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Background Predicting cause-specific mortality among people with HIV (PWH) could facilitate targeted care to improve survival. We assessed discrimination of the Veterans Aging Cohort Study (VACS) Index 2.0 in predicting cause-specific mortality among PWH on antiretroviral therapy (ART). Methods Using Antiretroviral Therapy Cohort Collaboration data for PWH who initiated ART between 2000 and 2018, VACS Index 2.0 scores (higher scores indicate worse prognosis) were calculated around a randomly selected visit date at least 1 year after ART initiation. Missingness in VACS Index 2.0 variables was addressed through multiple imputation. Cox models estimated associations between VACS Index 2.0 and causes of death, with discrimination evaluated using Harrell's C-statistic. Absolute mortality risk was modelled using flexible parametric survival models. Results Of 59 741 PWH (mean age: 43 years; 80% male), the mean VACS Index 2.0 at baseline was 41 (range: 0–129). For 2425 deaths over 168 162 person-years follow-up (median: 2.6 years/person), AIDS (n = 455) and non–AIDS-defining cancers (n = 452) were the most common causes. Predicted 5-year mortality for PWH with a mean VACS Index 2.0 score of 38 at baseline was 1% and approximately doubled for every 10-unit increase. The 5-year all-cause mortality C-statistic was.83. Discrimination with the VACS Index 2.0 was highest for deaths resulting from AIDS (0.91), liver-related (0.91), respiratory-related (0.89), non-AIDS infections (0.87), and non–AIDS-defining cancers (0.83), and lowest for suicides/accidental deaths (0.65). Conclusions For deaths among PWH, discrimination with the VACS Index 2.0 was highest for deaths with measurable physiological causes and was lowest for suicide/accidental deaths. [ABSTRACT FROM AUTHOR]

The article discusses the use of lenacapavir, an HIV capsid inhibitor, in preventing mother-to-child HIV transmission in a 31-year-old woman with poor adherence to oral antiretroviral therapy during pregnancy. Despite initial success, the patient developed resistance to lenacapavir due to non-adherence, highlighting the importance of strict treatment adherence. The study demonstrates transplacental transfer of lenacapavir without toxicity to the newborn, suggesting its potential as a long-acting treatment option for pregnant women with poor adherence to oral ART. Further research is needed to assess the safety and efficacy of lenacapavir in pregnant and lactating individuals. [Extracted from the article]

We evaluated people living with Human Immunodeficiency Virus' (PLWH) quality of life (QoL) and assessed whether their demographic, disease-related, socioeconomic, or behavioral characteristics were associated with poorer QoL. ANRS CO3 AQUIVIH-NA cohort participants (Nouvelle Acquitaine, France) were recruited to a cross-sectional study (2018–2020) and their QoL assessed (WHOQOL-BREF). We calculated median (Q1, Q3) QoL domain scores and assessed factors associated with poorer median QoL using bivariable and multivariable quartile regression. Of the 965 PLWH included, 98.4% were on antiretroviral therapy, 94.7% were virally-suppressed, 63.5% reported good/very good QoL. Median scores (0–100) were highest for physical (69;Q1, Q3: 56, 81) and environmental (69; 56, 75) QoL and lowest for social (56; 44, 69) and psychological (56; 44, 69) QoL. PLWH with ≥ 3 comorbidities, HIV-related stigma, or income of < 1500€/month had poorer median adjusted physical, psychological, social, and environmental QoL scores compared to reference groups. While more than half of PLWH reported good/very good QoL, we have not achieved good QoL in 90% of PLWH. Multi-morbidity, HIV-related stigma, and social determinants were consistently and independently associated with poorer QoL. Addressing structural factors in addition to those indirectly related to HIV is required to attain good QoL in all PLWH. [ABSTRACT FROM AUTHOR]

