bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydrogen Production by Photoreforming of Renewable Substrates
Authors: Rossetti Ilenia
Published: November 2012

This paper focuses on the application of photocatalysis to hydrogen production from organic substrates. This process, usually called photoreforming, makes use of semiconductors to promote redox reactions, namely, the oxidation of organic molecules and the reduction of H+to H2. This may be an interesting and fully sustainable way to produce this interesting fuel, provided that materials efficiency becomes sufficient and solar light can be effectively harvested. After a first introduction to the key features of the photoreforming process, the attention will be directed to the needs for materials development correlated to the existing knowledge on reaction mechanisms. Examples are then given on the photoreforming of alcohols, the most studied topic, especially in the case of methanol and carbohydrates. Finally, some examples of more complex but more interesting substrates, such as waste solutions, are proposed.
A Functioning Approach to Well Being Analysis in Rural Nigeria
Authors: Adeyemo Temitayo Adenike , A Oni Omobowale
Published: November 2012

The Nigerian rural population is described by low productivity, little formal education and poverty. The need for more studies on the issue of wellbeing of rural population is hinged on the continued development of approaches that give better understanding of the phenomenon. This paper attempted to use Amartya Sen’s capability approach to assess multidimensional well being in rural Nigeria in six functioning dimensions obtained from the Nigerian Core Welfare Indices Survey using the fuzzy set theory. A binary logistic regression was also carried out to isolate the factors that determine the attainment of a pre determined level of well being after computation with the fuzzy set analysis. The results showed that rural Nigeria is an agrarian society; the functioning with the highest level of achievement out of the six dimensions studied was Housing, while asset ownership/income was the least achieved dimension in rural Nigeria. Results further revealed that belonging to female headed households, increasing age and being employed in the private (formal) sector as well as having some form of post secondary education enhances well being while being employed within the agricultural sector significantly reduced the well being of rural households in Nigeria.
Clinical‐epidemiological features of HIV‐infected patients diagnosed at age of 50 years or older
Authors: Patterson P , Cahn S , Sued O , Fink V , Figueroa M , Cesar C , Rojo M , Ben G , Vázquez M , Cahn P
Published: November 2012

HIV/AIDS prevention and care efforts are directed to individuals of reproductive age (15–49 yrs). With the extension of sexual life of older people, they became a growing population at risk of HIV infection, usually not included in prevention strategies. In order to evaluate clinical profile of HIV/AIDS pts diagnosed at 50 yrs or older assisted in an HIV outpatient center in Buenos Aires, we retrospectively assessed clinical records of pts initiating care between Jan 1986 and Dec 2011. Age, CD4 cells and viral load (pVL) at HIV diagnosis and most recent value, opportunistic infections (OIs), co‐morbidities and antiretroviral therapy (ARV) were recorded. Of 10,998 pts assisted in the 26‐yr period, 495 (4.5%) were≥50 yrs old at HIV diagnosis; median annual diagnoses: 18.5 (IQR 3.3–30.3) without significant changes in the last 20 yrs. Demographics: median age 54.7 yrs (IQR 51.8–59.2, rank 50–80), 76.6% male. Risk behavior: HTX 61.4%, MSM 34.1%, others 4.4%. 55.4% of HIV diagnoses occurred during hospitalization or simultaneously with acute OIs. One third (n=176) had AIDS at diagnosis, 24% had history of STDs. HCV co‐infection 5.7%, past HBV infection 28.1% and chronic HBV infection 5.1%. Median CD4 cells at HIV diagnosis: 223.5 (13.7%) (IQR 98.8–420.3), initial pVL 60,000 cp/mL (IQR 9,995.5–208,391). 69.3% of pts started ARV therapy during follow‐up (FU), and the median time between diagnosis and treatment initiation was 3.4 mo (IQR 0.7–14); 56.9% of them started a non‐nucleoside‐based regimen (ZDV/3TC/EFV), 28.3% a PI‐based regimen (ZDV/3TC/IDV) and 14.6% a nucleoside‐based regimen (ZDV/ddI pre‐HAART era). After a year (±6 mo), 63.8% pts achieved undetectable pVL and gained 136 CD4 cells from BSL (IQR 83–204). After 40.6 mo of FU (IQR 6.7‐89.8), 66.3% are alive, 7.1% died (68.6% of HIV‐related diseases) and 26.7% are lost to FU. Co‐morbidities were present in 125 (25.3%), mainly hypertension, increased lipids, CVD and DBT. Among treated pts, 70.6% achieved pVL<50 cp/mL, with a median increase of CD4 cells up to 410 (22%) (IQR 281.5–563.9) from BSL. 51% (176) changed ARV therapy due to toxicity/AE: 54.5%, ARV failure: 29.5% and simplification: 14.8%. Stable HIV epidemic in older people reinforce the need of specific prevention approaches, while growing age of HIV individuals in care highlights to consider risks associated to older age. Late presentation to care needs to be specifically addressed. Response to treatment is remarkable high in this population.
HIV infection does not contribute to increased cardiovascular risk as assessed by Framingham risk score
Authors: Ramsay I , Pryce‐Roberts A , Williams S , Bolton E , Hannig E , Perry N , Fisher M , Rajkumar C
Published: November 2012

