bluuebunny/crossref_metadata_2025_split huggingface dataset:
Persisting Long-Term Benefit of Genotype-Guided Treatment for HIV-Infected Patients Failing Haart. The Viradapt Study: Week 48 Follow-Up
Authors: Clevenbergh P , Durant J , Halfon P , del Giudice P , Mondain V , Montagne N , Schapiro JM , Boucher CAB , Dellamonica P 
Published: April 2022

Objective We report the 12 months follow-up of the patients who participated in the Viradapt study. Methods A total of 108 HIV-infected patients failing antiretroviral (ARV) therapy (HIV RNA >10000 copies/ml, therapy >6 months with nucleoside reverse transcriptase inhibitors, >3 months with protease inhibitors (PIs) were randomized into two arms: standard of care in the control arm, and treatment according to the resistance mutations in the protease and reverse transcriptase genes in the study arm. After the first 6 months of the randomized study, open-label, genotype-guided treatment was offered in both arms. A multivariate analysis was performed to assess the predictive factors of treatment success (HIV RNA <200 copies/ml). Results The two arms were comparable in terms of risk factors, age, sex, previous treatments, CD4 cell count and log10 HIV-1 RNA at baseline. At week 24, an interim combined analysis showed a statistically significant difference in the drop in viral load at months 3 and 6 ( P=0.015, repeated measures analysis of variance) in favour of the genotype group. Patients in both arms were then offered open-label genotyping. Genotype analysis was performed every 3 months, and treatment changes could accordingly be made. As some of the patients in the control arm had already progressed to months 9 or 12, only 69% (30/43) of these patients received genotype-guided treatment changes. In the genotype arm, the mean drop in HIV RNA of 1.15 log10 copies/ml, obtained at month 6, persisted at months 9 and 12 (1.15 log10 copies/ml ±0.17). In the control arm, an additional drop in HIV RNA to 0.98 log10 ±0.22 copies/ml was observed by month 12. In control patients receiving open-label genotype, the percentage of patients with HIV-1 RNA levels below detection limit (200 copies/ml) rose from 14% at month 6 to 30.5% at month 12. This percentage in the study arm remained stable at 31.3% and 30% at months 9 and 12, respectively. Genotype-guided therapy, primary protease mutations and PI plasma concentrations were significantly correlated with virological success. Conclusions In this heavily pretreated patient population, genotype-guided therapy resulted in a sustained reduction in HIV RNA of greater than one log10 throughout a 1 year follow-up period. Performance of genotype-guided therapy may have contributed to the additional viral load reduction seen in patients in the control group who received open-label genotyping after the 6 month point. Multivariate analysis showed that the presence of primary protease mutations, performance of genotype-guided treatment changes and PI plasma concentrations independently affected virological response.
Virological Failure among Patients on Haart from across Europe: Results from the Eurosida Study
Authors: Mocroft A , Miller V , Chiesi A , Blaxhult A , Katlama C , Clotet B , Barton S , Lundgren Jens D 
Published: April 2022

Objectives To monitor the response to highly active anti-retroviral therapy (HAART) over time and the proportions of patients with poor virological control in order to help provide some insight into drug resistance. Design Analysis of data from the EuroSIDA study; an observational study initiated in 1994 of almost 8500 patients with HIV from across Europe. Methods Patients who initiated HAART, and had both a CD4 lymphocyte count and viral load measured in the 3 months prior to starting HAART, were included in analyses. The proportion of patients with a poor virological response (defined as a viral load of >10 000 copies/ml, using either a single measure or two consecutive measures) at 16 and 48 weeks was determined. Multivariate logistical regression was used to determine the factors associated with a poor virological response at both time points. Results Median CD4 cell count at starting HAART was 218 cells/mm3 [interquartile range (IQR), 113–327 cells/mm3] and median viral load was 4.36 log10 copies/ml (IQR, 3.57–5.04 log10 copies/ml). At 16 weeks, 16% had a viral load of >10 000 copies/ml based on a single viral load measure and 10% if the more stringent definition of two consecutive viral loads above this level was used. At 48 weeks these proportions were 19% and 13%, respectively. Compared with patients from Southern Europe, patients from both Central and Northern Europe had approximately half the chance of a poor virological response at 16 weeks (odds ratios 0.53 and 0.47, P=0.0015 and P<0.0001, respectively), while at 48 weeks both regions still had approximately a 25% reduced chance of a poor virological response, but this was no longer statistically significant (odds ratio 0.77 and 0.75, P=0.17 and P=0.13, respectively). Conclusions There were marked differences in virological response to HAART across regions of Europe, which may be partly explained by regional differences in access to HAART and utilisation. If drug resistance is closely related to virological failure, these results may help to provide an early insight into the potential problem of drug resistance across Europe. Continued follow-up is essential to monitor patients with poor virological control.
Effectiveness and Pitfalls of Initial Highly Active Antiretroviral Therapy in HIV-Infected Patients in Routine Clinical Practice
Authors: Moreno Ana , Perez-Elías María J , Casado Jose L , Muñoz Vicente , Antela Antonio , Dronda Fernando , Navas Enrique , Fortún Jesús , Quereda Carmen , Moreno Santiago 
Published: April 2022

