Socioeconomic status and treatment outcomes for individuals with HIV on antiretroviral treatment in the UK: cross-sectional and longitudinal analyses

Background: Few studies have assessed the effect of socioeconomic status on HIV treatment outcomes in settings with universal access to health care. Here we aimed to investigate the association of socioeconomic factors with antiretroviral therapy (ART) non-adherence, virological non-suppression, and virological rebound, in HIV-positive people on ART in the UK. Methods: We used data from the Antiretrovirals, Sexual Transmission Risk and Attitudes (ASTRA) questionnaire study, which recruited participants aged 18 years or older with HIV from eight HIV outpatient clinics in the UK between Feb 1, 2011, and Dec 31, 2012. Participants self-completed a confidential questionnaire on sociodemographic, health, and lifestyle issues. In participants on ART, we assessed associations of financial hardship, employment, housing, and education with: self-reported ART non-adherence at the time of the questionnaire; virological non-suppression (viral load >50 copies per mL) at the time of questionnaire in those who started ART at least 6 months ago (cross-sectional analysis); and subsequent virological rebound (viral load >200 copies per mL) in those with initial viral load of 50 copies per mL or lower (longitudinal analysis). Findings: Of the 3258 people who completed the questionnaire, 2771 (85%) reported being on ART at the time of the questionnaire, and 2704 with complete data were included. 873 (32%) of 2704 participants reported non-adherence to ART and 219 (9%) of 2405 had virological non-suppression in cross-sectional analysis. Each of the four measures of lower socioeconomic status was strongly associated with non-adherence to ART, and with virological non-suppression (prevalence ratios [PR] adjusted for gender/sexual orientation, age, and ethnic origin: greatest financial hardship vs none 2·4, 95% CI 1·6–3·4; non-employment 2·0, 1·5–2·6; unstable housing vs homeowner 3·0, 1·9–4·6; non-university education 1·6, 1·2–2·2). 139 (8%) of 1740 individuals had subsequent virological rebound (rate=3·6/100 person-years). Low socioeconomic status was predictive of longitudinal rebound risk (adjusted hazard ratio [HR] for greatest financial hardship vs none 2·3, 95% CI 1·4–3·9; non-employment 3·0, 2·1–4·2; unstable housing vs homeowner 3·3, 1·8–6·1; non-university education 1·6, 1·1–2·3). Interpretation: Socioeconomic disadvantage was strongly associated with poorer HIV treatment outcomes in this setting with universal health care. Adherence interventions and increased social support for those most at risk should be considered

A hepatitis C virus (HCV) fertőzés pathogenesise: a genetikai és az immunológiai tényezők, valamint az oxidativ stress szerepe és a kórokozó virus sajátosságai, különös tekintettel a HCV-okozta betegségekben és a tünetmentes virushordozó állapotban = Pathogenesis of hepatitis C virus (HCV) infection: the role of the genetic and immunological factors, the oxidative stress and the viral features in the HCV-related diseases and in the symptomfree virus carriers