We evaluated people living with Human Immunodeficiency Virus' (PLWH) quality of life (QoL) and assessed whether their demographic, disease-related, socioeconomic, or behavioral characteristics were associated with poorer QoL. ANRS CO3 AQUIVIH-NA cohort participants (Nouvelle Aquitaine, France) were recruited to a cross-sectional study (2018–2020) and their QoL assessed (WHOQOL-BREF). We calculated median (Q1, Q3) QoL domain scores and assessed factors associated with poorer median QoL using bivariable and multivariable quartile regression. Of the 965 PLWH included, 98.4% were on antiretroviral therapy, 94.7% were virally-suppressed, 63.5% reported good/very good QoL. Median scores (0–100) were highest for physical (69;Q1, Q3: 56, 81) and environmental (69; 56, 75) QoL and lowest for social (56; 44, 69) and psychological (56; 44, 69) QoL. PLWH with ≥ 3 comorbidities, HIV-related stigma, or income of < 1500€/month had poorer median adjusted physical, psychological, social, and environmental QoL scores compared to reference groups. While more than half of PLWH reported good/very good QoL, we have not achieved good QoL in 90% of PLWH. Multi-morbidity, HIV-related stigma, and social determinants were consistently and independently associated with poorer QoL. Addressing structural factors in addition to those indirectly related to HIV is required to attain good QoL in all PLWH. [ABSTRACT FROM AUTHOR]

Background: To evaluate drug use (alcohol, tobacco, cannabis and other drugs) and its association with mean CD4/CD8 T cell count ratio, a marker of chronic inflammation, in virally suppressed people living with HIV-1 (PLWH) in Nouvelle Aquitaine, France. Methods: A multi-centric, cross-sectional analysis was conducted in 2018–19 in the QuAliV study—ANRS CO3 AQUIVIH-NA cohort. Tobacco, alcohol, cannabis, and other drug use (poppers, cocaine, amphetamines, synthetic cathinones, GHB/GBL) were self-reported. CD4 and CD8 T cell counts and viral load measures, ± 2 years of self-report, and other characteristics were abstracted from medical records. Univariable and multivariable linear regression models, adjusted for age, sex, HIV risk group, time since HIV diagnosis, and other drug use were fit for each drug and most recent CD4/CD8 ratio. Results: 660 PLWH, aged 54.7 ± 11.2, were included. 47.7% [315/660] had a CD4/CD8 ratio of < 1. Their mean CD4/CD8 ratio was 1.1 ± 0.6. 35% smoked; ~ 40% were considered to be hazardous drinkers or have alcohol use disorder; 19.9% used cannabis and 11.9% other drugs. Chemsex-associated drug users' CD4/CD8 ratio was on average 0.226 (95% confidence interval [95% CI] − 0.383, − 0.070) lower than that of non-users in univariable analysis (p = 0.005) and 0.165 lower [95% CI − 0.343, 0.012] in multivariable analysis (p = 0.068). Conclusions: Mean differences in CD4/CD8 ratio were not significantly different in tobacco, alcohol and cannabis users compared to non-users. However, Chemsex-associated drug users may represent a population at risk of chronic inflammation, the specific determinants of which merit further investigation. Trial registration number: NCT03296202. [ABSTRACT FROM AUTHOR]

Background: Dexamethasone and tocilizumab are used to treat severely ill COVID-19 patients admitted to intensive care units (ICUs). We explored whether combination therapy increased the risk of superinfection compared to dexamethasone alone. Methods: This observational, retrospective study included critically ill COVID-19 adult patients admitted to our ICU because of respiratory failure. Patients received dexamethasone with (Group 1) or without (Group 2) tocilizumab. Data were collected from electronic medical files. Results: A total of 246 patients were included, of whom 150 received dexamethasone and tocilizumab, while 96 received dexamethasone alone. Acute respiratory distress syndrome was evident on admission in 226 patients, 56 of whom required mechanical ventilation (MV). Superinfections, mainly respiratory, were diagnosed in 59 patients, including 34/150 (23%) in Group 1 and 25/96 (26%) in Group 2 (p = 0.32). After multivariate analysis, the factors associated with a higher risk of superinfection included hematological malignancy (hazard ratio (HR): 2.47 (1.11–5.47), p = 0.03), MV (HR: 3.74 (1.92–7.26), p = 0.0001), and a higher SAPS-II score on admission (HR: 1.03 (1.01–1.06), p = 0.006). Conclusion: In critically ill COVID-19 patients, the addition of tocilizumab to dexamethasone was not associated with an increased risk of superinfection. [ABSTRACT FROM AUTHOR]

