bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of emphysema progression in HIV‐positive patients
Authors: Guaraldi Giovanni , Santoro Antonella , Besutti Giulia , Scaglioni Riccardo , Ligabue Guido , Zona Stefano , Man Paul , Sin Don , Leipsic Jonathon , Mussini Cristina
Published: November 2014

Introduction

The aim of the study was to find factors associated with emphysema progression (EP), assessed on sequential thoracic CT scans, in a large cohort of HIV‐positive patients.

Materials and Methods

This was an observational, prospective study of 448 consecutive HIV‐positive patients on antiretroviral therapy who underwent two sequential ECG‐gated coronary artery calcium scoring CT scans. Images were reviewed by three radiologists by consensus to assess lung emphysema using a visual semi‐quantitative score (0 to 4) for each of six lobes. EP was defined as an increase in emphysema score. Heavy smoking habit was defined as a self‐reported number of cigarettes per day smoked greater than 10. Immune reconstitution was defined as the change in CD4 cell count between first CT scan and CD4 nadir and it was divided into tertiles. Progressors and non‐progressors were compared using X2‐test for categorical variables and T‐test of Mann–Whitney U test for continuous variables where appropriate. Factors independently associated with EP were explored using multivariable logistic regression analyses. A p‐value <.05 was considered statistically significant.

Results

The mean age of the included patients was 47,9±7,7 years, 24,1% of them were females and 39,3% were smokers. The median interval between the two CT scans was 2,4 years (interquartile range 0,69–5,9 years). EP was significantly associated with HIV‐infection duration (p=0,056), smoking (p=0,007) and in particular heavy smoking habit (p=0,015) and time interval between the two scans (p=0,021), while the highest tertile of immune reconstitution was borderline in significance (p=0,075). Age and sex were not significantly related to EP and were not included in further analyses. HIV infection duration (OR=1,01; p=0,013), time interval between the two scans (OR=1,51; p=0,032) and heavy smoking habit (OR=3,36; p=0,041) remained independently associated with EP in multivariate analysis.

Conclusions

In this large cohort of HIV positive patients on antiretroviral therapy, HIV infection duration, time between CT scans and continued heavy cigarette smoking were independently associated with EP.
More safer sex intervention needed for HIV‐positive MSM with higher education level for prevention of sexually transmitted hepatitis C
Authors: Wai Chi Lin Ada , Hing Wong Ka , Chan Kenny
Published: November 2014

Introduction

The epidemiology of hepatitis C virus (HCV) infections in Chinese HIV‐infected men who have sex with men (MSM) remains obscure. More data is required to understand the epidemic and set up preventive strategy.

Materials and Methods

Baseline and annual testing of anti‐HCV was in place for all HIV‐infected MSM in the largest HIV clinic in Hong Kong. Logistic regression was used to compare those with HCV seroconversion (seroconverters) with those remained tested anti‐HCV negative (non‐seroconverters) to identify factors associated with incident HCV.

Results

From 1999 to 2013, 1311 patients were tested for anti‐HCV seroconversion, contributing to 6295 patient‐years of observation. Fourteen (1.1%) patients seroconverted, with genotype 3 being most commonly detected. The overall incidence rate of HCV infection was 0.22 per 100 patient‐years (PY) in the cohort. The incidence rate increased from 0.13 per 100PY before 2002 to 0.19 per 100PY in 2002–2007 and 0.47 per 100PY in 2008–2013. All the seroconverters were Chinese, with median age of anti‐HCV seroconversion at 38 years (range: 28–53 years). None of them were injecting drug users. As compared with the non‐seroconverters, seroconverters were of higher education level (85.7% vs 50.7% tertiary education or above, OR 5.28, p=0.021) and had prior history of sexually transmitted infection (92.9% vs 60.9%, OR 8.34, p=0.041). More seroconverters were found to have history of syphilis infection (57.1% vs 37.2%, p=0.134) but the difference was not statistically significant. Baseline CD4 count and HIV viral load, proportion on antiretroviral therapy and duration of antiretroviral therapy were not different between two groups.

Conclusions

The incidence of HCV has been increasing among HIV‐infected MSM non‐injecting drug users in Hong Kong. More education and intervention on safer sex is required to be targeted on those with higher education level.
Clinical and socio‐demographic predictors for virologic failure in rural Southern Africa: preliminary findings from CART‐1
Authors: Daniel Labhardt Niklaus , Bader Joëlle , Ramoeletsi Mojakisane , Kamele Mashaete , Ismael Lejone Thabo , Cheleboi Molisana , Motlatsi Mokete M. , Ehmer Jochen , Faturyiele Olatunbosun , Puga Daniel , Klimkait Thomas
Published: November 2014

Introduction

In 2013, the World Health Organization (WHO) recommended scaling up of routine viral load (VL) monitoring for patients on antiretroviral therapy (ART) in resource‐limited settings [1]. During the transition phase from no VL‐testing at all to routine VL‐monitoring, targeted VL for groups at particular risk of virologic failure (VF) may be an option [2]. We present socio‐demographic and clinical risk factors for VF in a cohort in rural Lesotho with no access to VL prior to the study.

Materials and Methods

Data derive from a cross‐sectional study providing multi‐disease screening as well as VL testing to adult patients (≥16 years old) on first‐line ART ≥6 months [3]. VF was defined as VL≥1000 copies/mL. Assessed potential predictors of VF were: (1) socio‐demographic (sex, age, wealth‐quintile, education, employment status, disclosure of HIV status to environment, travel‐time to facility); (2) treatment history (history of treatment interruption >2 days, previous drug substitution within first‐line ART, time on ART, ART‐base and ‐backbone); (3) adherence (pill count) and (4) clinical (clinical or immunological failure as defined by WHO guidelines [1], presence of papular pruritic eruption (PPE)). All variables with association to VF in univariate analysis were included in a multivariate logistic regression reporting adjusted Odds ratios (aOR).

