Long-Term Antiretroviral Treatment Adherence in HIV-Infected Adolescents and Adults in Uganda: A Qualitative Study

Background Long-term success of HIV antiretroviral therapy requires near-perfect adherence, maintained throughout one’s lifetime. However, perceptions towards ART and patterns of adherence may change during the life course. We assessed challenges to long-term adherence in adolescents and adults in three regional HIV treatment centers in Uganda. Methods We conducted 24 in-depth interviews and 2 focus group discussions with a total of 33 health-care providers and expert clients (HIV patients on long-term ART who assist with adherence support of fellow patients). Interview topics included experiences with patients on long-term treatment with either declining adherence or persistent poor adherence. Transcribed texts were coded and analyzed based on the social-ecological framework highlighting differences and commonalities between adolescents and adults. Results The overarching themes in adolescents were unstructured treatment holidays, delays in disclosure of HIV status by caretakers, stigma, which was mainly experienced in boarding schools, and diminishing or lack of clinical support. In particular, there was minimal support for early and gradual disclosure for caretakers to the infected children, diminishing clinical support for young adults during transition to adult-based care and declining peer-to-peer support group activities. The predominating theme in adults was challenges with treatment access among temporary economic migrants. Common themes to adults and adolescents were challenges with disclosure in intimate relationships, treatment related factors including side effects, supply of single tablets in place of fixed-dose combined drugs, supply of drug brands with unfavorable taste and missed opportunities for counseling due to shortage of staff. Conclusion Adherence counseling and support should be adapted differently for adolescents and adults and to the emerging life course challenges in long-term treated patients. Programs should also address constraints experienced by temporary economic migrants to ensure continuity of treatment within the host country

Improved mycobacterial protein production using a Mycobacterium smegmatis groEL1ΔC expression strain

<p>Abstract</p> <p>Background</p> <p>The non-pathogenic bacterium <it>Mycobacterium smegmatis </it>is widely used as a near-native expression host for the purification of <it>Mycobacterium tuberculosis </it>proteins. Unfortunately, the Hsp60 chaperone GroEL1, which is relatively highly expressed, is often co-purified with polyhistidine-tagged recombinant proteins as a major contaminant when using this expression system. This is likely due to a histidine-rich C-terminus in GroEL1.</p> <p>Results</p> <p>In order to improve purification efficiency and yield of polyhistidine-tagged mycobacterial target proteins, we created a mutant version of GroEL1 by removing the coding sequence for the histidine-rich C-terminus, termed GroEL1ΔC. GroEL1ΔC, which is a functional protein, is no longer able to bind nickel affinity beads. Using a selection of challenging test proteins, we show that GroEL1ΔC is no longer present in protein samples purified from the <it>groEL1ΔC </it>expression strain and demonstrate the feasibility and advantages of purifying and characterising proteins produced using this strain.</p> <p>Conclusions</p> <p>This novel <it>Mycobacterium smegmatis </it>expression strain allows efficient expression and purification of mycobacterial proteins while concomitantly removing the troublesome contaminant GroEL1 and consequently increasing the speed and efficiency of protein purification.</p

Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI 2 SD above the median). Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining https://researchonline.ljmu.ac.uk/images/research_banner_face_lab_290.jpgunderweight or thinness. Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesity

Diminishing benefits of urban living for children and adolescents’ growth and development

AbstractOptimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was &lt;1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.</jats:p

Curbing the rise of HIV drug resistance in low-income and middle-income countries: the role of dolutegravir-containing regimens

To improve virological suppression and address the emerging threat of HIV drug resistance, many low-income and middle-income countries are moving away from non-nucleoside reverse transcriptase inhibitors (NNRTI) and transitioning to dolutegravir as part of a more affordable and standardised antiretroviral therapy (ART). Although this transition could decrease the effect of rising NNRTI resistance and yield improved ART outcomes, it also presents new challenges. First, current safety concerns for dolutegravir use in women of childbearing potential require alternative solutions. Second, pre-existing resistance to the co-administered nucleoside reverse transcriptase inhibitors might reduce effectiveness and durability of dolutegravir, particularly if there is scarce access to viral load tests to monitor treatment outcomes. Third, there is inadequate information on the genetic correlates of resistance to dolutegravir, particularly in patients infected with HIV-1 non-B subtypes. Finally, clinical management of patients with confirmed virological failure on a dolutegravir-based regimen can pose challenges because of uncertainty around whether dolutegravir resistance has actually developed and switching is needed, or whether only interventions to improve adherence without switching are sufficient. These considerations should be addressed to consolidate expected gains from widespread introduction of dolutegravir in low-income and middle-income countries

The evolving landscape of HIV drug resistance diagnostics for expanding testing in resource-limited settings

