scholarly journals Durability of different initial regimens in HIV-infected patients starting antiretroviral therapy with CD4+ counts 5 log10 copies/mL

2019 ◽  
Vol 74 (9) ◽  
pp. 2732-2741 ◽  
Author(s):  
Nicola Gianotti ◽  
Patrizia Lorenzini ◽  
Alessandro Cozzi-Lepri ◽  
Andrea De Luca ◽  
Giordano Madeddu ◽  
...  

Abstract Objectives Our aim was to investigate the durability of different initial regimens in patients starting ART with CD4+ counts <200 cells/mm3 and HIV-RNA >5 log10 copies/mL. Methods This was a retrospective study of HIV-infected patients prospectively followed in the ICONA cohort. Those who started ART with boosted protease inhibitors (bPIs), NNRTIs or integrase strand transfer inhibitors (InSTIs), with CD4+ <200 cells/mm3 and HIV-RNA >5 log10 copies/mL, were included. The primary endpoint was treatment failure (TF), a composite endpoint defined as virological failure (VF, first of two consecutive HIV-RNA >50 copies/mL after 6 months of treatment), discontinuation of class of the anchor drug or death. Independent associations were investigated by Poisson regression analysis in a model including age, gender, mode of HIV transmission, CDC stage, HCV and HBV co-infection, pre-treatment HIV-RNA, CD4+ count and CD4+/CD8+ ratio, ongoing opportunistic disease, fibrosis FIB-4 index, estimated glomerular filtration rate, haemoglobin, platelets, neutrophils, calendar year of ART initiation, anchor drug class (treatment group) and nucleos(t)ide backbone. Results A total of 1195 patients fulfilled the inclusion criteria: 696 started ART with a bPI, 315 with an InSTI and 184 with an NNRTI. During 2759 person-years of follow up, 642 patients experienced TF. Starting ART with bPIs [adjusted incidence rate ratio (aIRR) (95% CI) 1.62 (1.29–2.03) versus starting with NNRTIs; P < 0.001] and starting ART with InSTIs [aIRR (95% CI) 0.68 (0.48–0.96) versus starting with NNRTIs; P = 0.03] were independently associated with TF. Conclusions In patients starting ART with <200 CD4+ cells/mm3 and >5 log10 HIV-RNA copies/mL, the durability of regimens based on InSTIs was longer than that of NNRTI- and bPI-based regimens.

2019 ◽  
Vol 6 (5) ◽  
Author(s):  
Sidonie Lambert-Niclot ◽  
Anders Boyd ◽  
Djeneba Fofana ◽  
Nadia Valin ◽  
Marc Wirden ◽  
...  

Abstract Background During antiretroviral therapy (ART), HIV-1-infected patients may present with ultralow (UL) HIV-RNA viral loads (VLs) below quantification levels of current assays. Reasons for UL-VL detection and its relation to virological rebound (VR) are unclear. Methods HIV-1-infected, ART-naïve patients followed at 2 university hospitals were included. All participants had an HIV-RNA &gt;200 copies/mL at ART initiation and achieved a VL &lt;50 copies/mL during ART. UL-VL was determined by the presence/absence of polymerase chain reaction signal detected using a commercially available assay (COBAS, TaqMan, Roche). Random-effects Poisson regression was used for assessing determinants of UL-VL not detected overtime and conditional risk set analysis for VR (1 VL &gt; 200 copies/mL or 2 VL &gt; 50 copies/mL) while accounting for frequency of VL measurements. Results Between 2009 and 2013, 717 patients initiated ART containing 2 nucleos(-t)ide reverse transcriptase inhibitors (NRTIs) plus a non-NRTI (29.4%), a protease inhibitor (58.4%), or an integrase-strand transfer inhibitor (INSTI; 12.1%). During a median (interquartile range) 3.4 (2.3–4.6) years, 676 (94.3%) patients achieved UL-VL not detected. In multivariable analysis, UL-VL not detected overtime was associated with younger age (P &lt; .001), female gender (P = .04), lower baseline VL (P &lt; .001), baseline CD4+ &gt;500 vs &lt;350/mm3 (P &lt; .001), and INSTI-containing ART (P = .009). One hundred thirty-one (18.3%) patients had VR during follow-up, which was independently associated with a CD4/CD8 ratio &lt;0.8 during follow-up (P = .01) and time spent with UL-VL not detected (P &lt; .001). When UL-VL not detected occurred for ≥50% of the follow-up duration (n = 290), faster time to reach UL-VL not detected (P &lt; .001), faster CD4+ T-cell count increase (P = .03), and faster CD4/CD8 ratio increase (P = .001) were observed. Conclusions VL suppression at an ultralow level is associated with INSTI-class ART initiation. Extensive VL suppression below ultralow detection could improve immune reconstitution.