Objective To assess the long-term effectiveness of and factors associated with response to protease inhibitors (PIs) in a cohort of treatment-naive HIV-infected patients. Design and setting Prospective study in a tertiary care centre. Subjects A total of 207 treatment-naive patients starting PIs from March 1996 to May 1998. Main outcome measures: Clinical, virological and immunological outcomes, and adherence to therapy after 12 months. Results Baseline median CD4 cell count and viral load were 160 cells/mm3 and 5 log10 copies/ml, respectively. After 48 weeks, 168 patients (81%) reached plasma HIV-RNA levels below 400 copies/ml, and the mean increase in CD4 cell count was 196 cells/mm3. Clinical events were observed in 29 patients (14%) after a median time of 100 days on therapy, yet mortality was extremely low (0.9%). By multivariate analysis, adherence over 90% [relative risk (RR), 16.66; 95% confidence interval (CI), 5.26–50; P=0.00001] and AIDS diagnosis at baseline (RR 0.35; 95% CI, 0.14–0.90; P=0.02) were the strongest predictors for virological suppression. An immunological recovery over 100 cells/mm3 was significantly associated with an initial virological response (RR 2.94; 95% CI, 1.31–6.66; P=0.009) and adherence over 90% (RR 3.44; 95% CI, 1.61–7.69; P=0.005). There were high rates of change with the first PI (40%), mostly due to adverse events (51%), but it did not compromise long-term effectiveness. Conclusions: Initial PI treatment in the clinical setting is able to reach equally good outcomes as those found in controlled trials. Changes in therapy due to toxicity do not compromise a successful outcome, which clearly depends on an adequate adherence to therapy.
Durable HIV-1 Suppression with Indinavir after Failing Lamivudine-Containing Double Nucleoside Therapy: A Randomized Controlled Trial
Authors: Foudraine Norbert A , Jurriaans Suzanne , Weverling Gerrit Jan , Burger David M , Hoetelmans Richard MW , Roos Marijke TL , Maas Jaap , Miedema Frank , Reiss Peter , Portegies Peter , de Wolf Frank , Lange Joep MA 
Published: April 2022

Objective To assess the durability of the antiretroviral effect in plasma and cerebrospinal fluid (CSF) of antiviral therapy intensification, produced by the addition of indinavir from week 12 onwards to the original regimen of zidovudine/lamivudine or stavudine/lamivudine, after 72 weeks of follow-up using an ultrasensitive HIV-1 RNA assay. To assess CSF concentrations of indinavir at week 48. Design In a prospectively, randomized, open, single-centre study, antiretroviral-naive patients (CD4 cell count ≥200 cells/μl and a plasma HIV-1 RNA level ≥10000 copies/ml) were assigned to a combination of zidovudine/lamivudine or stavudine/lamivudine. Indinavir could be added to the double nucleoside analogue regimen from week 12 or thereafter in case the plasma HIV RNA level was insufficiently suppressed (>500 copies/ml). Results Forty-seven patients were enrolled (23 stavudine/lamivudine and 24 zidovudine/lamivudine), of whom 33 completed a follow-up of 72 weeks. Indinavir was added in 89% (42/47) of the patients. Only one discontinuation occurred due to virological failure. At week 72, the median plasma HIV-1 RNA levels in the zidovudine/lamivudine group had decreased from 4.80 log10 copies/ml to <500 copies/ml in 100% of patients and <50 copies/ml in 86.6% of the patients. In the stavudine/lamivudine group the plasma HIV-1 RNA decreased from 4.98 log10 copies/ml at baseline to <500 copies/ml in 100% of patients and <50 copies/ml in 66.7% of the patients. On an intent-to-treat basis these figures were 54.2 and 52.2% for zidovudine/lamivudine and stavudine/lamivudine, respectively, for the 50 copies/ml assay. The median CD4 cell count increased from 315 cells/μl, with 150 cells/μl in the zidovudine/lamivudine arm, and from 290 cells/μl, with 310 cells/μl in the stavudine/lamivudine arm ( P=0.0001). However, the percentage of CD4 cells did not differ in each group. In the zidovudine/lamivudine group 9/10 and 5/5, and in the stavudine/lamivudine group 11/11 and 6/6 had a CSF HIV-1 RNA level <50 copies/ml at week 12 and 48, respectively. The CSF indinavir concentration ranged from 50 to 170 ng/ml. Conclusion The long-term HIV-1 suppression observed in this study is remarkable, as adding a single antiretroviral agent to a failing regimen goes against current notions of adequate therapy.
Using a Database of HIV Patients Undergoing Genotypic Resistance Test after Haart Failure to Understand the Dynamics of M184V Mutation
Authors: Zaccarelli Mauro , Perno Carlo Federico , Forbici Federica , Cingolani Antonella , Liuzzi Guiseppina , Bertoli Ada , Trotta Maria Paola , Bellocchi Maria Concetta , Di Giambenedetto Simona , Tozzi Valerio , Gori Caterina , D'Arrigo Roberta , De Longis Patrizio , Noto Pasquale , Girardi Enrico , De Luca Andrea , Antinori Andrea 
Published: April 2022

