bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Maturation Inhibitor Bevirimat (PA-457) can be Active in Patients Carrying HIV type-1 non-B Subtypes and Recombinants
Authors: Yebra Gonzalo , Holguín Africa 
Published: April 2022

Background Bevirimat (PA-457) is the first candidate of a new family of antiretroviral drugs, the maturation inhibitors. Its action is based on disruption of the protease cleavage of the Gag precursor region. Six resistance mutations have been described and analysed in virus from both treatment-naive and protease inhibitor (PI)-experienced patients, but only in the subtype B of HIV type-1 (HIV-1) virus. Thus, genotypic resistance in non-B subtypes still requires analysis. Methods HIV-1 sequences of different subtypes (54 B, 81 non-B and recombinants) were analysed for the presence of resistance mutations to bevirimat, located within the capsid (CA) protein and spacer peptide 1 (SP1) cleavage site. Results No resistance mutations were found, although polymorphisms appeared in some CA-SP1 residues. The C-terminal CA protein and the N-terminal SP1 presented high conservation, whereas C-terminal SP1 was highly variable in sequence and length, with unknown influence in resistance acquisition. Conclusions The results of the present study confirm an absolute conservation of the residues involved in bevirimat in vitro resistance in a large panel of HIV-1 subtypes and recombinants from both treatment-naive and PI- experienced patients. Treatment alone seemed to increase the polymorphisms account in CRF02_AG recombinant sequences; however, the influence of natural polymorphisms needs to be explored.
Virodynamic Predictors of Response to Pegylated Interferon and Lamivudine Combination Treatment of Hepatitis B e Antigen-Positive Chronic Hepatitis B
Authors: Mihm Ulrike , Chan Henry Lik-Yuen , Zeuzem Stefan , Chim Angel Mei-Ling , Hui Alex Yui , Wong Vincent Wai-Sun , Sung Joseph Jao-Yiu , Herrmann Eva 
Published: April 2022

Background Early identification of non-responders to interferon-α and development of stopping rules are needed in patients with chronic hepatitis B to reduce treatment-related costs and morbidity. Methods In total, 47 patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B received pegylated interferon-α2b for 8 weeks, lamivudine plus pegylated interferon-α2b combination therapy for 24 weeks and lamivudine monotherapy for 28 weeks. Sustained virological response was defined as HBeAg seroconversion and hepatitis B virus (HBV) DNA<105 copies/ml at the end of treatment and after 52 weeks of follow-up. The early HBV DNA data from the first 12 weeks of therapy were fitted by a viral kinetic model. Results Cutoff values for prediction of sustained virological response were defined as a rate of infected cell loss δ≥0.005 per day (negative predictive value [NPV] 100% and positive predictive value [PPV] 33.3%) and log values of the area under the mathematically predicted HBV DNA curve between baseline and week 12 of therapy ≤8.9 log10 copies/ml x days (NPV 100% and PPV 50%). By the latter cutoff, 25/36 (69.4%) patients without sustained virological response could be identified after 12 weeks of therapy. Conclusions In the present study, mathematical modelling of viral dynamics allowed prediction of sustained virological response after 12 weeks of therapy. Virodynamic predictors for sustained virological response should be further validated. The area under the mathematically predicted HBV DNA curve seems a promising candidate for potential cutoff values as it summarizes the influence of baseline HBV DNA and treatment effects.
Refining Abacavir Hypersensitivity Diagnoses using a Structured Clinical Assessment and Genetic Testing in the Swiss HIV Cohort Study
Authors: Rauch Andri , Nolan David , Thurnheer Christine , Fux Christoph A , Cavassini Matthias , Chave Jean-Philippe , Opravil Milos , Phillips Elizabeth , Mallal Simon , Furrer Hansjakob ,   the Swiss HIV Cohort Study
Published: April 2022

