Evaluating predictive markers for viral rebound and safety assessment in blood and lumbar fluid during HIV-1 treatment interruption

Background: Validated biomarkers to evaluate HIV-1 cure strategies are currently lacking, therefore requiring analytical treatment interruption (ATI) in study participants. Little is known about the safety of ATI and its long-term impact on patient health. Objectives: ATI safety was assessed and potential biomarkers predicting viral rebound were evaluated. Methods: PBMCs, plasma and CSF were collected from 11 HIV-1-positive individuals at four different timepoints during ATI (NCT02641756). Total and integrated HIV-1 DNA, cell-associated (CA) HIV-1 RNA transcripts and restriction factor (RF) expression were measured by PCR-based assays. Markers of neuroinflammation and neuronal injury [neurofilament light chain (NFL) and YKL-40 protein] were measured in CSF. Additionally, neopterin, tryptophan and kynurenine were measured, both in plasma and CSF, as markers of immune activation. Results: Total HIV-1 DNA, integrated HIV-1 DNA and CA viral RNA transcripts did not differ pre- and post-ATI. Similarly, no significant NFL or YKL-40 increases in CSF were observed between baseline and viral rebound. Furthermore, markers of immune activation did not increase during ATI. Interestingly, the RFs SLFN11 and APOBEC3G increased after ATI before viral rebound. Similarly, Tat-Rev transcripts were increased preceding viral rebound after interruption. Conclusions: ATI did not increase viral reservoir size and it did not reveal signs of increased neuronal injury or inflammation, suggesting that these well-monitored ATIs are safe. Elevation of Tat-Rev transcription and induced expression of the RFs SLFN11 and APOBEC3G after ATI, prior to viral rebound, indicates that these factors could be used as potential biomarkers predicting viral rebound

Epidemiological study of phylogenetic transmission clusters in a local HIV-1 epidemic reveals distinct differences between subtype B and non-B infections

<p>Abstract</p> <p>Background</p> <p>The number of HIV-1 infected individuals in the Western world continues to rise. More in-depth understanding of regional HIV-1 epidemics is necessary for the optimal design and adequate use of future prevention strategies. The use of a combination of phylogenetic analysis of HIV sequences, with data on patients' demographics, infection route, clinical information and laboratory results, will allow a better characterization of individuals responsible for local transmission.</p> <p>Methods</p> <p>Baseline HIV-1 <it>pol </it>sequences, obtained through routine drug-resistance testing, from 506 patients, newly diagnosed between 2001 and 2009, were used to construct phylogenetic trees and identify transmission-clusters. Patients' demographics, laboratory and clinical data, were retrieved anonymously. Statistical analysis was performed to identify subtype-specific and transmission-cluster-specific characteristics.</p> <p>Results</p> <p>Multivariate analysis showed significant differences between the 59.7% of individuals with subtype B infection and the 40.3% non-B infected individuals, with regard to route of transmission, origin, infection with <it>Chlamydia </it>(p = 0.01) and infection with Hepatitis C virus (p = 0.017). More and larger transmission-clusters were identified among the subtype B infections (p < 0.001). Overall, in multivariate analysis, clustering was significantly associated with Caucasian origin, infection through homosexual contact and younger age (all p < 0.001). Bivariate analysis additionally showed a correlation between clustering and syphilis (p < 0.001), higher CD4 counts (p = 0.002), <it>Chlamydia </it>infection (p = 0.013) and primary HIV (p = 0.017).</p> <p>Conclusions</p> <p>Combination of phylogenetics with demographic information, laboratory and clinical data, revealed that HIV-1 subtype B infected Caucasian men-who-have-sex-with-men with high prevalence of sexually transmitted diseases, account for the majority of local HIV-transmissions. This finding elucidates observed epidemiological trends through molecular analysis, and justifies sustained focus in prevention on this high risk group.</p

HEPATITIS C-SEROCONVERSION WITHIN THREE TO SIX MONTHS AFTER HAVING CONTRACTED CLINICAL SYPHILIS AND/OR LYMPHOGRANULOMA VENEREUM RECTITIS IN FIVE HOMOSEXUALLY ACTIVE, HIV SEROPOSITIVE MEN

Five Human Immunodeficiency Virus (HIV) seropositive homosexually active men experienced hepatitis C-seroconversion in the period between September 2004 and January 2007 at a single HIV Reference Center (University Hospital Ghent, Belgium). There was no history of intravenous drug use. All had unprotected anal sex with multiple other HIV seropositive men in the recent past. All of them had clinical syphilis and/or lymphogranuloma venereum rectitis within three to six months before the hepatitis C- seroconversion was detected

Determinants of adherence in a cohort of Belgian HIV patients: a pilot study

Since the era of highly active antiretroviral therapy (HAART), HIV is considered a chronic disease. Adherence to HAART is crucial for effectiveness. Non-adherence negatively impacts patient outcome and the larger economy. However, data on adherence among the Belgian HIV cohort are scarce. Therefore, the purpose of this pilot study was to identify determinants of adherence among HIV patients treated in Belgium. The study was conducted at the Aids Reference Centre of Ghent University Hospital between 1 January and 31 December 2012. Sociodemographic data were collected, along with the Simplified Medication Adherence Questionnaire (SMAQ), the Center for Adherence Support Evaluation (CASE) Adherence Index, the EuroQol-6D, the Medical Outcomes Study-HIV (MOS-HIV), the Beck Depression Inventory-II, and three neurocognitive complaints screening questions. To date, 218 patients participated in the study, among whom 173 (79·4%) were male. Mean age was 46·0±10·6 years and 133 patients (63·9%) were homosexual. According to the SMAQ and the CASE, 78·5% and 93·5% of the patients were adherent to antiretroviral therapy. Logistic regression analysis revealed that smoking, neurocognitive complaints, and female sex were independent determinants of non-adherence. In conclusion, there is an elevated risk for non-adherence in smokers, people experiencing neurocognitive problems, and women in our sample. The latter could reflect differences between male and female HIV patients in Belgium. Adherence improving initiatives should be tailored to these three risk groups