2020 ◽  
Vol 75 (6) ◽  
pp. 1604-1610 ◽  
Author(s):  
Sabina Herrera ◽  
Borja M Fernandez-Felix ◽  
Peter W Hunt ◽  
Steven G Deeks ◽  
Talía Sainz ◽  
...  

Abstract Background The CD4/CD8 ratio is an indicator of immunosenescence and a predictor of all-cause mortality in HIV-infected patients. The effects of different ART regimens on CD4/CD8 ratio recovery remain unclear. Methods Clinical cohort study of ART-treated patients from the CFAR Network of Integrated Clinical Systems (CNICS). We included ART-naive adults with HIV infection who achieved undetectable HIV RNA during the first 48 weeks of treatment and had additional follow-up 48 weeks after virological suppression (VS). Primary endpoints included increase in CD4/CD8 ratio at both timepoints and secondary endpoints were CD4/CD8 ratio recovery at cut-offs of ≥0.5 or ≥1.0. Results Of 3971 subjects who met the study criteria, 1876 started ART with an NNRTI, 1804 with a PI and 291 with an integrase strand transfer inhibitor (INSTI). After adjusting for age, sex, race, year of entry, risk group, HCV serostatus, baseline viral load and baseline CD4/CD8 ratio, subjects on an NNRTI showed a significantly greater CD4/CD8 ratio gain compared with those on a PI, either 48 weeks after ART initiation or after 48 weeks of HIV RNA VS. The greater CD4/CD8 ratio improvement in the NNRTI arm was driven by a higher decline in CD8 counts. The INSTI group showed increased rates of CD4/CD8 ratio normalization at the ≥1.0 cut-off compared with the PI group. Conclusions NNRTI therapy was associated with a greater increase in the CD4/CD8 ratio compared with PIs. NNRTI- and INSTI-based first-line ART were associated with higher rates of CD4/CD8 ratio normalization at a cut-off of 1.0 than a PI-based regimen, which might have clinical implications.


2016 ◽  
Vol 34 (27) ◽  
pp. 3276-3283 ◽  
Author(s):  
Elizabeth L. Yanik ◽  
Chad J. Achenbach ◽  
Satish Gopal ◽  
Anna E. Coghill ◽  
Stephen R. Cole ◽  
...  

Purpose The biology of HIV-associated cancers may differ depending on immunologic and virologic context during development. Therefore, an understanding of the burden of Kaposi's sarcoma (KS) and non-Hodgkin lymphoma (NHL) relative to antiretroviral therapy (ART), virologic suppression, and CD4 count is important. Patients and Methods KS and NHL diagnoses during 1996 to 2011 were identified among patients with HIV infection in eight clinical cohorts in the United States. Among patients in routine HIV clinical care, the proportion of cases in categories of ART use, HIV RNA, and CD4 count at diagnosis were described across calendar time. Person-time and incidence rates were calculated for each category. Results We identified 466 patients with KS and 258 with NHL. In recent years, KS was more frequently diagnosed after ART initiation (55% in 1996 to 2001 v 76% in 2007 to 2011; P-trend = .02). The proportion of patients with NHL who received ART was higher but stable over time (83% overall; P-trend = .81). An increasing proportion of KS and NHL occurred at higher CD4 counts (P < .05 for KS and NHL) and with undetectable HIV RNA (P < .05 for KS and NHL). In recent years, more person-time was contributed by patients who received ART, had high CD4 counts and had undetectable HIV RNA, whereas incidence rates in these same categories remained stable or declined. Conclusion Over time, KS and NHL occurred at higher CD4 counts and lower HIV RNA values, and KS occurred more frequently after ART initiation. These changes were driven by an increasing proportion of patients with HIV who received effective ART, had higher CD4 counts, and had suppressed HIV RNA and not by increases in cancer risk within these subgroups. An improved understanding of HIV-associated cancer pathogenesis and outcomes in the context of successful ART is therefore important.