Results

Data from 1,488 patients were analyzed. Overall VF‐prevalence was 6.9% (95% CI 5.7–8.3). In univariate analysis, the following were associated with VF: age <30, lower wealth‐quintile, no primary education, history of treatment interruption, nevirapine‐base, zidovudine‐backbone, history of drug substitution, travel‐time to clinic ≥2 hours, disclosure of HIV status to <5 persons, clinical failure, presence of PPE and immunological failure. In multivariate analysis, 6 out of the above 12 variables were independent predictors: age <30 years (aOR: 2.4; 95% CI 1.1–5.3, p=0.029), history of treatment interruption (2.5; 1.3–4.7, p=0.005), PPE (6.9; 2.5–18.9, p<0.001), immunological failure (11.5; 5.7–23.2, p<0.001), history of drug substitution (1.9; 1.0–3.7, p=0.043), disclosure of HIV status to <5 persons (1.8; 1.1–3.1, p=0.03).

Conclusion

In this cohort in rural Lesotho, several socio‐demographic and clinical predictors were associated with VF. Particularly age <30 years, history of treatment interruption, PPE and immunological failure were strongly associated with VF. These patients may be prioritized for targeted VL‐testing.
Longitudinal comparison of HIV‐1 plasma viral load and cellular proviral load
Authors: Schweitzer Finja , Mikkola Visa , Timmen‐Wego Monika , Jensen Björn , Fätkenheuer Gerd , Kaiser Rolf
Published: November 2014

Introduction

The goal of antiretroviral treatment (ART) in HIV‐1 infection is the permanent suppression of plasma viral load (pVL) below the currently existing limit of detection of 50 copies/mL (DAIG HIV‐therapy guidelines). Therefore, treatment effectiveness is based on pVL. pVL measurements however do not give any information about the viral reservoir in peripheral blood mononuclear cells (PBMCs). Therefore, the proviral DNA of HIV‐1 could be a useful marker for the investigation of viral reservoirs and monitoring ART in patients showing undetectable pVL.

Materials and Methods

Seventy‐seven treatment‐experienced HIV‐1 infected patients with pVL <50 copies/mL were randomly selected. pVL and proviral DNA load were measured using the Roche COBAS TaqMan HIV‐1 v2.0 assay. Additionally, CD4+ cell count per mL and the total white blood cell (wbc) count per mL were determined for each patient. Follow‐up data were collected 24 weeks after the time point of the first measurement. Proviral DNA load per mL, CD4+ cell count per mL as well as wbc count per mL were observed over time and differences were estimated using the Mann–Whitney U test. Additionally, correlations between the clinical parameters were analyzed using the two‐sided Pearson correlation analysis.

Results

Out of the 77 patients, 38 show a significant increase in proviral load per mL over time (p=0,001), whereas 39 patients show a significant decrease (p=0,001). No differences became visible in the CD4+ cell count per mL comparing week 0 and week 24 data. Thirty five patients show a significant increase in wbc count per mL over time (p<0,001), while 42 patients show a significant decrease (p<0,001). A significant correlation of increasing proviral load per mL and wbc count per mL for data of the first (p<0.001) and the second measurement (p<0.001) can be detected, while there are no correlations found between proviral load per mL and CD4+ cell count per mL.

Conclusions

Our data show that the presence of viral reservoirs in other cell types and not only CD4+ cells is most probable. HIV‐1 proviral DNA seems to be an interesting marker in patients with undetectable pVL and allows the assessment of replication under ART. Nevertheless, further longitudinal studies are needed to assess the usefulness and the clinical significance of this marker.
Accurate episomal HIV 2‐LTR circles quantification using optimized DNA isolation and droplet digital PCR
Authors: Malatinkova Eva , Kiselinova Maja , Bonczkowski Pawel , Trypsteen Wim , Messiaen Peter , Vermeire Jolien , Verhasselt Bruno , Vervisch Karen , Vandekerckhove Linos , De Spiegelaere Ward
Published: November 2014

Introduction

In HIV‐infected patients on combination antiretroviral therapy (cART), the detection of episomal HIV 2‐LTR circles is a potential marker for ongoing viral replication. Quantification of 2‐LTR circles is based on quantitative PCR or more recently on digital PCR assessment, but is hampered due to its low abundance. Sample pre‐PCR processing is a critical step for 2‐LTR circles quantification, which has not yet been sufficiently evaluated in patient derived samples.

Materials and Methods

We compared two sample processing procedures to more accurately quantify 2‐LTR circles using droplet digital PCR (ddPCR). Episomal HIV 2‐LTR circles were either isolated by genomic DNA isolation or by a modified plasmid DNA isolation, to separate the small episomal circular DNA from chromosomal DNA. This was performed in a dilution series of HIV‐infected cells and HIV‐1 infected patient derived samples (n=59). Samples for the plasmid DNA isolation method were spiked with an internal control plasmid.

Results

Genomic DNA isolation enables robust 2‐LTR circles quantification. However, in the lower ranges of detection, PCR inhibition caused by high genomic DNA load substantially limits the amount of sample input and this impacts sensitivity and accuracy. Moreover, total genomic DNA isolation resulted in a lower recovery of 2‐LTR templates per isolate, further reducing its sensitivity. The modified plasmid DNA isolation with a spiked reference for normalization was more accurate in these low ranges compared to genomic DNA isolation. A linear correlation of both methods was observed in the dilution series (R2=0.974) and in the patient derived samples with 2‐LTR numbers above 10 copies per million peripheral blood mononuclear cells (PBMCs), (R2=0.671). Furthermore, Bland–Altman analysis revealed an average agreement between the methods within the 27 samples in which 2‐LTR circles were detectable with both methods (bias: 0.3875±1.2657 log10).

