among PLHIV in the pre-, early- and late-HAART (highly active antiretroviral therapy) era. Methods We conducted a cohort study using population-based Danish medical registries including all adult HIV-infected residents of the Central Denmark Region during 1985-2017. For each HIV patient, we selected 10 comparisons from the background population matched by age, sex and municipality of residence. Based on hospital-related diagnoses we estimated the prevalence and incidence of specific NCD at diagnosis and at 5 and 10 years. Results We identified 1043 PLHIV and 10 430 matched comparisons. PLHIV had lower socioeconomic status and more were born outside western Europe. At HIV diagnosis, 21.9% of PHLIV vs. 18.2% of non-HIV individuals had at least one NCD, increasing to 42.2% vs. 25.9% after 10 years. PLHIV had higher prevalence and cumulative incidence of alcohol abuse, chronic obstructive pulmonary disease (COPD), ischaemic heart disease, mental disorders, renal and liver disease, but no increased risk of diabetes mellitus. Only PLHIV in the age groups 41-50 and > 51 years had an increased incidence of osteoporosis. From the pre- to the late-HAART era, 10-year mortality among PLHIV decreased from 45.5% to 9.4% but continued at more than twice that of uninfected comparisons. However, in the late-HAART era, the mortality of PLHIV who were alive 2 years after HIV diagnosis was approaching that of comparisons. Conclusions Even in the late-HAART era, PLHIV have an excess mortality, which may be attributable to several NCDs being more prevalent among PLHIV. The prevalence rates of ischaemic heart disease, diabetes, osteoporosis and renal disease tend to increase over calendar time. Therefore, improvement of survival and quality of life of PLHIV neets strategies to reduce the risk of developing NCDs, including avoiding toxic antiretroviral therapy and lifestyle changes.

21 citations


Journal ArticleDOI
TL;DR: In this paper, the authors conducted a longitudinal survey to assess the qualitative SARS-CoV-2 vaccine immunogenicity among people living with HIV (PLWH) after vaccination.
Abstract: OBJECTIVES: Effective and safe COVID-19 vaccines have been developed and have resulted in decreased incidence and severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and can decrease secondary transmission. However, there are concerns about dampened immune responses to COVID-19 vaccination among immunocompromised patients, including people living with HIV (PLWH), which may blunt the vaccine's efficacy and durability of protection. This study aimed to assess the qualitative SARS-CoV-2 vaccine immunogenicity among PLWH after vaccination. METHODS: We conducted targeted COVID-19 vaccination (all received BNT162b2 vaccine) of PLWH (aged ≥ 55 years per state guidelines) at Yale New Haven Health System and established a longitudinal survey to assess their qualitative antibody responses at 3 weeks after the first vaccination (and prior to receipt of the second dose of the COVID-19 vaccine) (visit 1) and at 2-3 weeks after the second vaccination (visit 2) but excluded patients with prior COVID-19 infection. Our goal was to assess vaccine-induced immunity in the population we studied. Qualitative immunogenicity testing was performed using Healgen COVID-19 anti-Spike IgG/IgM rapid testing. Poisson regression with robust standard errors was used to determine factors associated with a positive IgG response. RESULTS: At visit 1, 45 of 78 subjects (57.7%) tested positive for SARS-CoV-2 anti-Spike IgG after the first dose of COVID-19 vaccine. Thirty-nine subjects returned for visit 2. Of these, 38 had positive IgG (97.5%), including 20 of 21 subjects (95.2%) with an initial negative anti-Spike IgG. Our bivariate analysis suggested that participants on an antiretroviral regimen containing integrase strand transfer inhibitors [relative risk (RR) = 1.81, 95% confidence interval (CI): 0.92-3.56, p = 0.085] were more likely to seroconvert after the first dose of the COVID-19 vaccine, while those with a CD4 count < 500 cells/µL (RR = 0.59, 95% CI: 0.33-1.05, p = 0.071), and those diagnosed with cancer or another immunosuppressive condition (RR = 0.49, 95% CI: 0.18-1.28, p = 0.15) may have been less likely to seroconvert after the first dose of the COVID-19 vaccine. The direction of these associations was similar in the multivariate model, although none of these findings reached statistical significance (RRintegrase inhibitor = 1.71, 95% CI: 0.90-3.25, p = 0.10; RRCD4 count = 0.68, 95% CI: 0.39-1.19, p = 0.18; RRcancer or another immunosuppressive condition = 0.50, 95% CI: 0.19-1.33, p = 0.16). With regard to immunogenicity, we were able to record very high rates of new seroconversion following the second dose of the COVID-19 vaccine. CONCLUSIONS: Our study suggests that completing a two-dose series of BNT162b2 vaccine is critical for PLWH given suboptimal seroconversion rates after the first dose and subsequent improved seroconversion rates after the second dose.

19 citations


Journal ArticleDOI
TL;DR: In this paper, the authors describe the prevalence of self-reported recreational drug use and chemsex in HIV-positive men who have sex with men (MSM) accessing HIV services in four countries.
Abstract: Introduction Chemsex in a European context is the use of any of the following drugs to facilitate sex: crystal methamphetamine, mephedrone and gamma-hydroxybutyrate (GHB)/gamma-butyrolactone (GBL) and, to a lesser extent, cocaine and ketamine. This study describes the prevalence of self-reported recreational drug use and chemsex in HIV-positive men who have sex with men (MSM) accessing HIV services in four countries. It also examines the problematic impacts and harms of chemsex and access to chemsex-related services. Methods This is a cross-sectional multi-centre questionnaire study of HIV-positive MSM accessing nine HIV services in the UK, Spain, Greece and Italy. Results In all, 1589 HIV-positive MSM attending HIV services in four countries completed the questionnaire. The median age of participants was 38 years (interquartile range: 32-46 years) and 1525 (96.0%) were taking antiretroviral therapy (ART). In the previous 12 months, 709 (44.6%) had used recreational drugs, 382 (24.0%) reported chemsex and 104 (6.5%) reported injection of chemsex-associated drugs ('slamsex'). Of the 382 engaging in chemsex, 155 (40.6%) reported unwanted side effects as a result of chemsex and 81 (21.2%) as a result of withdrawal from chemsex. The reported negative impacts from chemsex were on work (25.1%, 96), friends/family (24.3%, 93) and relationships (28.3%, 108). Fifty-seven (14.9%) accessed chemsex-related services in the past year, 38 of whom (67%) felt the service met their needs. Discussion A quarter of participants self-reported chemsex in the past 12 months. There were high rates of harms from chemsex across all countries, including negative impacts on work, friends/family and relationships. Although a minority of those engaging in chemsex accessed support, most found this useful.

