bluuebunny/crossref_metadata_2025_split huggingface dataset:
Less frequent follow‐up in routine care than in trials does not impact resistance selection in patients failing DRV/r or ATV/r first line treatment
Authors: Marcelin Anne‐Genevieve , Charpentier Charlotte , Wirden Marc , Descamps Diane , Calvez Vincent 
Published: November 2014

IntroductionSelection of resistance mutations on antiretroviral therapy (ART) including darunavir (DRV/r) or atazanavir (ATV/r) has been reported infrequently but mainly in clinical trials where patients were followed very frequently (at least four to five clinical visits and viral load measurements per year). The aim of this study was to evaluate the rate of resistance at failure and mutational patterns emerging in patients receiving DRV/r or ATV/r based‐regimen as first line treatment and followed in standard clinical practice with less clinical visits and viral load measurements (median=2 per year).MethodsWe studied 1,518 patients starting their first line antiretroviral therapy and followed during at least two years (n=799 TVD+DRV/r, n=70 KVX+DRV/r, n=618 TVD+ATV/r, n=31 KVX+ATV/r). The median viral load at baseline was 76,000 copies/mL and the median CD4 cell count 384 cell/mm3. Virological failure was defined as two consecutive viral load=50 copies/mL after previous suppression <50 copies/mL, or failure to achieve <50 copies/mL. Predicted susceptibility was determined using the last ANRS algorithm.ResultsAmong the 1,518 patients, 193 (12.7%) failed during the two years of follow‐up. Among patients failing TVD+DRV/r (n=95), the emerging mutations observed were RT M184V (n=8; 8%) and Pro V32I (n=1; 1%). Among patients failing KVX+DRV/r (n=8), the emerging mutations observed were RT M184V (n=3; 37%) and Pro I47V (n=1; 12%). Among patients failing TVD+ATV/r (n=86), the emerging mutations observed were RT M184V (n=9; 10%), Pro N88S (n=2; 2%) and Pro I50L (n=1; 1%). Among patients failing KVX+ATV/r (n=4), the emerging mutations observed were RT M184V (n=2; 50%) and no Pro mutation. Most of patients retained virus predicted to be susceptible to all antiretrovirals (22 virus became resistant to 3TC/FTC and three became resistant to ATV). None of them became resistant to DRV.ConclusionsAmong 1,518 patients in routine care who started their first line treatment with DRV/r or ATV/r, very few of them (1.4%) selected resistance mutations at failure with three patients selecting an ATV resistant virus. None of them became resistant to DRV. The less frequent follow‐up of patients in routine care compared to clinical trials does not impact the resistance selection rate in patients treated by boosted DRV or ATV based regimen.
Comparison of HIV‐1 drug resistance profiles generated from novel software applications for routine patient care
Authors: Gonzalez Dimitri , Digmann Benjamin , Barralon Matthieu , Boulme Ronan , Sayada Chalom , Yao Joseph 
Published: November 2014

IntroductionClinical laboratories performing routine HIV‐1 genotyping antiviral drug resistance (DR) testing need reliable and up‐to‐date information systems to provide accurate and timely test results to optimize antiretroviral treatment in HIV‐1‐infected patients.Materials and MethodsThree software applications were used to compare DR profiles generated from the analysis of HIV‐1 protease (PR) and reverse transcriptase (RT) gene sequences obtained by Sanger sequencing assay in 100 selected clinical plasma samples from March 2013 through May 2014. Interpretative results obtained from the Trugene HIV‐1 Genotyping assay (TG; Guidelines v17.0) were compared with a newly FDA‐registered data processing module (DPM v1.0) and the research‐use‐only ViroScore‐HIV (VS) software, both of which use the latest versions of Stanford HIVdb (SD v7.0) and geno2pheno (G2P v3.3) interpretive algorithms (IA). Differences among the DR interpretive algorithms were compared according to drug class (NRTI, NNRTI, PI) and each drug. HIV‐1 tropism and integrase inhibitor resistance were not evaluated (not available in TG).ResultsOverall, only 17 of the 100 TG sequences obtained yielded equivalent DR profiles among all 3 software applications for every IA and for all drug classes. DPM and VS generated equivalent results with >99.9% agreement. Excluding AZT, DDI, D4T and rilpivirine (not available in G2P), ranges of agreement in DR profiles among the three IA (using the DPM) are shown in Table 1.ConclusionsSubstantial discrepancies (<75% agreement) exist among the three interpretive algorithms for ETR, while G2P differed from TG and SD for resistance to TDF and TPV/r. Use of more than one DR interpretive algorithm using well‐validated software applications, such as DPM v1.0 and VS, would enable clinical laboratories to provide clinically useful and accurate DR results for patient care needs.
