bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and risk factors of sleep disturbances in a large HIV‐infected adult population
Authors: Allavena Clotilde , Guimard Thomas , Billaud Eric , de la Tullaye Sylvie , Reliquet Véronique , Pineau Solène , Hüe Hervé , Supiot Christelle , Marie Chennebault Jean , Michau Christophe , Hitoto Hikombo , Vatan Rémi , Raffi François
Published: November 2014

Introduction

Sleep disturbances are frequently reported in HIV‐infected patients but there is a lack of large studies on prevalence and risk factors, particularly in the context of current improved immuno‐clinical status and use of the newest antiretrovirals (ARV).

Method

Cross‐sectional study to evaluate the prevalence and factors associated with sleep disturbance in adult HIV‐infected patients in six French centres of the region “Pays de la Loire”. Patients filled a self‐administered questionnaire on their health behaviour, sleep attitudes (Pittsburgh Sleep Quality Index PSQI), quality of life (WHO QOL HIV BREF questionnaire) and depression (Beck depression Inventory (BDI)‐II questionnaire). Socio‐demographic and immunovirologic data, medical history, ARVs were collected.

Results

From November 2012 to May 2013, 1354 consecutive non‐selected patients were enrolled. Patients’ characteristics were: 73.5% male, median age 47 years, active employment 56.7%, France‐native 83% and Africa‐native 14.7%, CDC stage C 21%, hepatitis co‐infection 13%, lipodystrophy 11.8%, dyslipidemia 20%, high BP 15.1%, diabetes 3%, tobacco smokers 39%, marijuana and cocaine users, 11.7% and 1.7% respectively, and excessive alcohol drinkers 9%. Median (med) duration of HIV infection was 12.4 years, med CD4 count was 604/mm3; 94% of Patients were on ARVs, 87% had undetectable viral load. Median sleeping time was 7 hours. Sleep disturbances (defined as PSQI score >5) were observed in 47% of the patients, more frequently in female (56.4%) than in male (43.9%) (p<0.05) and moderate to serious depressive symptoms (BDI score>19) in 19.7% of the patients. In multivariate analysis, factors associated with sleep disturbances (p<0.05) were depression (odds ratio [OR] 4.6; 95% confidence interval [CI] 3.2–6.8), male gender (OR 0.7; CI 0.5–0.9), active employment (OR 0.7; CI 0.5–0.9), living single (OR 1.5; CI 1.2–2.0), tobacco‐smoking (OR 1.3; CI 1.0–1.8), duration of HIV infection (>10 vs. <10 y.) (OR 1.5; CI 1.1–2.0), ARV regimen containing nevirapine (OR 0.7; CI 0.5–0.9) or efavirenz (OR 0.5; CI 0.3–0.7).

Conclusions

Prevalence of sleep disturbances is high in this HIV population and roughly similar to the French population. Associated factors are rather related to social and psychological status than HIV infection. Depression is frequent and should be taken in care to improve sleep quality.
Should the dose of tenofovir be reduced to 200–250 mg/day, when combined with protease inhibitors?
Authors: Hill Andrew , Khoo Saye , Back David , Pozniak Anton , Boffito Marta
Published: November 2014

Introduction

The approved dose of tenofovir disproxil fumarate, 300 mg once daily, was established in clinical trials in combination with efavirenz, which does not significantly affect tenofovir concentrations. Combining tenofovir with lopinavir/r, darunavir/r or atazanavir/r increases tenofovir concentrations, which could raise the risk of renal adverse events. Newly approved tenofovir tablets are available at lower strength (200 or 250 mg) for use in paediatrics.

Methods

A literature search was used to assess the effects of lopinavir/r, darunavir/r and atazanavir/r on tenofovir plasma Cmax, AUC and Cmin (Geometric Mean Ratio and 90% confidence intervals). Assuming linear dose‐proportional pharmacokinetics (as observed in dose‐ranging studies), the 250 mg tablet was predicted to achieve plasma concentrations 17% lower than the 300 mg dose, and the 200 mg tablet to achieve plasma levels 33% lower. Effects on tenofovir plasma Cmax, AUC and Cmin concentrations were assessed for combined dosing of each protease inhibitor with 250 or 200 mg daily doses of tenofovir, versus standard dose tenofovir (300 mg daily) without protease inhibitors.

Results

In drug‐drug interaction studies, lopinavir/ritonavir significantly increased tenofovir Cmax, AUC and Cmin. Effects of each PI on tenofovir Cmin were greater than effects on Cmax or AUC. Using a 250 mg paediatric dose of tenofovir with lopinavir/ritonavir, tenofovir Cmin was predicted to remain higher than tenofovir 300 mg used with efavirenz (GMR=1.26, 95% CI 1.14–1.38). Similar results were observed for use of tenofovir 250 mg with atazanavir/ritonavir (GMR=1.07, 95% CI 1.01–1.13) and with darunavir/ritonavir (GMR=1.14, 95% CI 0.99–1.31). Predicted tenofovir AUC levels for the 250 mg dose with protease inhibitors were all within the bioequivalence range, relative to use with efavirenz. Using a 200 mg paediatric dose of tenofovir with lopinavir/ritonavir, the tenofovir Cmin was predicted to be bioequivalent to tenofovir 300 mg used with efavirenz (GMR=1.02, 95% CI 0.92–1.11). Similar results were observed for use of tenofovir 200 mg with atazanavir/ritonavir (GMR=0.86, 95% CI 0.82–0.91) and with darunavir/ritonavir (GMR=0.92, 95% CI 0.80–1.05). All three results were within the bioequivalence limits of 0.8–1.25.

