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Background Mortality among people with human immunodeficiency virus (HIV) declined with the introduction of combination antiretroviral therapy. We investigated trends in mortality in people with HIV from 1999 through 2020. Methods Data were collected from the Data Collection on Adverse events of Anti-HIV Drugs (D:A:D) cohort between January 1999 through January 2015 and the International Cohort Consortium of Infectious Disease (RESPOND) from October 2017 through December 2020. Age-standardized all-cause and cause-specific mortality rates, classified using Coding Causes of Death in HIV, were calculated. Poisson models were used to assess mortality over time. Results Among 55 716 participants followed for median 6 years (interquartile range, 3–11), 5263 died (mortality rate [MR], 13.7/1000 person-years of follow-up [PYFU]; 95% confidence interval [CI], 13.4–14.1). Changing mortality was observed: AIDS mortality was most common between 1999–2009 (n = 952; MR, 4.2/1000 PYFU; 95% CI, 4.0–4.5) and non-AIDS–defining malignancy (NADM) between 2010–2020 (n = 444; MR, 2.8/1000 PYFU; 95% CI, 2.5–3.1). In multivariable analysis, all-cause mortality declined (adjusted mortality rate ratio [aMRR], 0.97 per year; 95% CI,.96–.98), mostly 1999–2010 (aMRR, 0.96 per year; 95% CI,.95–.97) but was stable 2011–2020 (aMRR, 1.00 per year; 95% CI,.96–1.05). Mortality due to all known causes except NADM also declined. Conclusions Mortality among people with HIV in the D:A:D and/or RESPOND cohorts declined between 1999–2009 and was stable over the period 2010–2020. This decline in mortality was not fully explained by improvements in immunologic–virologic status or other risk factors. [ABSTRACT FROM AUTHOR]

BackgroundWe compared Kaposi sarcoma (KS) risk in adults who started antiretroviral therapy (ART) across the Asia-Pacific, South Africa, Europe, Latin, and North America.MethodsWe included cohort data of human immunodeficiency virus (HIV)-positive adults who started ART after 1995 within the framework of 2 large collaborations of observational HIV cohorts. We present incidence rates and adjusted hazard ratios (aHRs).ResultsWe included 208140 patients from 57 countries. Over a period of 1066572 person-years, 2046 KS cases were diagnosed. KS incidence rates per 100000 person-years were 52 in the Asia-Pacific and ranged between 180 and 280 in the other regions. KS risk was 5 times higher in South African women (aHR, 4.56; 95% confidence intervals [CI], 2.73-7.62) than in their European counterparts, and 2 times higher in South African men (2.21; 1.34-3.63). In Europe, Latin, and North America KS risk was 6 times higher in men who have sex with men (aHR, 5.95; 95% CI, 5.09-6.96) than in women. Comparing patients with current CD4 cell counts ≥700 cells/µL with those whose counts were

Background: Expanding statin use may help to alleviate the excess burden of atherosclerotic cardiovascular disease in people iving with HIV (PLHIV). Pravastatin and pitavastatin are preferred agents due to their lack of substantial interaction with antiretroviral therapy. We aimed to evaluate the cost-effectiveness of pravastatin and pitavastatin for the primary prevention of atherosclerotic cardiovascular disease among PLHIV in the United States. Methods: We developed a microsimulation model that randomly selected (with replacement) individuals from the Data-collection on Adverse Effects of Anti-HIV Drugs study with follow-up between 2013 and 2016. Our study population was PLHIV aged 40 to 75 years, stable on antiretroviral therapy and not currently using lipid-lowering therapy. Direct medical costs and quality-adjusted life-years (QALYs) were assigned in annual cycles and discounted at 3% per year. We assumed a willingness-to-pay threshold of $100,000/QALY gained. The interventions assessed were as follows: (1) treating no one with statins; (2) treating everyone with generic pravastatin 40 mg/day (drug cost $236/year) and (3) treating everyone with branded pitavastatin 4 mg/day (drug cost $2,828/year). The model simulated each individual's probability of experiencing atherosclerotic cardiovascular disease over 20 years. Results: Persons receiving pravastatin accrued 0.024 additional QALYs compared with those not receiving a statin, at an incremental cost of $1338, giving an incremental cost-effectiveness ratio of $56,000/QALY gained. Individuals receiving pitavastatin accumulated 0.013 additional QALYs compared with those using pravastatin, at an additional cost of $18,251, giving an incremental cost-effectiveness ratio of $1,444,000/QALY gained. These findings were most sensitive to the pill burden associated with daily statin administration, statin costs, statin efficacy and baseline atherosclerotic cardiovascular disease risk. In probabilistic sensitivity analysis, no statin was optimal in 5.2% of simulations, pravastatin was optimal in 94.8% of simulations and pitavastatin was never optimal. Conclusions: Pravastatin was projected to be cost-effective compared with no statin. With substantial price reduction, pitavastatin may be cost-effective compared with pravastatin. These findings bode well for the expanded use of statins among PLHIV in the United States. To gain greater confidence in our conclusions it is important to generate strong, HIV-specific estimates on the efficacy of statins and the quality-of-life burden associated with taking an additional daily pill. Keywords: HIV; cardiovascular disease; statin; cost-effectiveness; United States; antiretroviral therapy Received 4 September 2020; Accepted 23 February 2021, 1 | INTRODUCTION People living with HIV (PLHIV) have an elevated risk of atherosclerotic cardiovascular disease (ASCVD) compared to people without HIV [1]. This is only partially explained by the [...]