Author(s):  
Graeme Meintjes ◽  
John Black ◽  
Francesca Conradie ◽  
Sipho Dlamini ◽  
Gary Maartens ◽  
...  

The most recent version of the Southern African HIV Clinicians Society’s adult antiretroviral therapy (ART) guidelines was published in December 2014. In the 27 August 2015 edition of the New England Journal of Medicine, two seminal randomised controlled trials that addressed the optimal timing of ART in HIV-infected patients with high CD4 counts were published: Strategic timing of antiretroviral therapy (START) and TEMPRANO ANRS 12136 (Early antiretroviral treatment and/or early isoniazid prophylaxis against tuberculosis in HIV-infected adults). The findings of these two trials were consistent: there was significant individual clinical benefit from starting ART immediately in patients with CD4 counts higher than 500 cells/μL rather than deferring until a certain lower CD4 threshold or clinical indication was met. The findings add to prior evidence showing that ART reduces the risk of onward HIV transmission. Therefore, early ART initiation has the public health benefits of potentially reducing both HIV incidence and morbidity. Given this new and important evidence, the Society took the decision to provide a specific update on the section of the adult ART guidelines relating to when ART should be initiated.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Stefanie Thöni ◽  
Felix Keller ◽  
Sara Denicolo ◽  
Susanne Eder ◽  
Laszlo Rosivall ◽  
...  

Abstract Background and Aims PROVALID is a prospective, observational, multinational cohort study in 4000 patients with type 2 diabetes mellitus. Our aim was to determine the incidence rate of renal and cardiovascular endpoints, as well as all-cause-mortality in different European countries and to identify risk factors associated with the investigated outcomes. Method Potential risk factors associated with the investigated outcomes were identified by calculation of the incidence rate ratio. Crude and adjusted incidence rates for every country were estimated using generalized linear (poisson) regression models and corresponding 95 % confidence intervals were computed. Incidence rates were adjusted for different risk factors including age, sex, estimated GFR, albuminuria, HbA1c, LDL, HDL, total cholesterol, systolic blood pressure, BMI and cardiovascular and renal comorbidities; among these several show significant impact on outcomes. The renal outcome was a composite of a sustained decline in the estimated GFR of at least 40%, a sustained increase in albuminuria of at least 30 % including the progression from normo- to micro- or macroalbuminuria, end-stage kidney disease, or death from renal causes. The cardiovascular composite endpoint was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Results 3461 participants of four European countries (Austria 18 %, Hungary 41 %, Netherlands 26 % and Scotland 15 %) with a mean follow up time of 3.9 years were included into this study. Participants from Poland were excluded due to missing follow-up data. In total, 9.2 % and 6.4 % participants reached the renal and cardiovascular composite endpoint, respectively. 7.0 % of the participants died within this timeframe. The adjusted incidence rate for the renal endpoint ranged from 14.5 to 25.3 (per 1000 patient-years) with no significant differences between countries. On average, the incidence rate was lower in Scotland (IR, 14.5; 95 % CI, 8.7 to 22.5) and in the Netherlands (IR, 15.7; 95 % CI, 10.9 to 21.8) compared to Hungary (IR, 25.3; 95 % CI, 20.7 to 30.6) and Austria (IR 21.3; 95 % CI, 16.2 to 27.5). The adjusted incidence rate for the cardiovascular endpoint ranged from 7.0 to 20.3 and was significantly lower in Hungary (IR, 7.0; 95 % CI, 5.1 to 9.3) and the Netherlands (IR, 7.6; 95 % CI, 4.4 to 12.2) compared to Austria (IR, 16.7; 95 % CI, 12.4 to 22.1) and Scotland (IR, 20.3; 95 % CI, 13.8 to 28.9). The adjusted incidence rate for all-cause-mortality ranged from 4.2 to 15.9 and was significantly lower in the Netherlands (IR, 4.2; 95 % CI, 2.2 to 7.6) compared to Scotland (IR, 15.9; 95 % CI, 10.9 to 22.6). No significant difference in the incidence rates between Austria (IR, 9.8; 95 % CI, 7.0 to 13.4) and Hungary (IR, 9.3; 95 % CI, 6.8 to 12.4) was found. Conclusion After adjustment for known risk factors, incidence rates of cardiovascular endpoints, as well as all-cause-mortality still vary significantly between four European countries. This may be due to manifold reasons. Further analysis of the national therapeutic practice pattern within the PROVALID cohort may provide additional information.


