Feasibility and acceptability of implementing early infant diagnosis of HIV in Papua New Guinea at the point of care: a qualitative exploration of health worker and key informant perspectives

Introduction: Early infant diagnosis (EID) of HIV and timely initiation of antiretroviral therapy can significantly reduce morbidity and mortality among HIV-positive infants. Access to EID is limited in many low-income and middle-income settings, particularly those in which standard care involves dried blood spots (DBS) sent to centralised laboratories, such as in Papua New Guinea (PNG). We conducted a qualitative exploration of the feasibility and acceptability of implementing a point-of-care (POC) EID test (Xpert HIV-1 Qualitative assay) among health workers and key stakeholders working within the prevention of mother-to-child transmission of HIV (PMTCT) programme in PNG. Methods: This qualitative substudy was conducted as part of a pragmatic trial to investigate the effectiveness of the Xpert HIV-1 Qualitative test for EID in PNG and Myanmar. Semistructured interviews were undertaken with 5 health workers and 13 key informants to explore current services, experiences of EID testing, perspectives on the Xpert test and the feasibility of integrating and scaling up POC EID in PNG. Coding was undertaken using inductive and deductive approaches, drawing on existing acceptability and feasibility frameworks. Results: Health workers and key informants (N=18) felt EID at POC was feasible to implement and beneficial to HIV-exposed infants and their families, staff and the PMTCT programme more broadly. All study participants highlighted starting HIV-positive infants on treatment immediately as the main advantage of POC EID compared with standard care DBS testing. Health workers identified insufficient resources to follow up infants and caregivers and space constraints in hospitals as barriers to implementation. Participants emphasised the importance of adequate human resources, ongoing training and support, appropriate coordination and a sustainable supply of consumables to ensure effective scale-up of the test throughout PNG. Conclusions: Implementation of POC EID in a low HIV prevalence setting such as PNG is likely to be both feasible and beneficial with careful planning and adequate resources

Disease activity and disability in children with juvenile idiopathic arthritis one year following presentation to paediatric rheumatology. Results from the Childhood Arthritis Prospective Study

Objective. Inflammatory arthritis in childhood is variable in terms of both presentation and outcome. This analysis describes disease activity in children with juvenile idiopathic arthritis (JIA) during the first year following presentation to a paediatric rheumatologist and identifies predictors of moderate to severe disability [defined using a Childhood HAQ (CHAQ) score ⩾0.75] at 1 year

A longitudinal, multi-level comparative study of quality and safety in European hospitals: the QUASER study protocol

although there is a wealth of information available about quality improvement tools and techniques in healthcare there is little understanding about overcoming the challenges of day-to-day implementation in complex organisations like hospitals. The 'Quality and Safety in Europe by Research' (QUASER) study will investigate how hospitals implement, spread and sustain quality improvement, including the difficulties they face and how they overcome them. The overall aim of the study is to explore relationships between the organisational and cultural characteristics of hospitals and how these impact on the quality of health care; the findings will be designed to help policy makers, payers and hospital managers understand the factors and processes that enable hospitals in Europe to achieve-and sustain-high quality services for their patients

Antiretroviral therapy in Papua New Guinea: biological and social factors contributing to HIV treatment failure and drug resistance