Conclusions

2‐LTR circles quantification in HIV‐infected patients proved to be more accurate with a modified plasmid DNA isolation procedure compared to total genomic DNA isolation. This method enables the processing of more blood cells, thus enhancing quantification accuracy and sensitivity. An improved quantification of 2‐LTR circles will contribute to the better understanding of ongoing replication in the HIV reservoir of patients on cART.
Outcomes of initial antiretroviral treatment (ART) among recently diagnosed HIV patients in HIV‐TR cohort, 2011–2012
Authors: Korten Volkan , Gökengin Deniz , Fincanci Muzaffer , Yildirmak Taner , Uzun Kes Nuray , Taşdelen Fişgin Nuriye , Inan Dilara , Eraksoy Haluk , Akalin Halis , Kaptan Figen
Published: November 2014

Introduction

HIV‐TR is a recently established (2012) multicentre cohort in Turkey. The aim of this study is to analyze epidemiological, immunologic and virologic data of recently diagnosed HIV patients.

Materials and Methods

Epidemiologic, clinical and laboratory data of all patients diagnosed in 2011 and 2012 were recorded by a web‐based data collection system, retrospectively.

Results

A total of 693 patients (561 male, 132 female) at 24 sites were enrolled. The median age at first presentation for HIV care was 36. The proportion of patients presenting with advanced HIV disease (CD4 count<200/mm3 or presenting with an AIDS‐defining event) was 30.6%; and 52.4% of patients were late presenters (CD4 count<350/mm3 or presenting with an AIDS‐defining event). Median CD4 counts at presentation and before treatment were 344 (IQR: 175–540) and 295 (IQR: 150–430), respectively. Pretreatment CD4 count was >500 copies/mL in 18.5% of patients. Of 531 patients receiving ART, initial combinations consist of tenofovir/emtricitabine (TDF/FTC) plus efavirenz (EFV) in 48.2% and TDF/FTC plus lopinavir/ritonavir (LPV/r) in 37.5% and other combinations in 14.3% of the patients. Pre‐treatment HIV‐RNA was over 100.000 copies/mL in 52.3% of patients. At Weeks 24 and 48, HIV‐RNA were<50 copies/mL in 63,4% of 385 patients and 82% of 311 patients reported to be still on ART and had a viral load measurement, respectively. Median pretreatment CD4 count was lower for TDF/FTC+LPV/r recipients than TDF/FTC+EFV recipients (250 vs 316) (p<0.05). The median increase from baseline CD4 cell count was 230 in TDF/FTC+LPV/r group, 193 in TDF/FTC+EFV group and 216 among all treated patients. Of 531 patients receiving ART, 11 had died and 19 were lost to follow‐up.

Conclusion

Despite 52.4% of recently diagnosed patients were late presenters; a high rate of virologic suppression was achieved in HIV‐TR Cohort. A national HIV testing strategy targeting subpopulations with higher risk is urgently needed.
Structural‐equation‐modelling of the tropism impact on achieving viral suppression within six months in naïve HIV patients
Authors: Mengoli Carlo , Andreis Samantha , Scaggiante Renzo , Cruciani Mario , Bosco Oliviero , Ferretto Roberto , Leone D. , Maffongelli Gaetano , Basso Monica , Sarmati Loredana , Andreoni Massimo , Palù Giorgio , Giuseppe Parisi Saverio
Published: November 2014

Introduction

Aim of the study was to evaluate the relevance of baseline (BL) plasma tropism of HIV on the achievement of a viral suppression within six months of antiviral therapy (ARV) in naïve patients by a structural‐equation‐modelling.

Materials and Methods

Two‐hundred and twenty‐seven patients were enrolled; viral tropism on plasma was determined at baseline (BL) by sequencing and interpretation by genotopheno algorithm. Booster atazanavir or lopinavir, or efavirenz or nevirapine were used, in combination with either abacavir/lamivudine or tenofovir‐emtricitabine.

Results

X4‐tropism correlate negatively with CD4 cell count at BL and follow‐up (FU), and CD4 correlate negatively with BL‐plasma viremia (PLV). BL‐PLV correlate positively with FU‐PLV. We have developed the hypothesis that the variables BL‐CD4 and BL‐PLV represent a mediators chain among X4‐tropism and outcome of plasma viraemia at six months. This model, after structural‐equation‐modelling (SEM, Stata13), is shown in Figure 1. The indirect effect of X4‐tropism on Fup‐PLV is significant (p<0.01) but about 10 fold lower than the direct effect by BL‐PLV. X4‐tropism also has a direct negative effect on BL‐CD4 (p<0.001) and an indirect positive effect on BL‐PLV (p<0.001), irrespective of the drug regimen. Path model explaining direct and mediated effects of “tro (tropism),” “gender,” “age,” “cd0 (BL‐CD4)” and “lrna0 (BL‐PLV)” on the final outcome (“lrna1‐Fup‐PLV),” where “tro,” “gender,” and “age” are exogenous, cd0 and lrna0 are endogenous (mediators). Numbers on the arrows indicate direct effects. Circles indicate residuals related to endogenous/dependent variables; numbers near to circles are the corresponding variances.

