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OBJECTIVES: HIV late presentation (LP) has been increasing in recent years in Europe. Our aim was to investigate the characteristics of LP in Greece using in addition to the traditional definition for LP, the time interval between HIV infection and diagnosis. METHODS: Our nationwide sample included HIV-1 sequences generated from 6166 people living with HIV (PLWH) in Greece during the period 1999-2015. Our analysis was based on the molecularly inferred HIV-1 infection dates for PLWH infected within local molecular transmission clusters of subtypes A1 and B. RESULTS: Analysis of the determinants of LP was conducted using either CD4 counts or AIDS-defining condition at diagnosis or the time from infection to diagnosis. Older age, heterosexual transmission risk group and more recent diagnosis were associated with increased risk for LP. In contrast to previous studies, people who inject drugs (PWID) had a shorter median time to diagnosis (0.63 years) compared to men who have sex with men (MSM) (1.72 years) and heterosexuals (2.43 years). Using HIV infection dates that provide an unbiased marker for LP compared to CD4 counts at diagnosis, which are age-dependent, we estimated that the time to diagnosis increased gradually with age. Migrants infected regionally do not differ with respect to LP status compared to native Greeks. CONCLUSIONS: We demonstrate that older people and heterosexuals are among those at higher risk for LP; and given the growing number of older people among newly diagnosed cases, tailored interventions are needed in these populations.
Subject(s)
Acquired Immunodeficiency Syndrome , HIV Infections , Sexual and Gender Minorities , Male , Humans , Aged , Heterosexuality , Homosexuality, Male , HIV Infections/diagnosis , Prognosis , Delayed Diagnosis , CD4 Lymphocyte Count , Risk FactorsABSTRACT
OBJECTIVES: Subtypes A1 and B are the most prevalent HIV-1 clades in Greece. Subtype A1 epidemic is highly monophyletic and corresponds to transmissions that occurred locally. Our aim in this molecular epidemiology analysis was to investigate the role of early treatment in preventing new HIV-1 transmissions. METHODS: Our analysis focused on 791 subtype A1 sequences from treatment-naïve individuals in Greece. Estimation of infection dates was performed by molecular clock calculations using Bayesian methods. We estimated the time interval between (1) the infection and sampling dates (linkage to care window), (2) the sampling dates and antiretroviral therapy (ART) initiation (treatment window), and (3) the infection dates and ART initiation (transmissibility window) for the study population. We also inferred the putative source of HIV infections between individuals of different groups divided according to the length of treatment, linkage to care or transmissibility window. RESULTS: A significant decline was detected for the treatment window during 2014-2015 versus the 2 previous years (p=0.0273), while the linkage to care interval remained unchanged during the study period. Inference of the putative source of HIV infections suggested that individuals with a recent diagnosis or narrow transmissibility window (time period between HIV infection and ART initiation) were not sources of HIV infections to other groups. Contrarily, a significant number of HIV infections originated from individuals with longer transmissibility window interval. CONCLUSIONS: Our findings showed that the treatment window is decreasing over time, presumably due to the updated treatment guidelines. Our study also demonstrates that people treated earlier after infection do not transmit at high rates, thus documenting the benefits of early ART initiation in preventing ongoing HIV-1 transmission.
Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , HIV Infections/transmission , HIV-1/genetics , Bayes Theorem , Greece/epidemiology , HIV Infections/epidemiology , HIV-1/classification , HIV-1/drug effects , HIV-1/isolation & purification , Humans , Molecular Epidemiology , PhylogenyABSTRACT
PURPOSE: A cross-sectional survey was conducted to better understand why chronically HIV-1-infected individuals stratified by CD4 count (≤349; 350-499; ≥500 cells/µL) were not on antiretroviral therapy (ART). METHODS: Before the consultation, treatment-naive patients and their physicians independently completed a 90-item-questionnaire about barriers and their readiness to start/defer ART. The study was carried out at 34 sites in nine countries in Europe and Australia. RESULTS: Between December 2011 and October 2012, 508 pairs of patient- and physician-questionnaires were completed. 426 (84 %) patients were male and 39 (8 %), 138 (27 %), and 330 (65 %) were in the three stratified groups based on CD4 count, respectively. In the category 'Body and symptoms' the most commonly identified reason for patients not to start was: "As long as I feel good I don't have to take medication" (44 %). Less than 20 % of respondents indicated fears of side effects and toxicity or problems to manage pills. Most patients were in the lowest stage of treatment-readiness (N = 323, 68 %), especially patients with CD4 cells ≥500 cells/µL (N = 240, 79 %). Physicians answered in 92 (18 %) cases that ART was not indicated for CD4 cells <500 cells/µL. Main reasons for physicians not starting treatment for these patients were their perception that patients were 'too depressed' (13 %) or that they had not known them long enough (13 %). CONCLUSIONS: Nowadays patient-barriers to ART are commonly related to health-and treatment-beliefs compared to fear of toxicity or ART manageability in the past. This new barrier pattern seems to reflect the era of well tolerated, easier ART regimens and has to be considered in light of the new recommendations to treat all HIV-infected individuals regardless of the CD4 cell count.