Impact of Delta 32-CCR5 heterozygosity on HIV-1 genetic evolution and variability - A study of 4 individuals infected with closely related HIV-1 strains

A cluster of four patients acutely infected with a genetically almost identical virus, allowed us to investigate genetic variability and disease progression in early HIV-1 infection with minimal interference of Virus specific factors. Two of the patients were heterozygous for the 32-bp deletion in the CCR5 coreceptor gene. Both showed a slower disease progression with lower viral load levels and a reduced rate of genetic evolution compared to the patients with normal CCR5 alleles. During 3 years of treatment-free follow-up, the mean pairwise genetic distance increased with 1.45% and 1.58% in the two patients with a 32-bp deletion allele Compared to 3.05% and 3.57% in the two patients with normal CCR5 alleles. The observed relation between slower disease progression and a reduced evolutionary rate illustrates the influence of the virus replicative capacity, here most possibly hampered by the CCR5 heterozygosity in two of the four individuals, on the genetic evolution of the virus in the host. (C) 2008 Elsevier Inc. All rights reserved

The SPICE study: 48-week activity of combinations of saquinavir soft gelatin and nelfinavir with and without nucleoside analogues

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Evaluating predictive markers for viral rebound and safety assessment in blood and lumbar fluid during HIV-1 treatment interruption

BACKGROUND: Validated biomarkers to evaluate HIV-1 cure strategies are currently lacking, therefore requiring analytical treatment interruption (ATI) in study participants. Little is known about the safety of ATI and its long-term impact on patient health. OBJECTIVES: ATI safety was assessed and potential biomarkers predicting viral rebound were evaluated. METHODS: PBMCs, plasma and CSF were collected from 11 HIV-1-positive individuals at four different timepoints during ATI (NCT02641756). Total and integrated HIV-1 DNA, cell-associated (CA) HIV-1 RNA transcripts and restriction factor (RF) expression were measured by PCR-based assays. Markers of neuroinflammation and neuronal injury [neurofilament light chain (NFL) and YKL-40 protein] were measured in CSF. Additionally, neopterin, tryptophan and kynurenine were measured, both in plasma and CSF, as markers of immune activation. RESULTS: Total HIV-1 DNA, integrated HIV-1 DNA and CA viral RNA transcripts did not differ pre- and post-ATI. Similarly, no significant NFL or YKL-40 increases in CSF were observed between baseline and viral rebound. Furthermore, markers of immune activation did not increase during ATI. Interestingly, the RFs SLFN11 and APOBEC3G increased after ATI before viral rebound. Similarly, Tat-Rev transcripts were increased preceding viral rebound after interruption. CONCLUSIONS: ATI did not increase viral reservoir size and it did not reveal signs of increased neuronal injury or inflammation, suggesting that these well-monitored ATIs are safe. Elevation of Tat-Rev transcription and induced expression of the RFs SLFN11 and APOBEC3G after ATI, prior to viral rebound, indicates that these factors could be used as potential biomarkers predicting viral rebound.status: publishe

Socio-economic, behavioural, (neuro)psychological and clinical determinants of HRQoL in people living with HIV in Belgium: a pilot study

Introduction: Due to highly active antiretroviral therapy (HAART), HIV-1 infection has evolved from a lethal to a chronic disease. As such, health-related quality of life (HRQoL) has become an important outcome variable. The purpose of this study was to identify socio-economic, behavioural, (neuro)psychological and clinical determinants of HRQoL among people living with HIV (PLHIV). Methods: This study was conducted between 1 January and 31 December 2012 at the AIDS Reference Centre of Ghent University Hospital, a tertiary care referral centre in Belgium. Validated self-report questionnaires were administered to collect socio-demographic data, to assess HRQoL (Medical Outcomes Study-HIV), depressive symptoms (Beck Depression Inventory-II) and adherence to HAART (Short Medication Adherence Questionnaire) and to screen for neurocognitive dysfunction. Results: A total of 237 people participated, among whom 187 (78.9%) were male. Mean age was 45.8±10.7 years and 144 (63.7%, 144/226) participants were homosexual. Median physical and mental health score (PHS, MHS) were 55.6 (IQR 48.2–60.6) and 52.0 (IQR 44.2–57.9), respectively. Multivariable regression analysis revealed that incapacity to work, depressive symptoms, neurocognitive complaints (NCCs), dissatisfaction with the patient–physician relationship and non-adherence were all negatively associated with HRQoL. Conclusions: Socio-economic (work status), behavioural (adherence) and (neuro)psychological (depressive symptoms, NCCs) determinants independently impact HRQoL among this cohort of PLHIV. Clinical parameters (viral load, CD4 cell count) were not independently associated with HRQoL