15 citations


Journal ArticleDOI
TL;DR: In this article, the authors evaluated the real-world effectiveness and discontinuations in people living with HIV-1 (PLHIV) switching to DTG with lamivudine (3TC) or rilpivirine (RPV) using a one-arm meta-analysis.
Abstract: OBJECTIVES Dolutegravir (DTG) is widely recommended within three-drug regimens However, similar efficacy and tolerability have also been achieved with DTG within two-drug regimens in clinical trials This study evaluated the real-world effectiveness and discontinuations in people living with HIV-1 (PLHIV) switching to DTG with lamivudine (3TC) or rilpivirine (RPV) METHODS This was a one-arm meta-analysis utilizing data from a systematic literature review Data from real-world evidence studies of DTG + RPV and DTG + 3TC were extracted, pooled and analysed The primary outcome was the proportion of patients with viral failure (VF; ≥ 50 copies/mL in two consecutive measurements and/or ≥ 1000 copies/mL in a single measurement) at week 48 (W48) and week 96 (W96) Other outcomes included virological suppression (VS; < 50 copies/mL) and discontinuations (W48 and W96) Estimates were calculated for VF, VS as per snapshot (VSS) and on treatment analysis (VSOT), and discontinuations RESULTS Pooled mean estimates of VF for DTG + 3TC and DTG + RPV were 08% [95% confidence interval (CI): 04-13] and 06% (95% CI: 00-16), respectively, at W48 VSS rate at W48 was 850% (95% CI: 823-875) for DTG + 3TC regimen and 924% (95% CI: 850-977) in the DTG + RPV regimen The DTG + 3TC and DTG + RPV regimens led to discontinuations in 136% (95% CI: 111-162) and 72% (95% CI: 21-144) of patients, respectively, at W48 Similar results were observed at W96 CONCLUSIONS Treatment with DTG + 3TC or DTG + RPV in clinical practice provides a low rate of VF and a high rate of VS when initiated in virologically suppressed PLHIV with diverse backgrounds

15 citations


Journal ArticleDOI
TL;DR: National guidelines in Botswana recommend baseline CD4 count measurement and both CD4 and HIV viral load (VL) monitoring post‐antiretroviral therapy (ART) initiation.
Abstract: OBJECTIVES National guidelines in Botswana recommend baseline CD4 count measurement and both CD4 and HIV viral load (VL) monitoring post-antiretroviral therapy (ART) initiation. We evaluated the utility of CD4 count measurement in Botswana in the era of universal ART. METHODS CD4 and VL data were analysed for HIV-infected adults undergoing CD4 count measurement in 2015-2017 at the Botswana Harvard HIV-Reference Laboratory. We determined (1) the proportion of individuals with advanced HIV disease (CD4 count < 200 cells/µL) at initial CD4 assessment, (2) the proportion with an initial CD4 count ≥ 200 cells/µL experiencing a subsequent decline in CD4 count to < 200 cells/µL, and (3) the proportion of these immunologically failing individuals who had virological failure. Logistic regression modelling examined factors associated with advanced HIV disease. CD4 count trajectories were assessed using locally weighted scatterplot smoothing (LOWESS) regression. RESULTS Twenty-five per cent (3571/14 423) of individuals with an initial CD4 assessment during the study period had advanced HIV disease at baseline. Older age [≥ 35 years; adjusted odds ratio (aOR) 1.9; 95% confidence interval (CI) 1.8-2.1] and male sex were associated with advanced HIV disease. Fifty per cent (7163/14 423) of individuals had at least two CD4 counts during the study period. Of those with an initial CD4 count ≥ 200 cells/µL, 4% (180/5061) experienced a decline in CD4 count to < 200 cells/µL; the majority of CD4 count declines were in virologically suppressed individuals and transient. CONCLUSIONS One-quarter of HIV-positive individuals in Botswana still present with advanced HIV disease, highlighting the importance of baseline CD4 count measurement to identify this at-risk population. Few with a baseline CD4 count ≥ 200 cells/µL experienced a drop below 200 cells/µL, suggesting limited utility for ongoing CD4 monitoring.

14 citations


Journal ArticleDOI
TL;DR: The objective of this study was to compare the prevalence and risk factors of obesity and disturbances in glucose homeostasis between PLWH treated with modern antiretroviral therapy and the general population.
Abstract: Objectives Comparative data on glucose disorders using fasting blood samples between people living with HIV (PLWH) and the general population are lacking. The objective of this study was to compare the prevalence and risk factors of obesity and disturbances in glucose homeostasis between PLWH treated with modern antiretroviral therapy and the general population. Methods Adjusted prevalence of obesity, features of insulin resistance (triglyceride:high-density lipoprotein cholesterol ratio and alanine aminotransferase), impaired fasting glucose (IFG), diabetes mellitus (DM) and combined dysglycaemia (presence of IFG or DM) were determined using fasting blood samples among 1041 PLWH and 7047 subjects representing the general population. Results People living with HIV had a lower prevalence of obesity [18.2%, 95% confidence interval (CI): 15.1-21.2 vs. 23.9%, 95% CI: 22.4-25.4], but a higher prevalence of insulin resistance and IFG (20.0%, 95% CI: 16.6-23.4 vs. 9.8%, 95% CI: 8.7-10.8) than the general population. Fasting glucose concentration was higher, but glycated haemoglobin (HbA1c) was lower, among PLWH. Prevalence of dysglycaemia for a given body mass index (BMI) was higher in PLWH than in the general population. The prevalence of DM did not differ between PLWH (13.2%, 95% CI: 10.2-15.9) and the general population (14.5%, 95% CI: 13.6-15.4). Conclusions The prevalence of obesity was lower, but the risk of dysglycaemia for a given BMI was significantly higher, among PLWH, highlighting the importance of prevention and treatment of obesity among HIV-infected subjects. Regardless of the increased prevalence of insulin resistance and IFG, DM was surprisingly not more common among PLWH, raising concern about the under-diagnosis of DM, possibly due to low sensitivity of HbA1c in this patient population.