Subject(s)
Anti-Retroviral Agents/administration & dosage , Anti-Retroviral Agents/therapeutic use , HIV Infections/drug therapy , HIV Infections/epidemiology , Time-to-Treatment/statistics & numerical data , Adult , CD4 Lymphocyte Count , Cross-Sectional Studies , Female , HIV-1 , Humans , Male , Middle Aged , Surveys and QuestionnairesABSTRACT
A serological screening was conducted to detect IgG antibodies against Leishmania infantum (L. infantum) in newly diagnosed human immunodeficiency virus (HIV) patients in Greece. The study also examined potential risk factors and the agreement of commercially available serological methods. IgG antibodies against L. infantum were detected using enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence antibody test (IFAT), and Western blot (WB). Out of 155 samples, 14 (9.0%) tested positive for IgG antibodies against L. infantum using at least two methods. Statistical analysis showed substantial agreement between WB and IFAT methods (Cohen's kappa = 0.75) but moderate overall agreement among the three methods (Fleiss' kappa = 0.42). Additionally, HIV+ intravenous drug users faced 3.55 times (p = 0.025) higher risk of testing positive for L. infantum IgG, positing that anthroponotic transmission between these patients is a plausible hypothesis based on existing literature. Non-invasive and cost-effective techniques are preferred to detect asymptomatic infections, and leishmaniasis screening should be conducted immediately after HIV diagnosis in endemic regions to enable prophylactic treatment for leishmaniasis in addition to antiretroviral therapy. To maximize sensitivity, performing at least two different serological methods for each patient is recommended.
ABSTRACT
This study aims to screen for IgG antibodies against Toxoplasma gondii (T. gondii) in the sera of 155 newly diagnosed Human Immunodeficiency Virus (HIV) positive patients under surveillance in Greek Infectious Disease Units. Additionally, risk factors based on patient demographics were examined, and a comparative evaluation of commercially available serological methods was conducted. Three methods were employed to detect IgG antibodies against T. gondii: Enzyme-Linked Immunosorbent Assay (ELISA), Indirect Immunofluorescence Antibody Test (IFAT), and Western Blot (WB), which was used as a reference here. Forty-nine sera samples were true-positive for IgG antibodies against T. gondii, resulting in a 31.61% positivity rate, and the immunoassay test statistical reliability analysis resulted in higher IFAT accuracy (90.97%) compared to ELISA (76.26%). Furthermore, statistical analysis of demographic and immunological data included in the study placed female and foreign/non-Greek individuals at 2.24 (p = 0.0009) and 2.34 (p = 0.0006) times higher risk of positive T. gondii IgG testing compared to their male and Greek counterparts, respectively. Our findings on positivity rates and comparative serology underscore the importance of early and suitable screening measures for newly diagnosed HIV+ patients to mitigate the life-threatening outcomes that may arise from a potential subsequent T. gondii activation.