HIV‐1‐infected patients are thought to be at higher risk of cardiovascular events. Measures of arterial stiffness are independently associated with cardiovascular risk [1]. The aim of our study was to determine if higher Framingham risk is associated with higher carotid femoral pulse wave velocity (cfPWV) in HIV‐infected volunteers (HIV cohort) and to establish whether there is a difference in cfPWV between the HIV cohort and age‐ and gender‐matched controls. We recruited 47 males (HIV cohort) on antiretroviral treatment, from a UK HIV clinic between October 2010 and March 2012 (31 low Framingham risk <10% and 16 high risk >20%). This group was matched with 46 healthy subjects from a contemporaneous study performed by our group. The inclusion criteria were: age 35–75 years with Framingham risk >20% or <10%, on antiretroviral treatment with undetectable viral load, no previous coronary heart disease, stroke or insulin therapy. Subjects underwent cfPWV measurement using Complior® (Artech, France). Student's t‐test was used to evaluate differences between high‐ and low‐risk groups and also between cases and controls. The mean age of the HIV cohort was 49.43±9.35 years (mean±SD) and in the control group 52.20±8.80 years (p=0.15). Mean duration of HIV infection was 13.83±7.25 years, mean CD4 count was 728.81±312.62×106/L and all viral loads were undetectable. In the HIV cohort, cfPWV was 8.39±1.09 m/s in the low‐risk group and 10.43±2.93 m/s in the high‐risk group (p=0.02). Multivariate analysis with cfPWV as dependent variable, and age, systolic blood pressure, cholesterol, smoking history, duration of HIV infection and antiretroviral therapy, zenith viral loads and nadir CD4 counts as independent variables was performed in the high‐ and low‐risk groups. This showed age alone to be a significant predictive factor (p=0.002). With Framingham risk as dependent variable and using the above factors as independent variables, no HIV‐related factors were significant predictors. The overall mean cfPWV for the HIV cohort (n=47) was 9.09±2.13 m/s compared to 11.95±2.37 m/s in the control group (n=46)(p<0.01). HIV infection does not contribute to increased cardiovascular risk as assessed by Framingham risk score or carotid‐femoral pulse wave velocity. This may be due to good control of traditional cardiovascular risk factors and a healthy lifestyle in this cohort.
Rates of sexual violence among HIV‐positive women: finding a way forward for a holistic service
Authors: R Manners
Published: November 2012

Rates of sexual violence are high, and several studies have suggested that rates are particularly high among HIV‐positive women. Experience of sexual violence can lead to numerous physical and psychological co‐morbidities as well as a wide range of social problems. On both a Scottish Government and an international level it has been suggested that routine questioning about sexual violence in vulnerable populations can help to ensure access to appropriate services. This study aimed to assess the level of engagement around sexual violence in one HIV centre looking specifically at how often it was discussed, rate of disclosure, advice given and the demographics of the population disclosing sexual violence. Through this the aim was to assess the prevalence of disclosed sexual violence, and how it was being dealt with, in order to improve service provision. This was achieved by undertaking a case note review of 50 female patients of 394 number being cared for by the genito‐urinary physicians. Sexual violence was discussed at least once in 63% of cases, most commonly at time of diagnosis in a GUM clinic or other centre. 50% of those women disclosed experience of sexual violence, of while 60% (n=28) were from sub‐Saharan Africa and 44% (n=21) had entered the country as asylum seekers or refugees. These results show that a large number of HIV‐positive women within this city have experienced sexual violence, in particular in the asylum seeking population. As such, if services for HIV‐positive women are to take account of the psychological and social needs of their service users they will need to be aware of this and make appropriate provisions. This could take the form of routine questioning around gender‐based violence and/or providing good information about internal and external support services.
High frequency of genotypic resistance in HIV‐1‐infected patients on highly active antiretroviral therapy with persistent low level viremia
Authors: Pellegrino D , Brígido L , Souza Cavalcanti J , Paula Ferreira J , Vidal J , Battaggia Gutierrez E
Published: November 2012

Background

Resistance is a major cause of virologic failure in HIV‐1‐infected patients; genotypic analyses optimize salvage therapy but technical constraints limit testing in plasma viral load (pVL) below 1000 copies/ml. Nevertheless a great amount of patients are failing therapy with a persistent low viral load, it is possible to obtain genotypic information at lower viremias although slight modifications are required during genotype standard procedures.

Objective

To assess genotypic resistance in HIV‐1‐infected patients with persistent low level viremia and virologic response after switching to genotype‐guided salvage therapy. To evaluate viral selection of mutation when previous genotypic information were available.

Study design

Cohort prospective study in which eligible patients were at least 18 years old, provided informed consent, were on HAART for at least 12 months with two consecutive pVL between 200–999 copies/ml after achieving and maintaining viral suppression (two pVL <50 copies/ml). Modifications in genotype standard procedures included a larger volume of starting plasma, concentrating the sample by centrifugation and higher viral RNA input. Resistance was defined as the detection of any NRTI, NNRTI or PR major resistance mutations. Virologic response was assessed 12 weeks after salvage therapy.

Results

Eighteen patients, 50% male, median age 52, median CD4 405 cells/mm3, median pVL 596 copies/ml, median of number of previous regimens 5, 17 (94%) with successful genotype. Resistance mutations were detected in 14 patients (77%). All patients had NRTI mutations, four patients had NNRTI mutations and ten patients had PR mutations, most common mutations were M41L, D67N, M184V, K103N, M46I, I47V, I54V and L90M. Of these fourteen patients, nine started a genotype‐guided salvage regimen and presented a pVL < 50 copies/ml after 12 weeks of follow up. For two patients there was previous genotypic information highlighting the selection and accumulation of resistance mutation during persistent low level viremia.

Conclusion

In this group of heavily pretreated patients with persistent low viremia, a high frequency of genotypic resistance was observed; obtaining genotypic information may prevent further accumulation of resistance mutation and preserve future therapeutic options.
HIV‐1 drug resistance testing at low viral load may help to differentiate between ongoing replication and release from reservoirs
Authors: Obermeier M , Ehret R , Kaiser R , Berg T
Published: November 2012

Purpose of the study

Low level viraemia in HIV‐infected patients treated with anti‐retroviral therapy (ART) is a phenomenon still not fully understood. If the observed viraemia is a result of ongoing replication or if virus is released from cellular reservoirs remains unclear. We analysed our database of genotypic resistance and interpretations to screen for an effect of viral load on frequency of detected drug resistance.

