Viral Load Status Research Articles

Comparison of Cycle Threshold and Clinical Status Among Different Age Groups of COVID-19 Cases.

IntroductionThe COVID-19 pandemic has shaken the entire world ever since its emergence in March 2020. The disease manifestation of COVID-19 has been more severe, with a high degree of mortality in the elderly than in the young population. The cycle threshold (Ct ) value obtained in the real-time polymerase chain reaction (RT-PCR) has been used as the surrogate marker of viral load. Therefore, assessing Ct value and clinical status among different age groups with SARS-CoV-2 infection is required to understand the viral kinetics and to assess the transmission potential of that particular age group.PurposeThe aim of this study was to compare the viral load and clinical status among different age groups with COVID-19 infection.Methods and materialsA retrospective cross-sectional study was carried out to analyze the Ct values of SARS-CoV-2 positive samples reported from April 2020 till May 2021. The results of 13,820 RT-PCR (reverse transcriptase-polymerase chain reaction) positive samples were included for analysis of Ct values. Ct values of confirmatory genes were taken into consideration, and Ct values below 25, >25 to 30, and >30 were categorized as high, moderate, and low viral load, respectively. Age group was stratified into ≤18 years (young), 18-60 years (adult), and >60 years (elderly). The data were analyzed using SPSS Windows Version 25.0.ResultsThe mean Ct values were 27.9, 26, and 26.2 in the young, adult, and elderly age groups, respectively. The mean Ct values of young patients were significantly higher as compared to adult and elderly patients (p<0.05). The percentage of high viral load (Ct<25) was found to be significantly higher in adults and elderly (44.6% & 43.7%) as compared to young (32.2%) (p<0.001). Majority of the COVID-19 positive cases younger than 18 years (75.9%) were asymptomatic as compared to 64.5% and 59.7% in the adult and elderly age groups, respectively.ConclusionThis study observed a significantly high proportion of viral load in the adult and elderly population, which plays a substantial contribution to SARS-CoV-2 transmission, whereas the majority of the young population being asymptomatic plays a major role as silent transmitters. The study reemphasizes the need for strict adherence to COVID-appropriate behaviors.

Risk of vertical transmission of chronic viral infections after invasive prenatal procedures.

Invasive prenatal procedures including amniocentesis, chorionic villus sampling (CVS) can be prenatally indicated for diagnostic purposes. Chronic viral infections with Human Immunodeficiency Virus (HIV), hepatitis C virus (HCV), hepatitis B virus (HBV) are not uncommon in women of reproductive age. The aim of this narrative literature review is to provide guidance on the best clinical practice in antenatal invasive testing and fetal surveillance in pregnancies with HIV, HCV, HBV and treponema pallidum infected women. A review of the literature was conducted in the database of PubMed to select full-length articles published in peer-reviewed journals between 1990 and 2020. The keywords along with respective combinations included in the search strategy were invasive testing, prenatal diagnosis, amniocentesis, chorionic villus sampling, cordocentesis, fetoscopy, chronic viral infections, hepatitis B, hepatitis C, HIV, treponema pallidum, syphilis, vertical transmission, MTCT. For patients with hepatitis B infection, it is important to assess the HBeAg status and HBV DNA levels and for those patients with high viral load, antiviral therapy (Tenofovir) for a few weeks may be needed to reduce the viral load prior to the invasive procedure. In women positive for HCV, the viral load and HIV status should be assessed to establish the risk of vertical transmission; while for patients with HIV, highly active antiretroviral therapy administration and low viral load are predictive for reduced vertical transmission even after performing an invasive procedure. In all cases invasive procedure should be replaced by non-invasive prenatal testing if this is a feasible alternative and when invasive testing is indeed required, transplacental passage should be avoided.

Antiretroviral drug switches to zidovudine-based regimens and loss to follow-up during the first COVID-19 lockdown in Bali, Indonesia.

