bluuebunny/crossref_metadata_2025_split huggingface dataset:
Holding Back or Letting Go? The Effect of Emotion Suppression on Relationship Viability in New Venture Teams
Authors: Ivanova Stela , Treffers Theresa , Langerak Fred , Groth Markus 
Published: April 2022

Drawing on emotion regulation theory, this study investigates if and how emotion suppression informs relationship viability within new venture teams (NVTs) when such teams face obstacles. In particular, we use a dyadic approach to examine the suppressor’s authenticity and team members’ perceptions of appropriateness as mediators in the link between emotion suppression and relationship viability. A round-robin study with 93 respondents nested in 37 NVTs, which generated 167 observations, provides empirical support for the theoretically derived model by showing that both authenticity and appropriateness fully mediate the relationship between emotion suppression and relationship viability. In particular, the findings show that the negative indirect effect of emotion suppression on relationship viability via authenticity is larger than the positive indirect effect via appropriateness. A follow-up study after two years indicates that relationship viability and emotion suppression significantly predict venture survival. Together, these findings make ample contributions to the literature and provide interesting opportunities for further research.
HIV Drug Susceptibility and Treatment Response to Mega-Haart Regimen in Patients from the Frankfurt HIV Cohort
Authors: Miller Veronica , Cozzi-Lepri Alessandro , Hertogs Kurt , Gute Peter , Larder Brendan , Bloor Stuart , Klauke Stefan , Rabenau Holger , Phillips Andrew , Staszewski Schlomo 
Published: April 2022

Objective To assess the relationship between viral susceptibility at baseline and virological response in human immunodeficiency virus (HIV)–infected patients treated with multi-drug salvage regimens after multiple previous treatment failures. Design Retrospective analysis of 50 patients from the Frankfurt HIV cohort who had received treatment with a minimum of six drugs, and for whom a sample for baseline viral phenotyping was available. Methods: Viral drug susceptibility was measured retrospectively from stored samples using the Antivirogram, a recombinant virus assay based method. Virological response was defined as a viral load of <400 copies/ml at week 24. For analysis of treatment response, drop-outs were dealt with in two ways, either as failures (DAF) or censored (DAC). Several logistical regression models were applied to identify predictors of response, including baseline virus load, number of new drugs and phenotypic sensitivity scores. Results At baseline, drug resistance was extensive: 96% of patients had viruses resistant to at least one drug class and 32% had viruses resistant to all three drug classes. In the DAF analysis, 39 patients experienced virological failure. In the DAC analysis, eight were censored and 31 patients experienced virological failure. In multivariate models that adjust for baseline viral load, the number of new drugs and total phenotypic sensitivity scores, the baseline viral load and phenotypic sensitivity score remained significantly associated with virological outcome, whereas in those adjusted for baseline viral load, the number of new drugs, NRTI phenotypic sensitivity score and PI phenotypic sensitivity score, only the latter remained significantly associated with virological outcome. Both the DAF and DAC analyses produced similar results. In all models used, virological failure was shown to be significantly associated with baseline viral load and phenotypic sensitivity score. Conclusions In this retrospective analysis based on a small number of patients, viral drug susceptibility at baseline was strongly associated with virological outcome at 24 weeks, independent of covariates such as baseline viral load and treatment history. Baseline viral load also maintained a significant, independent association with virological outcome in most models.
Genotypic and Phenotypic Nevirapine Resistance Correlates with Virological Failure during Salvage Therapy Including Abacavir and Nevirapine
Authors: Jørgensen Louise Bruun , Katzenstein Terese L , Gerstoft Jan , Mathiesen Lars R , Pedersen Court , Nielsen Claus 
Published: April 2022