Background We aimed to assess the value of a structured clinical assessment and genetic testing for refining the diagnosis of abacavir hypersensitivity reactions (ABC-HSRs) in a routine clinical setting. Methods We performed a diagnostic reassessment using a structured patient chart review in individuals who had stopped ABC because of suspected HSR. Two HIV physicians blinded to the human leukocyte antigen (HLA) typing results independently classified these individuals on a scale between 3 (ABC-HSR highly likely) and -3 (ABC-HSR highly unlikely). Scoring was based on symptoms, onset of symptoms and comedication use. Patients were classified as clinically likely (mean score ≥2), uncertain (mean score ≥-1 and ≤1) and unlikely (mean score ≤-2). HLA typing was performed using sequence-based methods. Results From 131 reassessed individuals, 27 (21%) were classified as likely, 43 (33%) as unlikely and 61 (47%) as uncertain ABC-HSR. Of the 131 individuals with suspected ABC-HSR, 31% were HLA-B*5701-positive compared with 1% of 140 ABC-tolerant controls ( P<0.001). HLA-B*5701 carriage rate was higher in individuals with likely ABC-HSR compared with those with uncertain or unlikely ABC-HSR (78%, 30% and 5%, respectively, P<0.001). Only six (7%) HLA-B*5701-negative individuals were classified as likely HSR after reassessment. Conclusions HLA-B*5701 carriage is highly predictive of clinically diagnosed ABC-HSR. The high proportion of HLA-B*5701-negative individuals with minor symptoms among individuals with suspected HSR indicates overdiagnosis of ABC-HSR in the era preceding genetic screening. A structured clinical assessment and genetic testing could reduce the rate of inappropriate ABC discontinuation and identify individuals at high risk for ABC-HSR.
IP-10 Correlates with Hepatitis C Viral Load, Hepatic Inflammation and Fibrosis and Predicts Hepatitis C Virus Relapse or Non-Response in HIV–HCV Coinfection
Authors: Reiberger Thomas , Aberle Judith H , Kundi Michael , Kohrgruber Norbert , Rieger Armin , Gangl Alfred , Holzmann Heidemarie , Peck-Radosavljevic Markus 
Published: April 2022

Background Interferon (IFN)-γ inducible protein 10 (IP-10) is increased in hepatitis C virus (HCV) monoinfection, correlates with hepatic inflammation and predicts non-response (NR) to antiviral therapy. We aimed to clarify the role of IP-10 in HIV-HCV coinfection. Methods Serum IP-10 levels of 30 HIV-HCV- coinfected patients treated with pegylated (PEG)-IFN-α2a (180 μg/week) and ribavirin (800-1,200 mg/day) were measured at baseline and 24 h after first IFN dose. The predictive value of IP-10 was compared with established markers of treatment outcome by applying a multivariate logistic regression model. Results Patients with NR (476 ±156 pg/ml) or virological relapse (508 ±298 pg/ml) had significantly higher baseline IP-10 levels compared with patients who had a sustained virological response (SVR; 293 ±97 pg/ml, P=0.001). The IFN-induced increase of IP-10 was significantly stronger in patients with an SVR ( P=0.017). IP-10 levels were associated with HCV viral load, alanine aminotransferase (ALT) levels, hepatic inflammatory activity and fibrosis stage. Advanced fibrosis, high HCV viral load, hepatovenous pressure gradient and pretreatment IP-10>400 pg/ml predicted NR to antiviral therapy. In the multivariate analysis, IP-10 was identified as the strongest baseline predictor of SVR with a specificity and sensitivity of 83.4% and 92.9%, respectively. Conclusions Pretreatment IP-10 levels correlated with HCV viral load, ALT levels, hepatic inflammation and fibrosis. An IP-10 cutoff level of 400 pg/ml might serve as a useful predictive marker for anti-HCV therapy in HIV–HCV-coinfected patients because it could discriminate patients with expected NR or HCV relapse after therapy from patients with an SVR before starting antiviral treatment.
Antiretroviral drug resistance surveillance among drug-naive HIV-1-infected individuals in Gauteng Province, South Africa in 2002 and 2004
Authors: Pillay Visva , Ledwaba Johanna , Hunt Gillian , Rakgotho Mpho , Singh Beverly , Makubalo Lindiwe , Bennett Diane E , Puren Adrian , Morris Lynn 
Published: April 2022