ObjectivesInternational lockdowns during the COVID‐19 pandemic impacted antiretroviral drug supplies in Indonesia. We assessed the impact of antiretroviral treatment (ART) provision and being lost to follow‐up (LTFU) on people living with HIV, attending a key population‐focused HIV clinic in Denpasar, Bali.MethodsThis was a retrospective note review of anonymized data from adult Indonesian patients living with HIV. We collected demographic data and information on being LTFU, and assessed the numbers of patients impacted by ART switches from fixed‐dose combination (FDC) tenofovir/lamivudine/efavirenz to multi‐pill zidovudine‐based regimens, during the first international lockdown from March 2020.ResultsRecords of 260 Indonesian adult patients registered for HIV care and prescribed ART were reviewed; 240 (92.3%) were men, and 90% were men who have sex with men. Between 13 March and 28 May 2020, 214 (87%) out of 247 patients (previously diagnosed with HIV) had to switch to individual, multi‐pill zidovudine‐based regimens from their FDC. The switch lasted a mean of 35 days (range 10–85). Twenty‐five patients (10%) were LTFU; patients who switched were more likely to remain in care. Data on viral load status and toxicity are lacking as laboratory testing requires self‐payment.ConclusionsThe majority of patients living with HIV had no choice but to switch to multi‐pill, zidovudine‐based regimens.Despite significant efforts to minimize the impact of lockdown on care, 10% of patients were LTFU. Patients switching ART required greater clinic attention and support, improving retention.Complete national data are needed to understand the impact of ART stockouts on virological suppression and drug resistance throughout Indonesia.

Association of viral load with age, gender, disease severity, and death in severe acute respiratory syndrome coronavirus 2 variants.

In this study, the relationship between viral load, demographic characteristics, and disease information in 1007 (48.5%) patients with Delta variant (B.1.617.2), and 1070 (51.5%) patients with Alpha variant (B1.1.7) were investigated. We found that there was a significant difference in viral load between patients who died from the Alpha variant and those who were discharged (p < 0.05). Nevertheless, no significant difference was observed in patients with the Delta variant. The viral load in patients who died from the Alpha variant was significantly higher than those who were discharged (p < 0.05). The viral load was found to be higher in females in patients with the Delta variant, whereas it was very close in males and females in patients with the Alpha variant (p > 0.05). No significant difference was detected between the cycle threshold values (Ct) and disease severity. In terms of the mean Ct values, statistical differences were observed in patients with Delta and Alpha variants. The Alpha variant was found to have a higher viral load than the Delta variant. Furthermore, the Delta variant was found to be higher in the 40-year-old and under-age group than the Alpha variant, whereas the Alpha variant was higher in the groups over 40 years old. Althoughthe rate of moderate and severe patients in the Alpha variant was found to be higher, the rate of mild survivors was found to be higher in the Delta variant. In conclusion, the increase in vaccination before the appearance of the Delta variant in our region may have influenced the viral load and clinical status of the patients.

Comparison of Cycle Threshold and Clinical Status Among Different Age Groups of COVID-19 Cases

PurposeAim of the study was to compare the viral load and clinical status among different age groups with COVID-19 infectionMethods & MaterialsA retrospective cross-sectional study was carried out to analyse the Ct values of positive samples reported during April 2020 till May 2021. Result of 13,820 number of RT-PCR positive samples were included for analysis of Ct values. Ct values of confirmatory genes were taken into consideration and Ct values below 25, >25 to 30 and >30 was categorized as high, moderate and low viral load respectively. Age group was stratified into ≤18 years, 18-60 and >60 years as young, adult and elderly respectively. The data was analysed using SPSS windows version 25.0.ResultsThe Mean Ct value was 27.9, 26, and 26.2 in young, adult and elderly age group respectively. Mean Ct value of young patients were significantly higher as compared to adult and elderly patients (p<0.05). The percentage of high viral load (Ct<25) was found to be significantly higher in adults and elderly (44.6% & 43.7%) as compared to young (32.2%) (p<0.001). Majority of the covid 19 positive cases belonging to <18 years age (75.9%) were asymptomatic as compared to 64.5% and 59.7% in adult and elderly age groups respectively.ConclusionPresent study observed a significantly high proportion of viral load in the adult and elderly population which plays a substantial contribution to SARS CoV-2 transmission, whereas the majority of the young population being asymptomatic play major role as silent transmitters. The study reemphasizes the need for strict adherence to COVID appropriate behaviours.

