Viral Load

Despite antiretroviral therapy (ART), HIV persists in latently-infected cells (the HIV reservoir) which decay slowly over time. Here, leveraging >500 longitudinal samples from 67 people living with HIV (PLWH) treated during acute infection, we developed a mathematical model to predict reservoir decay from peripheral CD4 + T cells. Nonlinear generalized additive models demonstrated rapid biphasic decay of intact DNA (week 0-5: t1/2 ~ 2.83 weeks; week 5-24: t1/2 ~ 15.4 weeks) that extended out to 1 year. These estimates were ~5-fold faster than prior decay estimates among chronic treated PLWH. Defective DNA had a similar biphasic pattern, but data were more variable. Predicted intact and defective decay rates were faster for PLWH with earlier timing of ART initiation, higher initial CD4 + T cell count, and lower pre-ART viral load. In this study, we advanced our limited understanding of HIV reservoir decay at the time of ART initiation, informing future curative strategies targeting this critical time.

Saliva has emerged as a promising diagnostic fluid for viral infections, enabling the direct analysis of viral genetic material and the detection of infection markers such as proteins, metabolites, microRNAs, and immunoglobulins. This comprehensive review aimed to explore the use of saliva as a diagnostic tool for viral infections, emphasizing its advantages and limitations. Saliva stands out due to its simplicity and safety in collection, along with the convenience of self-collection without the need for healthcare supervision, while potentially being comparable to urine and blood in terms of effectiveness. Herein, we highlighted the significant potential of saliva in assessing viral loads and diagnosing viral infections, such as herpesviruses, HPV, PyV, TTV, SARS-CoV-2, and MPXV. The detection of viral shedding in saliva underscores its utility in early diagnosis, the monitoring of infection progression, and evaluating treatment responses. The non-invasive nature of saliva collection makes it an appealing alternative to more invasive methods, promoting better patient compliance and facilitating large-scale screening and surveillance. As such, we further highlight current evidence on the use of saliva as a prognostic tool. Although a significant amount of data is already available, further investigations are warranted to more comprehensively assess the added benefit from the utilization of salivary biomarkers in the clinics. Salivary biomarkers show great promise for the early detection and prevention of viral infection complications, potentially improving disease management and control at the population level. Integrating these non-invasive tools into routine clinical practice could enhance personalized healthcare strategies and patient outcomes. Future studies should focus on establishing standardization protocols, validating the accuracy of salivary diagnostics, and expanding clinical research to enhance the diagnostic and monitoring capabilities of salivary biomarkers.

Previous research suggests that depression impacts HIV outcomes, including viral suppression. This meta-analysis quantifies the association between depression and HIV viral suppression. A systematic literature search was conducted in PubMed, Web of Science, EBSCO, and OVID to identify studies published through 2012 to 2022. The software Rayyan was used to evaluate eligibility of studies, and the 2020 Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines were used for abstracting data. A random effects meta-analysis was performed using Review Manager 5.4.1. Of the 1911 articles screened, 16 studies were included covering 80,103 participants. The results showed individuals without depression were more likely to achieve HIV viral suppression or undetectable viral load compared to individuals with depression (OR 1.30; 95%CI 1.15, 1.48; I2 = 76%). Subgroup analysis indicated this effect was significant among the general population of people living with HIV (n = 75,353; OR 1.32; 95%CI 1.12, 1.55; I2 = 85%) and cisgender women living with HIV (n = 4553; OR 1.28; 95%CI 1.09, 1.50; I2 = 16%), but not among cisgender men living with HIV (most identified as men who have sex with men) (n = 197; OR 2.13; 95%CI 0.43, 10.61; I2 = 83%). This meta-analysis shows a significant positive association between the absence of depression and achieving HIV viral suppression overall and among the subgroup of cisgender women. Public health interventions for people living with HIV should include strategies to identify and address the depressive symptoms that impact adherence to treatment, increase the risk of psycho-behavioral co-morbidities, and exacerbate social or structural factors impeding viral suppression.

Many viruses have adapted to persist in infected humans for life1,2. Variable host control of their ongoing abundance (viral load) can lead to clearance or disease3-5. Here we analysed the viral DNA load of 31 common viruses in human blood and saliva using whole-genome sequencing data from UK Biobank (n = 490,401), All of Us (n = 414,817) and Simons Foundation Powering Autism Research for Knowledge (SPARK; n = 12,519). Viral DNA load varied markedly with age, time of day and season; most viruses were also present at greater abundance in men than in women. Human genetic variation at dozens of loci associated with DNA load of seven viruses: Epstein-Barr virus (EBV, 45 loci), human herpesvirus (HHV)-7 (37 loci), HHV-6B, Merkel cell polyomavirus and three anelloviruses. Variation at the major histocompatibility complex (MHC) locus generated the strongest associations (P = 5.8 × 10-9 to 2.5 × 10-1459), which were specific to each virus. The HLA-B*08:01 allele also exhibited a host-virus genetic interaction with EBV subtype (P = 7.4 × 10-70). Other human genetic effects implicated genes encoding proteins that process peptides for antigen presentation, such as ERAP1 (HHV-7, P = 2.7 × 10-78) and ERAP2 (EBV, P = 4.6 × 10-111). Mendelian randomization analyses supported a strong causal effect of EBV DNA load on increased risk of Hodgkin's lymphoma (P = 1.8 × 10-3), but not multiple sclerosis (P = 0.52). This suggests that higher chronic EBV load increases lymphoma risk, whereas associations of EBV infection with autoimmune conditions reflect host immune responses to particular viral epitopes.