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 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.

Comparison of Clinical Outcomes of Persons Living With HIV by Enrollment Status in Washington, DC: Evaluation of a Large Longitudinal HIV Cohort Study (Preprint)

2019 ◽  
Author(s):  
Jenevieve Opoku ◽  
Rupali K Doshi ◽  
Amanda D Castel ◽  
Ian Sorensen ◽  
Michael Horberg ◽  
...  
Keyword(s):  
Cohort Study ◽  
Health Outcomes ◽  
Odds Ratio ◽  
Adjusted Odds Ratio ◽  
Hiv Care ◽  
Disease Stage ◽  
People Living With Hiv ◽  
Hiv Disease ◽  
Persons Living With Hiv ◽  
Living With Hiv

BACKGROUND HIV cohort studies have been used to assess health outcomes and inform the care and treatment of people living with HIV disease. However, there may be similarities and differences between cohort participants and the general population from which they are drawn. OBJECTIVE The objective of this analysis was to compare people living with HIV who have and have not been enrolled in the DC Cohort study and assess whether participants are a representative citywide sample of people living with HIV in the District of Columbia (DC). METHODS Data from the DC Health (DCDOH) HIV surveillance system and the DC Cohort study were matched to identify people living with HIV who were DC residents and had consented for the study by the end of 2016. Analysis was performed to identify differences between DC Cohort and noncohort participants by demographics and comorbid conditions. HIV disease stage, receipt of care, and viral suppression were evaluated. Adjusted logistic regression assessed correlates of health outcomes between the two groups. RESULTS There were 12,964 known people living with HIV in DC at the end of 2016, of which 40.1% were DC Cohort participants. Compared with nonparticipants, participants were less likely to be male (68.0% vs 74.9%, <i>P</i>&lt;.001) but more likely to be black (82.3% vs 69.5%, <i>P</i>&lt;.001) and have a heterosexual contact HIV transmission risk (30.3% vs 25.9%, <i>P</i>&lt;.001). DC Cohort participants were also more likely to have ever been diagnosed with stage 3 HIV disease (59.6% vs 47.0%, <i>P</i>&lt;.001), have a CD4 &lt;200 cells/µL in 2017 (6.2% vs 4.6%, <i>P</i>&lt;.001), be retained in any HIV care in 2017 (72.9% vs 59.4%, <i>P</i>&lt;.001), and be virally suppressed in 2017. After adjusting for demographics, DC Cohort participants were significantly more likely to have received care in 2017 (adjusted odds ratio 1.8, 95% CI 1.70-2.00) and to have ever been virally suppressed (adjusted odds ratio 1.3, 95% CI 1.20-1.40). CONCLUSIONS These data have important implications when assessing the representativeness of patients enrolled in clinic-based cohorts compared with the DC-area general HIV population. As participants continue to enroll in the DC Cohort study, ongoing assessment of representativeness will be required.

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.

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 834. Characterization of Heavily Treatment Experienced HIV-1 Infected Clinical Trial Participants Infected with SARS-CoV-2 COVID 19: Fostemsavir BRIGHTE Phase 3 Clinical Trial

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S509-S509
Author(s):  
Shiven Chabria ◽  
Stephane De Wit ◽  
Amy Pierce ◽  
Bronagh M Shepherd ◽  
Michael Warwick-Sanders ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Supplemental Oxygen ◽  
Multidrug Resistant ◽  
Cd4 Count ◽  
People Living With Hiv ◽  
Research Support ◽  
Increased Risk ◽  
Living With Hiv ◽  
Hiv 1