Neuroendocrine Tumor in a Patient Living with Human Immunodeficiency Virus

Neuroendocrine tumors (NETs) are epithelial neoplasms with predominant neuroendocrine differentiation, potentially arising from anywhere along the alimentary tract. We report a case of NET in a patient living with human immunodeficiency virus (HIV) (PLWH). A 58-year-old gentleman presented to the emergency department with a 2-week history of dry cough, loose motions, and fatigue; he had unintended weight loss ongoing during the past 4 months. Examination is significant for hepatomegaly (20 cm). On evaluation, a diagnosis of both HIV/AIDS and metastatic NET of gastrointestinal origin was confirmed. The chronic antigenic stimulation, cytokine dysregulation, and inflammation observed in PLWH are believed to influence the development of variety of malignancy. Hence, a high index of suspicion for neoplasms in HIV/AIDS (PLWH) regardless of their viral load or immunosuppression status is necessity when presented with red flag malignancies, especially with the overlapping symptoms of AIDS and the constitutional symptoms of cancers.

Postvaccination infections among staff of a tertiary care hospital after vaccination with severe acute respiratory syndrome coronavirus 2 vector and mRNA-based vaccines

ObjectivesThe identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen or RNA in respiratory specimens ≥14 days after administration of all recommended doses of authorized coronavirus disease 2019 (COVID-19) vaccines is defined as breakthrough infection. In the present investigation, mRNA and vector-based SARS-CoV-2 vaccines were analysed with respect to postvaccination infections in vaccinated hospital employees. MethodsA total of 8553 staff members were vaccinated with BNT162b2 (47%) or ChAdOx1-S (53%) between January and May 2021. In a retrospective observational cohort study, incidence of SARS-CoV-2 postvaccination infections was analysed in relation to demographic data, viral load, virus variants, vaccine brand and vaccination status at time of positive PCR test (fully vaccinated: ≥14 days since second dose; partially vaccinated: >21 days since first, but <14 days after second dose; insufficiently vaccinated: <22 days since first dose). ResultsWithin the follow-up period, ending on 31 July 2021, person-time at risk-adjusted monthly rates for SARS-CoV-2 postvaccination infections were 0.18% (BNT162b2) and 0.57% (ChAdOx1-S) for insufficiently vaccinated, 0.34% (BNT162b2) and 0.32% (ChAdOx1-S) for partially vaccinated and 0.06% (BNT162b2) and 0.04% (ChAdOx1-S) for fully vaccinated participants. The two vaccine types did not differ with respect to hazard ratios for any of the respective postvaccination infection types. No cases of COVID-19-related hospitalizations or deaths were reported. Genotyping of positive PCR specimens revealed 42 variants of concern: B.1.1.7 (Alpha variant; n = 34); B.1.351 (Beta variant; n = 2), B.1.617.2 (Delta variant; n = 6). ConclusionsBNT162b2 and ChAdOx1-S are both effective in preventing breakthrough infections; however, it seems important, that all recommended vaccine doses are administered.

Viral Load Status Before Switching to Dolutegravir-Containing Antiretroviral Therapy and Associations With Human Immunodeficiency Virus Treatment Outcomes in Sub-Saharan Africa.

Dolutegravir is being rolled out globally as part of preferred antiretroviral therapy (ART) regimens, including among treatment-experienced patients. The role of viral load (VL) testing before switching patients already on ART to a dolutegravir-containing regimen is less clear in real-world settings. We included patients from the International epidemiology Databases to Evaluate AIDS consortium who switched from a nevirapine- or efavirenz-containing regimen to one with dolutegravir. We used multivariable cause-specific hazards regression to estimate the association of the most recent VL test in the 12 months before switching with subsequent outcomes. We included 36393 patients at 37 sites in 5 countries (Democratic Republic of the Congo, Kenya, Rwanda, Tanzania, Uganda) who switched to dolutegravir from July 2017 through February 2020, with a median follow-up of approximately 11 months. Compared with those who switched with a VL <200 copies/mL, patients without a recent VL test or with a preswitch VL ≥1000 copies/mL had significantly increased hazards of an incident VL ≥1000 copies/mL (adjusted hazard ratio [aHR], 2.89; 95% confidence interval [CI], 1.99-4.19 and aHR, 6.60; 95% CI, 4.36-9.99, respectively) and pulmonary tuberculosis or a World Health Organization clinical stage 4 event (aHR, 4.78; 95% CI, 2.77-8.24 and aHR, 13.97; 95% CI, 6.62-29.50, respectively). A VL test before switching to dolutegravir may help identify patients who need additional clinical monitoring and/or adherence support. Further surveillance of patients who switched to dolutegravir with an unknown or unsuppressed VL is needed.

