scholarly journals A Comprehensive Genomics Solution for HIV Surveillance and Clinical Monitoring in Low-Income Settings

2020 ◽  
Vol 58 (10) ◽  
Author(s):  
David Bonsall ◽  
Tanya Golubchik ◽  
Mariateresa de Cesare ◽  
Mohammed Limbada ◽  
Barry Kosloff ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Viral Load ◽  
Low Income ◽  
Cost Effective ◽  
Clinical Monitoring ◽  
Resistance Mutations ◽  
Middle Income ◽  
Cd4 Cell Count ◽  
Genetic Sequencing ◽  
Hiv Surveillance

ABSTRACT Viral genetic sequencing can be used to monitor the spread of HIV drug resistance, identify appropriate antiretroviral regimes, and characterize transmission dynamics. Despite decreasing costs, next-generation sequencing (NGS) is still prohibitively costly for routine use in generalized HIV epidemics in low- and middle-income countries. Here, we present veSEQ-HIV, a high-throughput, cost-effective NGS sequencing method and computational pipeline tailored specifically to HIV, which can be performed using leftover blood drawn for routine CD4 cell count testing. This method overcomes several major technical challenges that have prevented HIV sequencing from being used routinely in public health efforts; it is fast, robust, and cost-efficient, and generates full genomic sequences of diverse strains of HIV without bias. The complete veSEQ-HIV pipeline provides viral load estimates and quantitative summaries of drug resistance mutations; it also exploits information on within-host viral diversity to construct directed transmission networks. We evaluated the method’s performance using 1,620 plasma samples collected from individuals attending 10 large urban clinics in Zambia as part of the HPTN 071-2 study (PopART Phylogenetics). Whole HIV genomes were recovered from 91% of samples with a viral load of >1,000 copies/ml. The cost of the assay (30 GBP per sample) compares favorably with existing VL and HIV genotyping tests, proving an affordable option for combining HIV clinical monitoring with molecular epidemiology and drug resistance surveillance in low-income settings.

scholarly journals Use of Dried Plasma Spots for HIV-1 Viral Load Determination and Drug Resistance Genotyping in Mexican Patients

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Juan Pablo Rodriguez-Auad ◽  
Othon Rojas-Montes ◽  
Angelica Maldonado-Rodriguez ◽  
Ma. Teresa Alvarez-Muñoz ◽  
Onofre Muñoz ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Viral Load ◽  
Attractive Alternative ◽  
Plasma Samples ◽  
Resistance Mutations ◽  
Resource Limited Settings ◽  
Middle Income ◽  
Subtype B ◽  
Resource Limited ◽  
Hiv 1

Monitoring antiretroviral therapy using measurements of viral load (VL) and the genotyping of resistance mutations is not routinely performed in low- to middle-income countries because of the high costs of the commercial assays that are used. The analysis of dried plasma spot (DPS) samples on filter paper may represent an alternative for resource-limited settings. Therefore, we evaluated the usefulness of analyzing DPS samples to determine VL and identify drug resistance mutations (DRM) in a group of HIV-1 patients. The VL was measured from 22 paired plasma and DPS samples. In these samples, the average VL was 4.7 log10copies/mL in liquid plasma and 4.1 log10copies/mL in DPS, with a correlation coefficient ofR= 0.83. A 1.1 kb fragment of HIVpolcould be amplified in 14/22 (63.6%) of the DPS samples and the same value was amplified in plasma samples. A collection of ten paired DPS and liquid plasma samples was evaluated for the presence of DRM; an excellent correlation was found in the identification of DRM between the paired samples. All HIV-1polsequences that were obtained corresponded to HIV subtype B. The analysis of DPS samples offers an attractive alternative for monitoring ARV therapy in resource-limited settings.

scholarly journals A comprehensive genomics solution for HIV surveillance and clinical monitoring in a global health setting

2018 ◽  
Author(s):  
David Bonsall ◽  
Tanya Golubchik ◽  
Mariateresa de Cesare ◽  
Mohammed Limbada ◽  
Barry Kosloff ◽  
...  
Keyword(s):  
Public Health ◽  
Drug Resistance ◽  
Viral Load ◽  
High Throughput ◽  
Genetic Sequencing ◽  
Hiv Surveillance ◽  
Viral Loads ◽  
True Variant ◽  
Technical Challenges ◽  
Additional Value

