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IntroductionProven resistance against HIV drugs, either by phenotyping or genotyping is a rare event in clinical trials. The overall assumption of drug resistance disappearing is additionally driven by the recommendations to screen for transmitted drug resistance, leading to large numbers of examinations with relatively low rates of resistance. Goal of our analysis was to assess if drug resistance in treatment failure is also decreasing outside of clinical trials.Materials and MethodsThe MIB database at timepoint of analysis consists of data from 2876 HIV infected patients. Besides various laboratory parameters, clinical data and treatment history is included. HIV‐1 protease and reverse transcriptase sequences were analyzed using the HIV‐GRADE drug resistance algorithm. As in only a small number of patients genotypic resistance testing for integrase inhibitors was performed, mainly due to reimbursement reasons, it was assumed that failing treatment on a previous integrase inhibitor containing regimen is equate to resistance.ResultsOf the 2876 patients in the database, 220 had a treatment change due to treatment failure between 2009 and 2012, a genotypic resistance testing at an appropriate timepoint of maximum four weeks before treatment change and a treatment duration of at least six months before treatment failure. In 2009, 61% of patients showed no drug resistance while 39% showed resistance against one or more drug classes (two or more drug classes: 19.5%; three or more drug classes: 2.4%, four drug classes 2.4%). In 2012, no resistance was found in 52% of patients while resistance against three or more drug classes was found in nearly 14% of patients (one or more: 48%; two or more 23%; four classes: 4.5%).ConclusionsTreatment failure with viral load sufficiently high for drug resistance testing was not frequently observed in our database. Nevertheless, treatment failure was often associated with drug resistance against at least one drug class. With more use of the newer drug classes, resistance against those new classes will become more common and rates of multiclass resistance will be increasing.

Paediatric antiretroviral treatment (ART) failure is an under‐recognized issue that receives inadequate attention in the field of paediatrics and within HIV treatment programmes. With paediatric ART failure rates ranging from 19.3% to over 32% in resource limited settings, a comprehensive evaluation of the causes of failure along with approaches to address barriers to treatment adherence are urgently needed.In partnership with the local Department of Health, a pilot programme has been established by Medecins Sans Frontieres (MSF) in Khayelitsha, South Africa, to identify and support paediatric HIV patients with high viral loads and potential treatment failure. Through detailed clinical and psychosocial evaluations and adherence support with an innovative counselling model, treatment barriers are identified and addressed.Demographic and clinical characteristics from the cohort show a delayed median start date for ART, prolonged viraemia including a large number of patients who have never achieved viral load (VL) suppression, a low rate of regimen changes despite failure, and a high percentage of pre‐adolescent and adolescent patients who have not gone through the disclosure process.Stemming this epidemic of paediatric treatment failure requires programmatic responses to high viral loads in children, starting with improved "case finding" of previously undiagnosed HIV‐infected children and adolescents. Viral load testing needs to be prioritized over CD4 count monitoring, and flagging systems to identify high VL results should be developed in clinics. Clinicians must understand that successful treatment begins with good adherence, and that simple adherence support strategies can often dramatically improve adherence. Moreover, appropriate adherence counselling should begin not when the child fails to respond to treatment. Establishing good adherence from the beginning of treatment, and supporting ongoing adherence during the milestones in these children's lives is key to sustaining treatment success in this vulnerable HIV‐infected patient population.

