Virologic and immunologic outcomes of treatment with integrase inhibitors in a real-world setting: The RESPOND cohort consortium.

Objectives: To compare virologic and immunologic outcomes of integrase inhibitor (INSTI)-containing, contemporary boosted protease inhibitor (PI/b)-containing and non-nucleotide reverse transcriptase inhibitor (NNRTI)-containing regimens in a real-life setting.

Methods: Using logistic regression, virologic and immunologic outcomes of INSTI use were compared to outcomes of PI/b or NNRTI treatment 12 months after treatment start or switch, for participants in the RESPOND cohort consortium. A composite treatment outcome (cTO) was used, defining success as viral load (VL) <200 copies/mL and failure as at least one of: VL ≥200 copies/mL, unknown VL in the time window, any changes of antiretroviral therapy (ART) regimen, AIDS, or death.

The effect of HIV status on the frequency and severity of acute respiratory illness.

Introduction: Antiretroviral therapy has improved the health of people living with HIV (PLW-HIV), though less is known about how this impacts on acute respiratory illness. These illnesses are a common cause of ill health in the general population and any increase in their frequency or severity in PLW-HIV might have significant implications for health-related quality of life and the development of chronic respiratory disease.

Methods: In a prospective observational cohort study following PLW-HIV and HIV negative participants for 12 months with weekly documentation of any acute respiratory illness, we compared the frequency, severity and healthcare use associated with acute respiratory illnesses to determine whether PLW-HIV continue to have a greater frequency or severity of such illnesses despite antiretroviral therapy.

Epidemiological characteristics and access to end-stage liver disease care for HIV-positive patients with HCV and/or HBV coinfections in Central/Eastern European and neighboring countries – data from the ECEE network.

Objectives: There is currently an urgent need to harmonize hepatitis standards of care for HIV-positive patients across Europe. The HIV epidemic in Central and Eastern Europe has often been driven by injecting drug use, therefore a higher rate of co-infection with HCV and HBV is expected in this region. We have investigated the epidemiological prevalence and treatment availability for end-stage liver disease in HIV/HCV/HBV coinfections in countries represented in the ECEE Network Group.

Engagement in care among youth living with parenterally-acquired HIV infection in Romania.

Transition from adolescent to adult care can be challenging for youth living with HIV. We conducted a cohort study of youth born between 1985 and 1993 and infected with HIV parenterally, followed by the same medical team from age 15 years or first clinic visit until age 25 years or 30 November 2016. A longitudinal continuum-of-care was constructed, categorizing individuals' status for each month of follow-up as: engaged in care (EIC); not in care (NIC: no clinic visits within past year); lost-to-follow-up (LTFU: NIC and did not return to clinic); or died.

Choice of first-line antiretroviral therapy regimen and treatment outcomes for HIV in a middle income compared to a high income country: a cohort study.

Background: The range of combination antiretroviral therapy (cART) regimens available in many middle-income countries differs from those suggested in international HIV treatment guidelines. We compared first-line cART regimens, timing of initiation and treatment outcomes in a middle income setting (HIV Centre, Belgrade, Serbia - HCB) with a high-income country (Royal Free London Hospital, UK - RFH).

Methods: All antiretroviral-naïve HIV-positive individuals from HCB and RFH starting cART between 2003 and 2012 were included.

Treatment intensification followed by interleukin-7 reactivates HIV without reducing total HIV DNA: a randomized trial.

Background: As a first step towards HIV cure, we assessed a strategy of antiretroviral therapy (ART) intensification followed by interleukin-7 (IL-7) used as an HIV-reactivating agent.

Methods: A multicentre, randomized clinical trial included patients on suppressive ART with CD4 cell counts at least 350/μl and HIV-DNA between 10 and 1000 copies/10 peripheral blood mononuclear cells (PBMCs). After an 8-week raltegravir and maraviroc intensification, patients were randomized to intensification alone or with 3 weekly IL-7 injections at weeks 8, 9 and 10.

Effect of management strategies and clinical status on costs of care for advanced HIV.

Objectives: To determine the association between preexisting characteristics and current health and the cost of different types of advanced human immunodeficiency virus (HIV) care.

Methods: Treatment-experienced patients failing highly active antiretroviral treatment (ART) in the United States, Canada, and the United Kingdom were factorial randomized to an antiretroviral-free period and ART intensification. Cost was estimated by multiplying patient-reported utilization by a unit cost.

Clinical relevance of the plasma load of cytomegalovirus in patients infected with HIV--a survival analysis.