905. Risk of Hepatitis B Reactivation in Patients Receiving Ibrutinib: The National VA Cohort

BackgroundIbrutinib, a bruton tyrosine kinase inhibitor was approved by Food and Drug Administration (FDA) in 2013 and became the first-line treatment for chronic lymphocytic leukemia in 2014. The risk Hepatitis B Virus (HBV) reactivation after initiation of ibrutinib is unclear. Here, we report the results of national Veterans Health Administration (VHA) pharmacy database review estimating the incidence of HBV reactivation after initiation of ibrutinib.MethodsVeterans who received ibrutinib between Feb 1, 2014 through October 31, 2019 were included in our study. Possible reactivations were identified by change of Hepatitis B Virus surface antigen (HBV sAg), HBV core antibody (Ab) or HBV viral load from no data or negative to positive after starting ibrutinib. Individual chart review was conducted to verify HBV reactivation due to ibrutinib. Cumulative incidence was calculated by identifying HBV reactivation cases among at risk patients, which was defined as prior exposure by positive HBV core Ab regardless of HBV sAg or HBV viral load status. For patients without any HBV serology, an estimated prevalence of HBV exposure in veterans from the literature is used. ResultsA total of 4130 veterans were on ibrutinib during the study period. Of 4130 patients, 1875 patients with HBV core Ab negative and 68 patients on antivirals against HBV prior to ibrutinib were excluded. Among the remaining 2187 patients, there were 170 patients with positive HBV core Ab and 2017 patients without HBV core Ab tested regardless of HBV sAg or HBV DNA status. We used the estimated 13.6% (95%CI 11.5-16.1) of HBV exposure in veterans and estimated that 274 (95%CI 232-325) out of 2017 patients would be at risk of HBV reactivation. Thirty-nine patients were identified to have HBV reactivation after ibrutinib. After detailed review, 7 HBV reactivations were attributable to initiation of ibrutinib. The cumulative incidence of HBV reactivation after ibrutinib was estimated as 1.5% (95% CI 1.4-1.7).ConclusionIn this large VHA study, we identified 7 cases of HBV reactivations among 444 at risk patients. The cumulative incidence of HBV reactivation after ibrutinib was 1.5% in patients with prior HBV exposure with positive HBV core Ab irrespective of HBV sAg or HBV DNA status, indicating a moderate risk of HBV reactivation.Disclosures All Authors: No reported disclosures

Effectiveness of tenofovir alafenamide for chronic hepatitis B patients with a poor response to the previously used nucleos(t)ide analogs.

Few studies have demonstrated the potency of tenofovir alafenamide (TAF) in patients with poor response to other nucleos(t)ide analogs (NAs). We conducted a retrospective study comprising consecutive 40 patients exhibiting a poor response to other NAs, who subsequently received TAF-containing regimens. The primary outcome was the prevalence of virological response (VR) at each time and maintained virological response (MVR) under TAF-containing regimens until week 96. In the entire cohort, the prevalence of MVR was 71.1% (27/38). Further, poor tenofovir disoproxil fumarate (TDF) response was significantly associated with a lower prevalence of MVR (p = 0.014). In TDF-naïve patients, the prevalence of MVR was 92.3% (12/13) and 62.5% (5/8) in patients with lamivudine resistance (LAM-r) and entecavir resistance (ETV-r), respectively. Further, viral load and HBeAg status at baseline were associated with a lower prevalence of MVR (p = 0.013). Among the seven patients with prior TDF exposure, 2 patients achieved MVR. Among them, one patient with development of viral breakthrough during TDF/LAM achieved MVR after switching to TAF/ETV. In contrast, one of the five patients with non-MVR had three substitutions (rtS106C, rtD134N/S, and rtL269I) of quadruple mutations in addition to ETV-r. Other patients with rtA181T + rtN236T also could not achieve MVR. TAF exhibited high antiviral potency in patients with LAM-r and ETV-r. However, TAF potency was associated with previous TDF response, viral load, and HBeAg status at baseline. Additionally, a quadruple mutation may impact tenofovir resistance; however, further studies are needed to verify this.

Virologic outcomes of people living with human immunodeficiency virus who started antiretroviral treatment on the same-day of diagnosis in Ethiopia: A multicenter observational study.