BackgroundWhen a clinical treatment fails or shows suboptimal results, the question of when to switch to another treatment arises. Treatment switching strategies are often dynamic because the time of switching depends on the evolution of an individual's time-varying covariates. Dynamic strategies can be directly compared in randomized trials. For example, HIV-infected individuals receiving antiretroviral therapy could be randomized to switching therapy within 90 days of HIV-1 RNA crossing above a threshold of either 400 copies/ml (tight-control strategy) or 1000 copies/ml (loose-control strategy).MethodsWe review an approach to emulate a randomized trial of dynamic switching strategies using observational data from the Antiretroviral Therapy Cohort Collaboration, the Centers for AIDS Research Network of Integrated Clinical Systems and the HIV-CAUSAL Collaboration. We estimated the comparative effect of tight-control vs. loose-control strategies on death and AIDS or death via inverse-probability weighting.ResultsOf 43 803 individuals who initiated an eligible antiretroviral therapy regimen in 2002 or later, 2001 met the baseline inclusion criteria for the mortality analysis and 1641 for the AIDS or death analysis. There were 21 deaths and 33 AIDS or death events in the tight-control group, and 28 deaths and 41 AIDS or death events in the loose-control group. Compared with tight control, the adjusted hazard ratios (95% confidence interval) for loose control were 1.10 (0.73, 1.66) for death, and 1.04 (0.86, 1.27) for AIDS or death.ConclusionsAlthough our effective sample sizes were small and our estimates imprecise, the described methodological approach can serve as an example for future analyses.

: Introduction: Randomized trials and observational studies have consistently reported rates of sustained virological response (SVR), equivalent to hepatitis C virus (HCV) cure, as high as 95% following treatment with direct‐acting antiviral (DAA) treatment in individuals with HIV and HCV co‐infection. However, large studies assessing whether SVR rates differ according to demographic and clinical strata are lacking. Additionally, the SVR rates reported in the literature were typically computed in non‐random samples of individuals with available post‐DAA HCV‐RNA measures. Here, we aimed to estimate the probability of SVR after DAA treatment initiation in persons with HIV and HCV co‐infection overall and by demographic and clinical characteristics with and without adjustment for missing HCV‐RNA testing. Methods: We included adults with HIV‐HCV co‐infection who received DAA treatment between 2014 and 2020 in HepCAUSAL, an international collaboration of cohorts from Europe and North America. We estimated the proportions of DAA recipients who had documented SVR (defined as an undetectable HCV‐RNA at least 12 weeks after the end of DAA treatment) overall and by strata defined by age, sex, presence of cirrhosis, calendar period, mode of HIV acquisition, CD4 cell count and HCV genotype at DAA treatment. We then compared these rates with those obtained using the parametric g‐formula to impute SVR status for individuals with no SVR assessment. Results and Discussion: A total of 4527 individuals who initiated DAA treatment (88% males, median [IQR] age 56 [50, 62] years) were included. Of the total of 642 (14%) individuals had no HCV‐RNA test on or after 12 weeks after the end of treatment. The overall observed and g‐formula imputed SVR rates were 93% (95% CI 93, 94) and 94% (95% CI 92, 95), respectively. SVR estimates were similarly high across all strata. A substantial proportion of individuals who received DAA treatment were never assessed for SVR post‐DAA and strategies for more systematic routine HCV‐RNA testing should be considered. Conclusions: Our estimates with and without adjustment for missing HCV‐RNA testing indicate SVR rates of approximately 95%, like those reported in clinical trials., INTRODUCTION Direct‐acting antiviral (DAA) treatment has revolutionized the treatment of hepatitis C virus (HCV) infection. The availability of DAAs is especially important for persons with HIV because HCV co‐infection, which [...]