ABSTRACT
BACKGROUND: Mortality rates among people with HIV have fallen since 1996 following the widespread availability of effective antiretroviral therapy (ART). Patterns of cause-specific mortality are evolving as the population with HIV ages. We aimed to investigate longitudinal trends in cause-specific mortality among people with HIV starting ART in Europe and North America. METHODS: In this collaborative observational cohort study, we used data from 17 European and North American HIV cohorts contributing data to the Antiretroviral Therapy Cohort Collaboration. We included data for people with HIV who started ART between 1996 and 2020 at the age of 16 years or older. Causes of death were classified into a single cause by both a clinician and an algorithm if International Classification of Diseases, Ninth Revision or Tenth Revision data were available, or independently by two clinicians. Disagreements were resolved through panel discussion. We used Poisson models to compare cause-specific mortality rates during the calendar periods 1996-99, 2000-03, 2004-07, 2008-11, 2012-15, and 2016-20, adjusted for time-updated age, CD4 count, and whether the individual was ART-naive at the start of each period. FINDINGS: Among 189 301 people with HIV included in this study, 16 832 (8·9%) deaths were recorded during 1 519 200 person-years of follow-up. 13 180 (78·3%) deaths were classified by cause: the most common causes were AIDS (4203 deaths; 25·0%), non-AIDS non-hepatitis malignancy (2311; 13·7%), and cardiovascular or heart-related (1403; 8·3%) mortality. The proportion of deaths due to AIDS declined from 49% during 1996-99 to 16% during 2016-20. Rates of all-cause mortality per 1000 person-years decreased from 16·8 deaths (95% CI 15·4-18·4) during 1996-99 to 7·9 deaths (7·6-8·2) during 2016-20. Rates of all-cause mortality declined with time: the average adjusted mortality rate ratio per calendar period was 0·85 (95% CI 0·84-0·86). Rates of cause-specific mortality also declined: the most pronounced reduction was for AIDS-related mortality (0·81; 0·79-0·83). There were also reductions in rates of cardiovascular-related (0·83, 0·79-0·87), liver-related (0·88, 0·84-0·93), non-AIDS infection-related (0·91, 0·86-0·96), non-AIDS-non-hepatocellular carcinoma malignancy-related (0·94, 0·90-0·97), and suicide or accident-related mortality (0·89, 0·82-0·95). Mortality rates among people who acquired HIV through injecting drug use increased in women (1·07, 1·00-1·14) and decreased slightly in men (0·96, 0·93-0·99). INTERPRETATION: Reductions of most major causes of death, particularly AIDS-related deaths among people with HIV on ART, were not seen for all subgroups. Interventions targeted at high-risk groups, substance use, and comorbidities might further increase life expectancy in people with HIV towards that in the general population. FUNDING: US National Institute on Alcohol Abuse and Alcoholism.
Subject(s)
Acquired Immunodeficiency Syndrome , HIV Infections , Neoplasms , Adult , Male , Humans , Female , Adolescent , HIV Infections/epidemiology , Cause of Death , Risk Factors , North America/epidemiology , Cohort Studies , Europe/epidemiologyABSTRACT
BACKGROUND: Candida auris was sporadically detected in Greece until 2019. Thereupon, there has been an increase in isolations among inpatients of healthcare facilities. AIM: We aim to report active surveillance data on MALDI-TOF confirmed Candida auris cases and outbreaks, from November 2019 to September 2021. METHODS: A retrospective study on hospital-based Candida auris data, over a 23-month period was conducted, involving 11 hospitals within Attica region. Antifungal susceptibility testing and genotyping were conducted. Case mortality and fatality rates were calculated and p-values less than 0.05 were considered statistically significant. Infection control measures were enforced and enhanced. RESULTS: Twenty cases with invasive infection and 25 colonized were identified (median age: 72 years), all admitted to hospitals for reasons other than fungal infections. Median hospitalisation time until diagnosis was 26 days. Common risk factors among cases were the presence of indwelling devices (91.1 %), concurrent bacterial infections during hospitalisation (60.0 %), multiple antimicrobial drug treatment courses prior to hospitalisation (57.8 %), and admission in the ICU (44.4 %). Overall mortality rate was 53 %, after a median of 41.5 hospitalisation days. Resistance to fluconazole and amphotericin B was identified in 100 % and 3 % of tested clinical isolates, respectively. All isolates belonged to South Asian clade I. Outbreaks were identified in six hospitals, while remaining hospitals detected sporadic C. auris cases. CONCLUSION: Candida auris has proven its ability to rapidly spread and persist among inpatients and environment of healthcare facilities. Surveillance focused on the presence of risk factors and local epidemiology, and implementation of strict infection control measures remain the most useful interventions.