IntroductionThere have been tremendous achievements in scaling-up antiretroviral therapy (ART) for treatment of human immunodeficiency virus (HIV), following universal “test and treat” policy implementation in low- and middle-income countries. However, its effects on virologic outcomes is not yet well investigated. We compared low viral load status in people living with HIV between those who were initiated on ART on the same-day and after 7 days of being diagnosed with HIV infection.MethodsWe conducted a retrospective cohort study of persons age ≥15 years-old who were newly diagnosed and started on ART between October 2016 and July 2018 at 11 public health facilities in northwest Ethiopia. Exposure was initiation of ART on the same-day of HIV diagnosis. The outcome was low viral load at 12-months following ART initiation. We used double-robust estimator using inverse-probability-weighted regression adjustment to compare the groups.ResultsA total of 398 people who started ART on the same-day of HIV diagnosis and 479 people who started 7 days after the initial diagnosis were included in this study. By 12-months following ART initiation, 73.4% (292) in the same-day group vs 83.7% (401) in the >7 days group achieved low viral load (absolute difference = 10.3% (95% CI: 4.9%, 15.8%)). After adjusting for baseline and follow-up covariates, there was statistically significant difference in low viral load status (adjusted difference = 8.3% (95% CI: 3.5%, 13.0%)) between the same-day group and the >7 days group.ConclusionsAchievement of low viral load by 12-months post-initiation of ART was not optimal among participants who started ART on the same-day of HIV diagnosis. Efforts should be made to reinforce treatment adherence while initiating same-day ART.

HIV program outcomes for Jamaica before and after "Treat All": A population-based study using the national treatment services database.

ObjectiveThe study aims to assess changes in HIV treatment outcomes for Jamaica after the implementation of the WHO Treat All strategy in January 2017, as well as identify variables associated with clinical stage at diagnosis and viral load status, in order to understand implications for enhancing the HIV clinical cascade and boosting progress towards the UNAIDS 90-90-90 targets.MethodThis is a population-based study using the National Treatment Service Information System. The sample consists of persons 15 years and older, placed on treatment before and after Treat All was implemented, across all 4 regional health authorities in Jamaica. Patients were assessed for two binary outcomes: 1. stage at HIV diagnosis (early/baseline CD4 cell count ≧350 cells/mm3, or late/ baseline CD4 <350 cells/mm3), 2. viral load status achieved after ART initiation (suppressed/<1000 copies/ml or non-suppressed/ ≥1000 copies/ml). Categorical variables: age/years, gender and health regions, were investigated using multivariable logistic regression. Adjusted odds ratios and 95% confidence intervals are reported.ResultsAfter Treat All, there was an increase in median baseline CD4 results as the proportion of late diagnoses decreased from 60% to 39%. There was a small increase in viral suppression from 76% to 80%, a decrease in baseline viral load testing from 61% to 46% and an increase in the uptake of first viral load testing after starting treatment from 13% to 19%. Males and persons 40+ years had higher odds of late diagnosis before and after Treat All.ConclusionJamaica’s HIV program outcomes have improved after Treat All was implemented. ART initiation time significantly decreased. Early diagnosis, viral load testing uptake and viral suppression increased. However, there is a need to implement targeted testing for men and persons over 40 years to decrease the frequency of late diagnosis.

Maternally Derived Antibody Levels Influence on Vaccine Protection against PCV2d Challenge.

Simple SummaryThe efficacy of vaccination against type 2 porcine circoviruses is influenced by the level of maternally derived antibodies present at the time of vaccination of the piglets. This aspect was investigated by using two types of vaccines either comprised of a whole virus or its single protein. Both vaccines were able to overcome the impact of the maternal antibodies, however, the immunity, measured by serum antibody levels, developed faster for the whole virus type vaccine. The correlation between the maternally derived antibody levels at the time of vaccination and the challenge viral load showed differences amongst the tested lymph nodes. Additionally, it was confirmed also in this study that group oral fluid samples provide a reliable and relatively easy animal welfare-friendly way of estimating the PCV2 status of groups of pigs.Piglets from a porcine circovirus type 2 (PCV2) stable farm of low and high levels of maternally derived antibodies (MDA) against PCV2 were vaccinated either with a whole virus type or a PCV2 ORF2 antigen-based commercial subunit vaccine at three weeks of age. Two non-vaccinated groups served as low and high MDA positive controls. At four weeks post vaccination, all piglets were challenged with a PCV2d-2 type virus strain and were checked for parameters related to vaccine protection over a four-week observation period. MDA levels evidently impacted the outcome of the PCV2d-2 challenge in non-vaccinated animals, while it did not have a significant effect on vaccine-induced protection levels. The humoral immune response developed faster in the whole virus vaccinates than in the subunit vaccinated pigs in the low MDA groups. Further, high MDA levels elicited a stronger negative effect on the vaccine-induced humoral immune response for the subunit vaccine than for the whole virus vaccine. The group-based oral fluid samples and the group mean viraemia and faecal shedding data correlated well, enabling this simple, and animal welfare-friendly sampling method for the evaluation of the PCV2 viral load status of these nursery piglets.