Time trends in HIV‐1 transmitted drug resistance mutation frequency in Poland
Authors: Parczewski Milosz , Witak‐Jedra Magdalena , Maciejewska Katarzyna , Bociaga‐Jasik Monika , Skwara Pawel , Garlicki Aleksander , Grzeszczuk Anna , Rogalska Magdalena , Jankowska Maria , Lemanska Malgorzata , Hlebowicz Maria , Baralkiewicz Grazyna , Mozer‐Lisewska Iwona , Mazurek Renata , Lojewski Wladyslaw , Grabczewska Edyta , Olczak Anita , Jablonowska Elzbieta , Rymer Weronika , Szymczak Aleksandra , Szetela Bartosz , Gasiorowski Jacek , Knysz Brygida , Urbanska Anna , Leszczyszyn‐Pynka Magdalena 
Published: November 2014

IntroductionIn Poland, the HIV epidemic has shifted recently from being predominantly related to injection drug use (IDU) to being driven by transmissions among men‐who‐have‐sex‐with‐men (MSM). The number of new HIV cases has increased in the recent years, while no current data on the transmitted drug resistance associated mutations (tDRM) frequency trend over time are available from 2010. In this study, we analyze the temporal trends in the spread of tDRM from 2008 to 2013.Materials and MethodsPartial pol sequences from 833 antiretroviral treatment‐naive individuals of European descent (Polish origin) linked to care in 9 of 17 Polish HIV treatment centres were analyzed. Drug resistance interpretation was performed according to WHO surveillance recommendations, subtyping with REGA genotyping 2.0 tool. Time trends were examined for the frequency of t‐DRM across subtypes and transmission groups using logistic regression (R statistical platform, v. 3.1.0).ResultsFrequency of tDRM proved stable over time, with mutation frequency change from 11.3% in 2008 to 8.3% in 2013 [OR: 0.91 (95% CI 0.80–1,05), p=0.202] (Figure 1a). Also, no significant differences over time were noted for the subtype B (decrease from 8.4% 2008 to 6.2% in 2013 [OR: 0.94 (95% CI 0.79–1.11), p=0.45] and across non‐B variants [change from 22.6% 2008 to 23.1% in 2013, OR: 0.94 (95% CI 0.75–1.19), p=0.62]. When patient groups were stratified according to transmission route, in MSM there was a trend for a NNRTI t‐DRM decrease (from 6.8% 2008 to 1% in 2013, OR: 0.61 (95% CI 0.34–1.02), p=0.0655, slope −0.74%/year) (Figure 1b), related to the subtype B infected MSM (decrease from 7% 2008 to 1% in 2013, OR: 0.61 (95% CI 0.34–1.03), p=0.0662, slope −0.75%/year). Overall tDRM frequency decrease was also noted for the heterosexually infected patients [from 17.6% 2008 to 10.3% in 2013, OR: 0.83 (95% CI 0.67–1.02, p=0.077, slope −2.041%/year)] but did not associate with drug class (Figure 1c). In IDUs, the trends in t‐DRM frequency were not significant over time (change from 1.9% in 2008 to 0 in 2013 [OR:1.24 (95% CI 0.73–2.26), p=0.4)].ConclusionsThe frequency of t‐DRM in Poland is generally stable over time. Decrease in the overall tDRM frequency in heterosexual infected cases and NNRTI resistance in subtype B infected MSM may be related to the higher treatment efficacy of current cART.