Objective M184V/I mutation is associated with high-level phenotypic resistance to lamivudine (3TC). The aim of the present analysis was to correlate the time of appearance/disappearance of M184V/I with duration of 3TC treatment. Methods Overall, 211 patients were selected from a database of HIV patients undergoing genotypic resistance test after virological failure of HAART regimens in two major reference centres in Rome between 1999 and 2001. At the time of genotyping, 120 of them (56.9%) were failing a 3TC-including HAART, while 91 (43.1%) received 3TC only in previous HAART. Duration of the current 3TC-containing regimen and the time from the end of last 3TC treatment to genotypic resistance test (GRT) were analysed. Results Among patients currently undergoing 3TC-containing HAART, the prevalence of M184V/I was 82.5% (78.3/4.2%, respectively) and significantly associated to current 3TC use at GRT. Prevalence of M184V/I was associated to longer history of 3TC (from 47.1% in patients treated with 3TC for <6 months, to 84.0% among those treated for 7–12 months; 100.0% of patients with >42 months of current 3TC carried M184V. At logistic regression analysis, the rate of increase of M184V/I in 3TC-failing patients was statistically significant (OR: 1.066 per month of current 3TC therapy, 95% CI: 1.020–1.114, P<0.01), suggesting a 6.6% monthly increase of probability of M184V/I. Among patients who interrupted 3TC, overall prevalence of M184V/I was 23.1%: proportion of patients carrying the M184V/I dropped from 83.3% among those who interrupted 3TC from ≤3 months, to 56.3, 20, 10.5 and 0% for those interrupting 3TC from 6, 12, 24 and ≥24 months, respectively. At logistic regression, the rate of disappearance of M184V/I was also statistically significant (OR: 0.883 per month, 95% CI: 0.804–0.970, P=0.01), indicating a 11.7% monthly decrease of probability of M184V/I after 3TC interruption. Conclusions Dynamics of appearance/disappearance of M184V/I mutation is rapid after 3TC failure/interruption, suggesting ease of development of such a mutation, but also suggesting a remarkable growth disadvantage for HIV. From the clinical perspective, recycling of drugs whose antiviral activity is affected by M184V mutation can be successful after appropriate drug wash-out, also in heavily pretreated patients.
ISDR Pattern and Evolution in Patients with Chronic Hepatitis C Treated with Standard Or Peg-Ifn plus Ribavirin
Authors: Cappiello Giuseppina , Abbate Isabella , Iacono Oreste Lo , Longo Roberta , Solmone Mariacarmela , Ferraro Donatella , Antonucci Giorgio , Di Marco Vito , Di Stefano Rosa , Craxì Antonio , Ippolito Giuseppe , Capobianchi Maria Rosaria 
Published: April 2022