Methods

1939 viral load and protease and reverse transcriptase sequence pairs from the years 2009 to 2011 were analysed. Drug resistance interpretation was performed by the HIV‐GRADE resistance interpretation rule set. Pairs were split up into viral load categories of below 200 cop/ml, 200–400, 400–1000, 1000–10,000, 10,000–100,000 and more than 100,000 cop/ml. Resistance interpretation was stratified in the following categories: no resistance, resistance against one, two or three drug classes. The collected data were then analysed using chi‐squared test (R Core Team; 2012; R: A language and environment for statistical computing).

Summary of results

1390 sequences showed no relevant drug resistance, while 336 sequences showed resistance against one drug class (two classes: 145, three classes: 38). In 25 samples viral load was below 200 cop/ml (200–400: 29, 400–1000: 63, 1000–10,000: 275, 10,000–100,000: 526, above 100,000: 472). In both groups below 400 cop/ml no significant increase of resistant variants was observed compared to the mean distribution, while in the groups with 400–1000 cop/ml and 1000–10,000 cop/ml significant more resistant variants were found than expected (p < 0.001). This reverses above 100,000 cop/ml, where significantly (p < 0.001) more susceptible variants were observed.

Conclusions

As in most of the samples with a viral load below 400 cop/ml, no mutations leading to resistance could be found, we conclude that virus in these cases is released from cellular reservoirs. Viral loads between 400 cop/ml and 10,000 cop/ml under ART are a clear sign for ongoing replication, because in this group the highest rate of drug resistance was observed. Viral loads above 100,000 cop/ml seems here to be a sign of missing selective pressure due to incompliance of the patients and thus no drug resistance was observed.
Integrase resistance variants among integrase inhibitor treatment‐naïve and treated patients from Northwestern Poland
Authors: Parczewski M , Leszczyszyn‐Pynka M , Urbanska A , Bander D , Boron‐Kaczmarska A
Published: November 2012

Purpose of the study

HIV integrase inhibitor use is limited by low genetic barrier to resistance and possible cross‐resistance among representatives of the class. The aim of this study was to analyse the sequence variability in the integrase region in treatment‐naïve and experienced patients with no prior integrase inhibitor (InI) exposure and to investigate the development of the InI drug resistance mutations following the virologic failure of the raltegravir (RAL)‐containing regimen.

Methods

Sequencing of HIV‐1 integrase region (866 base pair, HXB2 genome location: positions 4230–5096) from plasma samples of 80 integrase treatment‐naïve patients and treatment failing subjects from a group of the 46 RAL‐treated patients were analysed. Drug resistance mutations were called with Stanford DB database and grouped into major and minor mutations. For subtyping, bootstrapped phylogenetic analysis (1000 replicates) with under the GTR + I+gamma model with reference sequences.

image

Results

Majority of the integrase region sequences were classified as subtype B; the remaining ones being subtype D, C, G, and CRF01_AE, CRF02_AG and CRF13_cpx recombinants. No major integrase drug resistance mutations have been observed in InI‐treatment naïve patients. In 30 (38.5%) cases polymorphic variation, with predominance of the E157Q mutation was observed. This mutation was more common among subtype B (26 cases, 54.2%) than non‐B sequences (5 cases, 16.7%), p = 0.00099, OR: 5.91 (95% CI: 1.77–22.63)] (Figure 1a, 1b). Other variants included L68V, L74IL, T97A, E138D, V151I, R263. Of the RAL‐treated patients in 12 cases (26.1%) treatment failure was observed. In 4 cases major the following InI drug resistance mutations were found: N155H, V151I, E92EQ, V151I, G163R (3 cases) and Q148H, G140S mutant (one case). Time to the development of drug resistance ranged from 2.6 to 16.3 months with mean increase of HIV viral load of 4.34 (95% CI: 1.86–6.84) log HIV‐RNA copies/ml at the time of emergence of the major mutations. Baseline polymorphisms, including E157Q were not associated with the virologic failure on RAL (p = 0.5).

Conclusions

In InI treatment‐naïve patients polymorphic integrase sequence variation was common, with no major resistance mutants observed. In the failing patients selection of drug resistance occur rapidly, and follows the typical drug resistance pathways accumulation of mutations. Pre‐existing integrase polymorphisms were not associated with the treatment failure.
Antiretroviral drug resistance in HIV‐1 therapy‐naïve patients in Cuba, 2006–2011
Authors: Pérez L , Alemán Y , Correa C , Fonseca C , Aragones C , Alvarez A , Kourí V , Vandamme A , Van Laethem K
Published: November 2012

