scholarly journals Getting more from heterogeneous HIV-1 surveillance data in a high immigration country: estimation of incidence and undiagnosed population size using multiple biomarkers

2019 ◽  
Vol 48 (6) ◽  
pp. 1795-1803 ◽  
Author(s):  
Federica Giardina ◽  
Ethan O Romero-Severson ◽  
Maria Axelsson ◽  
Veronica Svedhem ◽  
Thomas Leitner ◽  
...  
Keyword(s):  
Dynamic Modelling ◽  
Direct Calculation ◽  
Hiv Infections ◽  
Credible Interval ◽  
Absolute Error ◽  
Surveillance Data ◽  
People Living With Hiv ◽  
Foreign Born ◽  
Multiple Biomarkers ◽  
Hiv 1

Abstract Background Most HIV infections originate from individuals who are undiagnosed and unaware of their infection. Estimation of this quantity from surveillance data is hard because there is incomplete knowledge about (i) the time between infection and diagnosis (TI) for the general population, and (ii) the time between immigration and diagnosis for foreign-born persons. Methods We developed a new statistical method for estimating the incidence of HIV-1 and the number of undiagnosed people living with HIV (PLHIV), based on dynamic modelling of heterogeneous HIV-1 surveillance data. The methods consist of a Bayesian non-linear mixed effects model using multiple biomarkers to estimate TI of HIV-1-positive individuals, and a novel incidence estimator which distinguishes between endogenous and exogenous infections by modelling explicitly the probability that a foreign-born person was infected either before or after immigration. The incidence estimator allows for direct calculation of the number of undiagnosed persons. The new methodology is illustrated combining heterogeneous surveillance data from Sweden between 2003 and 2015. Results A leave-one-out cross-validation study showed that the multiple-biomarker model was more accurate than single biomarkers (mean absolute error 1.01 vs ≥1.95). We estimate that 816 [95% credible interval (CI) 775-865] PLHIV were undiagnosed in 2015, representing a proportion of 10.8% (95% CI 10.3-11.4%) of all PLHIV. Conclusions The proposed methodology will enhance the utility of standard surveillance data streams and will be useful to monitor progress towards and compliance with the 90–90-90 UNAIDS target.

scholarly journals Getting more from heterogeneous HIV-1 surveillance data in a high immigration country: estimation of incidence and undiagnosed population size using multiple biomarkers

2018 ◽  
Author(s):  
Federica Giardina ◽  
Ethan Romero-Severson ◽  
Maria Axelsson ◽  
Veronica Svedhem ◽  
Thomas Leitner ◽  
...  
Keyword(s):  
Direct Calculation ◽  
Absolute Error ◽  
Surveillance Data ◽  
People Living With Hiv ◽  
List Type ◽  
Foreign Born ◽  
Persons Living With Hiv ◽  
Multiple Biomarkers ◽  
Living With Hiv ◽  
Hiv 1

AbstractBackgroundMost HIV infections originate from individuals who are undiagnosed and unaware of their infection. Estimation of this quantity from surveillance data is hard because there is incomplete knowledge about i) the time between infection and diagnosis (TI) for the general population and ii) the time between immigration and diagnosis for foreign-born persons.DevelopmentWe developed a new statistical method for estimating the number of undiagnosed people living with HIV (PLHIV) and the incidence of HIV-1 based on dynamic modeling of heterogenous HIV-1 surveillance data. We formulated a Bayesian non-linear mixed effects model using multiple biomarkers to estimate TI accounting for biomarker correlation and individual heterogeneities. We explicitly model the probability that an HIV-1 infected foreign-born person was infected either before or after immigration to distinguish between endogenous and exogeneous incidence. The incidence estimator allows for direct calculation of the number of undiagnosed persons.ApplicationThe model was applied to surveillance data in Sweden. The dynamic biomarker model was trained on longitudinal data from 31 treatment-naïve patients with well-defined TI, using CD4 counts, BED serology, polymorphisms in HIV-1 pol sequences, and testing history. The multiple-biomarker model was more accurate than single biomarkers (mean absolute error 1.01 vs ≥ 1.95). We estimate that 813 (95% CI 780-862) PLHIV were undiagnosed in 2015, representing a proportion of 10.8% (95% CI 10.4-11.3%) of all PLHIV.ConclusionsThe proposed methodology will enhance the utility of standard surveillance data streams and will be useful to monitor progress towards and compliance with the 90-90-90 UNAIDS target.Key messagesCombined heterogeneous HIV-1 surveillance data and biomarker data can be used to estimate both local incidence and the number of undiagnosed people living with HIV.Explicit modeling of the dynamics, heterogeneity, and correlation of multiple biomarkers over time improved estimation of time between infection and diagnosis.Explicit modeling of the probability that foreign-born persons were infected before or after immigration improves accuracy of estimates of endogenous incidence and undiagnosed persons living with HIV.The endogenous incidence of HIV-1 in Sweden is declining, despite continued immigration of HIV-1 infected persons.The proportion of undiagnosed PLHIV decreased over 2010-2015 and was estimated to be 10.8% (95% CI, 10.4-11.3%) in 2015.