Global scale-up of antiretroviral treatment (ART) has dramatically changed the prospects of HIV/AIDS disease rendering life-long chronic care and treatment a reality for millions of HIV-infected patients. Affordable technologies to monitor ART are needed to ensure long-term durability of limited available drug regimens. HIV drug resistance tests can complement existing strategies in optimizing clinical decision-making for patients with treatment failure, in addition to facilitating population-based surveillance of HIV drug resistance. This review assesses the current landscape of HIV drug resistance technologies and discuss the strengths and limitations of existing assays available for expanding testing in resource limited settings (RLS). These include sequencing-based assays (Sanger sequencing assays and next-generation sequencing), point mutation assays and genotype-free data-based prediction systems. The Sanger assays are currently considered gold standard genotyping technology, though available at a limited number of RLS reference and regional laboratories, but high capital and test cost have limited their wide expansion. The point mutation assays present opportunities for simplified laboratory assays, but HIV genetic variability, extensive codon redundancy at or near the mutation target sites with limited multiplexing capability have restricted their utility. Next-generation sequencing (despite high cost) may have potential to reduce the testing cost significantly through multiplexing in high-throughput facilities, although the level of bioinformatics expertise required for data analysis is currently still complex and expensive and lacks standardization. Web-based genotype-free prediction systems may provide enhanced ART decision-making without the need for laboratory testing, but require further clinical field evaluation and implementation science research in resource-limited settings

Primary resistance to integrase strand transfer inhibitors in patients infected with diverse HIV-1 subtypes in sub-Saharan Africa

Objectives To investigate the prevalence and patterns of major and accessory resistance mutations associated with integrase strand transfer inhibitors (INSTIs), across diverse HIV-1 subtypes in sub-Saharan Africa. Methods pol gene sequences were obtained using Illumina next-generation sequencing from 425 INSTI-naive HIV-infected adults from Kenya (21.2%), Nigeria (7.3%), South Africa (22.8%), Uganda (25.2%) and Zambia (23.5%). Drug resistance interpretation was based on the IAS 2017 mutation list and accessory mutations from Stanford HIVdb with resistance penalty scores of ≥10 to at least 1 INSTI. Resistance was further classified based on sensitivity thresholds of ≥20% (Sanger sequencing) and 1%–20% for low-frequency variants (next-generation sequencing). Results Of 425 genotypes, 48.7% were subtype C, 28.5% A, 10.1% D, 2.8% G and 9.9% were recombinants. Major INSTI resistance mutations were detected only at <20% threshold, at a prevalence of 2.4% (2.5% in subtype A, 2.4% C, 0% D, 8.3% G and 2.4% in recombinants) and included T66A/I (0.7%), E92G (0.5%), Y143C/S (0.7%), S147G (0.2%) and Q148R (0.5%). Accessory mutations occurred at a prevalence of 15.1% at the ≥20% threshold (23.1% in subtype A, 8.7% C, 11.6% D, 25% G and 23.8% in recombinants), and included L74I/M (10.4%), Q95K (0.5%), T97A (4%), E157Q (0.7%) and G163R/K (0.7%). Conclusions Major INSTI resistance mutations were rare and only occurred at low-level resistance detection thresholds. INSTI-based regimens are expected to be effective across the different major HIV-1 subtypes in the region

Systematic review of the performance and clinical utility of point of care HIV-1 RNA testing for diagnosis and care

Background Point of-care (POC) HIV-1 RNA tests which are accurate and easy to use with limited infrastructure are needed in resource-limited settings (RLS). We systematically reviewed evidence of POC test performance compared to laboratory-based HIV-1 RNA assays and the potential utility of these tests for diagnosis and care in RLS. Methods Studies published up to July 2018 were identified by a search of PUBMED, EMBASE, Web of Science, CINAHL and Cochrane Central Register of Controlled Trials. Studies evaluating the use of POC HIV-1 RNA testing for early infant diagnosis (EID), acute HIV infection (AHI) diagnosis, or viral load monitoring (VL), compared to centralized testing, were included. Separate search strategies were used for each testing objective. Results 197 abstracts were screened and 34 full-text articles were assessed, of which 32 met inclusion criteria. Thirty studies evaluated performance and diagnostic accuracy of POC tests compared to standard reference tests. Two of the thirty and two additional studies with no comparative testing reported on clinical utility of POC results. Five different POC tests (Cepheid GeneXpert HIV-1 Quantitative and Qualitative assays, Alere q HIV‐1/2 Detect, SAMBA, Liat HIV Quant and Aptima HIV‐1 Quant) were used in 21 studies of VL, 11 of EID and 2 of AHI. POC tests were easy to use, had rapid turnaround times, and comparable accuracy and precision to reference technologies. Sensitivity and specificity were high for EID and AHI but lower for VL. For VL, lower sensitivity was reported for whole blood and dried blood spots compared to plasma samples. Reported error rates for Cepheid GeneXpert Qual (2.0%-5.0%), GeneXpert Quant (2.5%-17.0%) and Alere q HIV‐1/2 Detect (3.1%-11.0%) were higher than in WHO prequalification reports. Most errors resolved with retesting; however, inadequate sample volumes often precluded repeat testing. Only two studies used POC results for clinical management, one for EID and another for VL. POC EID resulted in shorter time-to-result, rapid ART initiation, and better retention in care compared to centralised testing. Conclusions Performance of POC HIV-1 RNA tests is comparable to reference assays, and have potential to improve patient outcomes. Additional studies on implementation in limited-resources settings are needed