Conclusions

This model shows the relevance of BL‐tropism on the outcome of plasma viraemia in naïve patients after six months of therapy, irrespective of drug regimen used.
Monitoring of the lactonase activity of paraoxonase‐1 enzyme in HIV‐1‐infection
Authors: Dias Clara , Marinho Aline , Morello Judit , Almeida Gabriela , Caixas Umbelina , Soto Karina , Monteiro Emilia , Pereira Sofia
Published: November 2014

Paraoxonase‐1 (PON1) is a high‐density lipoprotein (HDL)‐associated enzyme known as a free radical scavenging system (1). PON‐1 has three main activities, responsible for its antioxidant and anti‐inflammatory potential: paraoxonase, arylesterase and lactonase (LACase), the latest to be discovered and pointed out to be its native activity (2). Among other physiological roles, the LACase might minimize the deleterious effects of hyperhomocysteinaemia in infection, by detoxifying the highly reactive metabolite homocysteine‐thiolactone (HcyTL) (3),4. In the present work, we have developed and applied a method to quantify LACase activity and to explore the role of this enzyme in HIV‐infection and virological response. The LACase activity was monitored in a cohort of HIV‐1‐infected patients, through the titration of 3‐(o‐hydroxyphenyl) propionic acid, formed upon the LACase‐mediated hydrolysis of the substrate dihydrocoumarin. The study protocol was approved by the Ethics Committee of Centro Hospitalar de Lisboa Central and Hospital Prof. Doutor Fernando Fonseca. All patients gave their written informed consent and were adults with documented HIV‐1‐infection, regardless of combined antiretroviral therapy (cART) use. Naïve patients and patients who had received continuous antiretroviral treatment for more than one month were included. A total of 179 HIV‐1‐infected patients were included on this study (51% Men, 39% non‐Caucasian, 45±13 years old). Patients with non‐suppressed viraemia, either from the non‐cART (n=89, 12±4 kU/L, p<0.01) or from the cART with detectable viral load (n=11, 10±5 kU/L, p<0.05) groups, had lower activity than the cART with suppressed viraemia (n=79, 15±7 kU/L) (Kruskal–Wallis test). Among naïve patients, higher viral load (> 31,500 cps/mL, Spearman r=−0.535, p=0.003) and lower CD4+ T‐cells count (< 500 cell/mm3, Pearson r=0.326, p=0.024) were associated with the LACase activity. The present study suggests that lower LACase activity is associated with uncontrolled HIV‐1‐infection, particularly with non‐suppressed viraemia, despite of cART. This data seems to point to LACase role in HIV‐infection, probably reflecting an increased formation of HcyTL deleterious species. A better knowledge of the LACase and its role in HcyTL pathophysiology might identify new therapeutic targets in HIV‐1‐infected patients.
Plasma HIV‐1 tropism and risk of short‐term clinical progression to AIDS or death
Authors: Casadellà Fontdevila Maria , Cozzi‐Lepri Alessandro , Phillips Andrew , Noguera Julian Marc , Bickel Marcus , Sedlacek Dalibor , Kronborg Gitte , Lazzarin Adriano , Zilmer Kai , Clotet Bonaventura , Lundgren Jens D , Paredes Roger
Published: November 2014

Introduction

It is uncertain if plasma HIV‐1 tropism is an independent predictor of short‐term risk of clinical progression / death, in addition to the CD4 count and HIV RNA level. We conducted a nested case‐control study within EuroSIDA to assess this question amongst people with current HIV RNA level >1000 copies/mL, including both people on ART and those ART naïve.

Methods

People with an AIDS diagnosis or who died from any causes for whom there was a stored plasma sample with HIV‐1 RNA (VL)≥1,000 copies/mL available in the time window of 3–12 months prior to the event were identified. At least one control was selected for each case matched for age, VL and HCV status at the time of sampling. Controls were event‐free after a matched duration of time from the date of sampling. Plasma HIV tropism was estimated using 454 and population sequencing (PS). Non‐R5 HIV was defined as: (a) ≥2% of sequences with a Geno2Pheno (G2P) FPR≤3.75% by 454, and (b) a G2P FPR≤10% by PS. We also compared CD4 slopes over the 12 months following the date of sampling using a linear mixed model with random intercept according to HIV tropism and ART status.

Results

The study included 266 subjects, 100 cases and 166 controls, with sample taken on average in 2006; 23% and 24% had non‐R5 HIV by 454 and PS respectively. There were 19% women, 25% MSM, 92% Caucasians, 22% HCV+. At the time of sampling, 26% were ART‐naïve, 25% had started but were off ART and 49% were receiving ART. The median age, CD4 and viral load was 41 years, 350 cells/mm3 and 4.81 log c/mL, respectively. Baseline characteristics were well balanced by tropism. Factors independently associated with clinical progression or death were female gender (OR=2.12; 95% CI=1.04, 4.36; p=0.038), CD4+ count (OR=0.90 per 100 cells/mm3 higher; 95% CI 0.80, 1.00; p=0.058), being on ART (OR=2.72; 95% CI 1.15, 6.41; p=0.022) and calendar year of sample (OR=0.84 per more recent year; 95% CI=0.77, 0.91; p<0.001). Baseline plasma tropism was not an independent risk factor for clinical progression or death by either 454 or PS. No significant interaction was observed between tropism and ART status. There were no significant differences in the CD4+ slope within or between tropism groups.

Conclusions

Plasma HIV‐1 tropism does not appear to add to the ability of CD4 count and viral load to predict the short term risk of AIDS and death outcomes, even with 454 sequencing.
Characteristics of late presentation of HIV infection in MSM and heterosexual adults in Portugal 2011–2013
Authors: Shivaji Tara , Diniz Antonio , Cortes‐Martins Helena
Published: November 2014

Introduction

It is estimated that over half of newly diagnosed HIV infections in Europe present late. An HIV positive individual presenting late to care represents a missed opportunity to benefit from treatment, increasing the risk of morbidity and mortality at an individual level, and onward disease transmission at population level. Reducing late presentation is a strategic priority of the Portuguese HIV/AIDS program. We set out to describe the characteristics of late presentation in the two largest transmission risk groups currently in Portugal to inform HIV prevention and treatment.

Methods

We extracted details of all notified cases from individuals over 15 years with a laboratory confirmed HIV diagnosis made between January 2011 and December 2013 from the Portuguese HIV surveillance database and selected cases from heterosexuals and men who have sex with men (MSM). We defined late presentation as an initial CD4 count <350 cells/mm3 or presence of AIDS‐defining disease at time of HIV diagnosis. We calculated adjusted odds ratios (aOR) with 95% confidence intervals (CI) for characteristics associated with late presentation in separate logistic regression for heterosexuals and MSM.