Background Surveillance for transmitted HIV-1 drug resistance was conducted among drug-naive HIV-1-infected pregnant women in South Africa, where single-dose nevirapine has been in use since 2001 and a national antiretroviral treatment programme started in 2004. Methods All subjects were from the Gauteng Province and were part of the 2002 and 2004 annual antenatal HIV seroprevalence survey conducted by the South African National Department of Health. All subjects met the inclusion criteria as set out by the World Health Organisation guidelines for HIV-1 transmitted drug resistance surveillance (women <22 years of age and in first pregnancy). Genotyping was performed on viral RNA by sequencing the protease and reverse transcriptase genes. Samples were also tested for the K103N mutation using a highly sensitive allele-specific realtime PCR assay (AS-PCR). Results Of 128 eligible participants from 2002, 65 (51%) samples were successfully amplified. None of them had evidence of resistance mutations by genotyping or by AS-PCR. Of 117 eligible participants from 2004, 48 (41%) samples were successfully amplified. Of these, one had T69D and one had the K70R resistance mutation, to give a total of 2/48 (4.2%) participants with evidence of resistance mutations by genotyping. One sample that was wild-type by genotyping was positive for K103N by AS-PCR. All samples clustered phylogenetically with HIV-1 subtype C, the predominant subtype circulating in South Africa. Conclusions Using the threshold survey, resistance prevalence overall and for each drug class in 2002 and 2004 was <5% for the Gauteng province of South Africa. The detection of a low frequency of resistance mutations in the 2004 survey suggests that surveillance should be conducted annually among untreated populations to determine if this increases with time.
Surveillance of transmitted HIV drug resistance in the Manzini-Mbabane corridor, Swaziland, in 2006
Authors: Maphalala Gugu , Okello Velephi , Mndzebele Sibongile , Gwebu Prudence , Mulima Nomsa , Dlamini Sandile , Nhlabatsi Bonisile , Ginindza Themba , Ghebrenegus Yohannes , Ntilivamunda Augustine , Mwanyumba Fabian , Ledwaba Johanna , Pillay Visva , Bennett Diane E 
Published: April 2022

Background In resource-limited settings where anti-retroviral treatment (ART) is being scaled-up, the World Health Organization (WHO) recommends the surveillance of transmitted HIV drug resistance (HIVDR). We used the WHO's HIVDR threshold survey method to assess transmitted HIVDR in three antenatal clinic (ANC) sites along the corridor between the two most populous cities in Swaziland, where ART was introduced in 2003. Methods From July–August 2006, remnant sera were aliquoted from HIV serosurvey specimens collected from 70 primagravidas <25 years old attending ANC during the national HIV serosurvey. Genotyping was performed at the National Institute for Communicable Diseases, South Africa. Transmitted resistance was defined by the WHO's surveillance list of mutations. HIVDR prevalence was categorized using the WHO's threshold survey binomial sequential sampling method. Results Among the 70 eligible specimens, 61 were sequenced – 60 (98%) were identified as subtype C and one as subtype B. No major nucleoside or non-nucleoside reverse transcriptase inhibitor mutations occurred among the first 34 consecutive specimens, which supported a transmitted resistance categorization to these drug classes as <5%. One protease inhibitor mutation, M46I, was seen among the first 44 specimens, supporting a categorization of PI resistance as <5%. Conclusion Our survey indicates that prevalence of transmitted HIVDR among recently infected pregnant women along the Manzini-Mbabane corridor is low (<5%). Surveys will be carried out in this area biannually and may be extended to other areas. Surveys for transmitted resistance make up one element among a spectrum of activities to assess and support minimization of HIVDR.
Perinatal zidovudine prophylaxis in HIV type-1-infected pregnant women with thalassaemia carriage in Thailand
Authors: Briand Nelly , Pornprasert Sakorn , Ngo-Giang-Huong Nicole , Galactéros Fréderic , Pissard Serge , Tatu Thanusak , Sanguansermsri Torpong , Jourdain Gonzague , Lallemant Marc , Le Coeur Sophie 
Published: April 2022

Background To investigate a possible interaction between α-thalassaemia, β-thalassaemia and haemoglobin-E trait and the haematological parameters of HIV type-1 (HIV-1)-infected pregnant women receiving zidovudine prophylaxis for the prevention of mother-to-child HIV-1 transmission in Thailand. Methods The study sample was composed of HIV-1-infected pregnant women receiving zidovudine (300 mg twice daily) from 28 weeks of gestational age to delivery as part of the Perinatal HIV Prevention Trial (PHPT-1), a large trial investigating zidovudine use in pregnancy. These women were randomly selected and screened for haemoglobin abnormalities. Haemoglobin levels, haematocrit and erythrocyte, leukocyte, absolute neutrophil and absolute lymphocyte counts were measured at 26, 32 and 35 weeks of gestation and at delivery. PCR genotyping techniques were used to screen for haemoglobin abnormalities, which included α-thalassaemia-1 Southeast Asian type deletion, β-thalassaemia mutation (codons 41/42 [-TCTT], codon 17 [A→T], intervening sequence-I nucleotide 1 [G→T], codons 71/72 [+A]) and haemoglobin-E trait. The evolution of haematological parameters between 26 weeks and delivery was compared according to thalassaemia carriage using linear mixed models adjusted for baseline sociodemographic characteristics, HIV clinical stage, CD4+ T-cell count and viral load. Results At baseline, women with thalassaemia or haemoglobin-E trait had significantly lower haemoglobin level and red blood cell counts than women with no haemoglobin abnormalities, whereas absolute neutrophil and leukocyte counts were significantly higher. Exposure to zidovudine until delivery did not increase this difference. Conclusions Zidovudine exposure did not appear to have increased haematological toxicity in HIV-1-infected pregnant women with thalassaemia.
Body image is a major determinant of sexual dysfunction in stable HIV-infected women
Authors: Luzi Kety , Guaraldi Giovanni , Murri Rita , De Paola Maria , Orlando Gabriella , Squillace Nicola , Esposito Roberto , Vincenzo Rochira , Zirilli Lucia , Martinez Esteban 
Published: April 2022