Genetikai, immunológiai és környezeti tényezők potenciális szerepe krónikus hepatitis C virus (HCV) infekcióban: összehasonlitó vizsgálatok aktiv HCV hepatitises betegekben és tünetmentes "egészséges" virushordozókban. 1. Sem a haemochromatosis gen mutációk, sem a CTLA4 polymorfizmusok nem befolyásolják a HCV-okozta májbetegség aktivitását, az angiotensin convertalo enzym (ACE) gen deletio azoban kedvező hatásu az anti-HCV terapia kimenetelére. 2. Az NK és B sejek felszinén levő CD81 molekula overexpressioja, valamint a regulatoros T sejtek termelte transformáló növekedési faktor (TGFbeta1), és az utóbbi által a cytotoxikus sejteken downregulált NKG2D aktiváló receptor - meghatározó szerepet játszanak a HCV infecióban kulcsfontosságu károsodott cellularis immunválaszban 3. A plasma TGFbeta1, a hyaluronsav és a procollagen-III-peptid szintek - mint a fibrogenesis markerei - kórosan emelkedettek krónikus aktiv HCV hepatitisben, de nem a tünetmentes virus-hordozókban. Az interferon + ribavirin antiviralis terapia gátolhatja a fibrogenesist, függetlenül a virológiai választól. 4. Mint additiv környezeti tényező, a SEN virus ko-infekció, gyakran előfordul HCV fertőzésben, és jelenléte negativan befolyásolja az anti-HCV terapia hatását krónikus C hepatitisben. | Genetic, immunologic and environmental factors and their potential role in the pathogenesis of chronic hepatitis C virus (HCV) infection: a comparison between active HCV hepatitis and symptomfree 'healthy' virus carriers. 1. Neither haemochromatosis gene mutations, nor CTLA4 polymorphisms influence the activity of HCV-related liver disease, however, ACE gene deletion has a favourable effect on the outcome of anti-HCV treatment in chronic hepatitis C. 2. Overexpression of CD81 molecule on NK and B cells, as well as transforming growth factor beta1 (TGFbeta1) secreted by regulatory T cells, and downregulated NKG2D activating receptor on cytotoxic effector cells, may play a privotal role in the impaired cell mediated immunity in active HCV infection 3. Plasma TGFbeta1, hyalurinic acid and procollagene-III-peptide levels - as markers of fibrogenesis - are elevated in active hepatitis C patients, but not in symptomfree carriers. Interferon + ribavirin therapy may inhibit fibrogenesis independently of virological response in chronic HCV hepatitis. 4. SEN virus co-infection, - as an additive environmetal factor - frequently occuring in HCV patients, decreases the effect of anti-HCV treatment

Effectiveness of dolutegravir-based regimens as either first-line or switch antiretroviral therapy: data from the Icona cohort

Introduction: Concerns about dolutegravir (DTG) tolerability in the real-life setting have recently arisen. We aimed to estimate the risk of treatment discontinuation and virological failure of DTG-based regimens from a large cohort of HIV-infected individuals. Methods: We performed a multicentre, observational study including all antiretroviral therapy (ART)-naïve and virologically suppressed treatment-experienced (TE) patients from the Icona (Italian Cohort Naïve Antiretrovirals) cohort who started, for the first time, a DTG-based regimen from January 2015 to December 2017. We estimated the cumulative risk of DTG discontinuation regardless of the reason and for toxicity, and of virological failure using Kaplan–Meier curves. We used Cox regression model to investigate predictors of DTG discontinuation. Results: About 1679 individuals (932 ART-naïve, 747 TE) were included. The one- and two-year probabilities (95% CI) of DTG discontinuation were 6.7% (4.9 to 8.4) and 11.5% (8.7 to 14.3) for ART-naïve and 6.6% (4.6 to 8.6) and 7.6% (5.4 to 9.8) for TE subjects. In both ART-naïve and TE patients, discontinuations of DTG were mainly driven by toxicity with an estimated risk (95% CI) of 4.0% (2.6 to 5.4) and 2.5% (1.3 to 3.6) by one year and 5.6% (3.8 to 7.5) and 4.0% (2.4 to 5.6) by two years respectively. Neuropsychiatric events were the main reason for stopping DTG in both ART-naïve (2.1%) and TE (1.7%) patients. In ART-naïve, a concomitant AIDS diagnosis predicted the risk of discontinuing DTG for any reason (adjusted relative hazard (aRH) = 3.38, p = 0.001), whereas starting DTG in combination with abacavir (ABC) was associated with a higher risk of discontinuing because of toxicity (aRH = 3.30, p = 0.009). TE patients starting a DTG-based dual therapy compared to a triple therapy had a lower risk of discontinuation for any reason (adjusted hazard ratio (aHR) = 2.50, p = 0.037 for ABC-based triple-therapies, aHR = 3.56, p = 0.012 for tenofovir-based) and for toxicity (aHR = 5.26, p = 0.030 for ABC-based, aHR = 6.60, p = 0.024 for tenofovir-based). The one- and two-year probabilities (95% CI) of virological failure were 1.2% (0.3 to 2.0) and 4.6% (2.7 to 6.5) in the ART naïve group and 2.2% (1.0 to 3.3) and 2.9% (1.5 to 4.3) in the TE group. Conclusions: In this large cohort, DTG showed excellent efficacy and optimal tolerability both as first-line and switching ART. The low risk of treatment-limiting toxicities in ART-naïve as well as in treated individuals reassures on the use of DTG in everyday clinical practice

Benefit of viral load testing for confirmation of immunological failure in HIV patients treated in rural Malawi.

