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IntroductionThe source and significance of residual plasma HIV‐1 RNA detection during suppressive ART remain controversial. It has been proposed that nevirapine (NVP)‐based regimens achieve a greater HIV‐1 RNA suppression than regimens containing a protease inhibitor (PI). The aim of this study was to compare the effect of receiving NVP‐ vs PI‐based ART on the virological markers of HIV persistence in peripheral blood.Material and MethodsThe study population comprised 161 HIV‐1 infected patients receiving either NVP‐based (n=81) or PI‐based (n=80) ART and showing a HIV‐1 RNA load stably suppressed <40 copies/mL for median of 5.2 years (IQR 2.2–8.0). Residual viraemia was detected by real‐time PCR with 50% and 95% detection thresholds of 1 and 3 HIV‐1 RNA copies/mL, respectively. Cell‐associated (CA) unspliced HIV‐1 RNA, total HIV‐1 DNA and 2 LTR circles were quantified in peripheral blood mononuclear cells (PBMCs) using droplet digital PCR. Groups were compared by standard non‐parametric tests; factors associated with HIV‐1 detection were analyzed by univariate regression analysis and generalized linear models (SPSS® V22 and Rstudio).ResultsPlasma HIV‐1 RNA was detected in 37/81 (45.7%) and 47/80 (58.8%) subjects on NVP‐ and PI‐based ART, with median (IQR) levels of 5 (3–6) and 5 (3–8) copies/mL, respectively. HIV‐1 RNA detection was associated with shorter duration of suppressive ART regardless of treatment arm (p=0.007), and lower CD4 nadir (p=0.015). HIV‐1 DNA levels were median 282 (120–484) and 213 (87–494) copies/106 PBMCs in the two groups respectively, and were lowest (<100 copies/106 PBMCs) in subjects with lower plasma HIV‐1 RNA (p=0.049), CA unspliced HIV‐1 RNA (p=0.0001), 2 LTR circles (p=0.005) and pre‐ART HIV‐1 RNA load (p=0.0001).ConclusionsIn this comprehensive characterization of patients on long‐term suppressive ART, we did not observe evidence for a greater suppressive activity of NVP‐based over PI‐based therapy on plasma and intracellular markers of virus persistence. Overall excellent correlation was observed between the markers, allowing the identification of a subset of treated patients with low HIV‐1 expression as an important cohort for future HIV cure studies.

IntroductionDue 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).MethodsThis 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.ResultsA 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.ConclusionsSocio‐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.

AbstractIntroductionThe chemokine receptor CCR5 is the main co‐receptor for R5‐tropic HIV‐1 variants. We have previously described a novel 24‐base pair deletion in the coding region of CCR5 among individuals from Rwanda. Here, we investigated the prevalence of hCCR5Δ24 in different cohorts and its impact on CCR5 expression and HIV‐1 infection in vitro.MethodsWe screened hCCR5Δ24 in a total of 3232 individuals which were either HIV‐1 uninfected, high‐risk HIV‐1 seronegative and seropositive partners from serodiscordant couples, Long‐Term Survivors, or HIV‐1 infected volunteers from Africa (Rwanda, Kenya, Guinea‐Conakry) and Luxembourg, using a real‐time PCR assay. The role of the 24‐base pair deletion on CCR5 expression and HIV infection was assessed in cell lines and PBMC using mRNA quantification, confocal analysis, flow and imaging cytometry.Results and DiscussionAmong the 1661 patients from Rwanda, 12 individuals were heterozygous for hCCR5Δ24 but none were homozygous. Although heterozygosity for this allele may not confer complete resistance to HIV‐1 infection, the prevalence of the mutation was 2.41% (95%CI: 0.43; 8.37) in 83 Long‐Term Survivors (LTS) and 0.99% (95%CI: 0.45; 2.14) in 613 HIV‐1 exposed seronegative members as compared with 0.35% (95% Cl: 0.06; 1.25) in 579 HIV‐1 seropositive members. The prevalence of hCCR5Δ24 was 0.55% (95%CI: 0.15; 1.69) in 547 infants from Kenya but the mutation was not detected in 224 infants from Guinea‐Conakry nor in 800 Caucasian individuals from Luxembourg. Expression of hCCR5Δ24 in cell lines and PBMC showed that the hCCR5Δ24 protein is stably expressed but is not transported to the plasma membrane due to a conformational change. Instead, the mutant receptor was retained intracellularly, colocalized with an endoplasmic reticulum marker and did not mediate HIV‐1 infection. Co‐transfection of hCCR5Δ24 and wtCCR5 did not indicate a transdominant negative effect of CCR5Δ24 on wtCCR5.ConclusionsOur findings indicate that hCCR5Δ24 is not expressed at the cell surface. This could explain the higher prevalence of the heterozygous hCCR5Δ24 in LTS and HIV‐1 exposed seronegative members from serodiscordant couples. Our data suggest an East‐African localization of this deletion, which needs to be confirmed in larger cohorts from African and non‐African countries.