The aim of the study was to characterize the interferon sensitivity determining region (ISDR) mutation pattern and its changes at 4 weeks of treatment in a population of patients infected with hepatitis C virus (HCV) genotype 1b receiving standard or PEG-IFN plus ribavirin (RBV), to find possible early correlates of therapy outcome. Forty-five patients with chronic hepatitis due to HCV 1b were treated by PEG-IFN-α2b (n=23) or IFN-α2b (n=22) plus RBV 1000–1200 mg/day. They were classified 24 weeks after stopping therapy as sustained responders (SR), relapsers (REL) or non-responders (NR). Sixteen patients were SR, 12 REL and 17 NR. ISDR mutations were evaluated by direct sequencing at baseline in all and after 4 weeks in patients with detectable viraemia (n=30). The frequency of the three ISDR types was 26.7% wild-type, 64.4% intermediate-type and 8.9% mutant-type, without significant difference in their frequency in SR, REL and NR, independent of IFN formulation. Average numbers of mutations in SR, REL and NR were 1.88 ±0.54, 1.33 ±0.33 and 0.94 ±0.25, respectively, P>0.05. The baseline number of ISDR mutations was not related to the extent of viral load decline in the first month of therapy. Sequence analysis of ISDR region performed 4 weeks after starting therapy revealed qualitative or quantitative changes of ISDR sequence in only seven patients, without correlation with response. Thus, in our patients the baseline pattern of ISDR was unrelated to treatment outcome. Selection towards a dominant IFN-resistant strain did not occur under standard or PEG-IFN plus RBV.
Total Lymphocyte Count as a Possible Surrogate of Cd4 Cell Count to Prioritize Eligibility for Antiretroviral Therapy among HIV-Infected Individuals in Resource-Limited Settings
Authors: Bedell Richard , Heath Katherine V , Hogg Robert S , Wood Evan , Press Natasha , Yip Benita , O'Shaughnessy Michael V , Montaner Julio SG 
Published: April 2022

Objective To characterize the value of total lymphocyte counts in predicting risk of death among patients initiating triple combination antiretroviral therapy. Methods Study subjects included antiretroviral-naive persons aged 18 years or older who initiated treatment with triple combination therapy between August 1 1996 and September 30 1999 in a population-based observational cohort of HIV-infected individuals. Total lymphocyte counts as well as CD4 count and plasma viral load were assessed at baseline. Separate Cox proportional hazards models were devised to evaluate the effect on survival of total lymphocyte count in lieu of or with CD4 count after adjustment for other prognostic factors including plasma viral load. Results A total of 733 antiretroviral-naive persons initiated triple drug combination antiretroviral therapy over the study period with a median follow-up of 29.5 months. In the first analysis, only baseline CD4 cell counts of 50–199 cells/μl or less than 50 μl were associated with an increased risk of mortality [adjusted relative risk (ARR) 2.90; 95% CI: 1.40, 5.98] and (ARR 6.30; 95% CI: 2.93, 13.54), respectively. When CD4 counts were excluded from the analysis as if unavailable, total lymphocyte count of between 0.8 and 1.4 G/l, and less than 0.8 G/l were both significantly associated with an increased risk of mortality (ARR 2.36; 95% CI: 1.16, 4.78) and (ARR 6.17; 95% CI: 2.93, 13.01), respectively. Conclusion Total lymphocyte count may provide a simple and cost-effective alternative for prioritizing therapy initiation in resource-limited settings. Our results suggest that, if appropriately validated, judicious application of total lymphocyte counts could overcome one of the practical obstacles to more widespread provision of antiretroviral therapy in resource-poor settings.
Medium-Term Survival, Morbidity and Immunovirological Evolution in HIV-Infected Adults Receiving Antiretroviral Therapy, Abidjan, Côte D'Ivoire
Authors: Seyler Catherine , Anglaret Xavier , Dakoury-Dogbo Nicole , Messou Eugène , Touré Siaka , Danel Christine , Diakité Nafissa , Daudié Alain , Inwoley André , Maurice Chantal , Tonwe-Gold Besigin , Rouet François , N'Dri-Yoman Thérèse , Salamon Roger ,   for the ANRS 1203 Study Group
Published: April 2022