Objective To study the development of resistance during 8 weeks of salvage therapy with abacavir and nevirapine in combination with other reverse transcriptase inhibitors (RTIs) and protease inhibitors (PIs). Methods Samples obtained at baseline and after 8 weeks of therapy from 16 heavily pretreated patients were analysed for genotypic and phenotypic resistance. Genotypic resistance was analysed in cell-associated DNA and plasma HIV-RNA using direct sequencing. Phenotypic resistance was analysed in a PBMC-based assay and in a recombinant virus assay. Plasma viral load was measured at baseline and after 2, 4 and 8 weeks of therapy. Results The majority of patients was genotypically and phenotypically resistant to lamivudine, abacavir, zidovudine and PIs, whereas 50% of the patients showed resistance to nevirapine at baseline in at least one of the methods used. After 8 weeks of salvage therapy, no additional development of resistance against nucleoside reverse transcriptase inhibitors and PIs could be detected. However, the amount of patients resistant to nevirapine increased to 83%. When the patients were divided into two groups according to baseline resistance against nevirapine, a significantly higher transient reduction in viral load was observed in patients with nevirapine-sensitive HIV at baseline compared to patients with resistant HIV at baseline. Conclusions The transient effect of salvage therapy including abacavir and nevirapine was due to the effect of nevirapine. The lack of effect of abacavir was most likely due to cross-resistance between abacavir and lamivudine/zidovudine used in previous treatment.
Experience with Nevirapine in Previously Treated HIV-1-Infected Individuals
Authors: Wit Ferdinand WNM ,   for the Dutch HIV-treating physicians
Published: April 2022

Objective To assess the tolerability, virological, immunological and clinical effects of nevirapine in the setting of a compassionate use programme in pretreated HIV-infected individuals. Design Retrospective observational cohort-study in 13 HIV-outpatient clinics in The Netherlands. Methods Main outcome measures: plasma HIV-1 RNA levels; CD4 cell counts; incidence of new AIDS-defining diseases; multivariate analysis of predictors for virological success; incidence of skin rashes. Results 187 HIV-infected individuals treated with nevirapine in the Nevirapine Named Patient Programme in The Netherlands were included. After 48 weeks, 38% of patients had an HIV-1 RNA level below 1000 copies/ml. In multivariate regression analysis, prior treatment with three or less nucleoside analogue reverse transcriptase inhibitors, and a higher baseline CD4 cell count was predictive of virological success. The median CD4 cell count remained stable over the 48 weeks. Eleven patients experienced a new AIDS-defining event. The total incidence of rash (including rash not leading to discontinuation of nevirapine) was 13.9 and 6.4% of the patients discontinued nevirapine because of rash. None of the 28 patients with undetectable HIV-1 RNA levels at baseline developed a rash. Conclusions We conclude that nevirapine when used as part of salvage therapy, is safe and most likely to give sustained suppression of HIV-1 in patients that have been less extensively pretreated. CD4 cell counts remained stable despite the low rate of virological success, this also occurred in patients not concurrently using protease inhibitors (PIs). The incidence of nevirapine-related rash in PI-pretreated patients and especially in patients with undetectable HIV-1 RNA levels at the start of nevirapine treatment, is considerably lower than previously reported for antiretroviral-naive patients.
A Dose-Ranging Study to Evaluate the Antiretroviral Activity and Safety of Amprenavir Alone and in Combination with Abacavir in HIV-Infected Adults with Limited Antiretroviral Experience
Authors: Schooley Robert T , Clumeck Nathan , Haubrich Richard , Thompson Melanie , Danner Sven A , van Der Ende Marchina E , Sereni Daniel , Antunes Francisco , Blake Denise , Myers Richard E , Tisdale Margaret , Millard Judith , Mustafa Norman , Nacci Pantaleo 
Published: April 2022