Primary drug resistance at diagnosis of HIV‐1 infection: a Portuguese cohort
Authors: Rocha Pereira Nuno , Duro Raquel , Piñero Carmela , Figueiredo Cristóvão , Sofia Santos Ana , Soares Jorge , Serrão Rosário , Sarmento António 
Published: November 2014

IntroductionPresence of viral mutations conferring resistance to antiretroviral drugs has potential impact on success of antiretroviral therapy (ART). The aim of this study was to describe the prevalence of resistance‐associated mutations in HIV‐infected patients without prior ART in a Portuguese cohort.Materials and MethodsRetrospective single‐centre study of patients newly diagnosed with HIV‐1 infection between 2006 and 2012. Resistance genotyping was obtained with HIV TRUGENE® and Viroseq® tests and the analysis of drug resistance was based on the Stanford University HIV Drug Resistance Database. Epidemiological data was also gathered. Continuous variables were summarized by mean and standard deviation, whereas categorical variables were presented as proportions. Comparison of proportions was performed with Chi square and Fisher exact test while means were compared with Student test. Statistical significance was assumed when p<0.05. Statistical analysis was performed with SPSS 21.0®.ResultsResistance testing was performed in 624 patients. General characteristics of the patients are summarized in Table 1. Mutations were found in 291 (46.6%) patients but resistance‐associated mutations were present in 79 (12.7%) patients. Resistances to different drug classes were the following: NNRTIs‐resistance in 42 (6.7%) patients; NRTIs‐resistance in 19 (3.0%) patients; PIs‐resistance in 30 (4.8%) patients. Only 10 (1.6%) patients presented simultaneous resistance‐associated mutations to more than one class of drugs. There were no statistical significant differences between the years at which HIV‐1 was diagnosed. Also no significant difference in the distribution of the parameters age, sex, CD4‐cell count, and viral load, between groups with and without resistance was identified. Resistance‐associated mutations were significantly more common in patients with non‐B HIV‐1 subtypes (15.4% vs 9.8%; p=0.048) and in those presenting with AIDS (18.2% vs 11.1%; p=0.03).ConclusionsPrevalence of resistance‐associated mutations identified in this study was similar to those reported in similar studies from Western Europe. Knowledge about the epidemiology of primary resistance in our country is important in order to improve HIV care.
Increased risk of virological failure to the first antiretroviral regimen in HIV‐infected migrants compared to natives: data from the ICONA cohort
Authors: Saracino Annalisa , Lorenzini Patrizia , Lo Caputo Sergio , Girardi Enrico , Castelli Francesco , Bonfanti Paolo , Galli Massimo , Caramello Pietro , Abrescia Nicola , Mussini Cristina , Monno Laura , d'Arminio Monforte Antonella 
Published: November 2014

IntroductionAim of the study was to evaluate possible disparities in access and/or risk of virological failure (VF) to the first antiretroviral (ART) regimen for migrants compared to Italian‐born patients and to assess determinants of failure for the migrants living with HIV.MethodsAll native and migrant naïve patients enrolled in ICONA in 2004–2014 were included. Firstly, variables associated to ART initiation were analyzed. In a second analysis, the primary endpoint was time to failure after at least six months of ART, defined as: (a) VF (first of two consecutive viral load (VL) >50 and >200 copies/mL); (b) treatment discontinuation (TD) for any reason; and (c) treatment failure (TF: confirmed VL >200 cp/mL or TD). A Poisson multivariable analysis was performed to control for confounders.ResultsA total of 5777 HIV‐pos ART‐naïve patients (1179 migrants and 4598 natives) were evaluated. Most migrants were from sub‐Saharan Africa (35.3%) and South‐Central America/Caribbean (29%). Median duration of residency in Italy was five years (IQR 1–10). Baseline characteristics significantly differed between the two groups (Table 1); in