Results

Of 4219 HIV positive cases notified, 2589 (61%) were heterosexuals and 1220 (29%) were MSM. A total of 1586 (38%) cases presented late of which 1037 (40%) were heterosexual and 328 (27%) were MSM. The median age at late presentation was 40 in heterosexual women, 46 in heterosexual men and 35 in MSM. A total of 1446 (55%) of heterosexual HIV positive adults were unaware of having had a high risk sexual contact. Late presentation among heterosexuals was associated with being male (aOR=1.58 95% CI 1.29–1.93), not knowing a partners’ HIV status (OR=1.59 95% CI 1.35–1.87) and age, increasing the odds of late presentation by a factor of 1.02 per year (95% CI 1.01–1.03). Among MSM, only age was associated with late presentation, increasing by 1.04 (95% CI 1.03–1.05) per year.

Conclusions

Portuguese HIV prevention programs need to increase the risk awareness of heterosexuals, particularly men, to reduce missed opportunities for early diagnosis. As half of all cases presenting late are aged 40 and over, we recommend that general HIV outreach services and specialist services for MSM review their accessibility and acceptability to both middle and older‐aged clients.
ART management in children perinatally infected with HIV from mothers who experience behavioural changes in Romania
Authors: Märdärescu Mariana , Cibea Alina , Petre Cristina , Neagu‐Drãghicenoiu Ruxandra , Ungurianu Rodica , Petrea Sorin , Maria Tudor Ana , Vlad Delia , Matei Carina , Alexandra Mãrdãrescu
Published: November 2014

Introduction

During the recent years the rate of HIV perinatally exposed children in Romania has increased as a consequence of the expanding number of HIV‐infected women. These women belong to Romania's long‐terms survivors, aged between 20 and 24 years and to the group of new HIV infection cases (20–24 years), acquired through unsafe sexual contact and use of new psychoactive substance (IV).

Materials and Methods

We focused on 396 HIV perinatally exposed children born between 2008 and 2013, under surveillance in National Institute for Infectious Diseases “Prof. Dr. Matei Bals,” Bucharest. Of them, 43 acquired HIV through materno‐foetal transmission. Our aim was to observe the characteristics in their evolution under antiretroviral treatment and to emphasize the causes of treatment failure. Children with perinatally acquired HIV infection were followed in a retrospective case series. We assessed maternal characteristics, HIV vertical transmission prophylaxis, timing of diagnosis, immunological and virologic status and features of the evolution under combined antiretroviral therapy (cART).

Results

The rate of mother‐to‐child HIV transmission was 10.8% versus the national rate registered in 2013, namely <5%. 16% of mothers belonged to the Romanian 1990s cohort and 84% were recently infected with HIV, through unprotected sexual contact (70%) or use of new psychoactive substances (14%). 51% of mothers were diagnosed postnatally as a consequence of their reluctance to access specific health services and in 57% CD4 value was <350 cell/mm. 41% of the monitored children were diagnosed with HIV infection at birth. Their median entry CD4 value was 23% and 49% had a CD4 >25%; median entry viral load was 7 log. 16 patients (37%) had undetectable viral load after six months of treatment. In 87.5% of them the virologic suppression was achieved and maintained with one single regimen (2 NRTIs+1 NNRTI or 2 NRTIs+1 PI/r). 15 children (35%) did not achieve suppression of viral load. 19 children (44%) faced special issues related to adherence to antiretroviral treatment, due to mothers’ poor adherence to a basic set of cares destined for their children.

Conclusions

Prevention programmes in Romania must be designed on the basis of the new economic context and emerging psychoactive substance use. Hence, women who use drugs should benefit from a wider access to medical and social services.
Effectiveness of the prevention of mother‐to‐child transmission of HIV protocol applied at Saint Camille Medical Centre in Ouagadougou, Burkina Faso
Authors: Theophile Soubeiga Serge , Bisseye Cyrille , Compaore Rebecca , Assengone Elsa , Ouermi Djeneba , Djigma Florencia , Sagna Tani , Pietra Virginio , Simpore Jacques
Published: November 2014

Introduction

Despite many prevention efforts, the number of children infected by HIV in sub‐Saharan Africa through vertical transmission remains high. This infection can be reduced through programmes of prevention of mother‐to‐child HIV transmission (PMTCT). The objective of this study was to evaluate the effectiveness of the PMTCT protocol at Saint Camille Medical Centre in Ouagadougou, Burkina Faso.

Methods

From August 2012 to September 2013, samples of dried blood spot (DBS) were collected from 160 children aged 6 weeks born to HIV‐1 positive mothers who were under PMTCT protocol at Saint Camille Medical Centre and 40 children of the same age group from orphanages and whose mothers were dead or unknown. The samples were tested using the Abbott Real Time HIV‐1 Qualitative kit. The clinical data of mothers were collected and analyzed using SPSS Version 17.0 and Epi Info Version 6.0 softwares.

Results

Among pregnant women in this study, 52.5% were predominantly young (24–29 years) and 60.62% were housewives. In total, 50.5% (101/200) were in combination of AZT/3TC/NVP and 29.5% (59/200) were on prophylaxis (AZT/3TC). The rate of vertical transmission of HIV‐1 was 0.0% (p<0.001) in children whose mothers were taking a combination of AZT/3TC/NVP (0/101) or were on a prophylaxis AZT/3TC treatment (0 /59). The rate of HIV‐1 transmission in orphaned children was 15.0% (6/40).