Objective To evaluate the antiretroviral activity and safety of multiple escalating doses of amprenavir administered alone, and in combination with abacavir in HIV-1-infected adults. Design Sixty-two HIV-1-infected subjects were enrolled in a multicentre, open-label, non-randomized, dose-escalating trial. Methods Subjects were assigned to one of six dose groups and received amprenavir 300 mg twice daily, 300mg three times daily, 900, 1050, or 1200 mg twice daily for 4 weeks. One dose group received amprenavir 900 mg twice daily in combination with abacavir 300 mg twice daily for 4 weeks. Antiretroviral activity was assessed by measuring changes from baseline in plasma HIV-1 RNA levels and CD4 cell counts. Safety was evaluated by monitoring clinical adverse events and changes in laboratory values. Genotypic and phenotypic analyses were performed using ABI sequencing and the recombinant virus assay, respectively. Results At week 4, amprenavir monotherapy (900, 1050, or 1200 mg twice daily) resulted in marked decreases in plasma HIV-1 RNA levels (1.3–1.6 log10 copies/ml), and substantial increases in CD4 cell counts in the two dose groups who received 1050 mg twice daily (118x106 cells/mm3) or 1200 mg twice daily (114x106 cells/mm3). Amprenavir/abacavir resulted in median plasma HIV-1 RNA reductions of 1.8 log10 copies/ml, and median CD4 cell count increases of 138x106 cells/mm3. Amprenavir was reasonably well tolerated with few treatment-limiting adverse events. No known active site mutations associated with amprenavir resistance were selected in any of the dose groups, and no significant phenotypic resistance to amprenavir developed during 4 weeks of therapy. Conclusions The antiviral effect of amprenavir monotherapy increased with escalating doses, and all amprenavir doses were reasonably well tolerated over 4 weeks of therapy. Amprenavir/abacavir combination therapy elicited a potent antiviral effect. The three highest doses of amprenavir (900, 1050 and 1200 mg twice daily) were selected to design subsequent Phase II and III studies that confirmed the safety profile and efficacy of amprenavir in combination regimens and led to the approval of amprenavir in the USA in 1999.
Antiretroviral Activity and Safety of Abacavir in Combination with Selected HIV-1 Protease Inhibitors in Therapy-Naive HIV-1-Infected Adults
Authors: McMahon Deborah , Lederman Michael , Haas David W , Haubrich Richard , Stanford James , Cooney Elizabeth , Horton James , Kelleher Dennis , Ross Lisa , Cutrell Amy , Lee Diana , Spreen William , Mellors John W 
Published: April 2022

Objective To assess antiretroviral efficacy and safety of abacavir in combination with selected HIV-1 protease inhibitors. Design A 48-week, open-label study. Materials and Methods Eighty-two antiretroviral naive HIV-1-infected adults (CD4 cell count ≥100 cells/mm3, plasma HIV-1 RNA ≥5000 copies/ml) were randomly assigned to receive abacavir (300 mg twice daily) in combination with standard doses of one of five protease inhibitors: indinavir, saquinavir soft-gel, ritonavir, nelfinavir or amprenavir. Adults who met protocol-defined switch criteria at or after week 8 could modify their randomized therapy. Antiretroviral activity was assessed by the proportion of subjects with plasma HIV-1 RNA ≤400 and ≤50 copies/ml, and by changes in plasma HIV-1 RNA levels and CD4 cell counts. Safety was assessed by monitoring clinical adverse events and laboratory abnormalities. Results At week 48, the proportion of subjects in the indinavir, saquinavir, ritonavir, nelfinavir and amprenavir groups with plasma HIV-1 RNA ≤400 copies/ml was 53, 50, 50, 41 and 56%, respectively, and the proportion with HIV-1 RNA ≤50 copies/ml was 47, 56, 50, 47, and 44%, respectively (by intent-to-treat analysis). Median reductions from baseline in plasma HIV-1 RNA for each group ranged from 1.7 to 2.4 log10 copies/ml. The median CD4 cell count increase from baseline was 195, 131, 116, 136 and 259 cells/mm3 in the indinavir, saquinavir, ritonavir, nelfinavir, and amprenavir groups, respectively. Overall, the most common adverse events attributed to study drugs were diarrhoea, nausea, malaise/fatigue, headache and perioral paresthesia. The frequency of treatment-limiting adverse events did not differ between groups. Conclusions: Abacavir is safe and effective when used in combination with a protease inhibitor.
Low-Rate Emergence of Thymidine Analogue Mutations and Multi-Drug Resistance Mutations in the HIV-1 Reverse Transcriptase Gene in Therapy-Naive Patients Receiving Stavudine plus Lamivudine Combination Therapy
Authors: Mouroux Mireille , Descamps Diane , Izopet Jacques , Yvon Anne , Delaugerre Constance , Matheron Sophie , Coutellier Anne , Valantin Marc-Antoine , Bonmarchand Manuella , Agut Henri , Massip Patrice , Costagliola Dominique , Katlama Christine , Brun-Vezinet Françoise , Calvez Vincent 
Published: April 2022