12 citations


Journal ArticleDOI
TL;DR: This review aims to summarize the common features of PrEP failure cases, discuss the implications of upscaling PrEP programmes, and summarize the potential risks and benefits of using PrEP in combination with other treatments.
Abstract: Objectives Early randomized controlled trials (RCTs) have confirmed high efficacy of pre-exposure prophylaxis (PrEP) for preventing HIV infection in men who have sex with men (MSM) with high HIV exposure risk. Nevertheless, some PrEP failure cases have been reported despite adequate drug adherence. This review aims to summarize the common features of PrEP failure cases and discuss the implications of upscaling PrEP programmes. Methods A search based on articles and clinical trials was conducted through Medline and OVID, with keywords for accessing publications reporting 'true' PrEP failure in the presence of documented adherence to daily regimen of co-formulated tenofovir disoproxil fumarate/emtricitabone. Results Ten cases of 'true' PrEP failure were identified, all of which were preceded by continued practice of condomless anal sex, despite documented adherence. Dried blood spot and/or hair analyses provided supporting evidence of adherence in eight cases. There was strong association of PrEP failure with recurrent or multiple sexually transmitted diseases and infection with resistant HIV viruses. Seroconversion was usually atypical or delayed because of significantly suppressed viral load, making diagnosis a clinical challenge. Discussion Although it is uncommon, 'true' PrEP failure can occur in a real-world situation, contrary to the outcome of early RCTs. Failure to identify HIV infection while on PrEP can potentially lead to the emergence of drug-resistant virus. To achieve effective HIV prevention, PrEP programmes should emphasize safer sexual practice in addition to drug adherence. Early identification of PrEP failure is crucial, which requires the development of highly sensitive assays and their clinical application.

Journal ArticleDOI
Q Tian, J Si, F Jiang, R Xu, B Wei, B Huang, Q Li, Z Jiang, T Zhao 
TL;DR: This study aimed to examine the clinical effectiveness and safety of caspofungin combined with TMP/SMZ as a first‐line therapy for moderate‐to‐severe PCP in HIV‐infected patients.
Abstract: Objectives The effectiveness of trimethoprim/sulfamethoxazole (TMP/SMZ) for pneumocystis pneumonia (PCP) is limited with adverse events. Caspofungin, by inhibiting the cyst form of Pneumocystis jirovecii, may be an alternative therapy for PCP. However, the availability of clinical data about caspofungin combined with TMP/SMZ in the treatment of PCP in HIV-infected patients is limited. Thus, we aimed to examine the clinical effectiveness and safety of caspofungin combined with TMP/SMZ as a first-line therapy for moderate-to-severe PCP in HIV-infected patients. Methods From January 2017 to December 2019, data of HIV-infected patients with moderate-to-severe PCP who received either TMP/SMZ alone or caspofungin combined with TMP/SMZ as first-line therapy were retrospectively reviewed to assess the effectiveness and safety of each regimen. The Kaplan-Meier curve and log-rank test were used for survival analysis. Results A total of 278 patients met the criteria. The overall positive response rate of PCP treatment was 48.92%, and the overall all-cause in-hospital mortality rate was 33.09%. Patients who received combination therapy consisting of caspofungin and TMP/SMZ had a better positive response rate (59.44% vs. 37.78%, P 30 cells/µL and patients who received combination therapy consisting of caspofungin and TMP/SMZ were more likely to survive from PCP (P = 0.011 and P = 0.002, respectively). There were no additional severe adverse events caused by adding caspofungin. Conclusions For HIV-infected patients with moderate-to-severe PCP, combination therapy with caspofungin and TMP/SMZ is an effective and promising first-line therapy with no greater number of adverse events compared with TMP/SMZ monotherapy. Patients who received caspofungin had better positive response rates and lower all-cause in-hospital mortality rates. Also, we recommend early initiation of caspofungin.

Journal ArticleDOI
TL;DR: In this paper, the authors compared the efficacy and durability of treatment switch to two-drug (2DR) vs. three-drug integrase inhibitor (3DR) based regimens in a real-life setting.
Abstract: OBJECTIVES The aim of the present study was to compare the efficacy and durability of treatment switch to two-drug (2DR) vs. three-drug (3DR) integrase inhibitor (InSTI)-based regimens in a real-life setting. METHODS Within the ODOACRE cohort, we selected adult patients with HIV RNA 1000 copies/mL or two consecutive HIV RNA > 50 copies/mL) and treatment discontinuation (TD, defined as any modification, intensification or interruption of the regimen), and to evaluate their predictors. RESULTS Overall, 1666 patients were included, of whom 1334 (80%) were treated with a 3DR (19.9%, 25.0% and 55.1% elvitegravir-, raltegravir- and dolutegravir-based, respectively) and 332 (20%) with a 2DR (79.2% dolutegravir + lamivudine and 20.8% dolutegravir + rilpivirine). Over a median (interquartile range) follow-up of 100 (52-150) weeks, 52 (3.1%) patients experienced VF with an incidence of 1.5/100 person-year of follow-up (PYFU). The estimated 96-week probability of VF was similar for the 2DR and 3DR groups (2.3% vs. 2.8%, P = 0.53), but it was higher for elvitegravir (4.9%) and raltegravir (5.0%) than for dolutegravir (1.5%) (P = 0.04). Four hundred (24%) patients discontinued their InSTI-based regimen, with an incidence of 11.3/100 PYFU. At 96 weeks, 3DRs showed a higher probability of TD for any reason (20.6% vs. 11.2%, P < 0.001) and TD for toxicity (9.0% vs. 6.6%, P = 0.02) when compared with 2DRs. A higher risk of TD for central nervous system toxicity was observed for dolutegravir than for elvitegravir and raltegravir (4.0% vs. 2.5% vs. 0.6%, P = 0.005). CONCLUSIONS In virologically suppressed HIV-infected patients, 2DRs showed an efficacy similar to 3DRs but with better tolerability.

Journal ArticleDOI
TL;DR: A review of the current literature investigating cART neurotoxicity, controversies in HAND prevalence estimates, CNS Penetration Effectiveness, and neuroprotective adjuvant therapies is presented in this paper.
Abstract: Objectives Although the advent of Combination Antiretroviral Therapy (cART) has greatly reduced the prevalence of HIV-Associated Dementia, the most severe form of HIV-Associated Neurocognitive Disorder (HAND), the incidence of the milder forms of HAND have risen. The explanations proposed include persistent central nervous system (CNS) viraemia and the neurotoxicity of chronic cART regimens. Nonetheless, controversies in HAND prevalence estimates, alongside a lack of consensus on the significance of CNS Penetration Effectiveness (CPE) have added to the complexity of elucidating the role of cART in HAND. The present review will evaluate the evidence underlying these explanations, as well as highlighting the need for improved trial designs and the incorporation of emerging biomarkers and neuroimaging tools. Methods A review of the current literature investigating cART neurotoxicity, controversies in HAND prevalence estimates, CNS Penetration Effectiveness, and neuroprotective adjuvant therapies. Conclusions Ultimately, the inadequacy of cART in achieving complete preservation of the CNS underscores the imminent need for neuroprotective adjuvant therapies, where the efficacy of combining multiple adjuvant classes presents a potential therapeutic frontier which must be interrogated.