Subject(s)
Antifungal Agents , Candida auris , Candidiasis , Cross Infection , Disease Outbreaks , Microbial Sensitivity Tests , Humans , Greece/epidemiology , Aged , Disease Outbreaks/statistics & numerical data , Male , Female , Retrospective Studies , Middle Aged , Aged, 80 and over , Antifungal Agents/therapeutic use , Antifungal Agents/pharmacology , Candidiasis/epidemiology , Candidiasis/microbiology , Cross Infection/epidemiology , Cross Infection/microbiology , Candida auris/genetics , Adult , Hospitals/statistics & numerical data , Health Facilities/statistics & numerical data , Infection Control , Risk Factors , Drug Resistance, Fungal , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Candida/isolation & purification , Candida/drug effects , Candida/classification , Hospitalization/statistics & numerical dataABSTRACT
In our hospital, adherence to the guidelines for peri-operative antimicrobial prophylaxis (PAP) is suboptimal, with overly long courses being common. This practice does not offer any incremental benefit, and it only adds to the burden of antimicrobial consumption, promotes the emergence of antimicrobial resistance, and it is associated with adverse events. Our objective was to study the effect of an electronic reminder on the adherence to each element of PAP after cardiac surgery. We conducted a single center, before and after intervention, prospective cohort study from 1 June 2014 to 30 September 2017. The intervention consisted of a reminder of the hospital guidelines when ordering PAP through the hospital information system. The primary outcome was adherence to the suggested duration of PAP, while secondary outcomes included adherence to the other elements of PAP and incidence of surgical site infections (SSI). We have studied 1080 operations (400 pre-intervention and 680 post-intervention). Adherence to the appropriate duration of PAP increased significantly after the intervention [PRE 4.0% (16/399) vs. POST 15.4% (105/680), chi-square p < 0.001]; however, it remained inappropriately low. Factors associated with inappropriate duration of PAP were pre-operative hospitalization for <3 days, and duration of operation >4 h, while there were significant differences between the chief surgeons. Unexpectedly, the rate of SSIs increased significantly during the study (PRE 2.8% (11/400) vs. POST 5.9% (40/680), chi-square p < 0.019). The implemented intervention achieved a relative increase in adherence to the guideline-recommended PAP duration; however, adherence was still unacceptably low and further efforts to improve adherence are needed.
ABSTRACT
BACKGROUND: Understanding demographic disparities in hospitalisation is crucial for the identification of vulnerable populations, interventions, and resource planning. METHODS: Data were from the Antiretroviral Therapy Cohort Collaboration (ART-CC) on people living with HIV in Europe and North America, followed up between January, 2007 and December, 2020. We investigated differences in all-cause hospitalisation according to gender and mode of HIV acquisition, ethnicity, and combined geographical origin and ethnicity, in people living with HIV on modern combination antiretroviral therapy (cART). Analyses were performed separately for European and North American cohorts. Hospitalisation rates were assessed using negative binomial multilevel regression, adjusted for age, time since cART intitiaion, and calendar year. FINDINGS: Among 23â594 people living with HIV in Europe and 9612 in North America, hospitalisation rates per 100 person-years were 16·2 (95% CI 16·0-16·4) and 13·1 (12·8-13·5). Compared with gay, bisexual, and other men who have sex with men, rates were higher for heterosexual men and women, and much higher for men and women who acquired HIV through injection drug use (adjusted incidence rate ratios ranged from 1·2 to 2·5 in Europe and from 1·2 to 3·3 in North America). In both regions, individuals with geographical origin other than the region of study generally had lower hospitalisation rates compared with those with geographical origin of the study country. In North America, Indigenous people and Black or African American individuals had higher rates than White individuals (adjusted incidence rate ratios 1·9 and 1·2), whereas Asian and Hispanic people living with HIV had somewhat lower rates. In Europe there was a lower rate in Asian individuals compared with White individuals. INTERPRETATION: Substantial disparities exist in all-cause hospitalisation between demographic groups of people living with HIV in the current cART era in high-income settings, highlighting the need for targeted support. FUNDING: Royal Free Charity and the National Institute on Alcohol Abuse and Alcoholism.