Conclusions

The PMTCT protocol is effective and reduces very significantly (p<0.001) the risk of transmission of HIV‐1 from mother to child. In addition, screening by PCR of orphaned children vertically infected with HIV, enabled them to receive an early treatment.
CD4/CD8 ratio is not predictive of multi‐morbidity prevalence in HIV‐infected patients but identify patients with higher CVD risk
Authors: Menozzi Marianna , Zona Stefano , Santoro Antonella , Carli Federica , Stentarelli Chiara , Mussini Cristina , Guaraldi Giovanni
Published: November 2014

Background

CD4/CD8<0.8 is a surrogate marker of immune‐activation/immunosenescence and independently predicts mortality in the HIV‐infected patients due to non‐AIDS related events. Most studies showed that patients on antiretroviral therapy (ART) often fail to normalize the CD4/CD8 ratio despite CD4 count normalization. Primary objective of the study was to explore the impact of CD4/CD8<0.8 as independent predictor of HIV‐associated non‐AIDS (HANA) conditions and multimorbidity (MM) in HIV patients. In patients with no previous history of cardiovascular disease (CVD) a particular insight is provided in the association between impact of CD4/CD8<0.8 and risk prediction of CVD or radiological markers of subclinical CVD.

Materials and Methods

914 consecutive patients attending Modena Metabolic HIV Clinic were evaluated in a cross‐sectional retrospective study. Inclusion criteria: stable ART from ≥2 years; HIV‐RNA plasma levels<40 copies/mL; stable CD4 count≥350/mmc. CD4/CD8 strata (0.8) was chosen as a cut off representing the median value of the cohort. MM was defined as the presence of≥2 HANA conditions including standard defined: chronic kidney disease, hypertension, previous CVD events, osteoporosis and diabetes mellitus. Calendar year of ART initiation was defined: “PreART” (<2000); “EarlyART” (2000–2005) and “LateART” (>=2006). High CVD risk was defined for Framingham Risk Score (FRS)≥6. Subclinical CVD was defined using cardiac CT scan for calcium score (CAC)≥100. Logistic univariate and multivariable adjusted analysis were performed to assess relationships between variables.

Results

Demographic and HIV‐specific variables distribution in patients with and without MM are shown in Table 1.

Figure 1 shows HANA distribution across CD4/CD8 strata: CVD prevalence only appeared to be higher in patients with no CD4/CD8>0.8.In multivariable analyses CD4/CD8<0.8 was not an independent predictor of MM (OR=1.225, CI 0.891; 1.681, p=0.211) after adjustment for age, gender and BMI. Patients with CD4/CD8<0.8 displayed higher CVD risk but not higher prevalence of subclinical CVD. At multivariable analyses CD4/CD8<0.8 remained predictor of higher CVD risk (OR=0.65, CI 0.47–0.917, p=0.014) after correction for sex, BMI, age strata and HIV infection duration.

Conclusions

Low CD4/CD8 ratio was not associated with MM prevalence. Patients with CD4/CD8<0.8 ratio displayed higher prevalence of CVD. At multivariable logistic regression CD4/CD8<0.8 is an independent prepredictor of enhanced CVD risk. This may support role of immune‐activation/senescence in the pathogenesis of CVD.
Relationship between innate immunity, soluble markers and metabolic‐clinical parameters in HIV+ patients ART treated with HIV‐RNA<50 cp/mL
Authors: Dentone Chiara , Fenoglio Daniela , Signori Alessio , Cenderello Giovanni , Parodi Alessia , Bozzano Federica , Guerra Michele , De Leo Pasqualina , Bartolacci Valentina , Mantia Eugenio , Orofino Giancarlo , Kalli Francesca , Marras Francesco , Fraccaro Paolo , Giacomini Mauro , Cassola Giovanni , Bruzzone Bianca , Ferrea Giuseppe , Viscoli Claudio , Filaci Gilberto , De Maria Andrea , Di Biagio Antonio
Published: November 2014

Introduction

The persistence of immune activation and inflammation in HIV patients with HIV‐RNA (VL) undetectable causes many co‐morbidities [1–3]. The aim of this study is to correlate monocytes (m) and NK cell activation levels, soluble markers and oxidative stress with clinical, biochemical and metabolic data in HIV‐1 infected patients with VL≤50 copies (cp)/mL on antiretroviral therapy.

Materials and Methods

Multicentre, cross‐sectional study in patients with VL≤50 cp/mL and on antiretroviral therapy by at least six months. We studied: activation/homing markers (CD38, HLA‐DR, CCR‐2, PDL‐1) on inflammatory, intermediate, proinflammatory m; activatory receptors NKp30, NKp46 and HLA‐DR on NK cells; soluble inflammatory (sCD14, adiponectina, MCP‐1) and stress oxidative markers (dRoms, antiRoms). Univariate analyses are performed with non‐parametric and Pearson tests. The significant correlations were adjusted for possible known confounding factors (smoking, Cytomegalovirus IgG serology, Raltegravir, Protease Inhibitor [PI] therapy and HCV‐RNA) with multivariate analysis.

Results

In the 68 patients the positive correlation between age and antiRoms was significant also after adjustment for PI use (p=0.05). The% CD8+T was associated with% proinflammatory m (p=0.043) and with their expression of CCR2 mean fluorescence intensity (MFI) (p=0.012). The% NKp46+ was positively correlated with CD4+T count (p=0.001). The fibrinogen was positively associated with dRoms (p=0.052) and the positive correlation between triglycerides and antiRoms has been confirmed (p<0.001); the impact of antiRoms on HDL/triglycerides ratio (p=0.006) was observed after adjustment for PI use. The BMI was associated with smoking (p=0.011). Only the maraviroc‐treated patients showed minimal arterial pressure, fibrinogen and antiRoms lower (p=0.001, 0.004 e 0.006) and sCD14 values higher (p=0.029).