Author(s):  
Jawad H Butt ◽  
Emil L Fosbøl ◽  
Thomas A Gerds ◽  
Charlotte Andersson ◽  
Kristian Kragholm ◽  
...  

Abstract Background On 13 March 2020, the Danish authorities imposed extensive nationwide lockdown measures to prevent the spread of the coronavirus disease 2019 (COVID-19) and reallocated limited healthcare resources. We investigated mortality rates, overall and according to location, in patients with established cardiovascular disease before, during, and after these lockdown measures. Methods and results Using Danish nationwide registries, we identified a dynamic cohort comprising all Danish citizens with cardiovascular disease (i.e. a history of ischaemic heart disease, ischaemic stroke, heart failure, atrial fibrillation, or peripheral artery disease) alive on 2 January 2019 and 2020. The cohort was followed from 2 January 2019/2020 until death or 16/15 October 2019/2020. The cohort comprised 340 392 and 347 136 patients with cardiovascular disease in 2019 and 2020, respectively. The overall, in-hospital, and out-of-hospital mortality rate in 2020 before lockdown was significantly lower compared with the same period in 2019 [adjusted incidence rate ratio (IRR) 0.91, 95% confidence interval (CI) CI 0.87–0.95; IRR 0.95, 95% CI 0.89–1.02; and IRR 0.87, 95% CI 0.83–0.93, respectively]. The overall mortality rate during and after lockdown was not significantly different compared with the same period in 2019 (IRR 0.99, 95% CI 0.97–1.02). However, the in-hospital mortality rate was lower and out-of-hospital mortality rate higher during and after lockdown compared with the same period in 2019 (in-hospital, IRR 0.92, 95% CI 0.88–0.96; out-of-hospital, IRR 1.04, 95% CI1.01–1.08). These trends were consistent irrespective of sex and age. Conclusions Among patients with established cardiovascular disease, the in-hospital mortality rate was lower and out-of-hospital mortality rate higher during lockdown compared with the same period in the preceding year, irrespective of age and sex.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S501-S502
Author(s):  
Humberto R Jimenez ◽  
Naana Boachie ◽  
Sangwon Park ◽  
Jin Suh