Conclusions

Use of approved paediatric doses of tenofovir (200–250 mg once daily) in combination with lopinavir/r,darunavir/r or atazanavir/r could compensate for known drug interactions. This dose modification could potentially improve renal safety.
Low isoniazid and rifampicin concentrations in TB/HIV co‐infected patients in Uganda
Authors: Sekaggya Wiltshire Christine , Lamorde Mohammed , Scherrer Alexandra , Musaazi Joseph , Corti Natascia , Allan Buzibye , Nakijoba Rita , Nalwanga Damalie , Henning Lars , Von Braun Amrei , Okware Solome , Castelnuovo Barbara , Kambugu Andrew , Fehr Jan
Published: November 2014

Introduction

There is limited data available on exposure to anti‐tuberculosis (TB) drugs in this region. Peloquin has described reference ranges [1] however some studies have demonstrated that patients actually achieve concentrations below these ranges [2]. There is limited data about exposure to anti‐TB drugs in the HIV/TB co‐infected population in Sub‐Saharan Africa. Our objective is to describe the concentration of anti‐TB drug levels in a well characterized prospective cohort of adult patients starting treatment for pulmonary TB.

Methods

This study is an ongoing study carried out in the TB/HIV integrated clinic at the Infectious Diseases Institute in Kampala, Uganda. Sputum culture and microscopy was done for all patients. We performed pharmacokinetic blood sampling of anti‐TB drugs for 1 hour, 2 hours and 4 hours post dose at 2 weeks, 8 weeks and 24 weeks after initiation of anti‐TB treatment using ultraviolet high‐performance liquid chromatography (UV‐HPLC). We described the maximum concentration (Cmax) of isoniazid (H), rifampicin (R), ethambutol (E) and pyrazinamide (Z) and compare them with the values observed by Peloquin et al. referenced in other studies.

Results

We started 113 HIV infected adults on a fixed dose combination of HREZ. The median age of our population was 33 years, of which 52% were male with a median BMI of 19 kg/m2 and a median CD4 cell count of 142 cells/µL. In 90% of the participants, the diagnosis of TB was based on microscopy and or cultures. The boxplot graph shows the median Cmax and IQR of H and R.

Levels of H were found to be below the reference ranges (3–6 µg/mL) in 54/77(70.1%), 38/59(64.4%) and 15/24(62.5%) participants at weeks 2, 8 and 24. Rif levels were also found to be below the reference ranges (8–24 µg/mL) in 41/66(62.1%), 26/48(54.2%) and 8/10(8%) participants at weeks 2, 8 and 24, respectively. The mean Cmax of E and Z were within the reference range at week 2 and 8; mean Cmax of 3.2±SD2.1 µg/mL and 4.0±SD3.1 µg/mL for E and 41.6±SD13.1 µg/mL and 42.6±SD16.4 µg/mL for Z.

Conclusion

We observed lower concentrations of isoniazid and rifampicin in our study population of HIV/TB co‐infected patients. The implications of these findings are not yet clear. We therefore need to correlate our findings with the response to TB treatment.
HIV positive asylum seekers receiving the order to leave the Belgian territory
Authors: Demeester Remy , Legrand Jean‐Claude
Published: November 2014

Introduction

In a human rights based approach, the Parliamentary Assembly of the Council of Europe has recently released a resolution about migrants and refugees and the fight against HIV [1]. It states that “an HIV positive migrant should never be expelled when it is clear that he will not receive adequate health care and assistance in the country to which he is being sent back. To do otherwise would amount to a death sentence for that person.” Nevertheless, in Belgium, for the last 2 years, none of the HIV‐infected migrants in care in the AIDS Reference Centers (ARC) received the right to stay in Belgium for medical reasons.

Methods

We identified all HIV‐infected asylum seekers in care between 1 July 2012 and 1 July 2014 in the ARC of Charleroi, Belgium, and we analyzed their medical and social files.

Results

Among the 302 patients in active follow up in our ARC, 45 HIV positive asylum seekers were in care during the last 2 years. Male/female ratio was 0/96. Mean age was 35 years. Countries of origin and reasons for migration are detailed in the Table 1. 18% (8/45) knew their seropositivity before arriving in Europe. All the patients introduced an asylum request, 29 (64%) have received a negative answer and an order to leave the territory, 4 (9%) were regularized for non‐medical reasons (see Table 1), 4 (9%) are waiting for an answer and for 8 (18%) outcome is unknown due to lost follow up (LFU). 31 (69%) patients have also introduced a request to stay for medical reasons: 18 (58%) have received a refusal, 7 (23%) are still waiting for an answer, and 6 (19%) are LFU. Only 23 (51%) patients are still in care in our ARC on 1 July 2014 (see Table 1). The immigration office bases its decisions on availability of the treatment in the country even if accessible only to a limited number of patients.

Conclusions

Decisions taken by the Belgian authorities for the last two years concerning HIV‐infected asylum seekers do not guarantee the continuity of care of those patients and push them towards illegality. Such decisions ignore the international commitments of Belgium in the fight against HIV [2] and are contradictory with the recommendations of the recent resolution of the Council of Europe [1]. An approach more respectful of Human Rights in the decisions concerning the seropositive asylum seekers patients taken by the authorities is urgently needed in Belgium. We invite our European colleagues to describe the situation of the HIV asylum seekers in their countries.
EATG training academy STEP‐UP: skills training to empower patients
Authors: Martynenko Oleksandr , Kelly Damian , Say Vanessa
Published: November 2014

Introduction

Most existing conventional capacity building and educational programs are currently executed on ad‐hoc basis. Such approach no longer responds to the needs and capabilities of patients, supporters and healthcare providers in their engagement with and contribution to response to HIV/AIDS. In contrast, long‐term, course‐like trainings have considerably broader thematic scope and are conducive to more effective and sustainable learning, exchange of experience and best practices.