Conclusions

Patients with long history of HIV infection and stable immunological and virological status showed interactions between acquired and innate immunity activation; moreover, the levels of some metabolic and inflammatory parameters correlate with oxidative stress values and innate immunity activation. The age, BMI and smoking impact metabolic and immunological parameters. The correlations between antiretroviral drugs and clinical‐immunological parameters need further confirmations.
Cerebrospinal fluid biomarkers in patients with plasma HIV RNA below 20 copies/mL
Authors: Calcagno Andrea , Atzori Cristiana , Romito Alessandra , Ecclesia Sara , Imperiale Daniele , Audagnotto Sabrina , Chiara Alberione Maria , Trentalange Alice , Di Perri Giovanni , Bonora Stefano
Published: November 2014

Introduction

Low level HIV‐1 CSF replication (CsfLLV) is often found even in patients with controlled plasma viraemia. The clinical consequences of such finding are uncertain; however, both symptomatic neurological disturbances and neurocognitive disorders may arise in the context of CSF‐escape. Two reports suggested that low level replication in the CSF may be associated with increased CSF neopterine although the impact on other markers of neuroinflammation/damage is currently unknown.

Materials and Methods

Patients with neurocognitive disorders, new neurological symptoms or followed in longitudinal studies were included provided that they were on HAART, with last available viral load below 20 copies/mL and without central nervous system (CNS)‐involving infections/neoplasms. After brain Magnetic Resonance (MR) CSF HIV RNA (CAP/CTM HIV‐1 v2.0) and biomarkers [total tau (t‐tau), phosphorylated tau (p‐tau), 1–42 Beta amyloid (Beta42), neopterine and S100beta] were measured through validated methods. Data are presented as medians (IQR); non‐parametric tests are used for all analysis.

Results

70 patients [66.7% male, median age 47.8 years (40–56), median BMI 22.2 kg/m2 (20–24)] were enrolled. Current and nadir CD4+ cell count were 379 (219–656) and 116 cell/mm3 (46–225); HIV RNA was undetectable since 19.7 months (9–53). CSF HIV RNA was undetectable in 24 (34.3%), below 20 copies/mL in 26 (37.1%), above 20 copies/mL in 25 patients [35.7%, median 69 copies/mL (41–134]). Median (IQR) CSF biomarkers values were as follows: t‐tau 109 pg/mL (<75–161), p‐tau 31.6 pg/mL (23.4–35.4), Beta42 818 pg/mL (623–973), neopterine 0.58 ng/mL (0.45–0.87) and S100beta 149 pg/mL (110–186). Patients with CsfLLV did not show significant differences as for demographic, therapeutic, virological, radiological variables. t‐tau (134 vs 92.6, p=0.05) and Beta42 (953 vs 675, p=0.007) were higher in patients with CsfLLV. Neopterine levels were directly associated with p‐tau (rho=0.42, p=0.01), with CSF HIV RNA (rho=0.24, p=0.06). and inversely with current CD4 cell count (rho=−0.29, p=03).

Conclusions

In patients with controlled HIV viraemia (below 20 copies/mL), CSF total tau, Beta42 and neopterine were higher in patients with detectable HIV RNA. Prospective and adequately powered studies are warranted for evaluating the clinical significance of compartmental viral replication and immune activation.
Tackling cardiovascular co‐morbidities in HIV‐positive patients: who, how and where?
Authors: Rolls Sophie , Denneny Emma , Marcus Rebecca , O'Connell Rebecca
Published: November 2014

Introduction

Cardiovascular disease (CVD) is a significant cause of non‐AIDS‐related morbidity and mortality in HIV‐positive individuals [1]. Management of CVD and associated risk factors in HIV are complicated by drug interactions [2]. Optimal management can require specialist input. A previous cohort review highlighted CVD, comorbidity and cardiovascular (CV) risk in our patients [3]. In response, a combined HIV and cardiovascular monthly clinic was established: an HIV consultant works in real time with a cardiologist. The clinic manages CV disease, complex CV co‐morbidities e.g. refractory hypertension, hyperlipidaemia, and assesses primary prevention. A dietician works alongside the clinic.

Aims

Describe the clinic caseload; record clinic interventions and outcomes; recommend service development.

Materials and Methods

We conducted a retrospective notes review of patients attending the co‐morbidity clinic from January 2012 to May 2014. Data collected: demographic, HIV, CVD, CV risk, investigations and clinical interventions.

Results

From a cohort of approximately 960 patients (70% African), 60 (6%) were seen in the co‐morbidity clinic over the specified time period. Median age was 53 (range 24‐80). Although 60% of our cohort is female, 43% (26/60) of the CVD clinic were female. 42 (70%) were African. The mean CD4 was 560 (range 48‐1339). All patients were on ART and 6 (10%) had a detectable viral load > 400 copies/mL. Clinic caseload: i) CVD: 9 had a prior CV event (ACS or CVA); 5 had CCF; new diagnoses included LVH (2), cardiac dysfunction (6); AF (2); atrial thrombus (1). ii) Co‐morbidities: 48(80%) had hypertension – 10 (16.6%) were on quadruple therapy; 17 (28%) had diabetes; 35 (58%) were on a statin. Three had their smoking status clearly documented. Seventeen (28%) were referred to the dietician. Investigations included echo, 24‐hour BP/ tape, CT angio, cardiac MR.

Conclusions

The joint clinic facilitated real‐time decision making on clinical interventions. Patient access to cardiac investigations was expedited. Patients attended fewer outpatient appointments. Both cardiology and HIV clinicians preferred the benefits of joint working. Clinical outcomes were difficult to assess and will need further definition. Recommendations for development include: improved CV risk assessment, improved outcome measures, links to smoking cessation services.
Two years of Truvada for pre‐exposure prophylaxis utilization in the US
Authors: Flash Charlene , Landovitz Raphael , Mera Giler Robertino , Ng Leslie , Magnuson David , Bush Wooley Staci , Rawlings Keith
Published: November 2014

Introduction

Truvada® (TVD) was approved in July 2012 by the US FDA for pre‐exposure prophylaxis (PrEP) in combination with safer sex practices to reduce the risk of sexually acquired HIV‐1 in high‐risk adults. This study explores the characteristics of US PrEP users and their prescribers over the past two years.