Journal ArticleDOI
TL;DR: In this paper, the proportion of patients diagnosed late and factors related to late presentation in Poland in 2016-2017 were analyzed, and the only independent factors associated with LP were older age, injecting drug use and route of transmission.
Abstract: Objectives Late presentation (LP) at HIV diagnosis is associated with worse prognosis and an increase in the number of new infections. We analyse the proportion of patients diagnosed late and factors related to LP in Poland in 2016-2017. Methods Data were obtained from 13 out of 17 HIV centres in Poland from 2016 and 2017, including date of diagnosis, age, sex, transmission route, anti-hepatitis C virus (anti-HCV), Venereal Diseases Research Laboratory (VDRL) antibodies, AIDS diagnosis, baseline HIV viral load and CD4 count. Results Out of 1522 patients, 88.9% were male with median age of 33.6 years. Men who have sex with men (MSM) comprised 69.4% of all new infections, heterosexual route of transmission (HTX) 18.2% and injecting drug use (IDU) 4.7%. Late presenters comprised 44.8% of the study group. Factors associated with LP were female sex [odds ratio (OR) = 1.5, 95% confidence interval (95% CI): 1.09-2.08], older age (OR = 1.59, 95% CI: 1.42-1.79 per decade), route of transmission (HTX: OR = 1.96, 95% CI: 1.50-2.56; IDU: OR = 3.17, 95% CI: 1.92-5.37), positive HCV results (OR = 1.90, 95% CI: 1.23-2.95) and syphilis diagnosis (OR = 2.06, 95% CI: 2.29-3.31). Adjusting for these factors, the only independent factors associated with LP were age (OR = 1.52, 95% CI: 1.35-1.71) and route of transmission (HTX: OR = 1.73, 95% CI: 1.23-2.44; IDU: OR = 2.24, 95% CI: 1.25-4.10). Conclusions Late presentation in Poland follows European trends. A total of 44.8% of all newly diagnosed patients in Poland continue to present late or at the AIDS stage. Independent factors associated with LP/AIDS were older age, IDU and HTX. Patients from these groups should be targeted to improve early diagnosis and medical care.

Journal ArticleDOI
TL;DR: Differences in clinical outcomes of COVID-19 hospitalisations in PLWH may be due to other important factors including increased frailty and comorbidities such as malignancies, rather than HIV-status alone.
Abstract: Background The contribution of HIV to COVID-19 outcomes in hospitalized inpatients remains unclear. We conducted a multi-centre, retrospective matched cohort study of SARS-CoV-2 PCR-positive hospital inpatients analysed by HIV status. Methods HIV-negative patients were matched to people living with HIV (PLWH) admitted from 1 February 2020 to 31 May 2020 up to a 3:1 ratio by the following: hospital site, SARS-CoV-2 test date ± 7 days, age ± 5 years, gender, and index of multiple deprivation decile ± 1. The primary objective was clinical improvement (two-point improvement or better on a seven-point ordinal scale) or hospital discharge by day 28, whichever was earlier. Results A total of 68 PLWH and 181 HIV-negative comparators were included. In unadjusted analyses, PLWH had a reduced hazard of achieving clinical improvement or discharge [adjusted hazard ratio (aHR) = 0.57, 95% confidence interval (CI): 0.39-0.85, p = 0.005], but this association was ameliorated (aHR = 0.70, 95% CI: 0.43-1.17, p = 0.18) after additional adjustment for ethnicity, frailty, baseline hypoxaemia, duration of symptoms prior to baseline, body mass index (BMI) categories and comorbidities. Baseline frailty (aHR = 0.79, 95% CI: 0.65-0.95, p = 0.011), malignancy (aHR = 0.37, 95% CI 0.17, 0.82, p = 0.014) remained associated with poorer outcomes. The PLWH were more likely to be of black, Asian and minority ethnic background (75.0% vs 48.6%, p = 0.0002), higher median clinical frailty score [3 × interquartile range (IQR): 2-5 vs, 2 × IQR: 1-4, p = 0.0069), and to have a non-significantly higher proportion of active malignancy (14.4% vs 9.9%, p = 0.29). Conclusions Adjusting for confounding comorbidities and demographics in a matched cohort ameliorated differences in outcomes of PLWH hospitalized with COVID-19, highlighting the importance of an appropriate comparison group when assessing outcomes of PLWH hospitalized with COVID-19.

Journal ArticleDOI
TL;DR: Nucleoside reverse transcriptase inhibitor (NRTI) transmitted drug resistance mutations (TDRMs) could increase the risk of virological failure (VF) of first‐line integrase strand transfer inhibitor (InSTI)‐based regimens.
Abstract: Objectives Nucleoside reverse transcriptase inhibitor (NRTI) transmitted drug resistance mutations (TDRMs) could increase the risk of virological failure (VF) of first-line integrase strand transfer inhibitor (InSTI)-based regimens. Methods Patients starting two NRTIs (lamivudine/emtricitabine plus abacavir/tenofovir) plus raltegravir or dolutegravir were selected from the EuResist cohort. The role of NRTI genotypic susceptibility score and of specific TDRMs in VF (i.e. two consecutive viral loads > 50 HIV-1 RNA copies/mL or a single viral load ≥ 200 copies/mL after 3 months from antiretroviral therapy start) was evaluated in the overall population and according to the InSTI employed. Results From 2008 to 2017, 1095 patients were eligible for the analysis (55.5% men, median age 39 years). In all, 207 VFs occurred over 1023 patient-years of follow-up. The genotypic susceptibility score (GSS) had no effect on the risk of VF in the overall population. However, the presence of M184V/I independently predicted VF of raltegravir- but not dolutegravir-based therapy when compared with a fully-active backbone [adjusted hazard ratio (aHR) = 3.09, P = 0.035], particularly when associated with other non-thymidine analogue mutations (aHR = 27.62, P = 0.004). Higher-zenith HIV-RNA and lower nadir CD4 counts independently predicted VF. Conclusions NRTI backbone TDRMs increased the risk of VF with raltegravir-based but not dolutegravir-based regimens.