Objectives To assess the effectiveness of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) among people poorly represented in clinical trials and potentially at higher risk of suboptimal response to ART. Methods Observational cohort study on persons with HIV (PWH) enrolled in ICONA who started BIC/FTC/TAF as initial therapy or as switching regimen while virologically suppressed. Primary endpoint was time to treatment failure (TF): new AIDS/death or virological failure (VF) or discontinuation for toxicity/failure. Secondary endpoints were time to treatment discontinuation for toxicity (TDT) and to VF. Groups of interest were those aged >50 years, female sex, and advanced HIV disease at first ART start. Probability of the events overall and according to groups and adjusted HR for every endpoint were calculated by Kaplan–Meier curves and Cox regression models. Results Nine hundred and thirty-three ART-naive and 1655 ART-experienced PWH initiated BIC/FTC/TAF. Over a median follow-up of 69.8 weeks, 89 (9.6%) PWH at their first regimen experienced TF. PWH aged >50 years had 1.83-fold (95% CI: 1.19–2.83) higher risk of TF; PWH with advanced HIV disease had 2.21-fold (95% CI: 1.53–3.82) higher risk; there were no differences in TF according to sex. Over a median follow-up of 146.3 weeks, 109 (6.6%) out of 1655 switching PWH experienced TF; no differences were found in the risk of TF, TDT and VF according to groups of interest. Conclusions Overall, BIC/FTC/TAF is well tolerated and virologically effective in the real-world scenario for ART-naive and -experienced PWH. Older ART-naive PWH and those with advanced HIV disease may respond less well as the burden of diseases might compromise treatment efficacy. [ABSTRACT FROM AUTHOR]

Background While use of some older antiretroviral drugs (ARVs) is associated with chronic liver enzyme elevation (cLEE), the impact of newer ARVs remains unknown. Methods People with HIV enrolled in the RESPOND cohort who started an ARV after January 1, 2012 were included (baseline). The primary outcome was first cLEE individuals were censored at first of cLEE, last visit, death, or December 31, 2021. Incidence rates (IRs; events/1000 person-years) were calculated for each ARV overall and by ARV exposure (6–12 months, 1–2 years, and 2+ years). Poisson regression was used to estimate the incidence rate ratio (IRR) of cLEE and its association with individual ARVs and ARV class. Results Of 17 106 individuals included contributing 87 924 person-years of follow-up, 1932 (11.3%) experienced cLEE (incidence rate [IR], 22.0; 95% CI, 21.0–23.0). There was no evidence of a cumulative ARV effect on cLEE incidence, (6–12 months: IR, 45.8; 95% CI, 41.4–50.19; 1–2 years: IR, 34.3; 95% CI, 31.5–37.4; and 2+ years: IR, 18.5; 95% CI, 17.4–19.7). Any use (vs no prior use) of non-nucleoside reverse transcriptase inhibitors (NNRTIs) as a class and tenofovir disoproxil fumarate (TDF) was independently associated with an increased IRR of cLEE, and any use of darunavir (DRV) was associated with a decreased risk of cLEE. Conclusions cLEE is common and more frequent during the first year after initiating new ARVs. With a >5-year median follow-up, we found no short-term liver safety concerns with the use of INSTIs. Use of NNRTIs and TDF was associated with an increased cLEE risk, while DRV was associated with lower risk. [ABSTRACT FROM AUTHOR]