Objectives To evaluate survival, morbidity, and CD4 and viral load (VL) evolution in HIV-infected adults receiving antiretroviral therapy (ART) in Côte d'Ivoire. Methods Since 1996, 723 HIV-infected adults have been followed up in the ANRS 1203 cohort study in Abidjan. For those patients who received ART, we describe data between ART initiation and August 2002. Results One-hundred-and-one adults (61% women) were followed up under ART for a median of 17 months. At ART initiation, median age, CD4 count and VL were 36 years, 135/mm3 and 5.3 log10 copies/ml, respectively. Initial ART regimens were two nucleoside reverse transcriptase inhibitors (NRTIs) plus one protease inhibitor in 74 patients, two NRTIs plus one non-nucleoside reverse transcriptase inhibitor in 16, and two NRTIs in 11. No patient was lost to follow-up. The most frequent causes of severe morbidity were bacterial infections [11.6/100 person-years (PY), 95% CI: 7.2–18.7], drug-related events (6.5/100 PY, 3.5–12.0), tuberculosis (3.1/100 PY, 1.3–7.4) and malaria (3.1/100 PY, 1.3–7.4). The incidence of death was 3.0/100 PY (1.1–8.0) in patients with baseline CD4 ≥50/mm3 and 16.1/100 PY (7.2–35.9) in patients with CD4 <50/mm3. Fifty percent of causes of death were active infections pre-existing ART initiation, mainly atypical mycobacteriosis. After 1 year, 51% of patients had undetectable VL, 28% had detectable VL reduced by more than 0.5 log10 copies/ml since ART initiation, and the median gain in CD4 was +115/mm3. Conclusion Medium-term survival under ART may be as good in Africa as in industrialized countries, provided that patients benefit from access to care for opportunistic infections, including bacterial diseases, tuberculosis and malaria.
Impact of Early versus Late Adherence to Highly Active Antiretroviral Therapy on Immuno-Virological Response: A 3-Year Follow-Up Study
Authors: Carrieri Maria Patrizia , Raffi François , Lewden Charlotte , Sobel Alain , Michelet Christian , Cailleton Valérie , Chêne Geneviève , Leport Catherine , Moatti Jean-Paul , Spire Bruno ,   the APROCO study group,   Scientific Committee, Leport C , Raffi F , Chêne G , Salamon R , Moatti J-P , Pierret J , Brun-Vézinet F , Fleury H , Peytavin G , Garraffo R ,   Other members, Costagliola D , Dellamonica P , Katlama C , Meyer L , Morin M , Sicard D , Sobel A , Ballereau F ,   Observers, Bach M-A , Bourdillon F , Choutet P , Delfraissy J-F , Dormont J , Souteyrand Y , Vildé J-L ,   Events Validation Committee, Dupon M , Le Moing V , Marchou B , May T , Morlat P , Waldner-Combernoux A ,   Monitoring and statistical analysis, Alfaro C , Boucherit S , Cailleton V , Charlois C , Droz C , Duran S , Ecobichon JL , Egouy C , Journot V , Lassalle R , Latour L , Le Moing V , Lewden C , Masquelier B , Nouioua W , Palmer G , Petit C , Préau M , Roloff S , Savès M , Spire B , Winum R ,   Sponsorship,   Other supports,   Scientific Committee,   Clinical centres (coordinators)
Published: April 2022

Objective To assess the impact of different patterns of adherence to highly active antiretroviral therapy (HAART), in particular, the relative impact of early and late adherence, on long-term immuno-virological response in HIV-infected individuals started on a protease inhibitor-containing regimen. Design Clinical, immuno-virological and self-reported adherence data were collected at 4 (M4), 12 (M12), 20 (M20), 28 (M28) and 36 (M36) months after HAART initiation in the French APROCO cohort. Methods A standardized self-administered questionnaire classified patients as non-adherent, moderately or highly adherent at each visit. Stable viral suppression at both M28 to M36, and a CD4 cell increase >200 between M0 and M36 were used as outcome measures. Results Of the 582 patients followed regularly through M36, 360 patients had complete adherence data. Although 59.2% were highly adherent at M4, only 25.8% maintained consistent high adherence throughout the follow-up. High adherence at M4 was independently associated with both stable viral suppression at M28–M36 [OR (95% CI): 2.8 (1.4–5.5)] and a CD4 cell increase >200 during the same period [OR (95% CI): 3.9 (1.7–9.7)]. However, ‘moderately adherent’ patients between M12 and M36 had the same likelihood [OR (95% CI): 1.9 (1.1–3.2)] as patients who were always high adherent [OR (95% CI): 1.9 (1.1–3.2)] of achieving stable viral load suppression, relative to those who reported non-adherence episodes. Conclusion Optimizing adherence in the early months of treatment is crucial to ensure long-term immuno-virological success. Moderate deviations from high adherence during follow-up have a less negative impact. Priority should be given to interventions aimed to improve adherence in the early months of HAART.