Method

Over the period of one year, the Academy trains a cohort of 20 activists (10 from East Europe and Central Asia and 10 from Western and Southern Europe). The Academy goes beyond “treatment only” paradigm. Conceptually, five training modules are grouped under three larger domains: treatment literacy, treatment advocacy and treatment activism, thus covering most of the topics pertinent to the current discourse of HIV and related co‐infections. To ensure cascade effect and sustainability of the learning, the trainees are offered participation in pan‐European HIV conferences (EACS and HIV Glasgow) and resources for follow‐up activities.

Results

The trainees empirically applied the knowledge to the benefits of their communities. In Uzbekistan, a trainee introduced EACS treatment guidelines to fellow medical students and junior doctors. In Armenia and Albania a series of small‐scale trainings were held, outreaching to young homeless people who were traditionally excluded from HIV treatment and prevention discourse in the two countries. A trainee from Spain used the materials of the Academy in his work in Mozambique and the Spanish Ministry of Health. Five trainees engaged in a joint European cross‐countries project on treatment literacy for young people who are most at risk of infection.

Conclusions

EATG Training Academy is a unique initiative in the WHO Europe region that both trains future treatment activists and addresses treatment literacy, advocacy and advocacy topics. This type of capacity building can respond to existing HIV‐related problems more effectively using less limited resources and reaching out to larger communities.
Hidden costs of HIV treatment in Spain: inefficiency of the antiretroviral drug packaging
Authors: Llibre‐Codina Josep M , Andreu‐Crespo Angels , Cardona‐Peitx Gloria , Sala‐Piñol Ferran , Clotet‐Sala Bonaventura , Bonafont‐Pujol Xavier
Published: November 2014

Introduction

Antiretroviral drugs in Spain are delivered by law only in hospital pharmacies. Commercial packages meet variable quality standards when dispensed drugs are returned due to treatment changes or adherence problems Nearly 20–25% of the initial regimens will be changed at 48 weeks for different reasons. We evaluated the economic impact on public health system of the inability of using returned drugs due to inefficient packaging.

Materials and Methods

We defined socially efficient packaging as the best adapted one to being delivered in unit dose to outpatients and classified: Class A ‐ Drug packed in unit doses with complete info (name of drug, dosage in mg, lot, and expiring date) in each unit, maintaining complete information of the drug if returned when the external package is opened. Class B ‐ packed in blisters with complete info in the blister, but not in unit doses, without special conservation conditions (should be re‐packed in unit doses in the pharmacy before its dispensation to assure a class A excellence). Class C ‐ packed in plastic containers with complete info written only on a label over the container, would allow repackaging only before its initial delivery, but not when returned. Class D ‐ drug packed in plastic containers with manufacturer's warning that the product cannot be placed outside of the original package due to special conditions of conservation (fridge, humidity) that doesn't allow a unit dose repackaging or reusing an opened container. We analysed a 12‐month period (July 2011–June 2012) in a hospital‐based HIV outpatient pharmacy that serves 2413 treated individuals.

Results

Patients generated 23,574 visits to pharmacy, and received 48,325 drug packages, with 2.529.137 pills delivered. The patients suffered 1051 treatment changes for any reason. A total amount of 122.945€ in treatment were returned to pharmacy in opened packages during the study period. 47.139.91€ would be totally lost, mainly due to being packaged in class C and D boxes, the equivalent of treating 78 patients with rilpivirine/TDF/FTC during 1 month. Class A and B packages in bad condition represented only 1.1% of the cost. However, 75.805€ came from returned packages in good condition that could potentially be reused. Most of the treatment changes were not foreseeable.

Conclusions

A significant economic budget is lost through socially inefficient antiretroviral packages. Newer treatments are packaged in C and D categories, therefore maintaining these hidden costs in the near future. Any improvement in the excellence of packaging by the manufacturer, and favouring the choice of drugs supplied through efficient packages (when efficacy, toxicity and convenience are similar) should minimize the treatment expenditures paid by national health budgets.
Early HIV diagnosis through use of rapid diagnosis test (RDT) in the community and direct link to HIV care: a pilot project for vulnerable populations in Athens, Greece
Authors: Kakalou Eleni , Papastamopoulos Vasileios , Ioannidis Panagiotis , Papanikolaou Kostas , Georgiou Ourania , Skoutelis Athanasios
Published: November 2014

Introduction

An increase in the incidence of HIV new infections among intravenous drug users (IDUs) by 1500%, was noted in the center of Athens in 2011. Increasing problematic drug use, homelessness, health cuts amidst the economic crisis, have contributed to the epidemic. New cases doubled within a year, challenging the HIV care delivery system [1].

Materials and Methods

A pilot project funded by the National Strategic Reference Framework (NSRF) 2007–2013 of the European Union (EU), was launched from August 2012 to March 2014. It was a partnership between the HIV Clinic of Evangelismos Hospital and the NGO PRAKSIS. The project is aimed at offering early diagnosis and comprehensive care to hard to reach populations. RDT diagnosis through mobile units, direct linkage to care, elimination of waiting times, flexibility, psychosocial support and link to harm reduction services for active IDUs were offered to the beneficiaries.