scholarly journals HIV-1 Drug Resistance Genotyping in Resource Limited Settings: Current and Future Perspectives in Sequencing Technologies

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1125
Author(s):  
Sontaga Manyana ◽  
Lilishia Gounder ◽  
Melendhran Pillay ◽  
Justen Manasa ◽  
Kogieleum Naidoo ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Sanger Sequencing ◽  
Clinical Diagnostics ◽  
Treatment Programs ◽  
People Living With Hiv ◽  
Resource Limited Settings ◽  
Gold Standard Method ◽  
Sequencing Technologies ◽  
Resource Limited ◽  
Hiv 1

Affordable, sensitive, and scalable technologies are needed for monitoring antiretroviral treatment (ART) success with the goal of eradicating HIV-1 infection. This review discusses use of Sanger sequencing and next generation sequencing (NGS) methods for HIV-1 drug resistance (HIVDR) genotyping, focusing on their use in resource limited settings (RLS). Sanger sequencing remains the gold-standard method for detecting HIVDR mutations of clinical relevance but is mainly limited by high sequencing costs and low-throughput. NGS is becoming a more common sequencing method, with the ability to detect low-abundance drug-resistant variants and reduce per sample costs through sample pooling and massive parallel sequencing. However, use of NGS in RLS is mainly limited by infrastructure costs. Given these shortcomings, our review discusses sequencing technologies for HIVDR genotyping, focusing on common in-house and commercial assays, challenges with Sanger sequencing in keeping up with changes in HIV-1 treatment programs, as well as challenges with NGS that limit its implementation in RLS and in clinical diagnostics. We further discuss knowledge gaps and offer recommendations on how to overcome existing barriers for implementing HIVDR genotyping in RLS, to make informed clinical decisions that improve quality of life for people living with HIV.

scholarly journals Consequences of COVID-19 crisis for persons with HIV: the impact of social determinants of health

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kristie C. Waterfield ◽  
Gulzar H. Shah ◽  
Gina D. Etheredge ◽  
Osaremhen Ikhile
Keyword(s):  
Public Health ◽  
Health Care ◽  
Clinical Care ◽  
Hiv Infections ◽  
People Living With Hiv ◽  
Negative Consequences ◽  
Persons Who Inject Drugs ◽  
Persons Living With Hiv ◽  
Living With Hiv ◽  
The Impact

Abstract Background With the indiscriminate spread of COVID-19 globally, many populations are experiencing negative consequences such as job loss, food insecurity, and inability to manage existing medical conditions and maintain preventive measures such as social distancing and personal preventative equipment. Some of the most disadvantaged in the COVID-19 era are people living with HIV/AIDS and other autoimmune diseases. Discussion As the number of new HIV infections decrease globally, many subpopulations remain at high risk of infection due to lack of or limited access to prevention services, as well as clinical care and treatment. For persons living with HIV or at higher risk of contracting HIV, including persons who inject drugs or men that have sex with men, the risk of COVID-19 infection increases if they have certain comorbidities, are older than 60 years of age, and are homeless, orphaned, or vulnerable children. The risk of COVID-19 is also more significant for those that live in Low- and Middle-Income Countries, rural, and/or poverty-stricken areas. An additional concern for those living the HIV is the double stigma that may arise if they also test positive for COVID-19. As public health and health care workers try to tackle the needs of the populations that they serve, they are beginning to realize the need for a change in the infrastructure that will include more efficient partnerships between public health, health care, and HIV programs. Conclusion Persons living with HIV that also have other underlying comorbidities are a great disadvantage from the negative consequences of COVID-19. For those that may test positive for both HIV and COVID-19, the increased psychosocial burdens stemming from stress and isolation, as well as, experiencing additional barriers that inhibit access to care, may cause them to become more disenfranchised. Thus, it becomes very important during the current pandemic for these challenges and barriers to be addressed so that these persons living with HIV can maintain continuity of care, as well as, their social and mental support systems.