In 2009, genotypic drug resistance testing was introduced for HIV‐1 patients failing antiviral therapy in Cuba. The high prevalence of drug resistance in this population indicated the need for surveillance of transmitted drug resistance (TDR) in therapy‐naïve patients. Therefore, the objectives of this study were to analyze the level and patterns of TDR and subtype in therapy‐naïve HIV‐1 patients in Cuba from 2006 to 2011, and to compare it with reported data from 2004 that indicated 4% TDR, solely restricted to NRTI. 153 plasma from HIV‐1 therapy‐naïve patients were collected between June 2006 and December 2011 and subsequently extracted, amplified and sequenced. Drug resistance was interpreted according to HIVdb v.6.1.1 and WHO list for TDR surveillance (2009) using the CPR tool v.6.0. Phylogenetic analysis was performed using Neighbour Joining (Kimura 2) in Mega 4. The majority of patients was male (82.4%), MSM (68.6%) and originated from Havana province (68.1%). 8.4% were recent infections. Subtype B was the most prevalent subtype (31.3%) followed by CRF20‐23‐24_BG (28.1%), CRF19 (18.3%) and CRF18 (13.0%). The prevalence of subtype B declined from 43.7% in the 2004 study to 31.3% in the present study, whereas BG recombinants increased from 14.4% to 28.1%. Overall, 12.4% (19/154) had evidence of TDR. 3.9% carried at least one NRTI, 1.9% at least one NNRTI and 1.9% at least one PI mutation. Drug resistance mutations against both NRTI and NNRTI were observed in 3.9%, whereas triple class resistance was found in only 0.6%. The most frequent NRTI mutations were M184V (55.5%), T215F/Y/rev (16.6%) and K70R (16.6%). The most frequent NNRTI mutations were K103N (61.1%) and G190A (22.2%). The most common PI mutation was L90M (5.5%). From the 19 patients with TDR, 13 (68.4%) were diagnosed with a recent HIV‐1 infection. AZT/D4T + 3TC + NVP may be effective in 6 of the patients with TDR (31.5%), partially effective in 6 (31.5%) and ineffective in 7 (36.8%). AZT/D4T + 3TC + IDV would be effective in 9 of the patients with TDR (47.3%), partially effective in 8 (42.1%) and ineffective in 2 (10.5%). This analysis confirmed the further expansion of BG recombinants in Cuba and revealed that antiretroviral drug resistance in HIV‐1 therapy‐naïve patients has increased to 12.4% in 2006–2011. The current study emphasizes the need to perform surveillance studies for TDR in therapy‐naïve patients, as the extent of TDR might jeopardize the effectiveness of first‐line regimens prescribed in Cuba.
The prevalence and economic burden of 1st‐generation NNRTI resistance
Authors: Snedecor S , Khachatryan A , Nedrow K , Chambers R , Li C , Haider S , Stephens J
Published: November 2012

The prevalence of NNRTI resistance in the community and costs associated with HIV disease and treatment failure are examined. NNRTI‐based HAART therapy using EFV is recommended as a 1st‐line treatment choice in international guidelines, and it is the most common component of initial therapy. Resistance to NNRTIs is common in the community (treated or untreated) and may impact economic burden. Published articles and conference abstracts detailing the epidemiology of NNRTI resistance, the economic burden of HIV disease progression, or the costs associated with treatment failure were located using PubMed/MEDLINE and Embase. NNRTI resistance data sources included randomized or observational trials, or cohort studies of European, US, or Canadian patients, published between years 2005–2011 in English. Inclusion criteria for cost data were studies reporting total direct medical costs of HIV disease in the US. Prevalence of NNRTI resistance early in infection (generally pre‐antibody response) was reported in 6 European studies and in 3 US studies. Among chronically‐infected treatment‐naïve patients, 13 studies reported prevalence of NNRTI resistance in Europe, 2 in US, and 2 in Canada. All studies collected data from 2009 and earlier, when 2nd‐generation NNRTIs were not available. The reported prevalence was generally higher in US/Canada than it was in Europe (range=7–10% vs. 2–10%). The prevalence of resistance among patients was similar in early vs. later infection for both regions (range=2.0–6.7% [median=3.7%] vs. 1.7–10.2% [3.0%] in Europe and 7.0–13.0% [8.8%] vs. 3.8–11.5% [7.6%] in US/Canada, respectively). Using UDS, the prevalence of NNRTI resistance in treatment‐naïve patients was reported at 24% (intra‐quasi‐species prevalences 0.34–98.8%). The most recent time‐based trends suggest that NNRTI‐resistance prevalence may be stable or reducing. Annual HIV medical costs increased 1) as CD4 cells decreased, driven in part by hospitalization at lower CD4 cell counts; 2) for treatment changes (cost of 3rd line 1.5‐fold higher than 1st or 2nd line), and 3) for each virologic failure. The economic burden of regimen failure and disease progression underlines the importance of ensuring optimal initial therapy choices and regimen succession. The possible erosion of efficacy or of therapy choices through resistance transmission or selection, even when present in an individual as a 1% minority, may become a barrier to the use of 1st generation NNRTIs.
Genotypic susceptibility to etravirine‐assessment in a population of NNRTI‐experienced patients
Authors: Piñeiro C , Xerinda S , Figueiredo C , Santos A , Soares J , Serrão R , Sarmento A
Published: November 2012

Background

With the availability of the 2nd‐generation non‐nucleoside reverse transcriptase inhibitor (NNRTI) etravirine (ETR), it is possible to obtain undetectable plasma viral load in HIV‐1‐infected treatment experienced patients with resistance mutations to NNRTIs. The purpose of this study is to determine the proportion of patients with prior exposure to NNRTIs who may benefit from a therapeutic regimen including ETR.

Patients and methods

Analysis of the genotypic resistance tests of patients having failed efavirenz (EFV) or nevirapine (NVP) antiretroviral‐based regimens, in a 5‐year period (2007–2011). Susceptibility to ETR was assessed using four different algorithms: HIVdb Stanford University HIV Drug Resistance Database, ANRS score, REGA score and Tibotec weighted genotypic score.