Journal ArticleDOI
TL;DR: In this paper, the authors used next-generation sequencing (NGS) to detect low-frequency variants of transmitted drug resistance (TDR) in antiretroviral therapy (ART) patients.
Abstract: Objectives The aim of this analysis was to characterize transmitted drug resistance (TDR) in Strategic Timing of Antiretroviral Treatment (START) study participants by next-generation sequencing (NGS), a sensitive assay capable of detecting low-frequency variants. Methods Stored plasma from participants with entry HIV RNA > 1000 copies/mL were analysed by NGS (Illumina MiSeq). TDR was based on the WHO 2009 surveillance definition with the addition of reverse transcriptase (RT) mutations T215N and E138K, and integrase strand transfer inhibitor (INSTI) surveillance mutations (Stanford HIVdb). Drug resistance mutations (DRMs) detected at three thresholds are reported: > 2%, 5% and 20% of the viral population. Results Between 2009 and 2013, START enrolled 4684 antiretroviral therapy (ART)-naive individuals in 35 countries. Baseline NGS data at study entry were available for 2902 participants. Overall prevalence rates of TDR using a detection threshold of 2%/5%/20% were 9.2%/5.6%/3.2% for nucleoside reverse transcriptase inhibitors (NRTIs), 9.2%/6.6%/4.9% for non-NRTIs, 11.4%/5.5%/2.4% for protease inhibitors (PIs) and 3.5%/1.6%/0.1% for INSTI DRMs and varied by geographic region. Using the 2% detection threshold, individual DRMs with the highest prevalence were: PI M46IL (5.5%), RT K103NS (3.5%), RT G190ASE (3.1%), T215ISCDVEN (2.5%), RT M41L (2.2%), RT K219QENR (1.7%) and PI D30N (1.6%). INSTI DRMs were detected almost exclusively below the 20% detection threshold, most commonly Y143H (0.4%), Q148R (0.4%) and T66I (0.4%). Conclusions Use of NGS in this study population resulted in the detection of a large proportion of low-level variants which would not have been detected by traditional Sanger sequencing. Global surveillance studies utilizing NGS should provide a more comprehensive assessment of TDR prevalence in different regions of the world.

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TL;DR: In this paper, the authors compared the characteristics and clinical outcomes of hospitalized individuals with COVID-19 with [people with HIV (PWH)] and without (non-PWH) HIV co-infection in Spain during the first wave of the pandemic.
Abstract: OBJECTIVES: We compared the characteristics and clinical outcomes of hospitalized individuals with COVID-19 with [people with HIV (PWH)] and without (non-PWH) HIV co-infection in Spain during the first wave of the pandemic. METHODS: This was a retrospective matched cohort study. People with HIV were identified by reviewing clinical records and laboratory registries of 10 922 patients in active-follow-up within the Spanish HIV Research Network (CoRIS) up to 30 June 2020. Each hospitalized PWH was matched with five non-PWH of the same age and sex randomly selected from COVID-19@Spain, a multicentre cohort of 4035 patients hospitalized with confirmed COVID-19. The main outcome was all-cause in-hospital mortality. RESULTS: Forty-five PWH with PCR-confirmed COVID-19 were identified in CoRIS, 21 of whom were hospitalized. A total of 105 age/sex-matched controls were selected from the COVID-19@Spain cohort. The median age in both groups was 53 (Q1-Q3, 46-56) years, and 90.5% were men. In PWH, 19.1% were injecting drug users, 95.2% were on antiretroviral therapy, 94.4% had HIV-RNA < 50 copies/mL, and the median (Q1-Q3) CD4 count was 595 (349-798) cells/µL. No statistically significant differences were found between PWH and non-PWH in number of comorbidities, presenting signs and symptoms, laboratory parameters, radiology findings and severity scores on admission. Corticosteroids were administered to 33.3% and 27.4% of PWH and non-PWH, respectively (P = 0.580). Deaths during admission were documented in two (9.5%) PWH and 12 (11.4%) non-PWH (P = 0.800). CONCLUSIONS: Our findings suggest that well-controlled HIV infection does not modify the clinical presentation or worsen clinical outcomes of COVID-19 hospitalization.

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TL;DR: In this paper, the authors describe COVID-19 mortality among people with and without HIV during the first wave of the pandemic in England, using negative binomial regression to assess the association between HIV and mortality, adjusting for gender, age and ethnicity.
Abstract: Objectives We describe COVID-19 mortality among people with and without HIV during the first wave of the pandemic in England. Methods National surveillance data on adults (aged ≥ 15 years) with diagnosed HIV resident in England were linked to national COVID-19 mortality surveillance data (2 March 2020?16 June 2020);HIV clinicians verified linked cases and provided information on the circumstances of death. We present COVID-19 mortality rates by HIV status, using negative binomial regression to assess the association between HIV and mortality, adjusting for gender, age and ethnicity. Results Overall, 99 people with HIV, including 61 of black ethnicity, died of/with COVID-19 (107/100 000) compared with 49 483 people without HIV (109/100 000). Compared to people without HIV, higher COVID-19 mortality rates were observed in people with HIV of black (188 vs. 122/100 000) and Asian (131 vs. 77.0/100 000) ethnicity, and in both younger (15?59 years: 58.3 vs. 10.2/100 000) and older (≥ 60 years: 434 vs. 355/100 000) people. After adjustment for demographic factors, people with HIV had a higher COVID-19 mortality risk than those without (2.18;95% CI: 1.76?2.70). Most people with HIV who died of/with COVID-19 had suppressed HIV viraemia (91%) and at least one comorbidity reported to be associated with poor COVID-19 outcomes (87%). Conclusions In the first wave of the pandemic in England, COVID-19 mortality among people with HIV was low, but was higher than in those without HIV, after controlling for demographic factors. This supports the strategy of prioritizing COVID-19 vaccination for people with HIV and strongly encouraging its uptake, especially in those of black and Asian ethnicity.