Abstract Background BRIGHTE is an ongoing global study evaluating the gp120 attachment inhibitor fostemsavir (FTR) in heavily treatment-experienced (HTE) adults with multidrug resistant (MDR) HIV-1 unable to form a viable antiretroviral (ARV) regimen. An estimated 2 million people living with HIV-1 have been infected with SARS-CoV-2. Those with HIV viremia and/or low CD4+ counts are at increased risk of serious adverse outcome. We describe the reported COVID cases in a clinical trial population of people living with MDR HIV and immune suppression. Methods At the start of the COVID pandemic, all ongoing BRIGHTE subjects had achieved ≥ 192 weeks on FTR and optimized background ARVs; results through Week 96 were presented previously. Investigators used WHO guidelines for COVID diagnosis and reported exposure, testing results and symptom presence. Figure 1. BRIGHTE Study Design Results 371 subjects [272 Randomized Cohort (RC), 99 Non-Randomized Cohort (NC)] were enrolled; 44% were ≥ 50 years of age and 86% had an AIDS history. Median CD4+ count at study start of was 80 cells/mm3 (IQR 11–202); 30% with ≤ 20 cells/mm3. 250 subjects remained in BRIGHTE at pandemic start. By April 2021, 17 subjects (14 RC, 3 NC) had confirmed COVID infection (positive PCR test). Severity was Grade 1-3, all cases resolved with no deaths. Six subjects were hospitalized (Table 1); most recent CD4+ count prior to COVID were 293-1641 cells/mm3 and 5/6 subjects were virologically suppressed. Treatments often included prophylactic anticoagulants and supplemental oxygen; no cART changes were made. The remaining 11/17 confirmed cases were managed outpatient. Five more subjects had suspect COVID not confirmed by PCR and 2 subjects had negative PCR tests. Table 1. Characterization of Participants with Serious AEs of Confirmed COVID-19 Infections – All Hospitalizations Conclusion A total of 22/250 COVID-19 cases (17 confirmed, 5 unconfirmed) have been reported in BRIGHTE. Outcomes were reassuring with no deaths or known persistent sequelae, despite having advanced HIV and comorbid diseases at baseline associated with poorer COVID outcomes. Outcomes may have benefitted from immunologic improvement during the trial. Disclosures Shiven Chabria, MD, Viiv Healthcare (Employee) Stephane De Wit, MD, Gilead (Grant/Research Support)Janssen (Grant/Research Support)Merck Sharpe & Dohme (Grant/Research Support)ViiV Healthcare (Grant/Research Support) Amy Pierce, BS, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Bronagh M. Shepherd, PhD, GlaxoSmithKline (Employee, Shareholder) Michael Warwick-Sanders, BM BSc DPM MFPM, GSK (Employee) Marcia Wang, PhD, GlaxoSmithKline (Employee, Shareholder) Andrew Clark, MD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Peter Ackerman, MD, GSK/ViiV Healthcare (Employee, Shareholder)

scholarly journals Improving Adherence to Anti-retroviral Therapy among Persons Living with HIV/AIDS in Enugu State, South East Nigeria

2019 ◽  
pp. 1-9
Author(s):  
C. P. Igweagu ◽  
O. H. Chime ◽  
C. N. Onwasigwe
Keyword(s):  
Health Education ◽  
Poor Adherence ◽  
Public Health Issue ◽  
People Living With Hiv ◽  
Study Group ◽  
Control Groups ◽  
Persons Living With Hiv ◽  
Enugu State ◽  
Living With Hiv ◽  
Hiv Aids

HIV/AIDS continues to be a major global public health issue, having claimed more than 32 million lives so far. There were approximately 37.9 million people living with HIV/AIDS (PLHIV) at the end of 2018. Anti-retroviral therapy (ART) has significantly reduced morbidity and mortality and improved quality of life among people with HIV infection. Aims: The study was conducted to improve the knowledge and adherence to anti-retroviral therapy among PLHIV in Enugu state, southeast Nigeria. Study Design: Interventional study. Place and Duration of Study: Anti-retroviral Therapy clinics within Enugu metropolis in Enugu state Nigeria between June to December 2018. Methodology: A health education intervention was carried out among 312 PLHIV receiving ART in Enugu metropolis to improve their perception and adherence to antiretroviral therapy. A structured questionnaire was used to collect data from 312 PLHIV (156 each in the study and control groups), who were selected by multistage sampling. Subsequently, health education was conducted among the study group. Three months after this intervention its effects were assessed through a survey using the same structured questionnaires employed in the baseline survey.  Results: The most frequently occurring reason given by the respondents for poor adherence to ART was forgetfulness (65.4% for study and 69.9% for control groups). Knowledge of the factors and consequences of poor adherence to treatment was significantly higher among the study group than the controls post-interventions p<0.001. Adherence to ART improved from 42.3% pre-intervention to 81.4% post-intervention. Conclusion: Intensive health education effectively improved adherence to ART among persons living with HIV/AIDS and this should be carried out regularly.

scholarly journals Guidelines for Diagnosing and Managing Disseminated Histoplasmosis among People Living with HIV