IL-10 -1082 A/G (rs1800896) Polymorphism is Effective in Clearing Hepatitis B Virus Infection

Background: Hepatitis B Virus (HBV) is a universal health challenge all around the world. Several factors like viral load, genetic characteristics, age, sex, and immune status contribute to variable clinical outcomes of HBV infection. The sequels of HBV infection vary remarkably among persons ranging from the spontaneous deletion of infection to persistent infection. Objective: The present study aimed to evaluate the association of single nucleotide polymorphisms IL10-1082 with HBV clearance. Methods: Sixty subjects with Chronic Hepatitis B (CHB) infection and 60 subjects who spontaneously recovered HBV were enrolled in the study. The IL-10-1082 polymorphisms were determined by Polymerase Chain Reaction with Restriction Fragment Length Polymorphism (PCR–RFLP). Results: The clearance of HBV infection demonstrated a significant association with IL-10-1082 polymorphisms in the GG genotype (P = 0.03), while there was no association with other genotypes. Reduced risk of chronic hepatitis B infection was associated with IL-10-1082 GG (OR: 2.33, 95% CI: 1.07 - 5.09). Besides, IL-10-1082 A/G alleles did not differ clearly between the two study groups (P = 0.07) Conclusions: The IL-10-1082 polymorphisms may be associated with a reduced risk of CHB infection and recovery after HBV infection.

Blood transcriptional biomarkers of acute viral infection for detection of pre-symptomatic SARS-CoV-2 infection: a nested, case-control diagnostic accuracy study

SummaryBackgroundWe hypothesised that host-response biomarkers of viral infections might contribute to early identification of individuals infected with SARS-CoV-2, which is critical to breaking the chains of transmission. We aimed to evaluate the diagnostic accuracy of existing candidate whole-blood transcriptomic signatures for viral infection to predict positivity of nasopharyngeal SARS-CoV-2 PCR testing.MethodsWe did a nested case-control diagnostic accuracy study among a prospective cohort of health-care workers (aged ≥18 years) at St Bartholomew's Hospital (London, UK) undergoing weekly blood and nasopharyngeal swab sampling for whole-blood RNA sequencing and SARS-CoV-2 PCR testing, when fit to attend work. We identified candidate blood transcriptomic signatures for viral infection through a systematic literature search. We searched MEDLINE for articles published between database inception and Oct 12, 2020, using comprehensive MeSH and keyword terms for “viral infection”, “transcriptome”, “biomarker”, and “blood”. We reconstructed signature scores in blood RNA sequencing data and evaluated their diagnostic accuracy for contemporaneous SARS-CoV-2 infection, compared with the gold standard of SARS-CoV-2 PCR testing, by quantifying the area under the receiver operating characteristic curve (AUROC), sensitivities, and specificities at a standardised Z score of at least 2 based on the distribution of signature scores in test-negative controls. We used pairwise DeLong tests compared with the most discriminating signature to identify the subset of best performing biomarkers. We evaluated associations between signature expression, viral load (using PCR cycle thresholds), and symptom status visually and using Spearman rank correlation. The primary outcome was the AUROC for discriminating between samples from participants who tested negative throughout the study (test-negative controls) and samples from participants with PCR-confirmed SARS-CoV-2 infection (test-positive participants) during their first week of PCR positivity.FindingsWe identified 20 candidate blood transcriptomic signatures of viral infection from 18 studies and evaluated their accuracy among 169 blood RNA samples from 96 participants over 24 weeks. Participants were recruited between March 23 and March 31, 2020. 114 samples were from 41 participants with SARS-CoV-2 infection, and 55 samples were from 55 test-negative controls. The median age of participants was 36 years (IQR 27–47) and 69 (72%) of 96 were women. Signatures had little overlap of component genes, but were mostly correlated as components of type I interferon responses. A single blood transcript for IFI27 provided the highest accuracy for discriminating between test-negative controls and test-positive individuals at the time of their first positive SARS-CoV-2 PCR result, with AUROC of 0·95 (95% CI 0·91–0·99), sensitivity 0·84 (0·70–0·93), and specificity 0·95 (0·85–0·98) at a predefined threshold (Z score >2). The transcript performed equally well in individuals with and without symptoms. Three other candidate signatures (including two to 48 transcripts) had statistically equivalent discrimination to IFI27 (AUROCs 0·91–0·95).InterpretationOur findings support further urgent evaluation and development of blood IFI27 transcripts as a biomarker for early phase SARS-CoV-2 infection for screening individuals at high risk of infection, such as contacts of index cases, to facilitate early case isolation and early use of antiviral treatments as they emerge.FundingBarts Charity, Wellcome Trust, and National Institute of Health Research.