Abstract Background As people with HIV (PWH) have experienced reductions in antiretroviral pill burden, there has been an increase in medications to manage non-AIDS-related co-morbidities. Previous studies have linked virologic failure to an increased pill burden. This study assessed whether polypharmacy and other variables affect success of HIV management in our population. Methods A retrospective, cross-sectional analysis of PWH receiving care at a Ryan White-funded clinic in New Jersey was performed. Eligible patients were ≥18 years old, had ≥2 visits in 2019 and were receiving antiretroviral therapy (ART). The primary endpoints were to determine the effect polypharmacy (defined as 5 or more non-ART pills per day) on virologic response rates (HIV RNA &lt; 200 copies/mL). Secondary endpoints accounted for the impact of age, gender, race/ethnicity, HIV transmission risk factor, and AIDS diagnosis on virologic response. A descriptive analysis of comorbidities and medication classes was also completed. Logistic regression, chi square and student’s t test were used for statistical analysis. Results 964 patients were included in the analysis, with 355 (37%) meeting the criteria for polypharmacy. Most patients were male (60%) and the mean age was 49 years of age. The racial/ethnic breakdown was 46% Hispanic, 45% Black and 8% White. Polypharmacy was associated with higher rates of virologic success compared to those with a lower pill burden: 94% vs 86% had an HIV RNA &lt; 200 copies/mL (P=0.0003), respectively. ART pill burden was statistically, but not clinically higher among those with polypharmacy (1.34 vs 1.45, P=0.025). Virologic response was found to be higher among Hispanics and Whites in comparison to Black patients (OR 2.2, CI 1.4-3.5 and 3.0, CI 1.1-8.2). Patients with an AIDS diagnosis were less likely to achieve virologic response (OR 0.64, CI 0.42-0.99). Conclusion Patients with polypharmacy were more likely to achieve virologic success than paitents with a low pill burden in our population. Disclosures Humberto R. Jimenez, PharmD, BCPS, AAHIVP, Gilead (Speaker’s Bureau)


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S551-S551
Author(s):  
Sneha Thatipelli ◽  
Chad Achenbach ◽  
Shannon Galvin

Abstract Background Integrase strand transfer inhibitors (InSTIs) as ART for HIV has been associated with clinically significant weight gain, in addition to the “return to health phenomenon”. Methods We conducted a cohort study on adults over 18 with HIV, who had baseline weights and an additional weight at least 6 months later. Individuals with malignancies, thyroid disorders, and disseminated tuberculosis or mycobacterium avium complex were excluded. To understand the impact of InSTIs on chronic vs. recently infected persons, we divided the cohort into four groups: (1) well-controlled on non-InSTI ART [WN] (2) well-controlled on InSTI ART [WI] (3) uncontrolled on non-InSTI ART [UN], and (4) uncontrolled on InSTI ART [UI]. Well-controlled persons (viral load &lt; 2000) were proxies for chronic infection on long-term ART and uncontrolled for recently infected and initiated on ART. New diagnoses of diabetes, hyperlipidemia, and hypertension were determined by ICD10 codes. Participants with a weight change more than 10 kg in 6 months were excluded. Results 612 of the initial 910 participants in the cohort met the inclusion criteria. Comparing those who remained on the designated regimen throughout the study led to 86 WN, 153 WI, 166 UN, and 145 UI. Mean weight change at 6 months for WN was +0.22 kg (95% CI [-0.86, 1.3]), at 1 year was -0.86 kg (95% CI [-2.94, 1.22]), and at 2 years was +0.026 kg (95% CI [-2.347, 2.399]). For WI, mean weight change at 6 months was +0.21 kg (95% CI [-0.79, 1.21]), at 1 year was -0.50 kg (95% CI [-2.02, 1.04]), and at 2 years was +0.43 kg (95% CI [-1.35, 2.21]). UN gained weight until the first year (+1.74 kg at 6 mo (95% CI [0.24, 3.24]) and +3.84 kg at 1 year (95% CI [1.57, 6.11])), but plateaued at 2 years (+2.42 kg (95% CI [-0.44, 5.28])). At 6 months mean weight gain for UI was +0.78 kg (95% CI [-0.15, 1.71]), at 1 year was +2.33 kg (95% CI [1.02, 3.64]), and at 2 years was +3.04 kg (95% CI [1.2, 4.85]). WI had a higher incidence of diabetes (37% vs. 32%, p=0.40), hyperlipidemia (32% vs. 29%, p=0.66), and hypertension (34% vs. 26%, p=0.19) compared to WN. Conclusion InSTIs may confer a larger and more sustained weight gain among individuals in the first two years after ART initiation. Well controlled individuals did not have statistically significant weight change, but those on Insti-based ART had more metabolic diseases. Disclosures All Authors: No reported disclosures


Author(s):  
Susanna Scharrer ◽  
Christian Primas ◽  
Sabine Eichinger ◽  
Sebastian Tonko ◽  
Maximilian Kutschera ◽  
...  