IntroductionEtravirine (ETR) and rilpivirine (RPV) are the second‐generation non‐nucleoside reverse transcriptase inhibitors (NNRTI) for treatment of HIV‐1 infection. Etravirine is recommended for patients with virologic failure from first generation NNRTI‐based regimen [1]. RPV has profile with similar properties to ETR but this agent is approved for treatment‐naïve patients [2]. In Thailand, ETR is approximately 45 times more expensive than RPV. We aimed to study the patterns of genotypic resistance and possibility of using RPV in patients with virologic failure from two common NNRTI‐based regimens: efavirenz (EFV)‐ or nevirapine (NVP)‐based regimen.Materials and MethodsData of clinical samples with confirmed virologic failure during 2003–2010 were reviewed. We selected the samples from patients who failed EFV‐ or NVP‐based regimen. Resistance‐associated mutations (RAMs) were determined by IAS‐USA Drug Resistance Mutations. DUET, Monogram scoring system and Stanford Genotypic Resistance Interpretation were applied to determine the susceptibility of ETR and RPV.ResultsA total of 2086 samples were analyzed. Samples from 1482 patients with virologic failure from NVP‐based regimen treatment failure (NVP group) and 604 patients with virologic failure from EFV‐based regimen treatment failure (EFV group) were included. 95% of samples were HIV‐1 CRF01_AE subtype. Approximately 80% of samples in each group had one to three NNRTI‐RAMs and 20% had four to seven NNRTI‐RAMs. 181C mutation was the most common NVP‐associated RAM (54.3% vs 14.7%, p<0.01). 103N mutation was the most common EFV‐associated RAM (56.5% vs 19.1%, p<0.01). The calculated scores from all three scoring systems were concordant. In NVP group, 165 (11.1%) and 161 (10.9%) patients were susceptible to ETR and RPV, respectively (p=0.81). In EFV group, 195 (32.2%) and 191 (31.6%) patients were susceptible to ETR and RPV, respectively (p=0.81). The proportions of viruses that remained susceptible to ETR and RPV in EFV group were significantly higher than NPV group (ETR susceptibility 32.2% vs 11.1%, p<0.01, RPV susceptibility 31.6% vs 10.9%, p<0.01), respectively.ConclusionsRPV might be a cost saving and reasonable second line NNRTI for patients who failed EFV‐ or NVP‐containing regimens, especially in resource‐limited setting because these two agents have comparable susceptibility identified by genotyping. From our study, approximately 30% of patients who failed EFV‐based regimens had viruses that remained susceptible to RPV.

Abstract
In post-socialist Mongolia, unsuccessful treatment, or worse, interventions that result in worsened health conditions, are common concerns. Patients and clients direct scepticism towards a range of practitioners, from biomedical physicians to shamans and 'folk' healers (domch). The gap between the ideal treatment and the actual outcome—the prevalence of treatment misfires—invites analysis of infrastructural changes to (health)care and wider contexts of relationality. As state-owned medicine was restructured in the 1990s, healing 'traditions' such as shamanism and Traditional Mongolian Medicine considered essentialised aspects of national identity have gained new legitimacy. Many people find it challenging to navigate the multiple authorities on health and wellbeing that exist in contemporary public. Patients and clients often questioned efficacy in terms of toxicity and poison (hor, horlol). Toxicity's associations with Soviet-era regulation and Buddhist medical contexts articulate the importance of both state-sanctioned regulation and the practitioner's specialised knowledge.

IntroductionPre‐treatment HIV drug resistance (PDR) is an increasing problem in sub‐Saharan Africa. Children are an especially vulnerable population to develop PDR given that paediatric second‐line treatment options are limited. Although monitoring of PDR is important, data on the paediatric prevalence in sub‐Saharan Africa and its consequences for treatment outcomes are scarce. We designed a prospective paediatric cohort study to document the prevalence of PDR and its effect on subsequent treatment failure in Nigeria, the country with the second highest number of HIV‐infected children in the world.MethodsHIV‐1‐infected children ≤12 years, who had not been exposed to drugs for the prevention of mother‐to‐child transmission (PMTCT), were enrolled between 2012 and 2013, and followed up for 24 months in Lagos, Nigeria. Pre‐antiretroviral treatment (ART) population‐based pol genotypic testing and six‐monthly viral load (VL) testing were performed. Logistic regression analysis was used to assess the effect of PDR (World Health Organization (WHO) list for transmitted drug resistance) on subsequent treatment failure (two consecutive VL measurements >1000 cps/ml or death).ResultsOf the total 82 PMTCT‐naïve children, 13 (15.9%) had PDR. All 13 children harboured non‐nucleoside reverse transcriptase inhibitor (NNRTI) mutations, of whom seven also had nucleoside reverse transcriptase inhibitor resistance. After 24 months, 33% had experienced treatment failure. Treatment failure was associated with PDR and a higher log VL before treatment initiation (adjusted odds ratio (aOR) 7.53 (95%CI 1.61–35.15) and 2.85 (95%CI 1.04–7.78), respectively).DiscussionPDR was present in one out of six Nigerian children. These high numbers corroborate with recent findings in other African countries. The presence of PDR was relevant as it was the strongest predictor of first‐line treatment failure.ConclusionsOur findings stress the importance of implementing fully active regimens in children living with HIV. This includes the implementation of protease inhibitor (PI)‐based first‐line ART, as is recommended by the WHO for all HIV‐infected children <3 years of age. Overcoming practical barriers to implement PI‐based regimens is essential to ensure optimal treatment for HIV‐infected children in sub‐Saharan Africa. In countries where individual VL or resistance testing is not possible, more attention should be given to paediatric PDR surveys.