Objective  Viral load testing is used in the HIV programme of Chiradzulu, Malawi, to confirm the diagnosis of immunological failure to prevent unnecessary switching to second-line therapy. Our objective was to quantify the benefit of this strategy for management of treatment failure in a large decentralized HIV programme in Africa. Methods  Retrospective analysis of monitoring data from adults treated with first-line antiretroviral regimens for >1 year and meeting the WHO immunological failure criteria in an HIV programme in rural Malawi. The positive predictive value of using immunological failure criteria to diagnose virological failure (viral load >5000 copies/ml) was estimated. Results  Of the 227 patients with immunological failure (185 confirmed with a repeat CD4 measurement), 155 (68.2%) had confirmatory viral load testing. Forty-four (28.4%) had viral load >5000 copies/ml and 57 (36.8%) >1000 copies/ml. Positive predictive value was 28.4% (95% CI 21.4-36.2%). Repeat CD4 count testing showed that 41% of patients initially diagnosed with immunological failure did no longer meet failure criteria. Conclusions  Our results support the need for confirming all cases of immunological failure with viral load testing before switching to second-line ART to optimize the use of resources in developing countries

Switch to maraviroc with darunavir/r, both QD, in patients with suppressed HIV-1 was well tolerated but virologically inferior to standard antiretroviral therapy: 48-Week results of a randomized trial

Objectives Primary study outcome was absence of treatment failure (virological failure, VF, or treatment interruption) per protocol at week 48. Methods Patients on 3-drug ART with stable HIV-1 RNA <50 copies/mL and CCR5-tropic virus were randomized 1:1 to maraviroc with darunavir/ritonavir qd (study arm) or continue current ART (continuation arm).Results In June 2015, 115 patients were evaluable for the primary outcome (56 study, 59 continuation arm). The study was discontinued due to excess of VF in the study arm (7 cases, 12.5%, vs 0 in the continuation arm, p = 0.005). The proportion free of treatment failure was 73.2% in the study and 59.3% in the continuation arm. Two participants in the study and 10 in the continuation arm discontinued therapy due to adverse events (p = 0.030). At VF, no emergent drug resistance was detected. Co-receptor tropism switched to non-R5 in one patient. Patients with VF reported lower adherence and had lower plasma drug levels. Femoral bone mineral density was significantly improved in the study arm. Conclusion Switching to maraviroc with darunavir/ritonavir qd in virologically suppressed patients was associated with improved tolerability but was virologically inferior to 3-drug therap

Predictability of IL-28B-polymorphism on protease-inhibitor-based triple-therapy in chronic HCV-genotype-1 patients: A meta-analysis

AIM: To investigate the predictability of interleukin-28B single nucleotide polymorphism rs12979860 with respect to sustained virological response (SVR) in chronically hepatitis C virus (HCV) genotype-1 patients treated with a protease-inhibitor and pegylated interferon-$\alpha$ (Peg-INF-$\alpha$) based triple-therapy. METHODS: We searched PubMed, the Cochrane Library and Web of Knowledge for studies regarding the interleukin 28B (IL-28B)-genotype and protease-inhibitor based triple-therapy. Ten studies with 2707 patients were included into this meta-analysis. We used regression methods in order to investigate determinants of SVR. RESULTS: IL-28B-CC-genotype patients achieved higher SVR rates (odds 5.34, CI: 3.81-7.49) than IL-28B-non-CC-genotype patients (1.88, CI: 1.43-2.48) receiving triple-therapy. The line of therapy (treatment-na\"ive or -experienced for Peg-INF-$\alpha$) did not affect the predictive value of IL-28B (p=0.1). IL-28B-CC-genotype patients treated with protease inhibitor-based triple-therapy consisting of Boceprevir, Simeprevir, Telaprevir or Vaniprevir showed odds of 1.86, 9.77, 4.51 and 0.89, respectively. The odds for CC genotype patients treated with Faldaprevir cannot be quantified, as only a single study with a 100% SVR rate was available. CONCLUSION: IL-28B-SNP predicts the outcome for chronic HCV genotype-1 patients receiving protease inhibitor-based triple-therapy. The predictive value varies between the different protease inhibitors.Comment: 21 pages, 3 figures, 1 tabl