Results

A total of 117 people enrolled in the program following HIV RDT offered by mobile units of the NGO PRAKSIS in community sites. Sixty‐eight percent were IDUs, 12% were men who have sex with men (MSM) and 19.5% were heterosexuals. Men were 74.3% and women were 25.6%. Country born patients were 43.5% and non‐country born patients were 56.4%. Nine people were HIV negative but needed post‐exposure prophylaxis (PEP), treatment for Hepatitis C and one test was false positive. Two deaths occurred and six people were deported. Of the remaining 100 patients, 84 enrolled in the care program. Of those 77% (65/84) remain in care for three months after the end of the project. Care retention was 73.5% (39/53) for IDUs, 91% (10/11) for MSM, 80% (16/20) for heterosexuals, 73% (25/35) for country born and 82% (40/49) for non‐country born individuals. Among those that remain in care, 77.7% (42/54) with <350 CD4 are on antiretroviral therapy (ART). Among those on ART >90% have undetectable viral load. Mean value of CD4 cells at enrollment was 298 cells/mm3. At follow up, three months after the end of the program, the mean value of CD4 cells was 464 cells/mm3.

Conclusions

The project has proven the feasibility of a novel approach of active case finding in the community with direct link to care. Retention to care was satisfactory as most of those patients would not have been able to access care through the normal ART delivery mode of the Public Health System. However, more obstacles to care remain. Being homeless, poor nutrition, complicated access to harm reduction services, lack of One Stop Shop services and police operations in the city center impede further progress [2,3].
Monitoring renal function during combination therapy with telaprevir in HIV/HCV co‐infected patients with advanced/fibrosis cirrhosis
Authors: Puzzolante Cinzia , Vecchia Marco , Zona Stefano , Borghi Vanni , Guaraldi Giovanni , Mussini Cristina
Published: November 2014

Introduction

Telaprevir (TVR) plus peg interferon (PEG‐IFN) and ribavirin (RBV) substantially increase treatment efficacy for genotype 1 chronic hepatitis C virus (HCV) infection but data about its safety in HIV patients with cirrhosis are lacking. Our purpose was to evaluate estimated Glomerular Filtration Rates (eGFR) variations during combination therapy in a difficult‐to‐treat HIV/HCV population with advanced fibrosis/cirrhosis through three different scores commonly used in clinical practice: CKD‐EPI (Chronic Kidney Disease Epidemiology Collaboration), Modification of Diet in Renal Disease (MDRD) scores (that consider gender, ethnicity, age, serum creatinine level [SCL]) and MDRD 6 variable (that considers the previous parameters plus blood urea nitrogen and serum albumin). Second objective was to identify any association between creatinin clearance and haemoglobin (Hb) variation during combination therapy.

Materials and Methods

We conducted an observational retrospective study including 18 HIV/HCV patients attending our clinic who started combination therapy for HCV, including in the analysis the first 16 weeks of therapy. Treatment included TVR 1125 mg BID (twice a day) for 12 weeks, PEG‐IFN α‐2a 180 mcg QW and RBV daily dose according to body weight (800 mg in individuals <60 kg; 1000 mg in individuals 60–75 kg; 1200 mg in individuals >75 kg). Advanced fibrosis was defined as Metavir score=F3 or Ishak 3–4 and cirrhosis was defined as Metavir score F4 or Ishak 5–6 assessed by liver biopsy or transient elastography respectively. P per trend were assessed to evaluate any change of SCL and eGFR (according to different formulas). Multilevel linear regression analysis was performed to estimate factors associated with reduction of Hb.

Results

Baseline characteristics and HCV virological responses were collected. Figure 1 shows median SCL and eGFR trends across follow‐up period: SCR p‐per‐trend was 0.28, for CKD‐EPI was 0.50, for MDRD was 0.48, for MDRD‐6 variables was 0.27. Hb trend was also assessed and a significant decrease of Hb across follow‐up (p per trend <0.001) was noted. Multilevel regression analysis found an association between SCL and Hb change, after adjustment for age, sex, basal BMI, tenofovir exposure and proteinuria (assessed at baseline) as shown in Table 1.

Conclusions

In our experience, combination therapy with TPV in cirrhotic HIV‐HCV patients did not significantly affect renal function. As expected, Hb levels decreased during treatment and it is likely related to RBV exposure. In multivariable analysis, reduction of Hb appeared to be related to SCL higher levels, thus suggesting even a mild decrease of renal function.
Evaluation of the degree of liver fibrosis and genetical characteristics in HIV patients with spontaneous clearance of HCV in Cartagena, Spain
Authors: Jesús Vera Méndez Francisco , Jimeno Almazán Amaya , Smilg Nicolás Clara , Alcaraz Vidal Begoña , Martínez Madrid Onofre , Alcalde Encinas Mar , García García Josefina , Martínez Fernández Lorena , Conesa Zamora Pablo , Ruiz Belmonte Elena , Escribano Viñas Paloma , Trujillo Santos Javier
Published: November 2014

Introduction

Single‐nucleotide polymorphisms (SNPs) in the region of the Interleukin 28B (IL28B) gene on chromosome 19, coding for the interferon (IFN)‐λ3, are involved in hepatitis c virus (HCV), spontaneous clearance. There is little information on the degree of liver fibrosis (LF) in HIV patients, who have had spontaneous clearance of HCV. Our objective in this study is to assess the degree of liver fibrosis in this population, as well as to identify key genetic characteristics associated with spontaneous clearance.

Materials and Methods

Retrospective descriptive study that evaluated from 1 January 2013 to 30 May 2014, the HIV‐HCV coinfected patients in which it has been demonstrated spontaneous clearance of HCV infection. The main variables analyzed were (1) genetics: Haplotype determination of genetic polymorphism SNP rs12979860 in the region of IL 28B gene and (2) grade of LF measured in kilopascals (kPa) by transient elastography (TE).