AbstractHigh-throughput viral genetic sequencing is needed to monitor the spread of drug resistance, direct optimal antiretroviral regimes, and to identify transmission dynamics in generalised HIV epidemics. Public health efforts to sequence HIV genomes at scale face three major technical challenges: (i) minimising assay cost and protocol complexity, (ii) maximising sensitivity, and (iii) recovering accurate and unbiased sequences of both the genome consensus and the within-host viral diversity. Here we present a novel, high-throughput, virus-enriched sequencing method and computational pipeline tailored specifically to HIV (veSEQ-HIV), which addresses all three technical challenges, and can be used directly on leftover blood drawn for routine CD4 testing. We demonstrate its performance on 1,620 plasma samples collected from consenting individuals attending 10 large urban clinics in Zambia, partners of HPTN 071 (PopART). We show that veSEQ-HIV consistently recovers complete HIV genomes from the majority of samples of different subtypes, and is also quantitative: the number of HIV reads per sample obtained by veSEQ-HIV estimates viral load without the need for additional testing. Both quantitativity and sensitivity were assessed on a subset of 126 samples with clinically measured viral loads, and with standardized quantification controls (VL 100 – 5,000,000 RNA copies/ml). Complete HIV genomes were recovered from 93% (85/91) of samples when viral load was over 1,000 copies per ml. The quantitative nature of the assay implies that variant frequencies estimated with veSEQ-HIV are representative of true variant frequencies in the sample. Detection of minority variants can be exploited for epidemiological analysis of transmission and drug resistance, and we show how the information contained in individual reads of a veSEQ-HIV sample can be used to detect linkage between multiple mutations associated with resistance to antiretroviral therapy. Less than 2% of reads obtained by veSEQ-HIV were identified as in silico contamination events using updates to the phyloscanner software (phyloscanner clean) that we show to be 95% sensitive and 99% specific at ‘decontaminating’ NGS data. The cost of the assay — approximately 45 USD per sample — compares favourably with existing VL and HIV genotyping tests, and provides the additional value of viral load quantification and inference of drug resistance with a single test. veSEQ-HIV is well suited to large public health efforts and is being applied to all ∼9000 samples collected for the HPTN 071-2 (PopART Phylogenetics) study.

scholarly journals HIV drug resistance: problems and perspectives

2013 ◽  
Vol 5 (1S) ◽  
pp. 5 ◽  
Author(s):  
Pleuni S. Pennings
Keyword(s):  
Drug Resistance ◽  
Low Income ◽  
Low Frequency ◽  
Low Income Countries ◽  
Resistance Mutations ◽  
Middle Income ◽  
Acquired Drug Resistance ◽  
Infected People ◽  
Middle Income Countries ◽  
Exposure Prophylaxis

Access to combination antiretroviral treatment (ART) has improved greatly over recent years. At the end of 2011, more than eight million HIV-infected people were receiving ART in low-income and middle-income countries. ART generally works well in keeping the virus suppressed and the patient healthy. However, treatment only works as long as the virus is not resistant against the drugs used. In the last decades, HIV treatments have become better and better at slowing down the evolution of drug resistance, so that some patients are treated for many years without having any resistance problems. However, for some patients, especially in low-income countries, drug resistance is still a serious threat to their health. This essay will review what is known about transmitted and acquired drug resistance, multi-class drug resistance, resistance to newer drugs, resistance due to treatment for the prevention of mother-to-child transmission, the role of minority variants (low-frequency drug-resistance mutations), and resistance due to pre-exposure prophylaxis.

Impact of genotypic diversity on selection of subtype-specific drug resistance profiles during raltegravir-based therapy in individuals infected with B and BF recombinant HIV-1 strains

2020 ◽  
Vol 75 (6) ◽  
pp. 1567-1574
Author(s):  
Daniela Sánchez ◽  
Solange Arazi Caillaud ◽  
Ines Zapiola ◽  
Silvina Fernandez Giuliano ◽  
Rosa Bologna ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Current Knowledge ◽  
Phylogenetic Analyses ◽  
Genotypic Diversity ◽  
Resistance Testing ◽  
Cross Resistance ◽  
Resistance Mutations ◽  
Middle Income ◽  
Subtype B ◽  
Hiv 1

