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

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.

SUBMITTER: Bonsall D

PROVIDER: S-EPMC7512176 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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

Bonsall David D Golubchik Tanya T de Cesare Mariateresa M Limbada Mohammed M Kosloff Barry B MacIntyre-Cockett George G Hall Matthew M Wymant Chris C Ansari M Azim MA Abeler-Dörner Lucie L Schaap Ab A Brown Anthony A Barnes Eleanor E Piwowar-Manning Estelle E Eshleman Susan S Wilson Ethan E Emel Lynda L Hayes Richard R Fidler Sarah S Ayles Helen H Bowden Rory R Fraser Christophe C

Journal of clinical microbiology 20200922 10

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 perform ...[more]

PMID: 32669382

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Project description:IntroductionNearly 40 years into the HIV epidemic, the persistence of HIV stigma is a matter of grave urgency. Discrimination (i.e. enacted stigma) in healthcare settings is particularly problematic as it deprives people of critical healthcare services while also discouraging preventive care seeking by confirming fears of anticipated stigma. We review existing research on the effectiveness of stigma interventions in healthcare settings of low- and middle-income countries (LMIC), where stigma control efforts are often further complicated by heavy HIV burdens, less developed healthcare systems, and the layering of HIV stigma with discrimination towards other marginalized identities. This review describes progress in this field to date and identifies research gaps to guide future directions for research.MethodsWe conducted a scoping review of HIV reduction interventions in LMIC healthcare settings using Embase, Ovid MEDLINE, PsycINFO and Scopus (through March 5, 2020). Information regarding study design, stigma measurement techniques, intervention features and study findings were extracted. We also assessed methodological rigor using the Joanna Briggs Institute checklist for systematic reviews.Results and discussionOur search identified 8766 studies, of which 19 were included in the final analysis. All but one study reported reductions in stigma following the intervention. The studies demonstrated broad regional distribution across LMIC and many employed designs that made use of a control condition. However, these strengths masked key shortcomings including a dearth of research from the lowest income category of LMIC and a lack of interventions to address institutional or structural determinants of stigma. Lastly, despite the fact that most stigma measures were based on existing instruments, only three studies described steps taken to validate or adapt the stigma measures to local settings.ConclusionsCombating healthcare stigma in LMIC demands interventions that can simultaneously address resource constraints, high HIV burden and more severe stigma. Our findings suggest that this will require more objective, reliable and culturally adaptable stigma measures to facilitate meaningful programme evaluation and comparison across studies. All but one study concluded that their interventions were effective in reducing healthcare stigma. Though encouraging, the fact that most studies measured impact using self-reported measures suggests that social desirability may bias results upwards. Homogeneity of study results also hindered our ability to draw substantive conclusions about potential best practices to guide the design of future stigma reduction programmes.

Project description:Commercially available HIV-1 drug resistance (HIVDR) genotyping assays are expensive and have limitations in detecting non-B subtypes and circulating recombinant forms that are co-circulating in resource-limited settings (RLS). This study aimed to optimize a low cost and broadly sensitive in-house assay in detecting HIVDR mutations in the protease (PR) and reverse transcriptase (RT) regions of pol gene. The overall plasma genotyping sensitivity was 95.8% (N?=?96). Compared to the original in-house assay and two commercially available genotyping systems, TRUGENE® and ViroSeq®, the optimized in-house assay showed a nucleotide sequence concordance of 99.3%, 99.6% and 99.1%, respectively. The optimized in-house assay was more sensitive in detecting mixture bases than the original in-house (N?=?87, P<0.001) and TRUGENE® and ViroSeq® assays. When the optimized in-house assay was applied to genotype samples collected for HIVDR surveys (N?=?230), all 72 (100%) plasma and 69 (95.8%) of the matched dried blood spots (DBS) in the Vietnam transmitted HIVDR survey were genotyped and nucleotide sequence concordance was 98.8%; Testing of treatment-experienced patient plasmas with viral load (VL) ? and <3 log10 copies/ml from the Nigeria and Malawi surveys yielded 100% (N?=?46) and 78.6% (N?=?14) genotyping rates, respectively. Furthermore, all 18 matched DBS stored at room temperature from the Nigeria survey were genotyped. Phylogenetic analysis of the 236 sequences revealed that 43.6% were CRF01_AE, 25.9% subtype C, 13.1% CRF02_AG, 5.1% subtype G, 4.2% subtype B, 2.5% subtype A, 2.1% each subtype F and unclassifiable, 0.4% each CRF06_CPX, CRF07_BC and CRF09_CPX.The optimized in-house assay is broadly sensitive in genotyping HIV-1 group M viral strains and more sensitive than the original in-house, TRUGENE® and ViroSeq® in detecting mixed viral populations. The broad sensitivity and substantial reagent cost saving make this assay more accessible for RLS where HIVDR surveillance is recommended to minimize the development and transmission of HIVDR.