scholarly journals HIV-1 subverts the complement system in semen to enhance viral transmission

2021 ◽  
Author(s):  
Bernadien M. Nijmeijer ◽  
Marta Bermejo-Jambrina ◽  
Tanja M. Kaptein ◽  
Carla M. S. Ribeiro ◽  
Doris Wilflingseder ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Virus Transmission ◽  
Sexual Contact ◽  
Target Cells ◽  
People Living With Hiv ◽  
Lectin Receptor ◽  
Pre Treatment ◽  
Living With Hiv ◽  
Hiv 1

AbstractSemen is important in determining HIV-1 susceptibility but it is unclear how it affects virus transmission during sexual contact. Mucosal Langerhans cells (LCs) are the first immune cells to encounter HIV-1 during sexual contact and have a barrier function as LCs are restrictive to HIV-1. As semen from people living with HIV-1 contains complement-opsonized HIV-1, we investigated the effect of complement on HIV-1 dissemination by human LCs in vitro and ex vivo. Notably, pre-treatment of HIV-1 with semen enhanced LC infection compared to untreated HIV-1 in the ex vivo explant model. Infection of LCs and transmission to target cells by opsonized HIV-1 was efficiently inhibited by blocking complement receptors CR3 and CR4. Complement opsonization of HIV-1 enhanced uptake, fusion, and integration by LCs leading to an increased transmission of HIV-1 to target cells. However, in the absence of both CR3 and CR4, C-type lectin receptor langerin was able to restrict infection of complement-opsonized HIV-1. These data suggest that complement enhances HIV-1 infection of LCs by binding CR3 and CR4, thereby bypassing langerin and changing the restrictive nature of LCs into virus-disseminating cells. Targeting complement factors might be effective in preventing HIV-1 transmission.

scholarly journals Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil

2021 ◽  
Vol 22 (10) ◽  
pp. 5304
Author(s):  
Ana Santos-Pereira ◽  
Vera Triunfante ◽  
Pedro M. M. Araújo ◽  
Joana Martins ◽  
Helena Soares ◽  
...  
Keyword(s):  
Drug Resistance ◽  
People Living With Hiv ◽  
Resistance Mutations ◽  
Subtype C ◽  
Viral Loads ◽  
Drug Resistance Mutations ◽  
Subtype B ◽  
Low Prevalence ◽  
Living With Hiv ◽  
Hiv 1

The success of antiretroviral treatment (ART) is threatened by the emergence of drug resistance mutations (DRM). Since Brazil presents the largest number of people living with HIV (PLWH) in South America we aimed at understanding the dynamics of DRM in this country. We analyzed a total of 20,226 HIV-1 sequences collected from PLWH undergoing ART between 2008–2017. Results show a mild decline of DRM over the years but an increase of the K65R reverse transcriptase mutation from 2.23% to 12.11%. This increase gradually occurred following alterations in the ART regimens replacing zidovudine (AZT) with tenofovir (TDF). PLWH harboring the K65R had significantly higher viral loads than those without this mutation (p < 0.001). Among the two most prevalent HIV-1 subtypes (B and C) there was a significant (p < 0.001) association of K65R with subtype C (11.26%) when compared with subtype B (9.27%). Nonetheless, evidence for K65R transmission in Brazil was found both for C and B subtypes. Additionally, artificial neural network-based immunoinformatic predictions suggest that K65R could enhance viral recognition by HLA-B27 that has relatively low prevalence in the Brazilian population. Overall, the results suggest that tenofovir-based regimens need to be carefully monitored particularly in settings with subtype C and specific HLA profiles.

scholarly journals Surface Plasmon Resonance Assay for Label-Free and Selective Detection of HIV-1 p24 Protein