Results

Of 170 patients with a history of failure or abandonment of regimens containing EFV or NVP, 68 (40%) had mutations conferring resistance to these NNRTIs (RAMs). Resistance tests were carried out from seven months before to 3 years after (X=48±207 days) the NNRTIs discontinuation. Of the HIV‐1 subtypes identified (n=67), most were were subtype B (53.7%) and G (34.3%) RAMs found in the 68 samples successfuly genotyped: V90I (n=2), A98G (n=1), L100I (n=7), K101E (n=5), K103N (n=38), K103S (n=2), V106A (n=1), V106M (n=1), V108I (n=4), V179D (n=4), Y181C (n=18), Y188C (n=1), Y188H (n=1), G190A (n=11), G190E (n=1), G190S (n=1), H221Y (n=6), P225H (n=1), F227L (n=3) and K238T (n=2). In 27 (39.7%) patients only one RAM was detected, 30 (44.1%) had 2, 6 had three mutations and 5 other patients had more than three RAMs to NNRTIs. Susceptibility to ETR varied depending on the used algorithm:

Susceptible
Intermediate resistance
Resistant

ANRS
60 (88.2%)
3 (4.4%)
5 (7.4%)

HIVdb
49 (72.0%)
17 (25.0%)
2 (3.0%)

REGA
40 (58.8%)
27 (39.7%)
1 (1.5%)

Tibotec
44 (64.7%)
23 (33.8%)
1 (1.5%)

Conclusion

In this population with resistant virus to EFV and NVP, we found a low frequency of mutations conditioning severely impacting on susceptibility to ETR. Based on these results, ETR could be a useful component of effective treatment regimens for the majority of these patients with prior exposure to 1st‐generation NNRTIs.
Analysis of HIV‐1 primary drug resistance in Kazakhstan
Authors: Lapovok I , Laga V , Vasilyev A , Kazennova E , Ludvikova E , Kovtunenko N , Dzisyuk N , Tukeev M , Bobkova M
Published: November 2012

Purpose of the study

Monitoring of primary resistance in HIV‐1 variants circulating in Russia and FSU countries is the important task of HIV infection molecular epidemiology. The data of HIV molecular epidemiology are absent or limited in many FSU countries. IDU‐A variant of HIV‐1 subtype A has been dominating in Russia (>90%) and other FSU countries since 1996. Additionally, the Central Asian region (e.g. Kazakhstan and Uzbekistan) is characterized by relatively wide spread of CRF02_AG recombinant. The aim of our study was the analysis of HIV primary drug resistance in HIV‐1 variants from Kazakhstan.

Methods

Blood collection from the HIV‐infected naïve patients was carried out by local specialists. The study was performed with the informed consent of patients. All sequences of pol gene were analyzed by COMETv0.1 and HIVdb on‐line programs. The phylogenetic analysis and tropism testing were carried out by MEGA4.0 and geno2pheno.

Summary of results

51 PBMC samples were analyzed. According to pol gene phylogenetic analysis and genotyping 24 (47.0%) samples belonged to recombinant CRF02_AG; 25 (49.0%)‐to subtype A1; 2 (3.9%)‐to CRF03_AB circulating in Russia and some FSU countries. Only one subtype A1 sample had D30N mutation in Pro‐region that cause high‐level resistance to NFV. All AG‐samples had K20I substitution which is characteristic for HIV‐1 subtype A and G and is believed to be associated with resistance to LPV and NFV. In addition, we found that 2 AG‐samples had L10V and L76I substitutions, accordingly. Two A1‐subtype samples studied had L10I and K43T, accordingly. A62V characteristic mutation in RT‐region was found in 12 (48%) subtype A1‐samples. One of them had M184I mutation as well. Besides, we found 3 A1‐samples harboring NNRTIs resistance mutations‐K103N, G190S, K238N, accordingly. Further we analyzed IN region of pol‐gene in 16 and env‐gene in 23 samples studied. We found only one E157Q mutation (in CRF03_AB sample) in IN region. As to tropism, only two subtype A1 and 1 CRF03_AB samples belonged to X4/X4R5 variant, all these A1‐subtype samples harbored A62V and one of them‐G190S in RT region of pol‐gene; the other samples were treated as R5 variants.

Conclusions

Our data demonstrated the low level of HIV primary drug resistance in Kazakhstan. HIV‐1 subtype A variant dominates on this territory, but CRF02_AG recombinant is rather widespread as well. CRF02_AG variant studied has characteristic features in Pro region compared with IDU‐A.
Effectiveness of first‐line antiretroviral therapy based on NNRTIs vs ritonavir‐boosted PIs in HIV‐1 infected patients with high plasma viral load
Authors: Imaz A , Llibre J , Navarro J , Curto J , Clotet B , Crespo M , Murillo O , Ferrer E , Saumoy M , Tiraboschi J , Podzamczer D
Published: November 2012

Purpose of the study

Few clinical trials have compared non‐nucleoside reverse transcriptase inhibitors (NNRTI) and ritonavir‐boosted protease inhibitors (PI/r) as initial combined antiretroviral therapy (cART) for HIV‐1‐infected patients with high plasma viral load (pVL), and non‐conclusive results have been reported. We compared the effectiveness between NNRTI and PI/r as first‐line cART for HIV‐1‐infected patients with high pVL.

Methods

Observational retrospective study of 664 consecutive treatment‐naïve HIV‐1‐infected patients with pVL (HIV‐1 RNA) >100,000 copies/mL who initiated NNRTI or PI/r‐based cART between 2000–2010 in three University hospitals. Only currently preferred or alternative regimens in clinical guidelines were included. Primary endpoint: percentage of therapeutic failures at week 48. Virologic failure was defined as: a) lack of virologic response (<1 log RNA HIV‐1 decrease in first 3 months); b) RNA HIV‐1 >50 c/mL at week 48; c) confirmed rebound >50 c/ml after a previous value <50 c/mL. Intent‐to‐treat (ITT noncompleter=failure) and on‐treatment (OT) analyses were performed.