Background Prevalence and factors associated with sexual dysfunction in HIV-positive women are poorly known. Methods This was a cross-sectional study in a cohort of HIV-infected women. Clinically stable women were invited to participate in a female sexual dysfunction (FSD) evaluation with Female Sexual Function Index (FSFI) exploring desire, arousal, lubrication, orgasm, pain and satisfaction. An FSFI score <23 was used for defining FSD. Variables evaluated included body appearance satisfaction, interference of body changes with habits, social life and attitudinal aspects of body image, health-related quality of life, hormonal assessment, menopause, cumulative exposure to antiretroviral drug classes and immune-virological parameters. Lipodystrophy was defined according to the HIV Outpatient Study definition. Results A total of 185 women completed the FSFI. The mean (±sd) age was 42 years (±5), 27% had CDC stage C, the mean (±sd) CD4+ T-cell count was 508 cells/μl (±251) and median HIV RNA was 1.7 log10 copies/ ml (interquartile range 1.7–2.6). Among 161 evaluable patients, 59 (32%) reported FSD. In a multiple linear regression analysis, desire, arousal and satisfaction domains were associated with interference of body changes with habits, social life and attitudinal aspects of body image (β=0.22, 95% confidence interval [CI] 0.06–0.37; β=0.29, 95% CI 0.10–0.48; and β=0.20, 95% CI 0.02–0.38, respectively). Lubrication and orgasm domains were associated with body image satisfaction (β=-0.49, 95% CI -0.88— 0.10 and β=-0.58, 95% CI -1.00—0.16, respectively). No significant associations with sex hormones, CDC stage, CD4+ T-cell count, HIV RNA viral load and cumulative exposure to antiretroviral drug classes were found. In women with FSD, severity of self-perceived abdominal fat accumulation showed a trend towards lower FSFI scores (ANOVA P=0.02). Conclusions FSD was highly prevalent in this cohort. Self-perceived body changes was identified as its major determinant.
Mortality and morbidity among HIV type-1-infected patients during the first 5 years of a multicountry HIV workplace programme in Africa
Authors: Van der Borght Stefaan F , Clevenbergh Philippe , Rijckborst Henk , Nsalou Paul , Onyia Ngozi , Lange Joep M , de Wit Tobias F Rinke , van der Loeff Maarten F Schim 
Published: April 2022

Background This study aimed to evaluate the effectiveness of an HIV workplace programme in sub-Saharan Africa. Methods The international brewing company, Heineken, introduced an HIV workplace programme in its African subsidiaries in 2001. Beneficiaries from 16 sites in 5 countries were eligible. HIV type-1 (HIV-1)-infected individuals were assessed clinically and immunologically, and started highly active antiretroviral therapy (HAART) if they had AIDS or had a CD4+ T-cell count <300 cells/μl. In this cohort, study patients were followed-up for vital status, new AIDS events, CD4+ T-cell count and haemoglobin. Results Over the first 5 years of the programme, 431 adults were found to be HIV-1-infected. The mortality rate among those not yet taking HAART was 2.6 per 100 person-years of observation (pyo). By October 2006, 249 patients had started HAART at a median CD4+ T-cell count of 170 cells/μl; 59 (23.7%) patients were in CDC stage C. Among patients on HAART, 25 died and 7 were lost to follow-up. The mortality rate was 3.7 per 100 pyo overall, 14 per 100 pyo in the first 16 weeks and 2.5 per 100 pyo thereafter ( P<0.0001). At 4 years after start of treatment, 89% of patients were known to be alive. The CD4+ T-cell count increased by a median of 153 and 238 cells/μl after 1 and 4 years of HAART, respectively. Conclusions In this HIV workplace programme in sub-Saharan Africa, long-term high survival was achieved.
Safety and efficacy of a double-boosted protease inhibitor combination, saquinavir and lopinavir/ ritonavir, in pretreated children at 96 weeks
Authors:   the HIV–NAT 017 Study Team, Bunupuradah Torsak , van der Lugt Jasper , Kosalaraksa Pope , Engchanil Chulapan , Boonrak Pitch , Puthanakit Thanyawee , Mengthaisong Tawan , Mahanontharit Apicha , Lumbiganon Pagakrong , Tompkins Emily , Burger David , Ruxrungtham Kiat , Ananworanich Jintanat 
Published: April 2022