Results

We evaluated 205 patients with HIV and HCV coinfection, of whom, 17 patients (8.3%), presented spontaneous clearance. Fourteen patients (82.4%) had HIV CV<20 copies/mL, while the mean CD4 cell count was 396 (SD: 245) cells/mcL. Nine (53%) patients were analyzed for SNP rs12979860 of IL 28B gene. Nine patients (100%) had the CC haplotypes, and no cases of CT and TT haplotypes were detected (p<0.001). LF was measured by TE in 12 (70.6%) patients. The median of LF (Kpa) was 5.95 (IQR 4.78). In four patients (33.3%) were observed significant LF (F3–F4). In the univariate analysis, no significant differences in the median of LF (Kpa) of HIV patients with spontaneous clearance of HCV were observed with respect to the coinfected HIV‐HCV patients with SVR to antiviral therapy (N=34; median 9.6 Kpa; IQR: 10.7; p=0.92) or the coinfected HIV‐HCV group who did not receive antiviral therapy (N=124; median 8.5 kPa; IQR: 7.65; p=0.85).

Conclusions

Spontaneous clearance of HCV in our series of patients coinfected with HIV infection represents an uncommon clinical phenomenon. The immune status was preserved and most patients had HIV virological suppression. In all patients in which the IL 28B genetic polymorphism was determined, CC haplotypes were found. The degree of LF (Kpa) in this population was low (<9.5 Kpa) and a low proportion of subjects showed significant LF (F3–F4). No differences in the degree of LF were found in this group compared to coinfected patients receiving HCV treatment with SVR and compared to untreated patients coinfected with HIV‐HCV.
Risk of liver decompensation assessed in HIV/HCV co‐infected individuals with advanced liver fibrosis: a faster countdown experience
Authors: Pedro Alves Joao , Peres Susana , Borges Fernando , Cláudia Miranda Ana , Baptista Teresa , Ventura Fernando , Antunes Isabel , Nina Jaime , José Campos Maria , Aldir Isabel , Mansinho Kamal
Published: November 2014

Introduction

Cirrhosis secondary to HCV infection is expected to peak in the next decade, particularly in the HIV co‐infected subgroup and has become a leading cause of morbidity among these individuals. Efforts must be done to estimate the risk of liver decompensation (LD) in the short term, in order to define the appropriate time for HCV treatment.

Materials and Methods

Retrospective observational cohort study aimed to assess the risk of LD among a group of HIV/HCV co‐infected patients diagnosed in the past 23 years in a central hospital of Lisbon. Inclusion criteria: (1) advanced liver fibrosis ≥F3; (2) HCV treatment naïve or without sustained virologic response (SVR). Patients had a one to five years period of follow‐up. Multiple linear regression, Mann‐Whitney and Kendall were the statistical tests performed.

Results

From 444 HIV/HCV co‐infections, 66 met the inclusion criteria, with preponderance of male gender (82%), 35–45 years of age (55%), genotype 1a (52%), a mean of 13 years of co‐infection and an AIDS stage documented in 65%, though the majority is under antiretroviral therapy (86%) and have TCD4+>500 µ/L (59%). Half (52%) showed evidence of steatosis, many of these (41%) presenting a history of alcoholism or overweight (BMI ≥25 Kg/m2). Pre‐cirrhotic (F3 or F3/4) or cirrhotic (F4) stage was documented in 36 and 30 patients respectively. After staging, 28 (42%) initiated HCV treatment and SVR was achieved in 8 (29%) of those. Five (14%) pre‐cirrhotic and twelve (40%) cirrhotic patients experienced at least one LD episode: 8 vs 28 cumulative events at five years and 2.8 vs 1.8 average years up to the first LD episode for pre‐cirrhotic vs cirrhotic. The probability of remaining free of LD for pre‐cirrhotic vs cirrhotic patients was 97% vs 78% (p≤0.01) at one year; 88% vs 65% (p≤0.001) at three years and 71% vs 44% (p≤0.001) at five years. Positive correlation was found between LD and the cirrhotic stage (vs pre‐cirrhosis, p≤0.001), baseline AST ≥100 µ/L (vs <100 µ/L, p≤0.01) and platelet count <120 x 109/L (vs >120 x 109/L, p≤0.05).

Conclusions

Cirrhosis accounts for a significant superior risk of LD. The time up to the first LD event differed in only one year between pre‐cirrhotic and cirrhotic, standing for the importance of a rapid treatment referral in both subgroups. Modifiable risk factors that accelerate fibrosis are prevalent in HIV/HCV co‐infected patients. Low platelet count, elevated AST and F4 stage predict the rapid progression to LD and the need for early HCV treatment. Large studies are required for further support of these results.
Increased incidence of sexually transmitted diseases in the recent years: data from the ICONA cohort
Authors: Cingolani Antonella , Zona Stefano , Girardi Enrico , Cozzi Lepri Alessandro , Monno Laura , Quiros Roldan Eugenia , Guaraldi Giovanni , Antinori Andrea , d'Arminio Monforte Antonella , Marcotullio Simone ,   on behalf of ICONA Foundation Study
Published: November 2014

Introduction

Sexually transmitted diseases (STDs) data collected in HIV+ patients could be used as indicator of risky sexual behaviour possibly linked to HIV transmission. We described the STDs incidence over time and identified higher incidence factors.

Methodology

All patients in the ICONA Foundation Study enrolled after 1998 were included. STDs considered: any‐stage syphilis, human papilloma virus (HPV) diseases, gonococcal and non‐gonococcal urethritis, herpes simplex virus (HSV) genital ulcers, vaginitis and acute hepatitis B virus (HBV), hepatitis A virus (HAV), and hepatitis C virus (HCV) infections (only for non‐IVDU (intravenous drug user) patients). STDs incidence rate (IR): number of STDs divided by person years of follow‐up (PYFU). Calendar periods: 1998–2002, 2003–2007 and 2008–2012. Predictors of STDs occurrence were identified using Poisson regression and sandwich estimates for the standard errors were used for multiple STD events.