Background A steady increase in HIV drug resistance (HIVDR) has been demonstrated globally in individuals initiating first-line antiretroviral therapy (ART). To support effective use of ART and prevent spread of HIVDR, monitoring is essential. Aim We piloted a surveillance system for transmitted HIVDR to assess the feasibility of implementation at the European level. Method All 31 countries in the European Union and European Economic Area were invited to retrospectively submit data on individuals newly diagnosed with HIV in 2015 who were tested for antiviral susceptibility before ART, either as case-based or as aggregate data. We used the Stanford HIV database algorithm to translate genetic sequences into levels of drug resistance. Results Nine countries participated, with six reporting case-based data on 1,680 individuals and four reporting aggregated data on 1,402 cases. Sequence data were available for 1,417 cases: 14.5% of individuals (n = 244) showed resistance to at least one antiretroviral drug. In case-based surveillance, the highest levels of transmitted HIVDR were observed for non-nucleoside reverse-transcriptase inhibitors (NNRTIs) with resistance detected in 8.6% (n = 145), followed by resistance to nucleoside reverse-transcriptase inhibitors (NRTI) (5.1%; n = 85) and protease inhibitors (2.0%; n = 34). Conclusion We conclude that standard reporting of HIVDR data was feasible in the participating countries. Legal barriers for data sharing, consensus on definitions and standardisation of interpretation algorithms should be clarified in the process of enhancing European-wide HIV surveillance with drug resistance information. ; Peer Reviewed

IntroductionWe studied factors associated with the continuum of HIV care in Belgium.MethodsData of the national registration of new HIV diagnosis and of the national cohort of HIV‐infected patients in care were combined to obtain estimates of and factors related with proportions of HIV‐infected patients in each step of the continuum of care from diagnosis to suppressed viral load (VL). Factors associated with ignorance of HIV seropositivity were analyzed among patients co‐infected with HIV and STI in the Belgian STI sentinel surveillance network. Associated factors were identified by multivariate logistic regression.ResultsAmong 4038 individuals diagnosed with HIV between 2007 and 2010, 90.3% were linked to care. Of 11684 patients in care in 2010, 90.8% were retained in care up to the following year, 88.3% of those were on ART, of whom 95.3% had suppressed VL (<500 cp/ml) (Figure 1). In multivariate analyses, factors associated with ignoring HIV+ status were being younger (p<0.001), being heterosexual compared to MSM, and of a region of origin other than Belgium, Sub‐Saharan Africa and Europe. Non‐Belgian regions of origin were associated with lower entry and retention in care (p<0.001 for both). Preoperative HIV testing was associated with lower entry in care (p=0.003). MSM had a higher retention in care (p<0.001), whilst IDU had lower retention (p=0.004). Low CD4 at first clinical contact and clinical reasons for HIV testing were independently associated with being on ART (p<0.001 for both); whilst prenatal HIV diagnosis was associated with lower proportion on ART (p=0.016) and lower proportion with suppressed VL among those on ART (p=0.005). Older age was associated with both being on ART and having suppressed VL among those on ART (p=0.007 and p<0.001 respectively), independently of time since HIV diagnosis (Table 1).ConclusionsRegions of origin and risk groups (MSM/heterosexual/IDU) are the main factors associated with ignorance of HIV seropositivity, entry and retention in care, but once the HIV patient is retained in care, no effect of these factors on the proportions on ART and with suppressed VL are observed. The association of prenatal HIV diagnosis and proportions on ART and with suppressed VL could be biased by transitory CD4 disturbances during pregnancy and ART discontinuation after pregnancy. The higher probabilities of older patients to be on ART and have suppressed VL once retained in care could be influenced by factors not studied here like comorbidities, adherence or duration on ART.

BACKGROUND: A steady increase in HIV drug resistance (HIVDR) has been demonstrated globally in individuals initiating first-line antiretroviral therapy (ART). To support effective use of ART and prevent spread of HIVDR, monitoring is essential. AIM: We piloted a surveillance system for transmitted HIVDR to assess the feasibility of implementation at the European level. METHOD: All 31 countries in the European Union and European Economic Area were invited to retrospectively submit data on individuals newly diagnosed with HIV in 2015 who were tested for antiviral susceptibility before ART, either as case-based or as aggregate data. We used the Stanford HIV database algorithm to translate genetic sequences into levels of drug resistance. RESULTS: Nine countries participated, with six reporting case-based data on 1,680 individuals and four reporting aggregated data on 1,402 cases. Sequence data were available for 1,417 cases: 14.5% of individuals (n = 244) showed resistance to at least one antiretroviral drug. In case-based surveillance, the highest levels of transmitted HIVDR were observed for non-nucleoside reverse-transcriptase inhibitors (NNRTIs) with resistance detected in 8.6% (n = 145), followed by resistance to nucleoside reverse-transcriptase inhibitors (NRTI) (5.1%; n = 85) and protease inhibitors (2.0%; n = 34). CONCLUSION: We conclude that standard reporting of HIVDR data was feasible in the participating countries. Legal barriers for data sharing, consensus on definitions and standardisation of interpretation algorithms should be clarified in the process of enhancing European-wide HIV surveillance with drug resistance information.