particular, lower CD4 counts and higher frequency of AIDS events were observed in migrants vs natives. When adjusting for baseline confounders, migrants presented a lower chance to initiate ART compared to natives (OR 0.78, 95% CI 0.65–0.93, p=0.006). After ART initiation, the incidence rate of VF >50 cp/mL was 15.5 per 100 person‐years (95% CI 12.8–18.8) in migrants and 8.9 in natives (95% CI 7.9–9.9), respectively. By multivariable analysis, migrants had a significantly higher risk of VF, both >50 cp/mL (OR 1.50, 95% CI 1.17–1.193, p=0.001) and >200 cp/mL (OR 1.59, 95% CI 1.23–2.05, p<0.001), and of TF (OR 1.15, 95% CI 1.00–1.32, p=0.045), while no differences were observed in TD risk. Among migrants, variables associated with a higher VF risk were age (for 10‐year increase, OR 0.96, 95% CI 0.93–0.98, p=0.002), unemployment (OR 1.96, 95% CI 1.20–3.20, p=0.007) and use of a boosted PI based‐regimen (OR 2.04, 95% CI 1.25–3.34, p=0.005 vs NNRTI‐based), while pregnancy was associated with TD (OR 3.73, 95% CI 2.36–5.90, p<0.001) and TF (OR 3.13, 95% CI 02.00–4.89, p<0.001).ConclusionsDespite the use of more potent and safer antiretroviral drugs in the last 10 years, and even in a setting of universal access to ART, migrants living with HIV still present barriers to ART initiation and increased risk of VF compared to natives.
Effectiveness and tolerability of abacavir‐lamivudine‐nevirapine (ABC/3TC/NVP) in a multicentre cohort of HIV‐infected, ARV‐naïve patients
Authors: Podzamczer Daniel , Fredy Rojas Jhon , Neves Isabel , Ferrer Elena , Llibre Josep M , Leal Manuel , Gorgolas Miguel , Jose Crusells M , Gatell Josep M , Correia Abreu Ricardo , Curto Jordi , Domingo Pere , Pilar Barrufet M , Rozas Nerea 
Published: November 2014

PurposeVery scarce information has been published to date with the combination of ABC/3TC/NVP but it is currently being used in clinical practice in Spain and Portugal. Our aim was to present the clinical experience with this regimen in a cohort of adult HIV‐infected antiretroviral (ARV)‐naïve patients.MethodsRetrospective, multicentre, cohort study. Consecutive adult HIV‐infected ARV‐naïve HLA‐B*5701‐negative patients, who started ABC/3TC/NVP between 2005‐2013, with at least one follow‐up visit, were included. Demographic, clinical and laboratory variables were assessed at baseline, month 1, and every three–four months thereafter. The primary end point was HIV‐1 viral load (VL)<40 c/mL at 48 weeks. Data were analyzed by intent‐to‐treat (ITT) (switch=failure, and missing=failure) and on treatment (OT) analyses.Results78 patients were included. Median follow up was 26 (0.1‐84) months. 86% were male, median age 41 (23‐69) years, 9% had AIDS, 8% were HCV+, baseline CD4 was 275 (10‐724) cells/µL and median VL 4.58 (3.02‐6.92) log. After 48 weeks, VL was<40 c/mL in 89.8% (OT), 79.7% (M=F) and 65.4% (S=F) and at 96 weeks in 88.5%, 78.9% and 61.6%, respectively. CD4 increased +246 (p<0.001) and +292 (p<0.001) cells/uL after 48 and 96 weeks, respectively. One or more drugs of the regimen were discontinued in 33 (42.3%) patients. In 15 (19.2%) patients (13 NVP, 2 ABC/3TC) therapy was stopped due to toxicity after a median of one month (in only two cases after six months of follow up): 80% of them had rash/liver toxicity. Six (7.7%) patients discontinued ART due to virologic failure, five (6.4%) because of other reasons and seven (9%) were lost to follow‐up. ALT but not AST significantly increased (+0.07 ukat/L at 96 weeks, p=0.033). A significant increase of 25%, 26% and 42% in total cholesterol, LDLc and HDLc, respectively, and a significant decrease in TC/HDL ratio (6%, p=0.008) was observed after 96 weeks.ConclusionsDespite a considerable proportion of patients had to stop therapy due to toxicity (most associated with NVP), those initially tolerating this regimen presented a high virologic and immunologic response after 96 weeks, as well as a favourable lipid profile. ABC/3TC/NVP may be a suitable alternative first regimen, mainly in countries with economic constraints.