Materials and Methods

A previously described algorithm was used to identify TVD for PrEP by excluding use for HIV treatment, post‐exposure prophylaxis, and off‐label treatment of chronic hepatitis B. National electronic patient level data from ~55% of all US retail pharmacies that dispensed TVD between January 1, 2012 and March 31, 2014 was collected. De‐identified patient‐level data including prescription refill data, medical claims and patient demographics were analyzed via logistic regression to estimate the odds of change by year.

Results

A total of 3253 unique individuals who started TVD for PrEP between January 1, 2012 and March 31, 2014 were included in this analysis. Women comprised 42.0% of PrEP users. Although mean age was 38.1+11.9 years, with males being significantly older (39.3+11.6) than females (36.4+12.3), 11.5% of individuals were under 25 years old. The proportion of males under 25 was 7.4% (95% CI 6.3–8.7); significantly lower than that of women, 17.2% (95% CI 15.3–19.3). New starts have increased from 293 in 2012 to 472 Q1 2014. During the 12‐month period ending March 31, 2013 and March 31, 2014 the number of new starts among females dropped from 44.5% to 22.9%.

Sixty‐eight percent of TVD for PrEP prescriptions were written by five specialties: internal medicine (19%), family practice (18%), infectious diseases (11%), nurse practitioners (10%) and physician assistants (10%).

Conclusions

The population of TVD for PrEP users in the US nationally appears to be shifting demographically. It continues to be initiated mostly by primary care providers. Over a two‐year period new starts of Truvada for PrEP have increased considerably among males. While the overall proportion of female users decreased between Q1 2012 and Q1 2014, females that started on PrEP are younger than males. More community‐level data on PrEP usage will be helpful in informing local efforts to integrate PrEP in HIV prevention messaging and services.
Attitudes and beliefs towards early ART initiation in MSM with primary HIV infection
Authors: Parsons Victoria , Porter Kholoud , Gilson Richard , Hart Graham
Published: November 2014

Introduction

ART initiation in primary HIV infection (PHI) could reduce risk of transmission to sexual partners at a time of high viraemia, although health benefit for the individual remains unknown. We examined attitudes to early ART and associated beliefs in men who have sex with men (MSM) with PHI.

Materials and Methods

Semi‐structured face‐to‐face in‐depth interviews were conducted with 13 MSM aged ≥16 years attending a central London HIV clinic, within 12 months of date of estimated HIV seroconversion. Audio recordings of interviews were transcribed verbatim and analyzed thematically.

Results

Median age was 33 years (range 22–47), majority were white British (n=8), educated to university level (n=11) and were not on ART (n=10). Great diversity in ART knowledge and expectations around starting were observed, with some men assuming they would be prescribed ART immediately upon diagnosis. Deferral until CD4<350 came as a surprise and counterintuitive when put into the context of treating other diseases. For many, the decision to start ART was a balance of current and future health and quality of life. Fear of side effects was prevalent, with many believing them inevitable and a reason to avoid early ART. A perceived lack of “good quality” evidence showing a health benefit of early ART caused confusion. Avoiding the decision to start or deferring to their HIV clinician was common, however reported clinicians’ views also varied. Some men voiced a desire to be proactive and start early ART to control viral replication. In these cases men also reported a belief that ART could be temporary as they expected a cure in their lifetime. Men commonly described feeling “infected” and reducing this infectiousness was seen as a major benefit of ART; not purely to reduce the risk of transmission to sexual partners but to facilitate disclosure to partners, reduce anxiety and guilt and restore sexual confidence commonly lost after HIV diagnosis. Having a long‐term HIV‐negative partner was a strong facilitator to starting ART to reduce transmission in the absence of good evidence of individual health benefit.

Conclusions

Factors involved in the decision to start ART in PHI were complex. Uncertainty over individual health benefits in conjunction with fear of toxicities were barriers to starting ART early. By contrast ART was seen as a facilitator to disclosure, and as a way to limit the consequences of infection until a cure is found.
Safety, tolerability and effectiveness of HIV non‐occupational prophylaxis in Taiwan
Authors: Li Hsing‐Chuan , Cheng Yu‐Ping , Yang Chia‐Jui
Published: November 2014

Introduction

Increasing numbers of new HIV infection is an important issue of public health in Taiwan. We aim to evaluate the safety, tolerability and effectiveness of HIV non‐occupational prophylaxis (nPEP) in Taiwan.

Materials and Methods

We conducted a prospective cohort observational study between March 2011 and May 2014. Three‐combined antiretroviral agents were prescribed for all the persons who sought for HIV post‐exposure prophylaxis after high risk sexual behaviour. HIV screening, health education and consultation were done before initiation of nPEP. Adverse effects were evaluated at Weeks 1, 2 and 4 and effectiveness was evaluated at Weeks 12 and 24. We also assessed adherence by pill count and regimen completion rates.

Results

During the study periods, 255 persons were enrolled. Among the enrolled cases, 43.9% (112/255) of them received zidovudine (AZT)‐based regimen while the others received tenofovir (TDF)‐based regimen and the third agent was composed of mostly lopinavir/ritonavir (81.4%). The completion rate of nPEP was 85.9% (219/255), and discontinuation rate of nPEP among AZT‐based regimen is higher than TDF‐based regimen (17.0% vs 8.2%). Any grade adverse effects are higher among AZT‐based regimen than TDF‐based regimen (62.5% vs 32.1%) although most adverse effects were grade 1–2. After a 24‐week follow‐up, only one person experienced HIV seroconversion and he had primary syphilis at the moment when he sought for nPEP.

Conclusions

NPEP could be an effective prevention method in a part of HIV prevention strategy and TDF‐based regimen had better tolerability in Taiwan.