Results

Data of 9,168 patients were analyzed (median age 37.3 (SD=9.3), 74% male, 30% MSM). Over 46,736 PYFU, 996 episodes of STDs were observed (crude IR 17.3/1,000 PYFU). Median (IQR) CD4/mmc and HIV‐RNA/mL at STD: 433 (251–600) and 10,900 (200–63,000). Highest crude IRs were observed for any‐stage syphilis (3.95, 95% CI 3.59–4.35), HPV diseases (1.96, 1.71–2.24) and acute hepatitis (1.72, 1.49–1.99). At multivariable analysis (variables of adjustment shown in Figure 1), age (IRR 0.82 per 10 years younger, 95% CI 0.77–0.89), MSM contacts (IRR 3.03, 95% CI 2.52–3.64 vs heterosexual) and calendar period (IRR 1.67, 95% CI 1.42–1.96, comparing 2008–2012 with 1998–2002) significantly increased the risk of acquiring STDs. Moreover, having a HIV‐RNA >50 c/mL (IRR 1.44, 95% CI 1.19–1.74 vs HIV‐RNA <50 c/mL) and current CD4+ cell count <100/mmc (IRR 4.66, 95% CI 3.69–5.89, p<0.001 vs CD4+ cell count >500) showed an increased risk of STDs. Being on ARV treatment significantly reduced the risk of developing an STD (IRR 0.37, 95% CI 0.32–0.43) compared to ART‐naïve people, even in the situation of temporary interruption of treatment (IRR 0.51, 95% CI 0.39–0.43) (see Figure 1).

Conclusions

The overall incidence of STDs has been increasing in the recent years. Interventions to prevent STDs and potential further spread of HIV infection should target the recently HIV diagnosed, the young population and MSM. Being on ARV treatment (potentially an indicator of whether a person is regularly seen for care) seems to reduce the risk of acquiring STDs independently of its viro‐immunological effect.
Predictors of lack of serological response to syphilis treatment in HIV‐infected subjects
Authors: Spagnuolo Vincenzo , Poli Andrea , Galli Laura , Cernuschi Massimo , Nozza Silvia , Maillard Myriam , Gianotti Nicola , Hasson Hamid , Bossolasco Simona , Lazzarin Adriano , Castagna Antonella
Published: November 2014

Introduction

The aim of this study was to determine factors associated with lack of serological response (LSR) to treatment of syphilis among HIV‐infected subjects.

Materials and Methods

Retrospective, longitudinal study on HIV‐infected subjects diagnosed and treated for syphilis and with an assessable serological response between 1 January 2004 and 15 September 2013. LSR was defined as a <4‐fold decline of rapid plasma reagin (RPR) titer or a failed reversion to nonreactive (if RPR ≤1:4 at diagnosis) after one year since treatment. Diagnoses of syphilis were staged in early syphilis (primary, secondary and early latent) or late syphilis (tertiary and late latent) according to clinical examination and patient's history. Syphilis was classified in new infections [NI: positive RPR and TPHA (Treponema pallidum Haemagglutination assay) titers in subjects without previous history of syphilis] or re‐infections [ReI: a ≥4‐fold increase of RPR titer in subjects previously successfully treated for syphilis]. Syphilis treatment was prescribed according to CDC guidelines. The crude incidence rates (IRs) of LSR were calculated per 1000‐person months of follow‐up (PMFU) as the total number of LSR episodes divided by the cumulative time contributed by all subjects (interval time since each syphilis diagnosis and the date of ascertainment of response). Results are described as median (IQR) or frequency (%).

Results

565 diagnoses of syphilis with an assessable serological response in 421 patients; 458 (81%) were early syphilis, 189 (33%) were NI, 376 (67%) were ReI. At first, diagnosis of syphilis median age was 41 (36–47) years, 419 (99.5%) males, 391 (93%) MSM, HIV‐infected since 7.7 (3.5–12.9) years, 75 (18%) HCV or HBV co‐infected, 56 (13%) with a previous AIDS diagnosis, 82 (19%) antiretroviral treatment naïve, 102 (24%) with HIV‐RNA ≥50 cp/mL, CD4+=576 (437–749) cells/mm3, nadir CD4+=308 (194–406) cells/mm3. LSRs were observed in 70/565 (12.4%) treated syphilis. Incidence of LSR decreased over time [2004–2008 IR=25.1 (17.2–33.1)/1000 PMFU; 2009–2010 IR=21.1 (12.3–29.9)/1000 PMFU; 2011–2013 IR=10.6 (5.1–18.2)/1000 PMFU; Poisson regression: p=0.001]. Results of univariate and multivariate analysis on the risk of LSR are reported in Table 1.

Conclusions

In HIV‐infected subjects we observed 12% of LSR to treatment of syphilis. LSR was associated with an older age, late syphilis, lower nadir CD4+ and detectable HIV viral load.
Ongoing epidemic of lymphogranuloma venereum in HIV‐positive men who have sex with men: how symptoms should guide treatment
Authors: Mohrmann Gerrit , Noah Christian , Sabranski Michael , Sahly Hany , Stellbrink Hans‐Jürgen
Published: November 2014

Introduction

Lymphogranuloma venereum (LGV) is a sexually transmitted infection (STI) caused by chlamydia trachomatis (CT) genotype L (L1, L2 and L3). Recent outbreaks of LGV in Europe and North America affected mainly men who have sex with men (MSM). Infections with CT serotypes D‐K are mostly associated with mild symptoms or may be clinically silent. However, infections with L genotypes are more invasive and induce anogenital ulcer or inguinal lymphadenopathy.

Materials and Methods

Between 2003 and 2013, anal or genital CT infections were diagnosed in 471 symptomatic patients attending the Infectious Diseases Center Hamburg (ICH). CT DNA was detected by PCR. CT genotyping of positive samples was performed by sequence analyses of omp1 PCR products (samples between 2003 and 2010). Samples between 2012 and 2013 were analyzed by genotype L specific real‐time PCR.