Results

62% of patients initiated NNRTI‐regimens (83% efavirenz) and 38% PI/r‐regimens (62% lopinavir/). Baseline characteristics: male 83%; median age 39 yrs; median CD4 count: 212/µL (NNRTI 232 vs PI/r 177, p=0.028); pVL 5.83 log10 c/mL (NNRTI 5.43 vs PI/r 5.55, p=0.007); AIDS 24% (NNRTI 21% vs PI/r 29%, p=0.015). NRTI backbones were tenofovir plus 3TC or FTC in 72%. The percentage of therapeutic failure was higher in the PI/r group (ITT NC=F 26% vs 18%, p=0.012) with no differences in virologic failures (PI/r 5%, NNRTI 6%, p=0.688). The rate of treatment changes due to toxicity and/or voluntary discontinuations was higher in the PI/r group (15% vs 8%, p=0.008). A multivariate analysis adjusted for age, gender, CD4 count, VL and AIDS showed NNRTI vs PI/r as the only variable associated with treatment response (OR 0.61, 95% CI 0.41–0.88). Median pVL and rate of resistance at virologic failure were higher in patients receiving NNRTI (3.97 vs 2.49 log copies/mL, p<0.001 and 62% vs 12%, p=0.004, respectively).

Conclusions

Initial NNRTI‐regimens showed higher effectiveness compared with PI/r‐regimens in HIV‐1‐infected patients with high pVL, although virologic failure rates were low and comparable. Resistance emergence was more frequent and pVL higher in patients failing NNRTI. However, more patients initiating PI/r‐based regimens changed or discontinued therapy.
Increasing subject compliance in pivotal phase III clinical trials of dolutegravir (DTG, S/GSK1349572) in HIV‐infected, ART‐naïve subjects
Authors: Harris J , Bomar M , Campbell M
Published: November 2012

To maximise the application of results of large‐scale clinical trials, recruitment and retention of a diverse subject population is key. With commonly used algorithms (Snapshot, TLOVR, missing = failure), all withdrawals in HIV studies, regardless of reason, are classed as failures in efficacy analyses. Good subject compliance therefore improves statistical power and the quality of trial results. In four recent GSK/ViiV‐sponsored phase IIIB/IV HIV ART‐naïve studies (HEAT, KLEAN, APV109141 and ARIES), 24% of subjects withdrew and approximately 2/3 of these withdrawals (16%) potentially were avoidable (i.e. not treatment related) [1]. To increase subject compliance in the phase III, treatment‐naïve studies of DTG (ING113086 “SPRING‐2” and ING114467 “SINGLE”), a more robust subject compliance program focussing on understanding subject needs and building sponsor‐site and site‐subject relationships was implemented. The compliance program included opt‐in study visit reminders, late study visit tracking, subject compliance support materials, subject transportation support, on‐going site training, relationship management and presentations on prior withdrawal rates and associated risk factors for attrition at investigator meetings. Week 48 withdrawals, both overall and for potentially avoidable reasons, were considerably lower in SPRING‐2 and SINGLE than historical HIV trials. Comparison of withdrawal rates prior to, and after implementation of robust patient compliance program. Addressing individual study subject needs with a customized approach in SPRING‐2 and SINGLE contributed to considerably lower percentages of withdrawals than in historical HIV studies. Identifying the specific impact of a single subject compliance initiative is difficult as study compliance can be influenced by overall study design, investigational product tolerability profile, current standard of care and treatment access for the disease under study. However, consistently reducing the number of avoidable withdrawals has the potential to lead to improved quality of trial results and smaller, quicker studies in the future, benefitting the whole HIV population.

Study
N
Week
Withdrawals from study n (%)
Withdrawals for unavoidable reasons*
Withdrawals for potentially avoidable reasons#

HEAT/KLEAN/APV109141/ARIES~
2290
36–96
552 (24%)
179 (8%)
373 (16%)…

SPRING‐2
822
48
103 (13%)
57 (7%)
46 (6%)

SINGLE
833
48
135 (16%)
79 (9%)
56 (7%)

Due to adverse events, lack of efficacy, protocol‐defined stopping criteria.

Due to lost to follow‐up, withdrew consent, protocol deviation, investigator discretion.

Pooled data from HEAT (EPZ104057), KLEAN (ESS100732), APV109141, ARIES (EPZ108859).

Week 48 Kaplan‐Meier estimates=15%, 13% and 9% respectively for HEAT, KLEAN and APV109141.
Retention on third agents in HAART regimens at the Maple Leaf Clinic in Toronto, Ontario, Canada
Authors: Crouzat F , Brunetta J , Kovacs C , Sandler I , Smith G , El‐Hadi W
Published: November 2012

This study evaluated the 12‐month retention rate of third agents in HAART (highly active anti‐retroviral therapy) regimens in routine clinical practice in a Canadian HIV clinic. This is a descriptive retrospective database analysis of HIV‐positive patients naïve to antiretroviral therapy (ART). The study included male and female HIV patients≥18 years of age at HAART initiation date, seen in routine consultation at the Maple Leaf Medical Clinic (MLMC), Toronto, Ontario, Canada. Data were extracted from the MLMC database for the period of September 1st, 2003 to August 31st, 2010 for patients who commenced a protease inhibitor (PI), a non‐nucleoside reverse‐transcriptase inhibitor (NNRTI), or an integrase inhibitor (II) ‐based regimen in combination with two nucleoside reverse transcriptase inhibitors (NRTI). Demographic and baseline disease characteristics were extracted and include age, gender, disease duration, baseline HIV‐1 RNA count, CD4 cell count, and hepatitis B and C co‐infection status at baseline. A total of 722 patients were included in the analysis. The primary outcome of the study was the proportion of HIV patients remaining on their initial third agent (PI, NNRTI, or II) at one year post‐treatment initiation. For therapies used by more than 10% of patients (efavirenz [EFV]=315, atazanavir [ATV]=104, lopinavir [LPV]=162, as other agents were used but in limited numbers), the percentage of patients still on the initial third agents at one year was 77%, 64% and 62%, respectively. In addition, viral load (VL) was less than 50 copies/mL in 95% of EFV, 79% of ATV and 76% of LPV patients at one year. The rate of discontinuation at 12 months from EFV, ATV, and LPV due to efficacy (i.e. lack of virologic suppression) or safety (i.e. adverse events) were 15.56%, 19.23%, and 19.75% respectively. In a clinical practice setting, the majority of patients treated with HAART regimens were maintained on therapy at one year and were able to suppress their viral load consistently. Of those reported here, EFV resulted in the best retention rate and viral suppression overall.
Long‐term durability of nevirapine‐based ART in a cohort of 82 patients after induction with protease inhibitor treatment
Authors: Rump J , Hoehl J , Rosenberg C
Published: November 2012