Biosensors ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 180
Author(s):  
Lucia Sarcina ◽  
Giuseppe Felice Mangiatordi ◽  
Fabrizio Torricelli ◽  
Paolo Bollella ◽  
Zahra Gounani ◽  
...  
Keyword(s):  
Limit Of Detection ◽  
Covalent Binding ◽  
Hiv Infections ◽  
Selectivity Ratio ◽  
Selective Detection ◽  
Label Free ◽  
Self Assembled Monolayer ◽  
Label Free Detection ◽  
P24 Protein ◽  
Hiv 1

The early detection of the human immunodeficiency virus (HIV) is of paramount importance to achieve efficient therapeutic treatment and limit the disease spreading. In this perspective, the assessment of biosensing assay for the HIV-1 p24 capsid protein plays a pivotal role in the timely and selective detection of HIV infections. In this study, multi-parameter-SPR has been used to develop a reliable and label-free detection method for HIV-1 p24 protein. Remarkably, both physical and chemical immobilization of mouse monoclonal antibodies against HIV-1 p24 on the SPR gold detecting surface have been characterized for the first time. The two immobilization techniques returned a capturing antibody surface coverage as high as (7.5 ± 0.3) × 1011 molecule/cm2 and (2.4 ± 0.6) × 1011 molecule/cm2, respectively. However, the covalent binding of the capturing antibodies through a mixed self-assembled monolayer (SAM) of alkanethiols led to a doubling of the p24 binding signal. Moreover, from the modeling of the dose-response curve, an equilibrium dissociation constant KD of 5.30 × 10−9 M was computed for the assay performed on the SAM modified surface compared to a much larger KD of 7.46 × 10−5 M extracted for the physisorbed antibodies. The chemically modified system was also characterized in terms of sensitivity and selectivity, reaching a limit of detection of (4.1 ± 0.5) nM and an unprecedented selectivity ratio of 0.02.

scholarly journals Performance of Bio-Rad and Limiting Antigen Avidity Assays in Detecting Recent HIV Infections Using the Quebec Primary HIV-1 Infection Cohort

PLoS ONE ◽  
2016 ◽  
Vol 11 (5) ◽  
pp. e0156023 ◽  
Author(s):  
Bouchra Serhir ◽  
Denis Hamel ◽  
Florence Doualla-Bell ◽  
Jean Pierre Routy ◽  
Sylvie-Nancy Beaulac ◽  
...  
Keyword(s):  
Hiv Infections ◽  
Hiv 1

Lower SARS-CoV-2-Specific Humoral Immunity in People Living With HIV-1 Recovered From Symptomatic Non-Hospitalized COVID-19

2022 ◽  
Author(s):  
Daniel J. Schuster ◽  
Shelly T. Karuna ◽  
Caroline Brackett ◽  
Martina Wesley ◽  
Shuying S. Li ◽  
...  
Keyword(s):  
Humoral Immunity ◽  
People Living With Hiv ◽  
Living With Hiv ◽  
Hiv 1

scholarly journals Direct Calculation of Thermodynamic Wet-Bulb Temperature as a Function of Pressure and Elevation

2013 ◽  
Vol 30 (8) ◽  
pp. 1757-1765 ◽  
Author(s):  
Sayed-Hossein Sadeghi ◽  
Troy R. Peters ◽  
Douglas R. Cobos ◽  
Henry W. Loescher ◽  
Colin S. Campbell
Keyword(s):  
Air Temperature ◽  
Mean Absolute Error ◽  
Direct Calculation ◽  
Ambient Air ◽  
Absolute Error ◽  
Mean Square ◽  
Air Temperatures ◽  
Order Polynomial ◽  
The Mean ◽  
Very High

Abstract A simple analytical method was developed for directly calculating the thermodynamic wet-bulb temperature from air temperature and the vapor pressure (or relative humidity) at elevations up to 4500 m above MSL was developed. This methodology was based on the fact that the wet-bulb temperature can be closely approximated by a second-order polynomial in both the positive and negative ranges in ambient air temperature. The method in this study builds upon this understanding and provides results for the negative range of air temperatures (−17° to 0°C), so that the maximum observed error in this area is equal to or smaller than −0.17°C. For temperatures ≥0°C, wet-bulb temperature accuracy was ±0.65°C, and larger errors corresponded to very high temperatures (Ta ≥ 39°C) and/or very high or low relative humidities (5% &lt; RH &lt; 10% or RH &gt; 98%). The mean absolute error and the root-mean-square error were 0.15° and 0.2°C, respectively.

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