Subject(s)
HIV Infections , Sexual and Gender Minorities , Male , Humans , Female , Ethnicity , Homosexuality, Male , Cohort Studies , HIV Infections/drug therapy , HIV Infections/epidemiology , North America/epidemiology , Europe/epidemiologyABSTRACT
OBJECTIVE: The aim of this study was to propose a unified continuum-of-care (CoC) analysis combining cross-sectional and longitudinal elements, incorporating time spent between stages. DESIGN: The established 90-90-90 target follows a cross-sectional four-stage CoC analysis, lacking information on timing of diagnosis, antiretroviral therapy (ART) initiation, and viral suppression durability. METHODS: Data were derived from the Athens Multicenter AIDS Cohort Study (AMACS). In the cross-sectional CoC, we added stratification of diagnosed people with HIV (PWH) by estimated time from infection to diagnosis; of those who ever initiated ART or achieved viral suppression by corresponding current status (in 2018); and cumulative incidence function (CIF) of ART initiation and viral suppression, treating loss-to-follow-up (LTFU) as competing event. Viral suppression was defined as viral load less than 500âcopies/ml. Viral suppression durability was assessed by the CIF of viral load rebound. FINDINGS: About 89.1% of PWH in 2018 were diagnosed (range of diagnoses: 1980-2018). Median time to diagnosis was 3.5âyears (IQR: 1.1-7.0). Among diagnosed, 89.1% were ever treated, of whom 86.7% remained on ART. CIF of ART initiation and LTFU before ART initiation were 80.9 and 6.0% at 5âyears since diagnosis, respectively. Among treated, 89.4% achieved viral suppression, of whom 87.4% were currently virally suppressed. The CIF of viral load rebound was 24.2% at 5âyears since first viral suppression but substantially reduced in more recent years. INTERPRETATION: The proposed analysis highlights time gaps in CoC not evident by the standard cross-sectional approach. Our analysis highlights the need for early diagnosis and identifies late presenters as a key population for interventions that could decrease gaps in the CoC.
Subject(s)
Anti-HIV Agents , HIV Infections , Anti-HIV Agents/therapeutic use , Cohort Studies , Continuity of Patient Care , HIV Infections/diagnosis , HIV Infections/drug therapy , HIV Infections/epidemiology , Humans , Incidence , Viral LoadABSTRACT
Our aim was to estimate the date of the origin and the transmission rates of the major local clusters of subtypes A1 and B in Greece. Phylodynamic analyses were conducted in 14 subtype A1 and 31 subtype B clusters. The earliest dates of origin for subtypes A1 and B were in 1982.6 and in 1985.5, respectively. The transmission rate for the subtype A1 clusters ranged between 7.54 and 39.61 infections/100 person years (IQR: 9.39, 15.88), and for subtype B clusters between 4.42 and 36.44 infections/100 person years (IQR: 7.38, 15.04). Statistical analysis revealed that the average difference in the transmission rate between the PWID and the MSM clusters was 6.73 (95% CI: 0.86 to 12.60; p = 0.026). Our study provides evidence that the date of introduction of subtype A1 in Greece was the earliest in Europe. Transmission rates were significantly higher for PWID than MSM clusters due to the conditions that gave rise to an extensive PWID HIV-1 outbreak ten years ago in Athens, Greece. Transmission rate can be considered as a valuable measure for public health since it provides a proxy of the rate of epidemic growth within a cluster and, therefore, it can be useful for targeted HIV prevention programs.
Subject(s)
Epidemics , HIV Infections/epidemiology , HIV Infections/virology , HIV-1/classification , HIV-1/genetics , Cluster Analysis , Europe/epidemiology , Female , Greece/epidemiology , HIV Infections/transmission , Humans , Male , Sexual and Gender MinoritiesABSTRACT
BACKGROUND: Although combined antiretroviral therapy has substantially improved the prognosis of people living with HIV (PLHIV), mortality remains higher compared to the general population, mainly due to higher prevalence of non-HIV-related comorbidities, including cardiovascular diseases (CVD). We assessed the prevalence of CVD risk and its contributing factors in adult PLHIV versus general population controls in Greece. SETTINGS: Cross-sectional comparison of PLHIV (Athens-Multicenter-AIDS-Cohort-Study; AMACS) versus general population controls (National health examination survey; EMENO). METHODS: All HIV-infected adults with ≥1 measurement of interest (blood pressure, lipids, glucose, weight, height) between 2012-2014 and all EMENO participants (2014-2016) were included. Ten-year total CVD risk was estimated using the Framingham (FRS) or the Systematic Coronary Risk Evaluation (SCORE) equations. RESULTS: 5839 PLHIV (median age:41.6 years, 85.4% males) and 4820 controls (median age:48 years, 48.4% males) were included. Adjusting for age, sex and origin, PLHIV were more likely to be current smokers (adjusted OR:1.53 [95% CI:1.35-1.74]) and dyslipidemic (aOR:1.18; [1.04-1.34]), less likely to be obese (aOR:0.44 [0.38-0.52], with no differences in hypertension, diabetes or high (≥20%) FRS but with greater odds of high (≥5%) SCORE (aOR:1.55 [1.05-2.30]). Further adjustment for educational level, anti-HCV positivity and BMI showed higher prevalence of hypertension in PLHIV. CONCLUSIONS: Despite the relative absence of obesity, PLHIV have higher prevalence of traditional CVD risk factors and higher risk of fatal CVD compared to general population. Regular screening and early management of CVD risk factors in PLHIV should be of high priority for CVD prevention.