Background: Combination therapy with hydroxychloroquine and darunavir/ritonavir or lopinavir/ritonavir has been suggested as an approach to improve the outcome of patients with moderate/severe COVID-19 infection.Objectives: To examine the safety of combination therapy with hydroxychloroquine and darunavir/ritonavir or lopinavir/ritonavir.Methods: This was an observational cohort study of patients hospitalized for COVID-19 pneumonia treated with hydroxychloroquine and darunavir/ritonavir or lopinavir/ritonavir. Clinical evaluations, electrocardiograms and the pharmacokinetics of hydroxychloroquine, darunavir and lopinavir were examined according to clinical practice and guidelines.Results: Twenty-one patients received hydroxychloroquine with lopinavir/ritonavir (median age 68 years; 10 males) and 25 received hydroxychloroquine with darunavir/ritonavir (median age 71 years; 15 males). During treatment, eight patients (17.4%) developed ECG abnormalities. Ten patients discontinued treatment, including seven for ECG abnormalities a median of 5 (range 2-6) days after starting treatment. All ECG abnormalities reversed 1-2 days after interrupting treatment. Four patients died within 14 days. ECG abnormalities were significantly associated with age over 70 years, coexisting conditions (such as hypertension, chronic cardiovascular disease and kidney failure) and initial potential drug interactions, but not with the hydroxychloroquine concentration.Conclusions: Of the patients with COVID-19 who received hydroxychloroquine with lopinavir or darunavir, 17% had ECG abnormalities, mainly related to age or in those with a history of cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background: Antiretroviral therapy has prolonged the lives of those with human immunodeficiency virus (HIV), but the effects of chronic infection on their health-related quality of life (HRQoL) remain a concern. Numerous instruments have been developed to measure HRQoL, yet evidence of their cross-cultural equivalence and continued applicability is limited. We adapted the WHOQOL-HIV BREF to French and assessed its psychometric properties in a sample of community-dwelling adults living with HIV who were mostly virally suppressed.Methods: We conducted a cross-sectional study within the ANRS CO3 Aquitaine cohort from July 2018 to May 2019. Five hundred eighty-six participants were consecutively enrolled at their HIV-consultations and completed either a web-based (n = 406) or paper self-administered assessment (n = 180). The means and standard deviations for items and domains were computed and the presence of floor and ceiling effects assessed. We evaluated internal consistency by calculating Cronbach's alpha coefficients per domain. We assessed construct validity by performing a Confirmatory Factor Analysis (CFA). Concurrent, convergent and discriminant validity were assessed with Pearson's correlations and known-group validity was assessed according to CD4 cell count, viral load, Centers for Disease Control and Prevention clinical categories for HIV, and hospitalization of more than 48 h within 2 years of the most recent consultation using one-way analysis of variance and independent t-tests.Results: Five hundred eighty-six PLWH were included in this analysis. Their median age was 55; 73% were male; 85% were of French descent; 99% were on ART and 93% were virally suppressed. We found floor effects for one and ceiling effects for 11 items. Four of the six domains showed good internal consistency (α range: 0.63-0.79). CFA showed that the WHOQOL-HIV BREF's six-domain structure produced an acceptable fit (SRMR = 0.059; CFI = 0.834; RMSEA = 0.07; 90% CI: 0.06-0.08). It showed good concurrent, convergent and discriminant validity. There was some evidence of known-group validity. The personal beliefs domain had the highest score (15.04 ± 3.35) and the psychological health domain had the lowest (13.70 ± 2.78).Conclusions: The French WHOQOL-HIV BREF has acceptable measurement properties. Its broad conceptualisation of HRQoL, going beyond physical and mental health, may be of particular value in our older, treatment-experienced and virally suppressed population.Trial Registration: ClinicalTrials.gov NCT03296202 (Archived by WebCite at http://www.webcitation.org/6zgOBArps ). [ABSTRACT FROM AUTHOR]