Abstract Background Current knowledge on HIV-1 resistance to integrase inhibitors (INIs) is based mostly on subtype B strains. This contrasts with the increasing use of INIs in low- and middle-income countries, where non-B subtypes predominate. Materials and methods HIV-1 drug resistance genotyping was performed in 30 HIV-1-infected individuals undergoing virological failure to raltegravir. Drug resistance mutations (DRMs) and HIV-1 subtype were characterized using Stanford HIVdb and phylogenetic analyses. Results Of the 30 integrase (IN) sequences, 14 were characterized as subtype F (47%), 8 as subtype B (27%), 7 as BF recombinants (23%) and 1 as a putative CRF05_DF (3%). In 25 cases (83%), protease and reverse transcriptase (PR-RT) sequences from the same individuals confirmed the presence of different BF recombinants. Stanford HIVdb genotyping was concordant with phylogenetic inference in 70% of IN and 60% of PR-RT sequences. INI DRMs differed between B and F IN subtypes, with Q148K/R/H, G140S and E138K/A being more prevalent in subtype B (63% versus 0%, P = 0.0021; 50% versus 0%, P = 0.0096; and 50% versus 0%, P = 0.0096, respectively). These differences were independent of the time on raltegravir therapy or viral load at the time of genotyping. INI DRMs in subtype F IN genomes predicted a lower level of resistance to raltegravir and no cross-resistance to second-generation INIs. Conclusions Alternative resistance pathways to raltegravir develop in subtypes B and F IN genomes, with implications for clinical practice. Evaluating the role of HIV-1 subtype in development and persistence of mutations that confer resistance to INIs will be important to improve algorithms for resistance testing and optimize the use of INIs.

HIV drug resistance in low-income and middle-income countries

2018 ◽  
Vol 5 (10) ◽  
pp. e588-e596 ◽  
Author(s):  
Raph L Hamers ◽  
Tobias F Rinke de Wit ◽  
Charles B Holmes
Keyword(s):  
Drug Resistance ◽  
Low Income ◽  
Middle Income ◽  
Hiv Drug Resistance ◽  
Middle Income Countries

scholarly journals Immunisation financing and programme performance in the Middle East and North Africa, 2010 to 2017

2019 ◽  
Vol 4 (2) ◽  
pp. e001248
Author(s):  
Helen Saxenian ◽  
Nahad Sadr-Azodi ◽  
Miloud Kaddar ◽  
Kamel Senouci
Keyword(s):  
Economic Growth ◽  
Middle East ◽  
North Africa ◽  
Low Income ◽  
Health Sector ◽  
Cost Effective ◽  
Middle Income ◽  
Middle Income Countries ◽  
Life Saving ◽  
Fiscal Space

Immunisation is a cornerstone to primary health care and is an exceptionally good value. The 14 low-income and middle-income countries in the Middle East and North Africa region make up 88% of the region’s population and 92% of its births. Many of these countries have maintained high immunisation coverage even during periods of low or negative economic growth. However, coverage has sharply deteriorated in countries directly impacted by conflict and political unrest. Approximately 1.3 million children were not completely vaccinated in 2017, as measured by third dose of diphtheria–pertussis–tetanus vaccine. Most of the countries have been slow to adopt the newer, more expensive life-saving vaccines mainly because of financial constraints and the socioeconomic context. Apart from the three countries that have had long-standing assistance from Gavi, the Vaccine Alliance, most countries have not benefited appreciably from donor and partner activities in supporting their health sector and in achieving their national and subnational immunisation targets. Looking forward, development partners will have an important role in helping reconstruct health systems in conflict-affected countries. They can also help with generating evidence and strategic advocacy for high-priority and cost-effective services, including immunisation. Governments and ministries of health would ensure important benefits to their populations by investing further in their immunisation programmes. Where possible, the health system can create and expand fiscal space from efficiency gains in harmonising vaccine procurement mechanisms and service integration; broader revenue generation from economic growth; and reallocation of government budgets to health, and from within health, to immunization.

scholarly journals Antiparasitic phytotherapy perspectives, scope and current development

Infectio ◽  
2019 ◽  
Vol 23 (2) ◽  
pp. 189 ◽  
Author(s):  
Jhon Carlos Castaño Osorio ◽  
Alejandra María Giraldo García
Keyword(s):  
Low Income ◽  
Public Health Problem ◽  
Cost Effective ◽  
Prolonged Treatment ◽  
Major Public Health Problem ◽  
Middle Income ◽  
Middle Income Countries ◽  
Commercial Markets ◽  
Health And Economic Development ◽  
New Treatments