Subject(s)
Cardiovascular Diseases/complications , Cardiovascular Diseases/epidemiology , HIV Infections/complications , Adolescent , Adult , Aged , Case-Control Studies , Female , Greece/epidemiology , Humans , Male , Middle Aged , Risk Factors , Young AdultABSTRACT
Our aim was to investigate the dispersal patterns and parameters associated with local molecular transmission clusters (MTCs) of subtypes A1 and B in Greece (predominant HIV-1 subtypes). The analysis focused on 1751 (28.4%) and 2575 (41.8%) sequences of subtype A1 and B, respectively. Identification of MTCs was based on phylogenetic analysis. The analyses identified 38 MTCs including 2-1518 subtype A1 sequences and 168 MTCs in the range of 2-218 subtype B sequences. The proportion of sequences within MTCs was 93.8% (1642/1751) and 77.0% (1982/2575) for subtype A1 and B, respectively. Transmissions within MTCs for subtype A1 were associated with risk group (Men having Sex with Men vs. heterosexuals, OR = 5.34, p < 0.001) and Greek origin (Greek vs. non-Greek origin, OR = 6.05, p < 0.001) and for subtype B, they were associated with Greek origin (Greek vs. non-Greek origin, OR = 1.57, p = 0.019), younger age (OR = 0.96, p < 0.001), and more recent sampling (time period: 2011-2015 vs. 1999-2005, OR = 3.83, p < 0.001). Our findings about the patterns of across and within country dispersal as well as the parameters associated with transmission within MTCs provide a framework for the application of the study of molecular clusters for HIV prevention.
Subject(s)
Epidemiological Monitoring , HIV Infections/epidemiology , HIV Infections/transmission , HIV-1/classification , Phylogeny , Adult , Cluster Analysis , DNA, Viral/genetics , Female , Genotype , Greece/epidemiology , Humans , Male , Middle Aged , Phylogeography , PrevalenceABSTRACT
OBJECTIVE: The aim of this study was to analyse the association of baseline biomarker data with cross-sectional lung function and subsequent decline in lung function in HIV-positive persons. DESIGN: Lung function was modelled in all START pulmonary substudy participants who had baseline biomarker data and good-quality spirometry. In longitudinal analyses, we restricted to those participants with at least one good-quality follow-up spirometry test. METHODS: We performed linear regression of baseline forced expiratory volume in 1âs (FEV1), forced vital capacity (FVC) and FEV1/FVC and their longitudinal slopes on log2-transformed baseline biomarkers with adjustment for age, sex, race, region, smoking status, baseline CD4+ T-cell counts and baseline HIV-RNA. Biomarkers included D-dimer, high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, IL-27, serum amyloid A, soluble intercellular adhesion molecule (sICAM)-1, soluble vascular cell adhesion molecule (sVCAM)-1, albumin and total bilirubin. RESULTS: Among 903 included participants, baseline median age was 36 years, CD4+ cell count was 647âcells/µl, and 28.5% were current smokers. In adjusted analyses, elevated markers of systemic inflammation (hsCRP, IL-6 and serum amyloid A) were associated with lower baseline FEV1 and FVC. Elevated D-dimer and IL-6 were associated with worse airflow obstruction (lower FEV1/FVC). Despite these cross-sectional associations at baseline, no associations were found between baseline biomarkers and subsequent longitudinal lung function decline over a median follow-up time of 3.9 years (3293 spirometry-years of follow-up). CONCLUSION: Commonly available biomarkers, in particular markers of systemic inflammation, are associated with worse cross-sectional lung function, but do not associate with subsequent lung function decline among HIV-positive persons with early HIV infection and baseline CD4 T-cell counts more than 500âcells/µl.