Long-term Trajectories of C-Reactive Protein Among Men Living With and Without HIV Infection in the Multicenter AIDS Cohort Study.

C-reactive protein (CRP) is an inflammatory biomarker associated with all-cause mortality and morbidities such as cardiovascular disease. CRP is increased with HIV infection and thought to increase with age, though trajectories of CRP with aging have not been well characterized. We investigated trajectories of CRP in men from the Multicenter AIDS Cohort Study, according to HIV infection and HIV viral load status. CRP measurements from 12 250 serum samples, provided by 2132 men over a span of 30 years, were categorized by HIV status at sample collection: HIV uninfected (HIV-, n = 1717), HIV infected with undetectable RNA (HIV+ suppressed, n = 4075), and detectable HIV RNA (HIV+ detectable, n = 6458). Age-related trajectories of CRP were fit to multivariable linear mixed models; we tested for differences in trajectories by HIV status. CRP increased with age in all sample groups. HIV+ detectable and HIV+ suppressed samples had higher CRP than HIV- samples throughout the observed age range of 20-70 years (p < .05). CRP concentrations at age 45 years were 38% (95% CI: 26%-50%) and 26% (15%-38%) higher in HIV+ detectable and HIV+ suppressed samples, respectively, relative to HIV- samples. HIV+ detectable samples showed more rapid linear increases with age (8% higher/decade, 0.3%-16%) than HIV- samples. We observed higher concentrations of CRP across 5 decades of age in men living with HIV, and steeper increases with age in men with detectable HIV RNA, relative to HIV- men. These results are consistent with a contribution of inflammation to the higher risk of age-related comorbidities with HIV infection.

Human Immunodeficiency Virus (HIV) Genetic Diversity Informs Stage of HIV-1 Infection Among Patients Receiving Antiretroviral Therapy in Botswana.

BackgroundHuman immunodeficiency virus (HIV)-1 genetic diversity increases during infection and can help infer the time elapsed since infection. However, the effect of antiretroviral treatment (ART) on the inference remains unknown.MethodsParticipants with estimated duration of HIV-1 infection based on repeated testing were sourced from cohorts in Botswana (n = 1944). Full-length HIV genome sequencing was performed from proviral deoxyribonucleic acid. We optimized a machine learning model to classify infections as < or >1 year based on viral genetic diversity, demographic, and clinical data.ResultsThe best predictive model included variables for genetic diversity of HIV-1 gag, pol, and env, viral load, age, sex, and ART status. Most participants were on ART. Balanced accuracy was 90.6% (95% confidence interval, 86.7%–94.1%). We tested the algorithm among newly diagnosed participants with or without documented negative HIV tests. Among those without records, those who self-reported a negative HIV test within <1 year were more frequently classified as recent than those who reported a test >1 year previously. There was no difference in classification between those self-reporting a negative HIV test <1 year, whether or not they had a record.ConclusionsThese results indicate that recency of HIV-1 infection can be inferred from viral sequence diversity even among patients on suppressive ART.

Cardiac Catheterization Procedures in Patients with HIV: A Retrospective Analysis.