To investigate whether asymptomatic cytomegalovirus (CMV) viraemia impact the course of human immunodeficiency virus (HIV) infection, this study evaluated the effect of CMV replication on progression of newly-diagnosed HIV infected individuals towards AIDS events and death. In a 3-year prospective study on co-infected patients, clinical, immunological, and virological tests were performed in a national reference hospital quarterly. CMV viraemia was quantified by RoboGene® HCMV DNA Quantification Kit (Analytik Jena, Germany), on ABI Prism® 7000 Sequence Detection System (Applied Biosystems, USA).

Higher risk of renal impairment associated with tenofovir use amongst people living with HIV in India: a comparative cohort analysis between Western India and United Kingdom.

Background: Data on the renal safety of Tenofovir (TDF) in Low and Middle Income Countries (LMICs) is scarce. We compared development of various forms of renal impairment with use of TDF-containing antiretroviral therapy (ART) between a cohort from the Institute of Infectious Diseases (IID) Pune, Western India and the Royal Free Hospital (RFH) London, UK.

Methods: This is a retrospective analysis of change in estimated glomerular filtration rates (eGFRs) at 6, 12 and 24 months post TDF initiation using the Modification of Diet in Renal Disease (MDRD) equation.

Lower healthcare costs associated with the use of a single-pill ARV regimen in the UK, 2004-2008.

Aim: Investigate the cost and effects of a single-pill versus two- or three pill first-line antiretroviral combinations in reducing viral load, increasing CD4 counts, and first-line failure rate associated with respective regimens at 6 and 12 months.

Methods: Patients on first-line TDF+3TC+EFV, TDF+FTC+EFV, Truvada®+EFV or Atripla® between 1996-2008 were identified and viral load and CD4 counts measured at baseline, six and twelve months respectively. Factors that independently predicted treatment failure at six and twelve months were derived using multivariate Cox's proportional hazard regression analyses.

British HIV Association guidelines for the treatment of HIV-1-positive adults with antiretroviral therapy 2012.

The overall purpose of these guidelines is to provide guidance on best clinical practice in the treatment and management of adults with HIV infection with antiretroviral therapy (ART). The scope includes: (i) guidance on the initiation of ART in those previously naïve to therapy; (ii)support of patients on treatment; (iii) management of patients experiencing virological failure; and (iv) recommendations in specific patient populations where other factors need to be taken into consideration. The guidelines are aimed at clinical professionals directly involved with and responsible for the care of adults with HIV infection and at community advocates responsible for promoting the best interests and care of HIV-positive adults.

Estimation of the effect of SLCO1B1 polymorphisms on lopinavir plasma concentration in HIV-infected adults.

Background: The organic anion transporting polypeptides (OATP)/SLCO family represents an important class of hepatic drug uptake transporters that mediate the sodium independent transport of a diverse range of amphipathic organic compounds, including the protease inhibitors. The SLCO1B1 521T>C (rs4149056) single nucleotide polymorphism (SNP) has been consistently associated with reduced transport activity in vivo, and we previously showed an association of this polymorphism with lopinavir plasma concentrations. The aim of this study was to develop a population pharmacokinetic (PK) model to quantify the impact of 521T>C.

The use of computational models to predict response to HIV therapy for clinical cases in Romania.

Introduction: A major challenge in Romania is the optimisation of antiretroviral therapy for the many HIV-infected adults with, on average, a decade of treatment experience. The RDI has developed computational models that predict virological response to therapy but these require a genotype, which is not routinely available in Romania. Moreover the models, which were trained without any Romanian data, have proved most accurate for patients from the healthcare settings that contributed the training data.

The cost-effectiveness of early access to HIV services and starting cART in the UK 1996-2008.

Aim: To calculate use, cost and cost-effectiveness of people living with HIV (PLHIV) starting routine treatment and care before starting combination antiretroviral therapy (cART) and PLHIV starting first-line 2NRTIs+NNRTI or 2NRTIs+PI(boosted), comparing PLHIV with CD4≤200 cells/mm3 and CD4>200 cells/mm3. Few studies have calculated the use, cost and cost-effectiveness of routine treatment and care before starting cART and starting cART above and below CD4 200 cells/mm3.

Methods: Use, costs and cost-effectiveness were calculated for PLHIV in routine pre-cART and starting first-line cART, comparing CD4≤200 cells/mm3 with CD4>200 cells/mm3 (2008 UK prices).

Cost-effectiveness of early treatment with first-line NNRTI-based HAART regimens in the UK, 1996-2006.

Aim: Calculate time to first-line treatment failure, annual cost and cost-effectiveness of NNRTI versus PIboosted first-line HAART regimens in the UK, 1996-2006.