Subject(s)
Biomarkers/analysis , HIV Infections/complications , HIV Infections/pathology , Lung Diseases/pathology , Lung/physiology , Respiratory Function Tests , Adult , Disease Progression , Female , Humans , Longitudinal Studies , MaleABSTRACT
The presence of human immunodeficiency virus type 1 (HIV-1) drug resistance among drug-naïve patients remains stable, although the proportion of patients with virological failure to therapy is decreasing. The dynamics of transmitted resistance among drug-naïve patients remains largely unknown. The prevalence of non-nucleoside reverse transcriptase inhibitors (NNRTI) resistance was 16.9% among treatment-naïve individuals in Greece. We aimed to investigate the transmission dynamics and the effective reproductive number (Re) of the locally transmitted NNRTI resistance. We analyzed sequences with dominant NNRTI resistance mutations (E138A and K103N) found within monophyletic clusters (local transmission networks (LTNs)) from patients in Greece. For the K103N LTN, the Re was >1 between 2008 and the first half of 2013. For all E138A LTNs, the Re was >1 between 1998 and 2015, except the most recent one (E138A_4), where the Re was >1 between 2006 and 2011 and approximately equal to 1 thereafter. K103N and E138A_4 showed similar characteristics with a more recent origin, higher Re during the first years of the sub-epidemics, and a declining trend in the number of transmissions during the last two years. In the remaining LTNs the epidemic was still expanding. Our study highlights the added value of molecular epidemiology to public health.
ABSTRACT
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/mm(3). At follow up, three months after the end of the program, the mean value of CD4 cells was 464 cells/mm(3). 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].
ABSTRACT
INTRODUCTION: The prevalence of drug resistance is approximately 10% in Europe and North America among newly infected patients. We aim to investigate the temporal patterns of resistance among drug naive HIV-infected individuals in Greece and also to determine transmission networking among those with resistant strains. MATERIALS AND METHODS: Protease (PR) and partial reverse transcriptase (RT) sequences were determined from 2499 newly diagnosed HIV-1 patients, in Greece, during 2003-2013. Genotypic drug resistance was estimated using the HIVdb: Genotypic Resistance Interpretation Algorithm. We identified transmission clusters of resistant strains on the basis of a large collection of HIV-1 sequences from 4024 seropositives in Greece. Phylodynamic analysis was performed using a Bayesian method. RESULTS: We estimated drug resistance levels among naïve patients on the basis of all resistance mutations in PR and partial RT. The overall prevalence of resistance was 19.6% (490/2499). Resistance to NNRTIs was the most common (397/2499, 15.9%) followed by PIs (116/2499, 4.6%) and NRTIs (79/2499, 3.2%). We found a significant trend for decreasing resistance to NRTIs over time (6.7%-1.6%). There was no time trend for the overall PI and NNRTI resistance. The most frequently observed major resistant sites in PR were V82 (2.0%) and L90 (1.8%). In RT, we found E138 (58.6%), K103 (13.1%), V179 (8.4%) and T215 (7.1%), M41 (4.7%) associated with resistance to NNRTIs and NRTIs, respectively. The prevalence of K103N and E138Q were significantly increased during 2003-2013. Crucially, we found that both K103N, E138Q are associated with transmission networking within men having sex with men (MSM) and intravenous drug user (IDU) local networks. The K103N network included seropositives across Greece, while the latter only from the recent IDU outbreak in Athens metropolitan area (1). Phylodynamic analyses revealed that the exponential growth for K103N network started in 2009 (Figure 1) and for the E138Q in 2010. CONCLUSIONS: The overall resistance has been stable in Greece over time; however, specific NNRTI resistance patterns are increasing. Notably, they are associated with local transmission networking, thus suggesting that this is the cause for the increased patterns of NNRTI resistance and not multiple transmissions of resistant strains from different sources among treated individuals. Our study highlights the advance of molecular epidemiology for understanding the dynamics of resistance.