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TL;DR: In this paper, the authors estimate the incidence of and the factors associated with RAHC, together with reinfection rates, among patients sexually infected by HIV, and show that men who have sex with men (MSM) carry the highest risk of HCV acquisition.
Abstract: Objectives Spain is close to HCV microelimination, so rates of recently acquired HCV infection (RAHC) should decrease. Nowadays, men who have sex with men (MSM) carry the highest risk of HCV acquisition. Our aim was to estimate the incidence of and the factors associated with RAHC, together with reinfection rates, among patients sexually infected by HIV. Methods Primary RAHC infection was diagnosed when anti-HCV antibody seroconversion was documented. In anti-HCV positive patients, initially without HCV viraemia, a diagnosis of reinfection was established if plasma HCV RNA was detected. Results All 350 patients tested negative for anti-HCV at baseline and had at least one follow-up visit. Among them, there were 16 RAHC cases from 2016 to 2019. RAHC incidence rates [IR (95% confidence interval, CI)] per 100 person-years were 3.77 (0.5-12.9) in 2016, 1.85 (0.6-4.3) in 2017, 1.49 (0.4-3.8) in 2018 and 1.98 (0.6-4.5) in 2019. Only previous sexually transmitted infections [incidence rate ratio (IRR) = 18.23, 95% CI: 1.93-172.1; P = 0.011], male sex (IRR = 8.33, 95% CI: 1.38-54.15; P = 0.026) and sharing chem-sex drugs (IRR: 4.93, 95% CI: 1.17-20.76; P = 0.030), were independently associated with RAHC. Four out of 42 (9.5%) patients became reinfected. Conclusions The incidence of RAHC among HIV-infected patients showed a decrease after 2016, although a lower but steady incidence of residual cases still remains. HCV reinfections showed a similar pattern. New infections were associated with sharing chem-sex drugs among MSM.

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TL;DR: Factors associated with PrEP awareness and willingness in the population are reported for Chinese young men who have sex with men.
Abstract: Objectives Despite being a key population in whom to initiate pre-exposure prophylaxis (PrEP), the awareness of and willingness to use PrEP are still unclear in Chinese young men who have sex with men (YMSM). We report factors associated with PrEP awareness and willingness in the population. Methods From 1 August to 31 December 2018, 495 participants aged 15-24 years were included in a cross-sectional study about awareness of and willingness to use PrEP among YMSM. Logistic regression models were used to identify factors associated with two outcomes: awareness of PrEP; and willingness to use PrEP. Results Among 495 eligible participants, 129 participants (26.1%) knew about PrEP. PrEP awareness among YMSM was associated with higher education level [adjusted odds ratio (aOR) = 1.812, 95% CI: 1.113-2.951] and previous HIV testing (aOR = 3.507, 95% CI: 1.261-9.752). YMSM with shorter local residence time (aOR = 0.317, 95% CI: 0.101-0.992) and internet-based partner-seeking (aOR = 0.171, 95% CI: 0.096-0.305) were less likely to be aware of PrEP. In those with previous knowledge of PrEP, 36 (27.9%) conveyed their willingness to use it. PrEP willingness was associated with internet-based partner-seeking (aOR = 9.593, 95% CI: 1.965-46.844). The main barriers influencing those who knew about PrEP but refused to use it were the high price of PrEP (69.9%), the need to use condoms consistently (52.7%), and concerns about side effects (39.8%) and effectiveness of prevention (22.6%). Conclusions Chinese YMSM have low awareness of and willingness to use PrEP. Adequate PrEP promotions should be implemented, especially on the Internet and dating software.

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TL;DR: Tenofovir disoproxil fumarate is associated with reduced bone mineral density (BMD) in women who switched from TDF, emtricitabine and a nonnucleoside reverse transcriptase inhibitor to abacavir, lamivudine and dolutegravir.
Abstract: Objectives Tenofovir disoproxil fumarate (TDF) is associated with reduced bone mineral density (BMD). We evaluated changes in BMD in women who switched from TDF, emtricitabine and a nonnucleoside reverse transcriptase inhibitor (TDF/FTC/NNRTI) to abacavir, lamivudine and dolutegravir (ABC/3TC/DTG). Methods We conducted a randomized controlled trial in which women aged ≥40 years were randomized 1:2 to continue TDF/FTC/NNRTI or switch to ABC/3TC/DTG. The primary endpoint was change in total hip BMD measured by dual-energy X-ray absorptiometry at week 48. Secondary endpoints were changes in BMD of the lumbar spine and femoral neck and markers of bone turnover and kidney function up to week 48. We conducted exploratory analyses of weight gain, insulin resistance and metabolic syndrome. Primary and secondary endpoints were analysed by linear regression, with multiple imputation for missing time points. Results In all, 91 women [mean age = 50.4 (standard deviation [SD] = 6.6) years, median CD4 cell count = 600 (interquartile range: 479-800) cells/µL] were randomized. Women who switched to ABC/3TC/DTG maintained viral suppression and experienced improvements in total hip BMD (mean adjusted difference = 1%, P = 0.027) and lumbar spine BMD (3%, P = 0.002), with no change in specific markers of bone turnover or renal tubular function. Although participants in the ABC/3TC/DTG arm gained more weight (1.8 kg, P = 0.046), the switch strategy was not associated with reduced insulin sensitivity or new-onset metabolic syndrome. Conclusions Switching from TDF/FTC/NNRTI to ABC/3TC/DTG resulted in improved BMD. Although weight gain was common in women who switched from TDF/FTC/NNRTI to ABC/3TC/DTG, we did not detect adverse effects on glucose homeostasis. Larger studies need to confirm these findings.