Results

In total, 221 LGV patients were identified (3 in 2003; 11 in 2004; 26 in 2005; 33 in 2006; 24 in 2007; 16 in 2008; 18 in 2009; 15 in 2010; 17 in 2011; 26 in 2012 and 32 in 2013). One hundred ninety‐eight of 221 (89.6%) patients with LGV were HIV‐infected; 10 of 221 (4.5%) were HIV‐negative, and the HIV‐status unknown in 13 (5.9%). The majority of LGV positive patients (204/221; 92%) had anorectal symptoms (bloody proctitis, rectal pain, purulent or mucous discharge, tenesmus, constipation), compared to 17/221 (8%) who presented with genital symptoms as urethritis, genital ulcer or inguinal lymphadenopathy. Of 283 CT‐positive patients with anorectal symptoms, genotype L was detected in 205 (72%), while non‐L genotypes (D‐K) were found in 78 (28%). In contrast, genotype L was found in only 6% of patients with genital symptoms (11/177), whereas 94% (166/177) were infected with non‐L genotypes only.

Conclusions

The epidemic of LGV among predominantly HIV+ MSM is ongoing. LGV might be underdiagnosed, especially in patients with anorectal symptoms. Infections with CT serotypes D‐K are more often associated with urogenital symptoms or asymptomatic infection, whereas LGV genotypes are found most frequently in patients with rectal/intestinal symptoms. Anorectal CT infections in MSM should be further characterized by genotyping for LGV, as for LGV three weeks of doxycycline treatment are recommended. CT genotypes D‐K generally require shorter antibiotic treatment. If CT genotyping is not available, the duration of treatment should be prolonged to three weeks empirically for CT‐positive patients with anorectal or intestinal symptoms.
Should screening for Chlamydia trachomatis and Neisseria gonorrhoeae in HIV‐men who have sex with men be recommended?
Authors: Pérez‐Hernández Isabel , Palacios Rosario , González‐Doménech Carmen , García Victoria , Márquez Manuel , Clavijo Encarnación , Santos Jesús
Published: November 2014

Introduction

Sexually transmitted infections (STI) like Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) have been associated with increased risk of HIV acquisition [1]. It has been also described as a high prevalence of asymptomatic CT and NG infections in men who have sex with men (MSM) [2]. The aim of this study was to know the prevalence of CT and/or NG infections in asymptomatic HIV‐MSM and the related factors.

Materials and Methods

Prospective study of a cohort of asymptomatic HIV‐MSM with follow‐up in Malaga (southern Spain) during October 2012–May 2014. Patients with an opportunistic event or who received active antibiotic therapy for CT and/or NG in the previous month were excluded. All of them completed a questionnaire about sexual behaviour, barrier methods and recreational drugs use. Demographical, epidemiological, clinical, analytical and therapeutic data were also collected. Pharyngeal and rectal swabs, and urine samples were collected to be tested for CT and NG by nucleic acid amplification test (c4800 CT/NG. Roche Diagnostics, Mannheim, Germany) [3]. Statistics analysis: SPSS 17.0.

Results

255 patients were asked to participate and 248 of them accepted. Median age was 37.7 (30.6–46.3) years, median time since HIV diagnosis was 47.7 (10.5–104.1) months, and median CD4 cells count was 607 (440–824) cell/µL. There were 195 (78.6%) patients on antiretroviral therapy; 81.5% of them had undetectable viral load. 80.5% of the patients had a past history of STI. Infection by CT and/or NG was diagnosed in 24 (9.7%) patients. Overall four urine samples, two pharyngeal, and 15 rectal ones were positive for CT, and five pharyngeal and five rectal swabs were positive for NG. Two patients were co‐infected by CT and NG: one with CT in urine and both in rectum, another with CT in urine and rectum and NG in pharynx. One patient presented CT in pharynx and rectum, and two patients NG in pharynx and rectum. Positive CT and/or NG tests were only related with detectable HIV viral load (OR 3.08, 95% CI 1.2–7.4; p=0.01). It was not related with sexual behaviour, nor with alcohol or recreational drugs use.

Conclusions

STI screening had a great acceptance in this population. There was a high prevalence of asymptomatic CT and/or NG infections. Rectum sample was the most effective one. Viral suppression could protect from these STI. Screening should be recommended in HIV‐MSM.
Service impact of a change in HIV‐1 viral load quantification assay
Authors: Tipple Craig , Oomeer Soonita , Dosekun Olamide , Mackie Nicola
Published: November 2014

Introduction

Due to discontinuation of the Siemens Versant HIV‐1 RNA (bDNA) assay in the UK, our laboratory switched to the Roche Cobas Ampliprep/Taqman HIV‐1 viral load (VL) assay (Roche) in April 2013. This assay has a lower cut‐off of 20 RNA copies/mL (compared with <50 for the Siemens assay). Our laboratory demonstrated previously that a significant proportion (18%) of patients undetectable using bDNA HIV‐1 RNA quantification exhibited low level viraemia (LLV) using the new assay. Local guidelines recommend that patients stable on therapy receive twice‐yearly VLs. We evaluated the impact of the introduction of the new assay on our clinical service.

Methods

A retrospective cohort analysis of treated patients with stable undetectable VL by bDNA (<50 copies/mL) followed by ≥ one low‐level (<400 copies/mL) VL with the Roche assay. Demographic data were collected in addition to frequency of VL testing and genotypic resistance assays. Referrals to virtual clinic (VC) were recorded. Patients were identified using laboratory data and information collected from electronic patient records. Results were analyzed with SPSS v18.