Four‐drugs regimen containing raltegravir is highly effective in HIV patients starting therapy with >500,000 copies/mL viral load
Authors: Sterrantino Gaetana , Zaccarelli Mauro , Prati Francesca , Boschi Andrea , Sighinolfi Laura , Borghi Vanni 
Published: November 2014

IntroductionAssessing virological response of four‐drugs antiretroviral regimen that include raltegravir (RAL) in naïve patients with high viral load (>500,000 copies/mL) selected from a multicentre Italian database.MethodsNaïve patients with HIV RNA>500,000 copies/mL, who began standard antiretroviral regimens either based on non‐nucleoside reverse transcriptase inhibitors (NNRTI) or boosted‐PI (PI/r), or a standard regimen plus RAL between 2008 and 2013 were analyzed. Observation was censored at 12 months and the percentage of patients who achieved a viral load below the limit of detection (BLD) was calculated. Virological failure was defined as two consecutive viral loads>40 copies/mL.ResultsOverall, 179 patients were included (13% with primary HIV infection (PHI), and 42.5% with AIDS diagnosis). Of them, 156 started standard three‐drugs antiretroviral regimen (75.6% PI/r‐based, 24.4% NNRTI‐based. Among patients with PHI, 23 patients (12.8%), 6 (25%) started a four‐drugs antiretroviral regimen containing both RAL and PI/r. Patients’ characteristics were as follows: males 74%, median age 42 years (IQR 35–51), sexually transmission 75.1%, median CD4 count 156 cells/µL (IQR 47–368) and median HIV‐RNA 6.1 log10 copies/mL (IQR 5.8–6.4). 91 of 179 patients (50.8%) reached BLD viral load during the twelve months of observation. Three patients (1.7%) who began regimens PI/r‐based with three‐drugs had virological rebound after reaching BLD viral load. By use of survival analysis, we show that those patients who added RAL to the standard regimen have reached the primary end point faster (mean 8.4 months (95% CI 7.2–9.6) vs 11.4 (95% CI 11.0–11.8) in PI group and 10.3 (95% CI 9.4–11.1) in NNRTI group; p<0.001, Figure 1). In the adjusted analysis, the choice of a standard regimen versus a four‐drugs regimen was driven only by higher baseline viral load (OR. 9.05; 95% CI 2.41–37.41; p=0.001).ConclusionsOnly half of the naïve patients who began antiretroviral therapy having >500,000 copies/mL HIV‐RNA had virological success at 12 months. The success was reached faster using the RAL‐containing four‐drugs regimen, suggesting that strengthening the initial regimen could be an option in patients with very high viral load to improve virological response.