Objectives Mutations usually associated with zidovudine exposure have been observed in zidovudine-naive patients treated by stavudine in combination. These mutations were named thymidine analogue mutations (TAMs). This fact, combined with phenotypical and biochemical findings provided additional evidence for cross-resistance between zidovudine and stavudine. A recent genotypic study in naive patients receiving stavudine/didanosine combination showed emergence of TAMs and a multidrug-resistance mutation (MDR), Q151M, in 36 and 10% of cases, respectively. Stavudine plus lamivudine is one of the most used binucleoside associations in the antiretroviral combinations. The objective of this study was to assess the genotypic changes in the HIV-1 reverse transcriptase (RT) gene in antiretroviral-naive patients treated by stavudine plus lamivudine. Methods We analysed the RT gene of 44 HIV-1 patients, naive of antiretroviral therapy, who were treated for 24 or 48 weeks with stavudine/lamivudine. Results: At the end of the follow-up, all patients acquired the lamivudine-associated mutation M184V. Only two subjects (4.5%) developed a TAM (T215Y; M41L), one subject developed a V75T/A mutation and one subject developed the particular MDR pattern F116Y, Q151M. Conclusions Our study clearly demonstrated that naive subjects treated with stavudine/lamivudine for 24–48 weeks selected a low rate of TAMs and MDR Q151M. One hypothesis explaining these results could be the development of the M184V mutation.
A Randomized Clinical Trial Comparing Nelfinavir Or Nevirapine Associated to Zidovudine/Lamivudine in HIV-Infected Naive Patients (The Combine Study)
Authors: Podzamczer Daniel , Ferrer Elena , Consiglio Ezequiel , Gatell José Mariá , Perez Pepa , Perez José Luis , Luna Elena , González Alicia , Pedrol Enric , Lozano Luisa , Ocaña Imma , Llibre Josep María , Casiró Arnaldo , Aranda Miquel , Barrufet Pilar , Martínez-Lacasa Javier , Miró José María , Badía Xavier , Casado Alfonso , Lupo Sergio , Cahn Pedro , Maños Manel , Estela Jordi ,   the Combine Study Team (members listed in Appendix), Barberá MJ , Santín M , Gudiol F , Hidalgo M , Knobel H , Azuaje C , Ribera E , Roget M , Force Lluis , Dalmau D , Suarez C 
Published: April 2022

Background Non-nucleoside reverse transcriptase inhibitor-containing regimens may be a valid alternative to protease inhibitor-containing regimens for initial antiretroviral therapy, but to date few studies comparing these two strategies have been performed. Objective To evaluate the efficacy and safety of nelfinavir or nevirapine associated to zidovudine/lamivudine in HIV-infected naive patients. Design Randomized, open-label, multicentre trial. Setting Twelve centres in Spain (9) and Argentina (3). Patients One hundred and forty-two HIV-infected naive patients without AIDS. Interventions Patients received combivir (zidovudine 300 mg/lamivudine 150 mg, twice-daily) plus either nelfinavir (1250 mg) twice-daily (zidovudine/lamivudine/nelfinavir, n=70) or nevirapine (200 mg) twice-daily (zidovudine/lamivudine/nevirapine, n=72), and were followed for 12 months. The primary endpoint was the proportion of patients with a plasma HIV-1 RNA (pVL) of less than 200 copies/ml by PCR at 12 months. pVL of less than 20 copies/ml (PCR), changes in CD4 counts, clinical progression and adverse events were also evaluated. Efficacy was assessed using intent-to-treat (ITT) (missing=failure) and on-treatment analysis. Results At 12 months in the ITT analysis the proportion of patients with pVL below 200 copies/ml was 60% (95% CI 48.5–71.5) in the zidovudine/lamivudine/nelfinavir arm and 75% (95% CI 65–85) in the zidovudine/lamivudine/nevirapine arm ( P=0.06), and the proportion below 20 copies/ml was 50% (95% CI 38.3–61.7) and 65% (95% CI 54.2–76.2), respectively ( P=0.06). No differences were found when comparing the subgroup of patients with baseline pVL of more than 100 000 copies/ml. A gain of +173 and +162 CD4 cells/mm3, respectively, was observed. Zidovudine/lamivudine/nelfinavir was discontinued in 21% of patients, and zidovudine/lamivudine/ nevirapine in 25%, due to toxicity ( P>0.2). Conclusions Our results suggest that zidovudine/ lamivudine/nevirapine is at least as effective as zidovudine/lamivudine/nelfinavir as first-line therapy for HIV disease.
Adherence to Antiretroviral Therapy and Outcomes in HIV-Infected Patients Enrolled in An Induction/Maintenance Randomized Trial
Authors: Flandre Philippe , Peytavin Gilles , Meiffredy Vincent , Saidi Yacine , Descamps Diane , Delagnes Martine , Brun-Vézinet Françoise , Raffi François ,   for the Trilège (Agence Nationale de Recherches sur le SIDA 072) Study Team
Published: April 2022