Project description:IntroductionAs prevalence of undiagnosed HIV declines, it is unclear whether testing programmes will be cost-effective. To guide their HIV testing programmes, countries require appropriate metrics that can be measured. The cost-per-diagnosis is potentially a useful metric.MethodsWe simulated a series of setting-scenarios for adult HIV epidemics and ART programmes typical of settings in southern Africa using an individual-based model and projected forward from 2018 under two policies: (i) a minimum package of "core" testing (i.e. testing in pregnant women, for diagnosis of symptoms, in sex workers, and in men coming forward for circumcision) is conducted, and (ii) core-testing as above plus additional testing beyond this ("additional-testing"), for which we specify different rates of testing and various degrees to which those with HIV are more likely to test than those without HIV. We also considered a plausible range of unit test costs. The aim was to assess the relationship between cost-per-diagnosis and the incremental cost-effectiveness ratio (ICER) of the additional-testing policy. The discount rate used in the base case was 3% per annum (costs in 2018 U.S. dollars).ResultsThere was a strong graded relationship between the cost-per-diagnosis and the ICER. Overall, the ICER was below $500 per-DALY-averted (the cost-effectiveness threshold used in primary analysis) so long as the cost-per-diagnosis was below $315. This threshold cost-per-diagnosis was similar according to epidemic and programmatic features including the prevalence of undiagnosed HIV, the HIV incidence and a measure of HIV programme quality (the proportion of HIV diagnosed people having a viral load <1000 copies/mL). However, restricting to women, additional-testing did not appear cost-effective even at a cost-per-diagnosis of below $50, while restricting to men additional-testing was cost-effective up to a cost-per-diagnosis of $585. The threshold cost per diagnosis for testing in men to be cost-effective fell to $256 when the cost-effectiveness threshold was $300 instead of $500, and to $81 when considering a discount rate of 10% per annum.ConclusionsFor testing programmes in low-income settings in southern African there is an extremely strong relationship between the cost-per-diagnosis and the cost-per-DALY averted, indicating that the cost-per-diagnosis can be used to monitor the cost-effectiveness of testing programmes.

Project description:BackgroundWorld Health Organization (WHO)/Joint United Nations Programme on AIDS (UNAIDS) has recommended adult male circumcision (AMC) for the prevention of heterosexually acquired HIV infection in men from communities where HIV is hyperendemic and AMC prevalence is low. The objective of this study was to investigate the feasibility of the roll-out of medicalized AMC according to UNAIDS/WHO operational guidelines in a targeted African setting.Methods and findingsThe ANRS 12126 "Bophelo Pele" project was implemented in 2008 in the township of Orange Farm (South Africa). It became functional in 5 mo once local and ethical authorizations were obtained. Project activities involved community mobilization and outreach, as well as communication approaches aimed at both men and women incorporating broader HIV prevention strategies and promoting sexual health. Free medicalized AMC was offered to male residents aged 15 y and over at the project's main center, which had been designed for low-income settings. Through the establishment of an innovative surgical organization, up to 150 AMCs under local anesthesia, with sterilized circumcision disposable kits and electrocautery, could be performed per day by three task-sharing teams of one medical circumciser and five nurses. Community support for the project was high. As of November 2009, 14,011 men had been circumcised, averaging 740 per month in the past 12 mo, and 27.5% of project participants agreed to be tested for HIV. The rate of adverse events, none of which resulted in permanent damage or death, was 1.8%. Most of the men surveyed (92%) rated the services provided positively. An estimated 39.1% of adult uncircumcised male residents have undergone surgery and uptake is steadily increasing.ConclusionThis study demonstrates that a quality AMC roll-out adapted to African low-income settings is feasible and can be implemented quickly and safely according to international guidelines. The project can be a model for the scale-up of comprehensive AMC services, which could be tailored for other rural and urban communities of high HIV prevalence and low AMC rates in Eastern and Southern Africa. Please see later in the article for the Editors' Summary.

Dataset Information

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

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

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