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TL;DR: It is suggested that people living with HIV (PLWH) have a four‐fold higher risk of diabetes compared with HIV‐negative people and in sub‐Saharan Africa, with 80% of the global burden of HIV, there is a relative paucity of data on the burden and determinants of prevalent and incident dysglycaemia.
Abstract: BACKGROUND Available data from high-income countries suggest that people living with HIV (PLWH) have a four-fold higher risk of diabetes compared with HIV-negative people. In sub-Saharan Africa, with 80% of the global burden of HIV, there is a relative paucity of data on the burden and determinants of prevalent and incident dysglycaemia. OBJECTIVES To assess the prevalence and incidence of pre-diabetes (pre-DM) and overt diabetes mellitus (DM) among PLWH in a Ghanaian tertiary medical centre. METHODS We first performed a cross-sectional comparative analytical study involving PLWH on combination antiretroviral therapy (cART) (n = 258), PLWH not on cART (n = 244) and HIV-negative individuals (n = 242). Diabetes, pre-DM and normoglycaemia were defined as haemoglobin A1C (HBA1c) > 6.5%, in the range 5.7-6.4% and < 5.7% respectively. We then prospectively followed up the PLWH for 12 months to assess rates of new-onset DM, and composite of new-onset DM and pre-DM. Multivariate logistic regression models were fitted to identify factors associated with dysglycaemia among PLWH. RESULTS The frequencies of DM among PLWH on cART, PLWH not on cART and HIV-negative individuals were 7.4%, 6.6% and 7.4% (P = 0.91), respectively, while pre-DM prevalence rates were 13.2%, 27.9% and 27.3%, respectively (P < 0.0001). Prevalent DM was independently associated with increasing age [adjusted odds ratio (95% confidence interval) (aOR, 95% CI) = 1.82 (1.20-2.77) for each 10-year rise], male sex [aOR = 2.64 (1.20-5.80)] and log(triglyceride/HDL cholesterol) [aOR = 8.54 (2.53-28.83)]. Prevalent pre-DM was independently associated with being on cART [aOR (95% CI) = 0.35 (0.18-0.69)]. There were a total of 12 cases of incident DM over 359.25 person-years, giving 33.4/1000 person-years of follow-up (PYFU) (95% CI: 18.1-56.8/1000), and an rate of incident pre-DM of 212.7/1000 PYFU (95 CI: 164.5-270.9/1000). The two independent factors associated with new-onset DM were having pre-DM at enrolment [aOR = 6.27 (1.89-20.81)] and being established on cART at enrolment [aOR = 12.02 (1.48-97.70)]. CONCLUSIONS Incidence rates of pre-DM and overt DM among Ghanaian PLWH on cART ranks among the highest in the literature. There is an urgent need for routine screening and a multidisciplinary approach to cardiovascular disease risk reduction among PLWH to reduce morbidity and mortality from the detrimental effects of dysglycaemia.

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TL;DR: In this paper, the authors evaluated the accuracy of serological biomarkers for non-alcoholic fatty liver disease (NAFLD) and advanced fibrosis (METAVIR-F3F4) in HIV mono-infected individuals.
Abstract: Objectives: We aimed to evaluate the accuracy of serological biomarkers for non-alcoholic fatty liver disease (NAFLD) and advanced fibrosis (METAVIR-F3F4) in HIV mono-infected individuals. Methods: In all, 674 participants from the PROSPEC-HIV study (NCT02542020), who had blood sample tests and transient elastography (TE) performed on the same day, were eligible. Exclusion criteria were viral hepatitis co-infection (n = 90), abusive alcohol intake (n = 61), missing data (n = 47) or unreliable TE (n = 39). NAFLD was defined by controlled attenuation parameter ≥ 248 dB/m and advanced fibrosis by liver stiffness measurement ≥ 8.7 kPa with M probe or ≥ 7.2 kPa with XL probe. Biomarkers for NAFLD [Steato-ELSA, Fatty Liver Index (FLI), Hepatic Steatosis Index (HSI), NAFLD-Liver Fat Score (NAFLD-LFS)] and fibrosis [Fibrosis-4 score (FIB-4), Aspartate-to-Platelet Ratio Index (APRI) and NAFLD Fibrosis Score (NFS)] were calculated. Results: A total of 437 patients [57% female, age = 44 (interquartile range: 35-52) years, body mass index (BMI) = 26.1 (23.4-29.3) kg/m2 , CD4 = 660 (427-901) cells/μL] were included. The prevalence [95% confidence interval (CI)] of NAFLD and advanced fibrosis were 38.2% (33.8-42.9) and 10.5% (8.0-13.8), respectively. The areas (95% CI) under the receiver operator curve (AUROCs) for diagnosis of NAFLD were 0.854 (0.818-0.889), 0.840 (0.804-0.877), 0.805 (0.762-0.847) and 0.793 (0.750-0.836) for Steato-ELSA, FLI, HSI and NAFLD-LFS (P 90%. Conclusion: Biomarkers for NAFLD had a good accuracy and those for fibrosis had high specificities and NPVs. These tests should be integrated to HIV care to detect NAFLD and to exclude advanced liver fibrosis.

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TL;DR: In this paper, a tailored pre-exposure prophylaxis (PrEP) service based in the local homeless health centre was developed to optimise the uptake and adherence of people who inject drugs (PWID).
Abstract: Objectives HIV prevention strategies including pre-exposure prophylaxis (PrEP) must reach all in need to achieve elimination of transmission by 2030. Mainstream provision may inadvertently exclude key populations. Incidence of HIV in people who inject drugs (PWID) in Glasgow, Scotland's largest city, is increasing, partly due to sexual transmission. Scotland provides publicly funded oral PrEP for individuals at sexual risk of HIV through sexual health services; however, uptake by PWID has been negligible. We developed a tailored outreach PrEP service based in the local homeless health centre. We used active case finding, flexibility of assessment location, supervised community daily dispensing and active follow-up to optimise uptake and adherence. We describe a two-year service evaluation. Methods We reviewed the case records of all PWID identified by the outreach team as being at higher risk of sexual acquisition for whom PrEP was considered between November 2018 and November 2020. Evaluation focused on PrEP uptake, adherence and monitoring. We conducted a descriptive statistical analysis. Results Of 41 PWID assessed as eligible, 32 (78.0%) commenced PrEP. The proportion of PrEP-covered days was 3320/3400 days (97.6%); 31/32 (96.9%) had regular HIV serology monitoring. The service was feasible to run, but it relied on outreach provision and liaison with other services. Discussion Tailored PrEP services can reach PWID effectively. Uptake and adherence were high but the model was resource-intensive. Appropriately tailored PrEP delivery may be required to meet the needs of this and other key populations who experience barriers to accessing mainstream services.

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TL;DR: In this article, the trends of non-communicable diseases (NCDs) and death among people living with HIV (PLWH) and uninfected controls in South Korea were compared, and adjusted incidence rate ratios for outcomes across ages, calendar years and times after HIV diagnosis were calculated.
Abstract: OBJECTIVES We aim to compare the trends of non-communicable diseases (NCDs) and death among people living with HIV (PLWH) and uninfected controls in South Korea. METHODS We identified PLWH from a nationwide database of all Korean citizens enrolled from 1 January 2004 to 31 December 2016. A control cohort was randomly selected for PLWH by frequency matching for age and sex in a 20:1 ratio. To compare NCD trends between the groups, adjusted incidence rate ratios for outcomes across ages, calendar years and times after HIV diagnosis were calculated. RESULTS We included 14 134 PLWH and 282 039 controls in this study; 58.5% of PLWH and 36.4% of the controls were diagnosed with at least one NCD. The incidence rates of cancers, chronic kidney disease, depression, osteoporosis, diabetes and dyslipidaemia were higher in PLWH than in the controls, whereas those of cardiovascular disease, heart failure, ischaemic stroke and hypertension were lower in PLWH. Relative risks (RRs) for NCDs in PLWH were higher than controls in younger age groups. Trends in the RRs of NCDs tended to increase with the calendar year for PLWH vs. controls and either stabilized or decreased with time after HIV diagnosis. The RR of death from PLWH has decreased with the calendar year, but showed a tendency to rise again after 2014 and was significant at the early stage of HIV diagnosis. CONCLUSIONS Although the RR of each NCD in PLWH showed variable trends compared with that in controls, NCDs in PLWH have been increasingly prevalent.