Purpose of the study

There is still an open question how to start antiretro‐viral therapy (ART). This retrospective study shows results of a de‐escalation strategy starting with a protease inhibitor (PI), followed by a nevirapine‐based regimen over a period of five years.

Methods

All patients were ART‐naïve and received PI in combination with two NRTIs. The PI was changed to nevirapine, when viral load (VL) stayed at least 12 months below the detection limit (50 or 40 copies/ml plasma). The median time to negative VL was measured. CD4, VL and liver tests were followed in 82 patients over at least 5 years before ART, during PI phase and over a median of 48 months after change to nevirapine. Resistance tests were performed ‐ if possible ‐ in patients before initiating ART.

Summary of results

20 female and 62 male patients were treated for an average of 28 months with PI (43×lopinavir, 5×indinavir, 6×invirase/r and 3×fortovase/r, 8×nelfinavir, 14×atazanavir/r, 3×norvir‐mono plus two backbone NRTI in various combinations). There were 2 cases of hepatitis B and 5 HCV positives in the cohort. The mean CD4 before starting ART was 246/µl and the average VL was 421,038 copies/ml plasma (ranging from 1,050–9,000,000 copies/ml plasma). The median time to negative VL was 188 days. CD4 cells were rising by 364/µl during PI treatment to 610/µl. This was followed by a steady increase of another 70 cells/µl during the first year after changing to nevirapine. The median follow up after de‐escalation to nevirapine was 48 months. Although the median CD4 was above 400/µl in all patients when changed to nevirapine, no severe liver toxicity was seen in the cohort. Change to NNRTI was safe in the group of 20 women with CD4 cells above 400/µl. Allergic skin reactions where seen in 7 out of 82 patients during the first 3 months after changing to nevirapine. No events of resistancies were seen in the group of 82 patients before and under treatment.

Conclusions

Long‐term durability of nevirapine containing ART regimens following an induction phase with PIs is very high. No risk of treatment failure by resistance mutations was seen in a follow up of more than 48 months. Liver toxicity was not seen when ART was changed to nevirapine neither in female nor in male patients. The study was supported by Boehringer Ingelheim Pharma GmbH.
Causes for switch‐infected patients: the NEXT study
Authors: Casado J , Domingo P , Gutiérrez F , Hevia H , Ledesma F , Palazuelos M
Published: November 2012

Purpose of the study

NNRTIs are commonly used to initiate HAART. Despite their demonstrated efficacy, tolerability and resistance issues could lead to a treatment change. The objective of the NEXT study was to evaluate the reasons for switching an initial non‐nucleoside based regimen in the clinical setting, and the alternative regimen selected.

Methods

A retrospective multicentre study was undertaken between April and October 2009. Patients from 38 Spanish centres who had changed the initial EFV or NVP‐based regimen in the previous six‐month period were included. Social‐demographic and HIV‐related data was collected from medical records. Responsible physicians were interviewed about reasons for switching the non‐nucleoside and the alternative regimen of choice.

Summary of results

A total of 391 HIV‐1 infected patients had changed the initial EFV or NVP‐based regimen in the previous six months. Data were available for 316 (80.8%) of them. 245/316 patients received EFV as first line (77.5%). Median time to switch the NNRTI regimen was 16.9 months, shorter in case of EFV‐based regimen, 15.4 months, than NVP‐based regimen, 20.8 months. Most of changes were observed in the first month after initiation, representing 51.3% of the discontinuations, especially in case of EFV (57.1% EFV; 31% NVP). 9.2% of the patients switched due to chronic toxicity (after the first month of treatment). CNS toxicity was the most common reason for switching therapy in the acute term in 63% of the patients. Other tolerability issues that led to treatment discontinuation in the short term were lipid abnormalities due to EFV (4.1%) and liver enzyme elevations related to NVP (7%). Rash led to a similar rate discontinuation with both NNRTIs (12%). The second reason to discontinue the first‐generation NNRTI was virological/immunological failure in 40.5% of the patients (128/316). The new regimen selected was a boosted PI regimen in 52% of the cases, and was another NNRTI based regimen in 62.3%. Physicians marked safety/tolerability as the main reason for switching in 58.5% of cases (185/316).

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Conclusions

In the clinical setting, both acute and chronic intolerance/toxicity represents the main cause of the first line treatment change based on a first generation NNRTI, mainly EFV. CNS toxicity was the most common reason for switching therapy in the acute term. Therefore, the tolerability profile of the alternative regimen played a relevant role when switching regimens.
Switching to darunavir/ritonavir monotherapy (DRV/r mx): effect on kidney function and lipid profile
Authors: Martinez‐Colubi M , Pérez Elías M , Sanz J , Gomez C , Estrada V , Sepúlveda M , Moreno A , Muriel A , Carranza M , De Palacio M , Dronda F , Gómez‐Ayerbe C , Casado J , Moreno S
Published: November 2012

Purpose of the study

DRV/r mx is proposed as a therapeutic option for patients with NNRTI toxicity. We aimed to evaluate the impact of switching to DRV/r mx in kidney function and lipid profile.