Background Monitoring patient response with viral load, which is the gold standard, is not feasible in resource limited settings. Therefore it's essential to look for factors that can be used to identify those patients at higher risk of treatment failure in these settings. Objective To explore factors that can be used to identify those at a higher risk of treatment failure. Method A Nested case-control study from a cohort of HIV patients on ART at government hospitals in Addis Ababa was conducted through review of medical records. A total sample size of 423 with 141 patients with failure of their first line regimen (cases) and 282 patients without failure (controls) is used. Base line socio-demographic and clinical information were collected. Comparison of survival times were made through Kaplan Meier and Log-rank tests. Independent predictors of treatment failure were identifies using multivariate COX regression analysis. Results The mean survival time (without treatment failure) was 53 months (95% CI, 50 – 57). Females were found to have a higher survival time of 57months (95%CI, 52-62, P= 0.01) and males have a significantly higher risk of developing treatment failure with an adjusted HR of 1.518 (95%CI, 1.084-2.125, P=0.01). Those with two or more episodes of poor adherence during their follow-up have a significantly higher adjusted hazard ratio of 4.02 (95% CI, 2.71, 5.96, P=<0.001) compared to those with no episode of poor adherence. Missed appointment is another independent predictor of treatment failure with adjusted HR of 1.77 (1.11, 2.96, P= 0.03). Conclusion This study has shown that non- adherence to medication and clinic visits are independently associated with treatment failure. Following patients closely for their level of adherence and their trend of missing clinic visits can be used to help identify those at higher risk of treatment failure. Providing intense adherence counseling for these patients may prevent occurrence of failure.

Background Monitoring patient response with viral load, which is the gold standard, is not feasible in resource limited settings. Therefore it's essential to look for factors that can be used to identify those patients at higher risk of treatment failure in these settings. Objective To explore factors that can be used to identify those at a higher risk of treatment failure. Method A Nested case-control study from a cohort of HIV patients on ART at government hospitals in Addis Ababa was conducted through review of medical records. A total sample size of 423 with 141 patients with failure of their first line regimen (cases) and 282 patients without failure (controls) is used. Base line socio-demographic and clinical information were collected. Comparison of survival times were made through Kaplan Meier and Log-rank tests. Independent predictors of treatment failure were identifies using multivariate COX regression analysis. Results The mean survival time (without treatment failure) was 53 months (95% CI, 50 – 57). Females were found to have a higher survival time of 57months (95%CI, 52-62, P= 0.01) and males have a significantly higher risk of developing treatment failure with an adjusted HR of 1.518 (95%CI, 1.084-2.125, P=0.01). Those with two or more episodes of poor adherence during their follow-up have a significantly higher adjusted hazard ratio of 4.02 (95% CI, 2.71, 5.96, P=<0.001) compared to those with no episode of poor adherence. Missed appointment is another independent predictor of treatment failure with adjusted HR of 1.77 (1.11, 2.96, P= 0.03). Conclusion This study has shown that non- adherence to medication and clinic visits are independently associated with treatment failure. Following patients closely for their level of adherence and their trend of missing clinic visits can be used to help identify those at higher risk of treatment failure. Providing intense adherence counseling for these patients may prevent occurrence of failure.