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TL;DR: This study investigated the prevalence of respiratory symptoms and CB in PWH and HIV‐negative people in the Pharmacokinetic and clinical Observations in PeoPle over fiftY (POPPY) study.
Abstract: Objectives High rates of respiratory symptoms and chronic bronchitis (CB) are reported in people with HIV infection (PWH). We investigated the prevalence of respiratory symptoms and CB in PWH and HIV‐negative people in the Pharmacokinetic and clinical Observations in PeoPle over fiftY (POPPY) study. Methods Assessment of respiratory symptoms and CB was undertaken using the modified form of the St. George’s Respiratory Questionnaire for chronic obstructive pulmonary disease (COPD). Univariate (χ2 tests, Mann–Whitney U tests and Spearman’s rank correlation) and multivariable (linear and logistic regression) analyses were performed to consider associations of respiratory symptoms with demographic, lifestyle and HIV‐related parameters, and with depressive symptoms and quality of life. Results Among the 619 participants, respiratory Symptom scores were higher in older and younger PWH compared to older HIV‐negative people, with median (interquartile range) scores of 17.7 (6.2, 39.5), 17.5 (0.9, 30.0) and 9.0 (0.9, 17.5), respectively (P = 0.0001); these differences remained significant after confounder adjustment. Sixty‐three participants (10.2%) met the criteria for CB [44 (14.0%) older PWH, 14 (9.2%) younger PWH, and five (3.3%) older HIV‐negative people; P = 0.002], with these differences also remaining after adjustment for confounding variables, particularly smoking status [older vs. younger PWH: odds ratio (OR) 4.48 (95% confidence interval (CI) 1.64, 12.30); P = 0.004; older PWH vs. HIV‐negative people: OR 4.53 (95% CI 1.12, 18.28); P = 0.03]. Respiratory symptoms and CB were both associated with greater depressive symptom scores and poorer quality of life. No strong associations were reported between CB and immune function, HIV RNA or previous diagnosis of any AIDS event. Conclusions Respiratory symptoms and CB are more common in PWH than in demographically and lifestyle‐similar HIV‐negative people and are associated with poorer mental health and quality of life.

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TL;DR: In this article, the authors investigated the risk of AIDS and mortality after transition from paediatric to adult care in a UK cohort of young people with perinatally acquired HIV, using Kaplan-Meier and Cox regression.
Abstract: Objectives To investigate risk of AIDS and mortality after transition from paediatric to adult care in a UK cohort of young people with perinatally acquired HIV. Methods Records of people aged ≥ 13 years on 31 December 2015 in the UK paediatric HIV cohort (Collaborative HIV Paediatric Study) were linked to those of adults in the UK Collaborative HIV Cohort (CHIC) cohort. We calculated time from transition to a new AIDS event/death, with follow-up censored at the last visit or 31 December 2015, whichever was the earliest. Cumulative incidence of and risk factors for AIDS/mortality were assessed using Kaplan-Meier and Cox regression. Results At the final paediatric visit, the 474 participants [51% female, 80% black, 60% born outside the UK, median (interquartile range) age at antiretroviral therapy (ART) initiation = 9 (5-13) years] had a median age of 18 (17-19) years and CD4 count of 471 (280-663) cell/μL; 89% were prescribed ART and 60% overall had a viral load ≤ 400 copies/mL. Over median follow-up in adult care of 3 (2-6) years, 35 (8%) experienced a new AIDS event (n = 25) or death (n = 14) (incidence = 1.8/100 person-years). In multivariable analyses, lower CD4 count at the last paediatric visit [adjusted hazard ratio = 0.8 (95% confidence interval: 0.7-1.0)/100 cells/μL increment] and AIDS diagnosis in paediatric care [2.7 (1.4-5.5)] were associated with a new AIDS event/mortality in adult care. Conclusions Young people with perinatally acquired HIV transitioning to adult care with markers of disease progression in paediatric care experienced poorer outcomes in adult care. Increased investment in multidisciplinary specialized services is required to support this population at high risk of morbidity and mortality.

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TL;DR: The aim of the study was to investigate the efficacy and safety of first‐line antiretroviral therapy with integrase inhibitor (INI) or protease inhibitor (PI)‐based regimens in patients with low CD4 cell counts and/or an AIDS‐defining disease.
Abstract: OBJECTIVES The aim of the study was to investigate the efficacy and safety of first-line antiretroviral therapy (ART) with integrase inhibitor (INI) or protease inhibitor (PI)-based regimens in patients with low CD4 cell counts and/or an AIDS-defining disease. METHODS We conducted a retrospective, multicentre analysis to investigate discontinuation proportions and virological response in patients with CD4 cell counts < 200 cells/µL and/or AIDS-defining disease when starting first-line ART. Proportions of those discontinuing ART were compared using univariate analysis. Virological response was analysed using the Food & Drug Administration (FDA) snapshot analysis (HIV-1 RNA < 50 HIV-1 RNA copies/mL at week 48). RESULTS Two hundred and eighteen late presenters were included in the study: 13.8% were women and 23.8% were of non-European ethnicity, and the mean baseline CD4 count was 91 cells/µL (standard deviation 112 cells/µL). A total of 131 late presenters started on INI- and 87 on PI-based treatment. It was found that 86.1% of patients treated with INIs and 81.1% of patients treated with PIs had a viral load < 50 copies/mL at week 48; proportions of discontinuation because of adverse events were 6.1% in the INI group and 11.5% in the PI group. No significant differences in discontinuation proportions were observed at week 12 or 48 between INI- and PI-based regimens (P = 0.76 and 0.52, respectively). Virological response was equally good in those receiving INIs and those receiving PIs (86.1% vs. 81.1%, respectively; P = 0.36). CONCLUSIONS In a European cohort of late presenters starting first-line INI or PI-based ART regimens, there were no significant differences in discontinuation proportions or virological response at week 48.