Abstract Background Little is known about the bleeding risk in patients with inflammatory bowel disease (IBD) and venous thromboembolism (VTE) treated with anticoagulation. Our aim was to elucidate the rate of major bleeding (MB) events in a well-defined cohort of patients with IBD during anticoagulation after VTE. Methods This study is a retrospective follow-up analysis of a multicenter cohort study investigating the incidence and recurrence rate of VTE in IBD. Data on MB and IBD- and VTE-related parameters were collected via telephone interview and chart review. The objective of the study was to evaluate the impact of anticoagulation for VTE on the risk of MB by comparing time periods with anticoagulation vs those without anticoagulation. A random-effects Poisson regression model was used. Results We included 107 patients (52 women, 40 with ulcerative colitis, 64 with Crohn disease, and 3 with unclassified IBD) in the study. The overall observation time was 388 patient-years with and 1445 patient-years without anticoagulation. In total, 23 MB events were registered in 21 patients, among whom 13 MB events occurred without anticoagulation and 10 occurred with anticoagulation. No fatal bleeding during anticoagulation was registered. The incidence rate for MB events was 2.6/100 patient-years during periods exposed to anticoagulation and 0.9/100 patient-years during the unexposed time. Exposure to anticoagulation (adjusted incidence rate ratio, 3.7; 95% confidence interval, 1.5-9.0; P = 0.003) and ulcerative colitis (adjusted incidence rate ratio, 3.5; 95% confidence interval, 1.5-8.1; P = 0.003) were independent risk factors for MB events. Conclusion The risk of major but not fatal bleeding is increased in patients with IBD during anticoagulation. Our findings indicate that this risk may be outweighed by the high VTE recurrence rate in patients with IBD.


Author(s):  
Keerti L Dantuluri ◽  
Jean Bruce ◽  
Kathryn M Edwards ◽  
Ritu Banerjee ◽  
Hannah Griffith ◽  
...  

Abstract Background Antibiotic use is common for acute respiratory infections (ARI) in children, but much of this use is inappropriate. Few studies have examined whether rurality of residence is associated with inappropriate antibiotic use. We examined whether rates of ARI-related inappropriate antibiotic use among children vary by rurality of residence. Methods We conducted a retrospective cohort study of children aged 2 months – 5 years enrolled in Tennessee Medicaid between 2007 and 2017 and diagnosed with ARI in the outpatient setting. Study outcomes included ARI, ARI-related antibiotic use, and ARI-related inappropriate antibiotic use. Multivariable Poisson regression was used to measure associations between rurality of residence, defined by the United States Census Bureau, and the rate of study outcomes, while accounting for other factors including demographics and underling comorbidities. Results 805,332 children met selection criteria and contributed 1,840,048 person-years (p-y) of observation. Children residing in completely rural, mostly rural, and mostly urban counties contributed 70,369 (4%) p-y, 479,121 (26%) p-y, and 1,290,558 p-y (70%), respectively. Compared with children in mostly urban counties (238 per 1000 p-y), children in mostly rural (450 per 1000 p-y) and completely rural counties (468 per 1000 p-y) had higher rates of inappropriate antibiotic use (adjusted incidence rate ratio [aIRR]: 1.34 (95% confidence interval [CI]: 1.33 – 1.35) and aIRR: 1.33 (CI: 1.32 – 1.35), respectively). Conclusion Inappropriate antibiotic use is common among young children with ARI, with higher rates in rural compared to urban counties. These differences should inform targeted outpatient antibiotic stewardship efforts.


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