Long‐term effect of a four‐drugs induction regimen for patients with high baseline viral load
Authors: Maggiolo Franco , Masini Giulia , Astuti Noemi , Di Filippo Elisa , Benatti Simone , Valenti Daniela , Callegaro Anna Paola , Rizzi Marco 
Published: November 2014

IntroductionThe long‐term effects of an intensified induction regimen are unknown. In this pilot, randomized, prospective study we evaluate the effect of a short‐term four‐drugs induction regimen in patients with high baseline viral load.MethodsNaive patients with HIV‐RNA>100.000 copies/ml receiving TDF+FTC+EFV+RAL (group ER) for 4 months and were then simplified to TDF+FTC+EFV. Two randomized control groups treated ab‐initio with TDF+FTC+EFV (E) or TDF+FTC+RAL (R) were used.Results19 patients with a mean age of 38 years and mean baseline CD4 count of 334 (SD 216) cells/mcL and HIV‐RNA of 5.47 log (SD 0.32) copies/mL were enrolled. No baseline significant difference was observed among groups. Early HIV‐RNA reduction was significantly higher in ER compared to the other groups from week 1 to week 4 (P from 0.026 to 0.003) (figure 1), thereafter HIV‐RNA values were comparable among the groups. At week 96, all patients had an HIV‐RNA < 50 copies/mL, however only patients in the ER group had in all cases an HIV‐RNA level < 3 copies/mL with a statistically significant difference compared to E (60%; P=0.038) and R (50%; P=0.020). At 96 weeks, CD4 cell median counts were 765 cells/mcL for ER, 600 cells/mcL for E and 771 for R (P=0.16), however patients in the ER group presented a lower proportion of activated CD4+CD38+HLADR+ cells (1.9% versus 3.9 and 3.8%) and CD8+CD38+HLADR+ cells (10.3% versus 16.8 and 16.5%) and a significantly better CD4/CD8 ratio (0.98 versus 0.53 and 0.61; P=0.03).ConclusionsA four‐drug regimen in naive patients with high pre‐therapy viral load improves early virologic response. A quick drop of HIV‐RNA seems to correlate with a sustained virologic response. Although limited in time (four months), the four‐drug regimens correlates with an improved immunological response as measured by the CD4/CD8 ratio or the percentage of activated CD4+ and CD8+ cells. The reasons why this happens deserve further studies. This study highlights the importance of a personalised therapy especially in high risk patients.
Who gets single tablet regimens (STR), and why?
Authors: Tarrier Laura , Kegg Stephen 
Published: November 2014

IntroductionThe BHIVA guidelines now feature three single tablet regimens (STRs) as recommended treatments for HIV‐positive people new to therapy [1]. They are popular with patients and are attractive in a number of clinical scenarios. We sought to determine how our use of STRs had developed over a three‐year period, and how the decision to opt for an STR was made.MethodsRetrospective case‐note review and database interrogation of all patients starting anti‐retroviral therapy (ART) from 1st March 2011 to 31st March 2014.Results215 patients started ART. 58% (125/215) were black‐African and 47% (100/215) were female. Median CD4 at baseline was 272 cells/µL (range 1‐1044 cells/µL). 69 (32%) had a viral load (VL) >100,000 copies/mL. 7 individuals had evidence of transmitted drug resistance. 88 patients started an STR. Two tested positive for HLAB5701. None had a 10 year CVS risk score of >20% and 36% had a baseline VL >100,000 copies/mL. 127 patients started a non‐STR regimen, 29% had a VL >100 000 copies/mL and none had an elevated CVS risk. Information regarding baseline renal function and HLAB5701 will be provided at the conference. The use of STRs increased over the three years (25% 2011–12; 57.1% 2012–13; 44% 2013–14). There was no difference in STR prescribing between men and women. In men, heterosexual male patients were more likely to be prescribed an STR than MSM males (54% versus 43%, p 0.005). In 43% (38/88) patients had indicated a preference for an STR and 32/88 expressed a preference for a particular drug. 2% (2/88) requested to be on the same treatment as a partner. In those patients who expressed an interest in a particular drug, four had received information from a friend or partner. In 33% (29/88) cases an STR was felt by the clinician to be the best option, largely based on concerns around pill‐burden and adherence (31%), viral load (16%) and renal or cardiac risk (7%).ConclusionsUse of STRs is increasing. This is not driven on in our cohort by cardiovascular risk of HLAB5701 carriage but by patient and clinician preference, and to a lesser extent by higher baseline viral loads.