Viral Load Monitoring of Antiretroviral Therapy, cohort viral load and HIV transmission in Southern Africa: A Mathematical Modelling Analysis

In low-income settings, treatment failure is often identified using CD4 cell count monitoring. Consequently, patients remain on a failing regimen, resulting in a higher risk of transmission. We investigated the benefit of routine viral load monitoring for reducing HIV transmission

Discordant responses to antiretroviral treatment: prevalence, risk factors and associated mortality in Rwanda

Mexico AIDS Conference 200

Modeling long-term longitudinal HIV dynamics with application to an AIDS clinical study

A virologic marker, the number of HIV RNA copies or viral load, is currently used to evaluate antiretroviral (ARV) therapies in AIDS clinical trials. This marker can be used to assess the ARV potency of therapies, but is easily affected by drug exposures, drug resistance and other factors during the long-term treatment evaluation process. HIV dynamic studies have significantly contributed to the understanding of HIV pathogenesis and ARV treatment strategies. However, the models of these studies are used to quantify short-term HIV dynamics ($<$ 1 month), and are not applicable to describe long-term virological response to ARV treatment due to the difficulty of establishing a relationship of antiviral response with multiple treatment factors such as drug exposure and drug susceptibility during long-term treatment. Long-term therapy with ARV agents in HIV-infected patients often results in failure to suppress the viral load. Pharmacokinetics (PK), drug resistance and imperfect adherence to prescribed antiviral drugs are important factors explaining the resurgence of virus. To better understand the factors responsible for the virological failure, this paper develops the mechanism-based nonlinear differential equation models for characterizing long-term viral dynamics with ARV therapy. The models directly incorporate drug concentration, adherence and drug susceptibility into a function of treatment efficacy and, hence, fully integrate virologic, PK, drug adherence and resistance from an AIDS clinical trial into the analysis. A Bayesian nonlinear mixed-effects modeling approach in conjunction with the rescaled version of dynamic differential equations is investigated to estimate dynamic parameters and make inference. In addition, the correlations of baseline factors with estimated dynamic parameters are explored and some biologically meaningful correlation results are presented. Further, the estimated dynamic parameters in patients with virologic success were compared to those in patients with virologic failure and significantly important findings were summarized. These results suggest that viral dynamic parameters may play an important role in understanding HIV pathogenesis, designing new treatment strategies for long-term care of AIDS patients.Comment: Published in at http://dx.doi.org/10.1214/08-AOAS192 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

A Retrospective Survey of HIV Drug Resistance Among Patients 1 Year After Initiation of Antiretroviral Therapy at 4 Clinics in Malawi

In 2004, Malawi began scaling up its national antiretroviral therapy (ART) program. Because of limited treatment options, population-level surveillance of acquired human immunodeficiency virus drug resistance (HIVDR) is critical to ensuring long-term treatment success. The World Health Organization target for clinic-level HIVDR prevention at 12 months after ART initiation is ≥ 70%. In 2007, viral load and HIVDR genotyping was performed in a retrospective cohort of 596 patients at 4 ART clinics. Overall, HIVDR prevention (using viral load ≤ 400 copies/mL) was 72% (95% confidence interval [CI], 67%-77%; range by site, 60%-83%) and detected HIVDR was 3.4% (95% CI, 1.8%-5.8%; range by site, 2.5%-4.7%). Results demonstrate virological suppression and HIVDR consistent with previous reports from sub-Saharan Africa. High rates of attrition because of loss to follow-up were noted and merit attention