The results confirmed the relation between CXCR4-use at diagnosis and low baseline CD4+ T cell counts. Significantly more CXCR4-use was predicted in 01_AE infections, which may impose constraints on the use of CCR5 antagonists in certain regions of the world. Observations from the transmission cluster analysis contradict the hypothesis that R5 viruses are selected at transmission, and support the idea that R5 or X4/DM infections result from a stochastic process.

The results of this study indicate the sustained lower fitness of mutant strains in vivo. As a result, wild-type virus remains capable of outcompeting the RT or protease mutant strains very fast after removal of the drug. These findings highlight the importance of 'treatment history' in addition to genotypic and phenotypic markers determined at one time-point, when making therapeutic decisions for patients.

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.

The aim of this study was to determine whether drug-resistant virus persists in peripheral blood mononuclear cells (PBMCs) after long-term suppression of virus replication. Proviral DNA was extracted from the PBMCs of 11 patients on long-term highly active antiretroviral therapy (HAART). Genotyping of the reverse transcriptase (RT) and protease gene of several proviral variants was performed using limiting dilution polymerase chain reaction and single-copy sequencing. All patients were on successful HAART for a mean period of 59 months but had a history of suboptimal therapy and genotypic drug resistance before. Comparison of the amino acid sequence of the RT and protease gene in the different proviral variants, with that of the plasma virus isolated before HAART treatment, revealed that the different drug-resistant viral variants that evolved during the process of gradually building up resistance were still detectable in the PBMCs in 10 of the 11 patients tested. The proportion of resistant variants was found to correlate with the time that the resistant variants had been able to replicate. These data clearly show that virus variants that are able to replicate for a certain period enter the latent reservoir and remain archived in the PBMCs for a very long period.

This study is the first prospective study to assess the prevalence, epidemiology, and risk factors of HIV-1 drug resistance in newly diagnosed HIV-infected patients in Belgium. In January 2003 it was initiated as part of the pan-European SPREAD program, and continued thereafter for four inclusion rounds until December 2006. Epidemiological, clinical, and behavioral data were collected using a standardized questionnaire and genotypic resistance testing was done on a sample taken within 6 months of diagnosis. Two hundred and eighty-five patients were included. The overall prevalence of transmitted HIV-1 drug resistance in Belgium was 9.5% (27/285, 95% CI: 6.6-13.4). Being infected in Belgium, which largely coincided with harboring a subtype B virus, was found to be significantly associated with transmission of drug resistance. The relatively high rate of baseline resistance might jeopardize the success of first line treatment as more than 1 out of 10 (30/285, 10.5%) viruses did not score as fully susceptible to one of the recommended first-line regimens, i.e., zidovudine, lamivudine, and efavirenz. Our results support the implementation of genotypic resistance testing as a standard of care in all treatment-naive patients in Belgium.