Background: Population costs for HIV services are increasing in the UK and interventions need to be effective and efficient to reduce or stabilize costs. 2NRTIs + NNRTI regimens are cost-effective regimens for first-line HAART, but these regimens have not been compared with first-line PI(boosted) regimens.

Effect of treatment interruption and intensification of antiretroviral therapy on health-related quality of life in patients with advanced HIV: a randomized, controlled trial.

Background: The effect of antiretroviral therapy (ART) interruption or intensification on health-related quality of life (HRQoL) in advanced HIV patients is unknown.

Objective: To assess the impact of temporary treatment interruption and intensification of ART on HRQoL.

Design: A 2 x 2 factorial open label randomized controlled trial.

Rising population cost for treating people living with HIV in the UK, 1997-2013.

Background: The number of people living with HIV (PLHIV) is increasing in the UK. This study estimated the annual population cost of providing HIV services in the UK, 1997-2006 and projected them 2007-2013.

Methods: Annual cost of HIV treatment for PLHIV by stage of HIV infection and type of ART was calculated (UK pounds, 2006 prices).

Health-related quality of life in a randomized trial of antiretroviral therapy for advanced HIV disease.

Objective: To assess and compare alternative approaches of measuring preference-based health-related quality of life (HRQoL) in treatment-experienced HIV patients and evaluate their association with health status and clinical variables.

Design: Cross-sectional study.

Setting: Twenty-eight Veterans Affairs hospitals in the United States, 13 hospitals in Canada, and 8 hospitals in the United Kingdom.

Stability of antiretroviral regimens in patients with viral suppression.

Objective: To study the rate of treatment change due to toxicities in patients who achieved viral suppression within 6 months of starting antiretroviral therapy and who have never experienced virological failure.

Methods: Included patients attended the Royal Free Hospital in London, started antiretroviral therapy in 2000-2005, and achieved viral suppression within 6 months. Included follow-up (censored at virological failure) was spent on a regimen of lamivudine or emtricitabine, with a second nucleoside/nucleotide reverse transcriptase inhibitor, and either a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor.

TILT: a randomized controlled trial of interruption of antiretroviral therapy with or without interleukin-2 in HIV-1 infected individuals.

Objective: We aimed to see if structured treatment interruption (STI) could be supported safely with the use of two cycles of IL-2 (4.5 MIU q12h subcutaneously 5 days) before STI to prolong the time before therapy restarted.

Methods: Subjects were randomly allocated to either A - continuous ART; B - continue for 9 weeks, then STI; restart with the same ART when the CD4 count falls below 200 cells; or C - two cycles of IL-2, 8 weeks apart, while still on ART; at week 9 stop ART and use a new cycle of IL-2 alone whenever the CD4 count falls < 300 cells.

Acetyl-L-carnitine in HIV-associated antiretroviral toxic neuropathy.

Nucleoside analogue reverse transcriptase inhibitors (NRTIs), used as part of highly active antiretroviral therapy for the treatment of HIV and AIDS, disrupt neuronal mitochondrial DNA synthesis, resulting in antiretroviral toxic neuropathy (ATN). Acetyl-L-carnitine (ALC) enhances neurotrophic support of sensory neurons, potentially causing symptom relief and nerve regeneration, and in addition has numerous other effects on metabolic function that might be of benefit in such patients.ALC has been given to HIV patients with symptomatic ATN in a number of clinical studies administered either twice daily intramuscularly or as oral sachets or tablets.

Overview of boosted protease inhibitors in treatment-experienced HIV-infected patients.

Antiretroviral drug combinations that include two nucleoside reverse transcriptase inhibitors and a protease inhibitor (PI) can suppress HIV replication to undetectable levels, improving the prognosis of HIV-infected individuals. The aim of therapy is complete virological suppression, with a current goal of <50 copies/mL HIV-1 RNA, in order to minimize the occurrence of drug resistance. Improved understanding of the pharmacology of PIs, primarily the importance of adequate drug exposure, has led to the widespread administration of PIs combined with a low 'boosting' dose of ritonavir.

The influence of HIV infection and antiretroviral therapy on the mitochondrial membrane potential of peripheral mononuclear cells.

Objectives: Clinical disorders occurring in HIV-infected patients on antiretroviral therapy (ART) have been linked to mitochondrial dysfunction, for example, lactic acidosis and lipodystrophy. Mitochondrial membrane potential (delta psi m) is the most direct measure of the state of energization of the mitochondria. We analysed delta psi m, of peripheral blood mononuclear cells (PBMCs) in HIV-negative, healthy subjects (n=8), HIV-infected, treatment-naive patients (n=30), and HIV-infected patients on ART (n=58).