Background Human immunodeficiency virus (HIV) infection leads to chronic immune activation/inflammation that can persist in virally suppressed persons on fully active antiretroviral therapy (ART) and increase risk of malignancies. The prognostic role of low CD4:CD8 ratio and elevated CD8 cell counts on the risk of cancer remains unclear. Methods We investigated the association of CD4:CD8 ratio on the hazard of non-AIDS defining malignancy (NADM), AIDS-defining malignancy (ADM) and most frequent group of cancers in ART-treated people with HIV (PWH) with a CD4 and CD8 cell counts and viral load measurements at baseline. We developed Cox proportional hazard models with adjustment for known confounders of cancer risk and time-dependent cumulative and lagged exposures of CD4:CD8 ratio to account for time-evolving risk factors and avoid reverse causality. Results CD4:CD8 ratios below 0.5, compared to above 1.0, were independently associated with a 12-month time-lagged higher risk of ADM and infection-related malignancies (adjusted hazard ratio 2.61 [95% confidence interval {CI }1.10–6.19] and 2.03 [95% CI 1.24–3.33], respectively). CD4 cell counts below 350 cells/μL were associated with an increased risk of NADMs and ADMs, as did infection, smoking, and body mass index-related malignancies. Conclusions In ART-treated PWH low CD4:CD8 ratios were associated with ADM and infection-related cancers independently from CD4 and CD8 cell counts and may alert clinicians for cancer screening and prevention of NADM. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to study hepatitis D virus (HDV) prevalence and risk of progression to severe liver-related events (SLRE) in HBsAg positive people living with HIV (PLWH) in Italy; role of HDV-RNA copy levels, HCV coinfection and nadir CD4 counts were also investigated. Methods: People living with HIV (PLWH) from Italian Foundation cohort Naïve antiretrovirals (ICONA) with available HBsAg and HDV Ab were enrolled. HBsAg, HDV Ab, HDV-RNA and HDV genotypes were tested. Primary end-point: time from first HDV screening to Severe Liver Related Events (SLRE: decompensated cirrhosis, liver transplantation, HCC). Fine-grey regression models were used to evaluate the association of HDV Ab, HDV-RNA, HDV/HCV coinfection, CD4 nadir and outcome. Secondary end-points: time to SLRE or death; HDV Ab and HDV-RNA prevalence. Results: A total of 152/809 (18.8%) HBsAg positive PLWH showed HDV Ab reactivity; 63/93 (67.7%) were HDV-RNA positive. Being male, persons who inject drugs (PWID), HCV Ab positive, with FIB-4 > 3.25 were independent factors of HDV Ab positivity. In a median follow-up of 5 years, 37 PLWH (4.1% at 5-year) developed SLRE and 97 (12.0%) reached the SLRE or death end-point. HDV-RNA positive (independently from HDV-RNA copy level) PLWH had a 4.6-fold (95%CI 2.0--10.5) higher risk of SLRE than HDV negatives. PLWH positive for both HCV Ab and HDV Ab showed the highest independent risk of SLRE (ASHR: 11.9, 95%CI: 4.6--30.9 vs. HCV neg/HDV neg). Nadir CD4 < 200/mL was associated with SLRE (ASHR: 3.9, 95% 1.0--14.5). Conclusions: One-fifth of the HBsAg positive PLWH harbour HDV infection, and are at high risk of progression to advanced liver disease. HCV contributes to worse outcomes. This population needs urgently effective treatments. [ABSTRACT FROM AUTHOR]

Introduction: There is paucity of data related to potential gender differences in the use of interventions to prevent and treat cardiovascular disease (CVD) among HIV-positive individuals. We investigated whether such differences exist in the observational D:A:D cohort study. Methods: Participants were followed from study enrolment until the earliest of death, six months after last visit or February 1, 2015. Initiation of CVD interventions [lipid-lowering drugs (LLDs), angiotensin-converting enzyme inhibitors (ACEIs), anti-hypertensives, invasive cardiovascular procedures (ICPs) were investigated and Poisson regression models calculated whether rates were lower among women than men, adjusting for potential confounders. Results: Women (n = 12,955) were generally at lower CVD risk than men (n = 36,094). Overall, initiation rates of CVD interventions were lower in women than men; LLDs: incidence rate 1.28 [1.21, 1.35] vs. 2.40 [2.34, 2.46]; ACEIs: 0.88 [0.82, 0.93] vs. 1.43 [1.39, 1.48]; anti-hypertensives: 1.40 [1.33, 1.47] vs. 1.72 [1.68, 1.77] and ICPs: 0.08 [0.06, 0.10] vs. 0.30 [0.28, 0.32], and this was also true for most CVD interventions when exclusively considering periods of follow-up for which individuals were at high CVD risk. In fully adjusted models, women were less likely to receive CVD interventions than men (LLDs: relative rate 0.83 [0.78, 0.88]; ACEIs: 0.93 [0.86, 1.01]; ICPs: 0.54 [0.43, 0.68]), except for the receipt of anti-hypertensives (1.17 [1.10, 1.25]). Conclusion: The use of most CVD interventions was lower among women than men. Interventions are needed to ensure that all HIV-positive persons, particularly women, are appropriately monitored for CVD and, if required, receive appropriate CVD interventions. Keywords: Cardiovascular disease; gender; cardiovascular disease interventions; cohort studies; HIV; women; myocardial infarction; stroke, 1 | INTRODUCTION HIV-positive individuals are known to be at increased risk of cardiovascular disease (CVD) compared to the general population [1,2], partly due to an increased prevalence of some [...]