We evaluated an elvitegravir–cobicistat–emtricitabine–tenofovir alafenamide single-tablet regimen for human immunodeficiency virus postexposure prophylaxis. The completion rate and adherence were good, and the tolerance was acceptable; no seroconversion was observed. We confirm that this regimen could be appropriate for postexposure prophylaxis. Clinical Trials Registration NCT02998320. [ABSTRACT FROM AUTHOR]

The article presents case series of acute primary HIV infection patient to demonstrate high decay of blood HIV reservoir after administration of tenofovir/emtricitabine/elvitegravir/cobicistat. It states that efficacy of integrase strand transfer inhibitor (INSTI) is affected by natural polymorphism of the integrase gene varies and minor mutations.

Objective: To describe trends and determinants of severe morbidity in HIV-infected women and men. Design: A French prospective cohort of HIV-infected patients of both sexes and all transmission categories. Methods: We used hospital admission data from January 2000 to December 2008. A severe morbid event (SME) was defined as a clinical event requiring hospitalization for ≥48 h, several events could be reported during hospitalization. Yearly incidence rates of SME were estimated and compared using Generalized Estimating Equations. Results: Among 4,987 patients (27% women), followed for a median of 8.7 years, 1,473 (30%) were hospitalized (3,049 hospitalizations for 5,963 SME). The yearly incidence rate of hospitalization decreased in men, from 155 in 2000 to 80/1,000 person-years (PY) in 2008 and in women, from 125 to 71/1,000 PY, (p<0.001). This trend was observed for all SME except for hepatic events, stable in men (15 to 13/1,000 PY) and increasing in women (2.5 to 11.5), cardiovascular events increasing in men (6 to 10/1,000 PY) and in women (6 to 14) and non-AIDS non-hepatic malignancies increasing in men (4 to 7/1,000 PY) and stable in women (2.5). Intraveneous drug users, age >50 years, HIV RNA >10,000 copies, CD4 <500/mm3, AIDS stage, hepatitis C co-infection and cardiovascular risk factors (diabetes, high blood pressure, and tobacco use) were associated with SME. Conclusions: HIV-infected individuals in care in France require less and less frequently hospitalization. Women are now presenting with severe hepatic and cardio-vascular events. Disparities in SME between men and women are primarily explained by different exposure patterns to risk factors. Women should be targeted to benefit cardiovascular prevention policies as well as men. [ABSTRACT FROM AUTHOR]