2020 ◽  
Keyword(s):  
Health Care Providers ◽  
Guideline Development ◽  
Critical Evaluation ◽  
World Health ◽  
People Living With Hiv ◽  
Care Providers ◽  
Advisory Boards ◽  
Disseminated Histoplasmosis ◽  
Persons Living With Hiv ◽  
Living With Hiv

Histoplasmosis is a disease caused by the fungus Histoplasma capsulatum. This disease is highly endemic in some regions of North America, Central America, and South America and is also reported in certain countries of Asia and Africa. It often affects people with impaired immunity, including people living with HIV, among whom the most frequent clinical presentation is disseminated histoplasmosis. The symptoms of disseminated histoplasmosis are non-specific and may be indistinguishable from those of other infectious diseases, especially disseminated tuberculosis (TB), thus complicating diagnosis and treatment. Histoplasmosis is one of the most frequent opportunistic infections caused by fungal pathogens among people living with HIV in the Americas and may be responsible for 5–15% of AIDS-related deaths every year in this Region. These guidelines aim to provide recommendations for the diagnosis, treatment, and management of disseminated histoplasmosis in persons living with HIV. Although the burden of disease is concentrated in the Americas, the recommendations presented within these guidelines are applicable globally. These guidelines were produced in accordance with the World Health Organization (WHO) handbook for guideline development. The Guideline Development Group elaborated the final recommendations based on a systematic review of scientific literature and critical evaluation of the evidence available using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. These guidelines are intended for health-care providers, HIV program managers, policy-makers, national treatment advisory boards, researchers, and other professionals involved in caring for people who either have or may be at risk of developing disseminated histoplasmosis.

scholarly journals Comorbidities associated with HPV and HSV infections among people living with HIV-1 in the Southeastern US: a retrospective clinical cohort study

2019 ◽  
Author(s):  
Yuanfan Ye ◽  
Greer A. Burkholder ◽  
Howard W. Wiener ◽  
Russell Griffin ◽  
Stella Aslibekyan ◽  
...  
Keyword(s):  
Large Scale ◽  
White Women ◽  
Incidence Rates ◽  
People Living With Hiv ◽  
Anogenital Warts ◽  
Gender And Race ◽  
Clinical Cohort ◽  
Southeastern Us ◽  
Living With Hiv ◽  
Hiv 1

Abstract Background The southeastern US is a domestic epicenter for incident HIV with high prevalence of human papillomavirus (HPV) and herpes simplex virus (HSV) co-infections. However, epidemics of HPV and HSV- associated clinical conditions (CC) among people living with HIV-1 infection (PLWH) are not fully known. Methods Electronic medical records (EMR) of PLWH attending one of the leading HIV clinics in the southeastern US between 2006 and 2018 were reviewed and analyzed. The retrospective study was nested within the University of Alabama at Birmingham HIV clinical cohort, which has electronically collected over 7000 PLWH’s clinical and sociobehavioral data since 1999. Incidence rates of HPV-related CC including anogenital warts, penile, anal, cervical, and vaginal/vulvar low- and high-grade squamous intraepithelial lesions (LSIL and HSIL) and HSV- related CC including anogenital herpetic ulcers were estimated in per 10000 person years. Joinpoint regressions were performed to examine temporal changes in the trends of incident CC. All rates and trends were stratified by gender and race. Results Of the 4,484 PLWH eligible individuals (3,429 men, 1,031 women, and 24 transgender), we observed 1,038 and 425 patients with HPV-and HSV-related CC respectively, and 163 patients with both conditions. The mean log10 viral load (VL) was higher in all of the case groups than the non-cases with neither conditions (5.0) (whereas the median nadir CD4 counts (cells/uL) was higher in the non-cases than in any of the case groups (P<0.05). Anogenital warts, anal LSIL, HSIL, and cancer were more likely to be diagnosed among HIV-infected men than women. White men presented more frequently with anal LSIL and anal and penile cancers than black men (P<0.03). White women were also more likely to be diagnosed with cervical HSIL (P=0.023) and cancer (P=0.037) than black women By contrast, herpetic ulcers were more frequent in women than men. Conclusions There were significant differences between gender and race with incidence of HPV- and HSV-related CC among HIV patients. EMR-based studies provide insights on understudied epidemics; however, large-scale studies in other regions are needed to generalize current findings and draw public health attention to co-infection induced non-AIDS defining comorbidities among PLWH.

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