Background This study aimed to assess the long-term efficacy, safety and use of therapeutic drug monitoring (TDM) of a double-boosted protease inhibitor (PI) combination, saquinavir (SQV) and lopinavir/ritonavir (LPV/r), in Thai HIV type-1 (HIV-1)-infected children who had failed on reverse transcriptase inhibitors. Methods In total, 50 children from two sites in Thailand were treated with standard dosing of SQV and LPV/r. CD4+ T-cell count and percentage, viral load (VL; HIV-1 RNA), minimum plasma drug concentrations (Cmin) and drug safety laboratory evaluations were monitored. Virological failure was defined as having two consecutive VL measures >400 copies/ml after week 12. An intention-to-treat analysis was performed. Results Baseline data were a median age of 9.3 years (interquartile range [IQR] 7.1–11.2), VL 4.8 log10 copies/ ml (IQR 4.5–5.1) and CD4+ T-cell percentage 7% (IQR 3.0– 9.5). CDC classifications were N=4%, A=14%, B=68% and C=14% of participants. Median CD4+ T-cell percentage and CD4+ T-cell count increase were 14% (IQR 7–19) and 558 cells/mm3 (IQR 308–782), respectively (both P<0.001). Overall, 37 (74%) children achieved VL<50 copies/ml with significant differences between sites (90% versus 63%). Over 96 weeks, 10 patients had virological failure. Total cholesterol and high-density lipoprotein increased significantly over time, whereas the triglycerides and low-density lipoprotein did not. Approximately 50% of participants reported no change in body shape, and 33%, 43% and 39% reported fatter arms, face and abdomen, respectively. LPV and SQV Cmin were high and stable over time. Conclusions Double-boosted SQV+LPV/r was an effective and safe alternative for a second-line regimen in children. Hypercholesterolaemia needs close follow-up. On the basis of the TDM results, PI dose reduction in this population should be considered.
Self-reported alcohol consumption and its association with adherence and outcome of antiretroviral therapy in the Swiss HIV Cohort Study
Authors:   the Swiss HIV Cohort Study, Conen Anna , Fehr Jan , Glass Tracy R , Furrer Hansjakob , Weber Rainer , Vernazza Pietro , Hirschel Bernard , Cavassini Matthias , Bernasconi Enos , Bucher Heiner C , Battegay Manuel 
Published: April 2022

Background Alcohol consumption leading to morbidity and mortality affects HIV-infected individuals. Here, we aimed to study self-reported alcohol consumption and to determine its association with adherence to antiretroviral therapy (ART) and HIV surrogate markers. Methods Cross-sectional data on daily alcohol consumption from August 2005 to August 2007 were analysed and categorized according to the World Health Organization definition (light, moderate or severe health risk). Multivariate logistic regression models and Pearson's χ2 statistics were used to test the influence of alcohol use on endpoints. Results Of 6,323 individuals, 52.3% consumed alcohol less than once a week in the past 6 months. Alcohol intake was deemed light in 39.9%, moderate in 5.0% and severe in 2.8%. Higher alcohol consumption was significantly associated with older age, less education, injection drug use, being in a drug maintenance programme, psychiatric treatment, hepatitis C virus coinfection and with a longer time since diagnosis of HIV. Lower alcohol consumption was found in males, non-Caucasians, individuals currently on ART and those with more ART experience. In patients on ART ( n=4,519), missed doses and alcohol consumption were positively correlated ( P<0.001). Severe alcohol consumers, who were pretreated with ART, were more often off treatment despite having CD4+ T-cell count <200 cells/μl; however, severe alcohol consumption per se did not delay starting ART. In treated individuals, alcohol consumption was not associated with worse HIV surrogate markers. Conclusions Higher alcohol consumption in HIV-infected individuals was associated with several psychosocial and demographic factors, non-adherence to ART and, in pre-treated individuals, being off treatment despite low CD4+ T-cell counts.