Background In high-income settings, the spectrum of morbidity and mortality experienced by Human Immunodeficiency Virus (HIV)-infected individuals receiving combination antiretroviral therapy (cART) has switched from predominantly AIDS-related to non-AIDS-related conditions. In the context of universal access to care, we evaluated whether that shift would apply in Brazil, a middle-income country with universal access to treatment, as compared to France. Methods Two hospital-based cohorts of HIV-infected individuals were used for this analysis: the ANRS CO3 Acquitaine Cohort in South Western France and the Evandro Chagas Research Institute (IPEC) Cohort of the Oswaldo Cruz Foundation in Rio de Janeiro, Brazil. Severe morbid events (AIDS- and non-AIDS-related) were defined as all clinical diagnoses associated with a hospitalization of ≥48 hours. Trends in the incidence rate of events and their determinants were estimated while adjusting for within-subject correlation using generalized estimating equations models with an auto-regressive correlation structure and robust standard errors. Result Between January 2000 and December 2008, 7812 adult patients were followed for a total of 41,668 person-years (PY) of follow-up. Throughout the study period, 90% of the patients were treated with cART. The annual incidence rate of AIDS and non-AIDS events, and of deaths significantly decreased over the years, from 6.2, 21.1, and 1.9 AIDS, non-AIDS events, and deaths per 100 PY in 2000 to 4.3, 14.9, and 1.5/100 PY in 2008. The annual incidence rates of non-AIDS events surpassed that of AIDS-events during the entire study period. High CD4 cell counts were associated with a lower incidence rate of AIDS and non- AIDS events as well as with lower rates of specific non-AIDS events, such as bacterial, hepatic, viral, neurological, and cardiovascular conditions. Adjusted analysis showed that severe morbidity was associated with lower CD4 counts and higher plasma HIV RNAs but not with setting (IPEC versus Acquitaine). Conclusions As information on severe morbidities for HIV-infected patients remain scarce, data on hospitalizations are valuable to identify priorities for case management and to improve the quality of life of patients with a chronic disease requiring life-long treatment. Immune restoration is highly effective in reducing AIDS and non-AIDS severe morbid events irrespective of the setting. [ABSTRACT FROM AUTHOR]

Background: Transient elastography (TE) is widely used for non-invasive assessment of liver fibrosis in HIV-HCV co-infected patients. TE, however, cannot determine liver morphology. Acoustic radiation force impulse (ARFI) imaging is a novel procedure enabling assessment of liver fibrosis during a conventional ultrasonographic examination. This study evaluated the correlation between liver fibrosis measurements by TE and ARFI. Methods: Each of 46 HIV-HCV patients underwent both ARFI and TE within 6 months. Patients were evaluated by the “equivalent METAVIR” scoring system, using previously established cut-off values. Agreements between the ARFI and TE scores were estimated by Kappa coefficients, with Kappa values ≥0.40, ≥0.60, and ≥0.80 defined as moderate, good and very good agreement, respectively. Results: ARFI and TE yielded "Equivalent Metavir" fibrosis scores of F1 in 26 and 31 patients, respectively; F2 in nine and seven, respectively; F3 in three and two, respectively; and F4 in eight and six, respectively. The two methods showed very good agreement in predicting overall stages [Kappa = 0.82] and for F ≥3 [Kappa = 0.80] and moderate agreement in predicting significant fibrosis F ≥2 [Kappa = 0.50]. Morphologic ultrasound analysis concomitant to ARFI detected two hepatocarcinomas. Conclusions: ARFI showed promising results in the non-invasive assessment of liver fibrosis in HIV-HCV patients, with liver fibrosis staging similar to that of TE. Moreover, ARFI can assess morphology and fibrosis during the same session. [ABSTRACT FROM AUTHOR]

We evaluated the impact of cytomegalovirus (CMV)–induced immune responses, autoimmune-induced immune responses, and microbial translocation on immune activation in 191 human immunodeficiency virus type 1–infected patients from the ANRS CO3 Aquitaine Cohort. All enrolled subjects had achieved long-term virological suppression during receipt of combination antiretroviral therapy (cART). HLA-DR+/CD38+ expression was 16.8% among CD8+ T cells. Independent of age, CD4+ T-cell count, 16S ribosomal DNA load, and regulatory T-cell count, positive results of Quantiferon CMV analysis (P = .02), positive results of CMV-pp65 enzyme-linked immunosorbent spot analysis (P = .01), positive results of CMV-pp65–specific CD8+ T-cell analysis (P = .05), and CMV seropositivity (P = .01) were associated with a higher percentage of CD8+ T cells that expressed HLA-DR+/CD38+. Autoimmune response and microbial translocation were not associated with immune activation. Therefore, the CMV-induced immune response seems to be associated with chronic immune activation in cART recipients with sustained virological suppression. [ABSTRACT FROM AUTHOR]