Combination antiretroviral therapy (ART) has transformed HIV from a progressive, ultimately fatal illness to a manageable chronic infection. However, the long term benefits of ART are compromised by the development of HIV drug resistance (HIVDR) which is propelled by sub-optimal therapy and non-adherence. The issue of HIVDR is more problematic in low-and –middle income countries where treatment options and laboratory resources to monitor treatment failure and HIVDR are limited. There are >12,000 people living with HIV (PLHIV) accessing ART in Papua New Guinea (PNG). Like many RLS, the delivery of HIV services is often challenged by economic, structural, cultural, and social issues. Monitoring and management of ART in PNG remains a challenge exacerbated by the absence of proper immunological and virological monitoring tools as faced in similar settings globally. Adherence becomes an issue hard to maintain in the face of constant challenges. The aims of the study were to determine the levels of transmitted drug resistance (TDR) in ART naïve patients and acquired drug resistance (ADR) in ART experienced patients in PNG, identify factors that affect adherence, and to characterise HIV subtypes responsible for the PNG HIV epidemic. A cohort of 210 PLHIV consisting of 102 ART experienced and 108 ART naïve were recruited from two major sexual health clinics that administer ART in two Highlands provinces. This study reports low levels of TDR (2.1%, 2/96) whilst ADR was detected in 40.0% (6/15) of ART experienced patients. Over three quarters (77.5%; 79/102) of ART experienced participants had an undetectable viral load, however a significant number of individuals (15.9%, n=13) on treatment were failing therapy according to the WHO definition. Although the majority of participants self-reported excellent ART adherence in the last seven days (78.9%, 75/91), pill count measurements indicated only 40.5% (34/84) with >95% adherence in the last month. Almost half (n=49, 52.0%) of the participants were consistently taking ART outside of recommended time since they started treatment. Taken together, these findings indicate that non-adherence to ART is high in this study cohort. This study confirms that the PNG HIV epidemic is dominated by subtype C strains that are unique to PNG. The HIV epidemic in appears to be the result of a limited number of related strains circulating within the country rather than continuous introduction of unrelated strains from other countries. Further phylogenetic analysis revealed that there is no geographical segregation of subtype C strains in PNG. These findings shows that HIV is spread locally by mobile populations, therefore, targeting these populations will be important for limiting new infections. In conclusion, whilst first line therapy is still largely effective in PNG, there is evidence of virological failure in some ART experienced individuals and drug resistance was detected in both ART naive and experienced participants. Drug resistance monitoring and persistent counselling and education on ART adherence are necessary for the longevity of successful ART program in PNG

Development of a simple microarray for genotyping HIV-1 drug resistance mutations in the reverse transcriptase gene in rural Tanzania

Aiming at a simple, inexpensive and robust tool for HIV-1 drug resistance genotyping during antiretroviral therapy (ART) we developed and validated a microarray-based detection of 25 drug resistance mutations most relevant for the Tanzanian ART regimen.; A reverse transcriptase gene fragment was reverse-transcribed and amplified by reverse transcription-polymerase chain reaction (RT-PCR). Primers for mini-sequencing were designed based on alignments of the most prevalent local HIV-1 variants. Tagged primers were extended by fluorochrome-labelled dideoxynuclotide triphosphate (ddNTPs) to indicate the single-nucleotide polymorphism (SNP) allele of the sample tested, followed by hybridisation on treated microarray slides. Images were analysed with a laser scanner and genotype calling was performed using in-house developed software.; The microarray was validated with four cloned HIV-1 genome fragments from a Swiss HIV-1 cohort and 102 HIV-1 sequences amplified from the Tanzanian target population (field samples). Results were concordant with the Sanger sequencing SNP profile in 92.7% of 2550 SNP data points compared. Lack of signals in small number of SNPs was due to either failure in the extension reaction or hybridisation owing to mismatches between PCR product and extension primer.; Our study demonstrates the feasibility of hybridisation-based genotyping of drug resistance mutations of HIV, even though our microarray, which was designed for population studies, achieved only correct assignment of 92% of all SNPs in the tested samples

Model Order Determination and Segmentation of Analog-Digital Converters Integral Non Linearity

Analog-digital converter (ADC) integral nonlinearity (INL) modeling is investigated. The model is comprised of two entities: a low code frequency (LCF) component modeled by an L-order polynomial, and a static high code frequency component (HCF), modeled by P linear disjoint segments centered around zero. Both model components are functions of the ADC output code k. A methodical way of estimating the LCF polynomial order L and the set of segments (number of and their borders), is suggested. The method computes the polynomial order L and the set of segments (number and borders) that minimizes the root mean square (RMS) distance between the INL data and its model. The method is applied to measured INL sequences of a 12-bit Analog Devices pipeline ADC (AD9430).© 2010 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works.QC 2011111

Demographic and clinical characteristics of the study population (n = 95).

<p>*Tertiary institutions includes Technical/Vocational and University.</p><p>**Baseline CD4 T-cell count prior to ART initiation.</p><p>***Patients on ART ≥6 months on ART and having >1000 RNA copies/mL.</p><p>Demographic and clinical characteristics of the study population (n = 95).</p

Barriers to life time adherence to ART (n = 47).

<p>* Participants were allowed to cite more than one reason for missing doses.</p><p># Includes, I vomit when I take medicine, I don’t feel well with medicine, medicines are hard to swallow, medicine reminds me of my HIV status and I was taking medicines for other illness.</p><p>Barriers to life time adherence to ART (n = 47).</p

Participants’ responses to ways of avoiding HIV transmission (n = 95).

<p>*Participants were allowed to provide multiple responses</p><p>Participants’ responses to ways of avoiding HIV transmission (n = 95).</p