Results

One hundred and ninety patients were included. Demographics: 79.5% male; 60.6% homosexual; mean age of 46 years. Duration on stable treatment was 46.35 (std. dev. 38.15) months. Current treatment regimens were 43.3% PI‐based; 43.3% NNRTI‐based and 13.7% other. Patients were stratified into VL 20–49 copies/mL (n=109); VL 50–199 copies/mL (n=71) and VL 200–399 copies/mL (n=10). In total, there were 471 VLs measured of which 274 were additional as a result of the assay switch. This resulted in six HIV‐1 genotype requests and 16 VC discussions (Table 1). Longer duration on HAART was associated with reduced frequency of VL testing. The relative risk of ongoing detectability according to drug class are: PI 1.62 (95% CI 1.18–2.21); NNRTI 0.507 (95% CI 0.30–0.85) and other 1.09 (95% CI 0.48–2.43).

Conclusions

Changes in assay can result in difficulties in interpretation of patient results. The assay switch in our service had significant impact on patient and staff time and cost with an increase in patient recalls; increased frequency of VL measurement, genotypes and discussions in VC. Choice of assay is paramount to running an efficient and cost‐effective clinical service.
Characterization of HIV‐1 subtypes in a Portuguese cohort
Authors: Rocha Pereira Nuno , Duro Raquel , Piñero Carmela , Malheiro Luís , Soares Jorge , Serrão Rosário , Sarmento António
Published: November 2014

Introduction

Distribution of HIV‐1 subtypes is variable around the world, with the most common subtype in western Europe being subtype B. The aim our study was to describe the prevalence of different HIV‐1 subtypes in newly diagnosed patients and identify demographic and epidemiological characteristics related with different subtypes.

Materials and Methods

Retrospective single‐centre study of patients newly diagnosed with HIV‐1 infection between 2006 and 2012. Epidemiological data was gathered and genotyping was performed in each patient identified. Demographic and epidemiological characteristics were compared between patients with subtype B and other subtypes. Continuous variables were summarized by mean and standard deviation whereas categorical variables were presented as proportions. Comparison of groups was performed using the Chi square, Fisher exact test and Student T test. Statistical significance was assumed when p<0.05.

Results

In the period of the study, 624 patients newly diagnosed with HIV‐1 infection were submitted to genotypic testing but information about subtype was available only for 592 patients. General characteristics of the patients are summarized in Table 1. The distribution of the identified subtypes was the following: 286 (48.3%) patients had subtype B, 157 (26.5%) had subtype G, 54 (9.1%) had subtype C, 36 (6.1%) had subtype A, 32 (5.4%) had subtype F and 25 (4.2%) had CRF's. Patients with subtype B were more commonly male (p=0.001) and younger (p<0.0001) than those with subtypes other than B. Subtype B was more common in MSM patients, while non‐B subtypes were more common in heterosexual patients and in injecting drug users (p=0.001). CD4‐cell count, viral load and AIDS at presentation were not significantly different between subtypes. Resistance associated mutations were significantly more common in patients with non‐B subtypes (15.4% vs 9.8%; p=0.048).

Conclusions

The most commonly identified subtype was B in accordance with previous reports from other western European countries. However, in our cohort the proportion of non‐B subtypes is higher than that reported for other European countries, probably reflecting the influence of strong bonds with Portuguese speaking African countries. Knowledge about HIV subtypes distribution may help understanding transmission dynamics and can be an important tool in the design of preventive measures.
Severe birth defects in children perinatal exposed to HIV from a “real‐world” setting: Infectious Diseases National Institute, Bucharest, Romania
Authors: Maria Tudor Ana
Published: November 2014

Introduction

The shift in epidemic trends in recent years in Romania shows new problems in regard of HIV vertical transmission, firstly in intravenous drug user's mothers co‐infected with hepatitis viruses and with social problems, and secondly the children of young mothers with an old HIV infection and long antiretroviral therapy history.

Materials and Methods

We studied all HIV perinatal exposed children routinely followed up in the Paediatric Department of the National Institute of Infectious Diseases, since January 1st 2006 till December 31st 2012. The analyses consisted of describing the birth defects and association with certain risk factors: gender, mother's age at birth and exposure to antiretrovirals in the first trimester of pregnancy.

Results

We analyzed 244 children born to HIV‐infected mothers. The incidence of HIV infection was 16.39%. The rate of birth defects was 39.34% (96/244 cases). The most frequent findings were cardiac malformations (47/96), followed by musculoskeletal defects (24/96), neurologic defects (20/96), urogenital malformations (13/96), digestive tract defects (3/93), metabolic disorders (2/96) and genetic disorders (2/96). We found nine cases of severe congenital anomalies: complex heart defect, total congenital aganglionic megacolon, anal imperforation, Dandy‐Walker syndrome, gangliosidosis, Niemann‐Pick syndrome, Down syndrome, true hermaphroditism and cleft palate. Two children died during first year of life due to severe malformations. 9% of cases had associated malformations. The gender rate was in favour of males in group with birth defects (58/38) and with no birth defects (82/66). The median age at birth in mothers was 22 years, similar in both groups. The highest mean age at birth was in offspring's mothers with neurologic congenital defects 25, 15 years old, but is not statistically significant (p=0.1). In the studied period the highest number of birth defects were found in 2012, 37 children, compared with less than 15 in previous years (not statistically significant, p=0.07). In our studied patients the risk of birth defects was not statistically associated with HIV transmission or with exposure to antiretrovirals before and in first trimester of pregnancy (p=0.88).

Conclusion

The rate of birth defects among HIV‐exposed children was not significantly associated with antiretroviral exposure, but we identify very rare and severe congenital conditions. We have noticed also a trend to increasing number of birth defects in 2012 among studied patients compared to previous years.