We proposed a new HIV-1 therapeutic vaccine based on conserved cytotoxic T lymphocyte (CTL) epitopes of archived HIV-1 DNA according to their affinity to the dominant HLA-A and -B alleles of the population investigated. Our proposal (Hla Fitted VAC, HFVAC) was composed of 15 peptides originating from the RT, gag and nef parts of proviral DNA. Our aim was to investigate baseline immune reactivity to the vaccine in HIV-1 chronically infected patients at success of antiretroviral therapy (ART) who would be eligible for a therapeutic vaccine. Forty-one patients were tested. Most of them had been infected with HIV-1 subtype B and all had been receiving successful ART for 2 to 20 years. The predominant HLA-A and -B alleles were those of a Caucasian population. ELISPOT was carried out using the HFVAC peptides. In 22 patients, the PD-1 marker was investigated on CD4+ and CD8+ T cells by flow cytometry in order to evaluate global T cell exhaustion. ELISPOT positivity was 65% overall and 69% in patients exhibiting at least one HLA allele fitting with HFVAC. The percentages of CD4+ and CD8+ T cells expressing PD-1 were high (median values 23.70 and 32.60, respectively), but did not seem to be associated with an impairment of the immune response investigated in vitro. In conclusion, reactivity to HFVAC was high in this ART-treated population with dominant HLA alleles, despite potential cellular exhaustion associated with the PD-1 marker. [ABSTRACT FROM AUTHOR]

Background: In high-income settings, the spectrum of morbidity and mortality experienced by Human Immunodeficiency Virus (HIV)-infected individuals receiving combination antiretroviral therapy (cART) has switched from predominantly AIDS-related to non-AIDS-related conditions. In the context of universal access to care, we evaluated whether that shift would apply in Brazil, a middle-income country with universal access to treatment, as compared to France.Methods: Two hospital-based cohorts of HIV-infected individuals were used for this analysis: the ANRS CO3 Aquitaine Cohort in South Western France and the Evandro Chagas Research Institute (IPEC) Cohort of the Oswaldo Cruz Foundation in Rio de Janeiro, Brazil. Severe morbid events (AIDS- and non-AIDS-related) were defined as all clinical diagnoses associated with a hospitalization of ≥48 hours. Trends in the incidence rate of events and their determinants were estimated while adjusting for within-subject correlation using generalized estimating equations models with an auto-regressive correlation structure and robust standard errors.Result: Between January 2000 and December 2008, 7812 adult patients were followed for a total of 41,668 person-years (PY) of follow-up. Throughout the study period, 90% of the patients were treated with cART. The annual incidence rate of AIDS and non-AIDS events, and of deaths significantly decreased over the years, from 6.2, 21.1, and 1.9 AIDS, non-AIDS events, and deaths per 100 PY in 2000 to 4.3, 14.9, and 1.5/100 PY in 2008. The annual incidence rates of non-AIDS events surpassed that of AIDS-events during the entire study period. High CD4 cell counts were associated with a lower incidence rate of AIDS and non-AIDS events as well as with lower rates of specific non-AIDS events, such as bacterial, hepatic, viral, neurological, and cardiovascular conditions. Adjusted analysis showed that severe morbidity was associated with lower CD4 counts and higher plasma HIV RNAs but not with setting (IPEC versus Aquitaine).Conclusions: As information on severe morbidities for HIV-infected patients remain scarce, data on hospitalizations are valuable to identify priorities for case management and to improve the quality of life of patients with a chronic disease requiring life-long treatment. Immune restoration is highly effective in reducing AIDS and non-AIDS severe morbid events irrespective of the setting. [ABSTRACT FROM AUTHOR]