With the advent of effective antiretroviral therapies, there has been a decrease in HIV-related mortality, but an increase in non-AIDS-related comorbidities including cardiovascular disease (CVD). We sought to investigate current status of cardiac catheterization (CC) procedures in people with HIV (PWH). This is a retrospective study done at a University Hospital in South Florida between 2017 and 2019. Medical records from 985 PWH indicated that CC was performed in 1.9% of the cases. Of the PWH who underwent CC, 68% were found to have obstructive coronary artery disease (CAD). Among obstructive CAD cases, PCI was performed in 77% and CABG in 21% of cases; 26% had a repeat procedure and 11% died from non-cardiac causes. When comparing PWH who had CC to those who did not, there was a significantly higher rate of statin use (63% vs. 25%, p < 0.015) and a higher prevalence of low ejection fraction (38% vs. 11%, p = 0.004) among those patients who underwent CC. However, there was no significant difference in the prevalence of hypertension (p = 0.13), HbA1c levels (p = 0.32), CD4 count (p = 0.45) nor in undetectable viral load status (p = 0.75) after controlling for age, sex and BMI. Despite the finding of traditional CVD risk factors among PWH, there were no differences in HIV-related factors among patients requiring CC, supporting the importance of optimization of traditional CVD risk factors in this population.

Dental caries in association with viral load in children living with HIV in Phnom Penh, Cambodia: a cross\u2010sectional study

BackgroundOral health status is associated with the overall health among people living with human immunodeficiency virus (HIV) infection. However, it is unclear whether dental caries is associated with the viral load in this population. Particularly, dental caries among children living with HIV needs better understanding as this can affect their overall health and future well-being. This study assessed the association between dental caries and viral load among children living with HIV in Phnom Penh, Cambodia.MethodsThis cross-sectional study, conducted at the National Pediatric Hospital as a baseline survey of a randomized controlled trial, included 328, 3–15-year-old children living with HIV and their primary caregivers. Calibrated and trained examiners conducted oral examinations for dental caries (DMFT/dmft index) in the children and retrieved the latest HIV viral load data from the hospital’s patient information system. On the dental examination day, the children and their caregivers were invited to answer a questionnaire-based interview. Multiple logistic regression analysis was conducted to assess the association between dental caries and viral load. The cut-off point for undetectable viral load was set at < 40 copies/mL.ResultsData from 328 children were included in the analysis; 68.3% had an undetectable viral load. The mean DMFT/dmft was 7.7 (standard deviation = 5.0). Adjusted regression analysis showed that dental caries in permanent or deciduous teeth was positively associated with detectable viral load (adjusted odds ratio [AOR]: 1.07, 95% confidence interval [CI]: 1.01–1.14). Conversely, antiretroviral therapy of ≥ 1 year and self-reported better adherence to antiretroviral drugs were negatively associated with detectable viral load. Among children with detectable viral load, dental caries in permanent or deciduous teeth was positively associated with non-suppression of viral load (> 1000 copies/mL) (AOR: 1.12, CI: 1.03–1.23).ConclusionsDental caries was associated with viral load status detection among children living with HIV. This finding suggests that dental caries may affect their immune status. The oral health of children living with HIV should be strengthened, and further research is needed to clarify the causal relationship between viral load and oral health status.

Undetectable or Unknown? A Longitudinal Event-Level Analysis of Disclosure of HIV Serostatus and Undetectability Among Gay, Bisexual, and Other Men Who have Sex with Men (gbMSM) in Metro Vancouver.

We examined temporal trends and factors associated with reporting partner's serostatus and viral load among a sample of gay, bisexual and other men who have sex with men (gbMSM) in Vancouver, Canada. Participants were recruited using respondent-driven sampling and we collected prospective cohort data from 09/2014 to 02/2017 using a computer-assisted questionnaire and nurse-administered STI/HIV testing. Our study included 481 participants reporting on 3780 sexual events. Among HIV-negative/unknown gbMSM we found a trend towards decreased proportions of sexual events reporting an unknown HIV-status partner (42-19%; p = < 0.001) and found increased proportions among gbMSM living with HIV (11-27%; p = 0.043). More participants living with HIV reported sex with undetectable partners, compared to HIV-negative/unknown participants (14.8% versus 5%). Our multivariable model found that compared with unknown status partners, undetectable partners were older, were from longer sexual relationships and were more likely to engage in condomless anal sex. Findings indicate that HIV-negative gbMSM seem more aware of the serostatus of their partners over time, but knowledge of partners' viral load over time was not significant. Further research should assess the degree to which new campaigns such as Undetectable = Untransmittable (U = U) are associated with discussions about HIV disclosure and viral load status.