Tropical protozoan diseases are currently a major public health problem throughout the world and are strongly linked with poverty, this combined with a lack of commercial markets for potential drugs has created a large burden on the health and economic development of low-income and middle-income countries in Africa, Asia, and the Americas. Due to the low research interest and the high increase of resistance against the existing treatments, as well as increasing inefficiency, toxicity, prolonged treatment schedules and costs, there is an urgent need for cost-effective, safe and easy-to-administer, new effective compounds with novel mechanisms of action. Several studies of crude plant extracts have already identified potential compounds to treat Chagas’ disease, Leishmaniasis, Toxoplasmosis, Giardiasis, and Malaria among other protozoan parasites. Natural compounds of medicinal plants have shown lower toxicity together with higher specificity, creating an optimistic view of new treatments for diseases. Out of 1010 new active substances approved as drugs for medical conditions by regulatory agencies during the past 25 years, 490(48.5%) were from a natural origin.

scholarly journals Assessing the value of human papillomavirus vaccination in Gavi-eligible low-income and middle-income countries

2020 ◽  
Vol 5 (10) ◽  
pp. e003006
Author(s):  
Jessica Ochalek ◽  
Kaja Abbas ◽  
Karl Claxton ◽  
Mark Jit ◽  
James Lomas
Keyword(s):  
Human Papillomavirus ◽  
Low Income ◽  
Hpv Vaccination ◽  
Cost Effective ◽  
Health Impact ◽  
Healthcare Intervention ◽  
Human Papillomavirus Vaccination ◽  
Middle Income ◽  
Maximum Price ◽  
Healthcare Interventions

IntroductionEstimating the value of providing effective healthcare interventions in a country requires an assessment of whether the improvement in health outcomes they offer exceeds the improvement in health that would have been possible if the resources required had, instead, been made available for other healthcare activities in that country. This potential alternative use of the same resources represents the health opportunity cost of providing the intervention. Without such assessments, there is a danger that blanket recommendations made by international organisations will lead to the adoption of healthcare interventions that are not cost effective in some countries, even given existing donor mechanisms intended to support their affordability.MethodsWe assessed the net health impact to 46 Gavi-eligible countries of achieving one of the WHO’s proposed 90-70-90 targets for cervical cancer elimination, which includes 90% coverage of human papillomavirus (HPV) vaccination among girls by 15 years of age, using published estimates of the expected additional benefits and costs in each country and estimates of the marginal productivity of each healthcare system. We calculated the maximum price each country could afford to pay for HPV vaccination to be cost effective by assessing the net health impact that would be expected to be generated at different potential prices.ResultsAt Gavi negotiated prices, HPV vaccination offers net health benefits across most Gavi-eligible countries included in this study. However, if Gavi-eligible countries faced the average price faced by non-Gavi eligible countries, providing HPV vaccination would result in reduced overall population health in most countries.ConclusionEstimates of the net health impact of providing a healthcare intervention can be used to assess the benefit (or lack of) to countries of adhering to global guidance, inform negotiations with donors, as well as pricing negotiations and the value of developing new healthcare interventions.

scholarly journals Estimating health opportunity costs in low-income and middle-income countries: a novel approach and evidence from cross-country data

2018 ◽  
Vol 3 (6) ◽  
pp. e000964 ◽  
Author(s):  
Jessica Ochalek ◽  
James Lomas ◽  
Karl Claxton
Keyword(s):  
Health Outcomes ◽  
Low Income ◽  
Health Expenditure ◽  
Cost Effective ◽  
Opportunity Costs ◽  
Donor Funding ◽  
Middle Income ◽  
Novel Approach ◽  
Healthcare Interventions ◽  
Country Specific

The economic evaluation of healthcare interventions requires an assessment of whether the improvement in health outcomes they offer exceeds the improvement in health that would have been possible if the additional resources required had, instead, been made available for other healthcare activities. Therefore, some assessment of these health opportunity costs is required if the best use is to be made of the resources available for healthcare. This paper provides a framework for generating country-specific estimates of cost per disability-adjusted life year (DALY) averted ‘thresholds’ that reflect health opportunity costs. We apply estimated elasticities on mortality, survival, morbidity and a generic measure of health, DALYs, that take account of measures of a country’s infrastructure and changes in donor funding to country-specific data on health expenditure, epidemiology and demographics to determine the likely DALYs averted from a 1% change in expenditure on health. The resulting range of cost per DALY averted ‘threshold’ estimates for each country that represent likely health opportunity costs tend to fall below the range previously suggested by WHO of 1–3× gross domestic product (GDP) per capita. The 1–3× GDP range and many other previous and existing recommendations about which interventions are cost-effective are not based on an empirical assessment of the likely health opportunity costs, and as a consequence, the health effects of changes in health expenditure have tended to be underestimated, and there is a risk that interventions regarded as cost-effective reduce rather than improve health outcomes overall.

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