Objective To examine the effect of adherence to therapy on early virological response, later virological failure, and occurrence of adverse events in HIV-infected patients. Design A randomized trial of 3-month induction period of zidovudine/lamivudine/indinavir followed by a maintenance phase of zidovudine/lamivudine/indinavir, zidovudine/lamivudine or zidovudine/indinavir. Main outcomes Adherence was assessed by pill count. In the induction phase, early virological response was defined as plasma HIV-RNA<500 copies/ml at month 2 and in the maintenance phase, virological failure was defined as plasma HIV-RNA >500 copies/ml in two consecutive specimens. Results The median adherence rate was 97% in both induction ( n=366) and maintenance phase ( n=237). In the maintenance phase, pairwise comparisons showed a lower adherence rate in zidovudine/lamivudine/indinavir versus zidovudine/lamivudine ( P=0.03), or versus zidovudine/indinavir ( P=0.05). Only 13% of patients had an adherence over the maintenance phase of 80% or lower, while 40% of patients occasionally had an adherence rate of 80% or lower during this phase. Among the 362 patients with documented HIV-RNA at month 2, 86% had an early virological response. Adherence of 80% or greater was the only variable statistically predictive to early virological response ( P<0.001), while baseline CD4, baseline HIV-RNA, and adherence of 95% or greater were not associated to virological response. In the maintenance phase, adherence, baseline HIV-RNA, HIV-RNA at month 3 and treatment groups were independently predictive to time to virological failure. Analysis by randomized groups indicated that difficulty in adherence (<80%) was predictive to time to failure ( P<0.001) only in both indinavir-containing regimens. Occurrence of two or more severe adverse events (grade 3 and 4) was higher in patients with poor adherence although not statistically associated ( P=0.12), while no association was found with minor adverse events. Conclusion Adherence rate was globally lower in patients maintaining the original triple-drug therapy compared with those receiving less intensive regimens. Adherence rate was a time-dependent variable. Adherence to antiviral regimen of 80% or greater was predictive to early virological response, and adherence rate lower than 80% or 95% was predictive to virological failure, especially in indinavir-containing regimens. Occurrence of adverse events was not clearly associated to adherence.
Analysis of Virological Efficacy in Trials of Antiretroviral Regimens: Drawbacks of Not Including Viral Load Measurements after Premature Discontinuation of Therapy
Authors: Kirk Ole , Pedersen Court , Law Matthew , Gulick Roy M , Moyle Graeme , Montaner Julio , Eron Joseph J , Phillips Andrew N , Lundgren Jens D 
Published: April 2022

Objectives To compare two analytic approaches to assess the virological effect of HAART according to the intention-to-treat (ITT) principle. Material Data from 2318 patients enrolled in 10 randomised clinical trials (RCTs) and from 3091 patients followed in an observation cohort (EuroSIDA) starting their first HAART regimen. Methods Two classifications of defining virological response 48 weeks after starting the therapy to be evaluated were compared: 1) only patients remaining on the therapy and having a plasma viral load (pVL) below a given cut-off level at week 48 were classified as responders (ITT/s=f); and 2) patients with a pVL below a given cut-off at week 48 whether they remained on initial assigned therapy or switched therapy were responders (ITT/s incl). In both analyses, patients with missing data at week 48 were classified as failures (i.e., non-responders). Results According to ITT/s=f, 22–70% of the patients starting a HAART regimen in a RCT experienced a virological response at week 48. Only two RCTs had complete follow-up data ( n=424): between 29 and 62% achieved a virological response at week 48 in the six treatment arms evaluated in the studies according to ITT/s=f, and 41–72% according to ITT/s incl. Among those who discontinued the therapy to be evaluated in these two trials, 13–45% (cohort: 39–74%) subsequently experienced a virological response at week 48. The subsequent response rates were associated with the reason for discontinuation (toxicity versus confirmed virological failure: 63 vs 33%), varied largely across regimens and were not associated with the discontinuation rate. Conclusions Discontinuation of follow-up at switch from the therapy to be evaluated remains common in anti-retroviral treatment trials, but leads to an imprecise and incomplete assessment of the intrinsic effect of a given regimen. Complete follow-up of all patients should be encouraged strongly as this will allow for several complementary analytic approaches and a focus on optimal treatment strategies rather than specific regimens.