Methods

From March 2009 to June 2012 we conducted an observational, retrospective multicenter study evaluating patients switching to DRV/r mx. Kidney function and lipid levels were measured at baseline and at 48 weeks of DRV/r mx. Renal function was estimated by MDRD GFR. Comparative analyzes were performed using Student's t test for paired samples.

Summary of results

We identified 147 patients: women 30.6%, age 49±7yr, 45% IDU, 27.9% heterosexuals, AIDS 41.5%, Caucasian 58.5%, HCV‐coinfected 48%, baseline HIV‐RNA <1.7 log 93.2%, nadir and baseline CD4 count 180±150 and 663±297 cells/mm3, length of antiretroviral therapy 12.83±4.6 years and of HIV‐RNA <1.7 62±43 months. The rate of HIV‐RNA <1.7 at week 48 were 78.9% ITT; 92.6% OTT. Improvement was observed in kidney function after 48 w of DRV/r mx, mean 0 w vs 48 w MDRD (84.43±22.32 vs. 87.88±23.24; p=0.001). Subgroup analysis demonstrated significantly higher increases in MDRD in patients with a prior tenofovir‐based regimen (TDF), 83.14±21.86 and 48 w 88.97±21.23; p=0.000, and those with a protease inhibitor plus TDF‐based regimen (mean 0 w vs 48 w MDRD 80.66±22.53 87.09±23.37; p=0.002). Lipid profile improved significantly in terms of reduction in total cholesterol (mean 0 w col: 192.47±42.44 vs mean 48 w col 170.48±70.79; p=0.013) with an improvement in the ratio total cholesterol/ HDL (0 w 4.46±1.62 vs 48 w ratio 3.97±2.12; p=0.000). There were no significant changes in lipid profile in subgroup analysis according to previous antiretroviral treatment change.

Conclusions

Patients switching to DRV/r monotherapy showed significant improvement in kidney function and lipid profile at 48 w, both implied on cardiovascular risk.
Experimental study of EIT-Like phenomenon in a metamaterial plasma waveguide
Authors: Wang W. , Zhang L. , Fang K. , Zhang Y. W.
Published: November 2012

This paper demonstrates the realization of the electromagnetically induced transparency (EIT)-like transmission in a metamaterial plasma waveguide with double side defects based on transmission lines. The waveguide with a single side defect works as a plasma resonator and the resonance wavelength is determined by the Fabry-Perot resonance of surface plasma. While in a waveguide with double side defects, a transmission peak appears between the two resonators frequencies because of the destructive interference between the resonance modes of the two resonators, which indicates a pronounced EIT phenomenon. The experiment results agree well with simulations in microwave frequencies.
Self‐Assembly of Selective Interfaces in Organic Photovoltaics
Authors: Mauger Scott A. , Chang Lilian , Friedrich Stephan , Rochester Christopher W. , Huang David M. , Wang Peng , Moulé Adam J.
Published: November 2012

The composition of polymer‐fullerene blends is a critical parameter for achieving high efficiencies in bulk‐heterojunction (BHJ) organic photovoltaics. Achieving the “right” materials distribution is crucial for device optimization as it greatly influences charge‐carrier mobility. The effect of the vertical concentration profile of materials in spin‐coated BHJs on device properties has stirred particularly vigorous debate. Despite available literature on this subject, the results are often contradictory and inconsistent, likely due to differences in sample preparation and experimental considerations. To reconcile published results, the influence of heating, surface energy, and solvent additives on vertical segregation and doping in polymer‐fullerene BHJ organic photovoltaics are studied using neutron reflectometry and near edge X‐ray absorption fine structure spectroscopy. It is shown that surface energies and solvent additives greatly impact heat‐induced vertical segregation. Interface charging due to Fermi level mismatch increases (6,6)‐phenyl‐C61‐butyric acid methyl ester (PCBM)‐enrichment at the BHJ/cathode interface. Current–voltage measurements show that self‐assembly of interfaces affects the open‐circuit voltage, resulting in clear changes to the power conversion efficiency.
Highly efficient and economical nitrogen oxides controlled by an in‐furnace urea solution pyrolysis coupled with SCR system for a coal‐fired utility boiler
Authors: Zhou Hao , Hu Shantao , Mo Guiyuan , Tang Qi , Cen Kefa
Published: November 2012

An in‐furnace urea pyrolysis coupled with selective catalytic reduction (SCR) system was applied on a 125 MW tangentially coal‐fired utility boiler in China. The coupling system was well‐designed to distribute NO and NH3 more uniformly in the flue gas at the inlet of the SCR reactor. The experimental results showed that the homogeneous NO and NH3 concentrations distribution could result to better performance of the SCR reaction. A 15 wt% urea solution directly injected into the furnace at the same flow rate of 1.2 t/h in Cases 4–6, corresponded to the normalized stoichiometric ratio of 1.40, 1.47 and 1.35. The coupling system showed a high NO reduction efficiency of up to 85–89% and could control NO emission to as low as 40, 34 and 27 ppm, respectively, with NH3 slip less than 5 ppm. The calculated urea utilization efficiency was above 58% in the cases. The high utilization efficiency of the urea solution would significantly reduce the running cost of the system. There were only five injectors at the boiler's front wall, and one layer of total 90.3 m3 catalysts in the two SCR reactors, which would drastically reduce the initial investment. The effects of the urea solution flow rates were studied at 100  and 125 MW boiler loads; it was found that 1.2 t/h was the suitable flow rate of the urea solution, and the NO emission could be controlled lower than 40 ppm. The coupling system was stable, efficient and cost‐efficient in industrial operation. © 2012 Curtin University of Technology and John Wiley & Sons, Ltd.