After the start of antiretroviral therapy (ART), plasma HIV-RNA levels should fall below the limit of detection (LOD) within 24 weeks. Hence, the prolonged decline of HIV-RNA after ART initiation is defined as persistent viremia (PV). In this retrospective study, we analyzed factors associated with PV. Next-generation sequencing of viral RNA/DNA was performed to study viral evolution and the emergence of drug-resistance mutations in HIV-infected patients with PV (n = 20). In addition, HIV-DNA species, immunological parameters, and clinical data of the patients were analyzed. We found that the possible causes for PV were divers, and both virologic and host parameters of this particular cohort were heterogeneous. We identified viruses with therapy-associated DRMs in six patients (30%); two of these were detected as minority variants. Five patients had sub-optimal drug levels (25%) and the baseline plasma viral loads were relatively high. Strikingly, we observed that >40% of the PV patients finally reaching HIV levels below the LOD later on showed up with episodes of low-level viremia (LLV). However, the amount of PBMC derived HIV-DNA species was not correlated with the likelihood of LLV after PV. According to our data, we conclude that drug-resistant viruses, sub-optimal drug level, and high baseline viral loads might be probable reasons for the prolonged RNA decline only in a sub-set of patients. In the absence of emerging DRMs and/or compliance issues, the clinical implications of PV remain unclear; however, PV appears to be a risk factor for episodes of LLV.

It has been suggested that low-level viremia or blips in HIV-infected patients on antiretroviral treatment are related to assay variation and/or increased sensitivity of new commercial assays. The 50-copy cut-off for virologic failure is, therefore, under debate.

Several poxviruses can infect humans and cause diseases of varying severity. Besides the eradicated Variola virus that induced high mortality rates, numerous further human pathogenic orthopoxviruses are potentially fatal but generally cause less severe infections. While infection-related viremia was described for Variola virus and seems to be rare for Monkeypox virus, it is still debated for Vaccinia virus. So far, viremia in Cowpox virus-infected humans has not been reported.

During antiretroviral therapy (ART) that suppresses HIV replication to below the limit-of-quantification, virions produced during ART can be detected at low frequencies in the plasma, termed residual viremia (RV). We hypothesized that a reservoir of HIV-infected cells actively produce and release virions during ART that are potentially infectious, and that following ART-interruption, these virions can complete full-cycles of replication and contribute to rebound viremia. Therefore, we studied the dynamics of RV sequence variants in 3 participants who initiated ART after ~3 years of infection and were ART-suppressed for >6 years prior to self-initiated ART-interruptions. Longitudinal RV C2V5env sequences were compared to sequences from pre-ART plasma, supernatants of quantitative viral outgrowth assays (QVOA) of cells collected during ART, post-ART-interruption plasma, and ART-re-suppression plasma. Identical, "putatively clonal," RV sequences comprised 8-84% of sequences from each timepoint. The majority of RV sequences were genetically similar to those from plasma collected just prior to ART-initiation, but as the duration of ART-suppression increased, an increasing proportion of RV variants were similar to sequences from earlier in infection. Identical sequences were detected in RV over a median of 3 years (range: 0.3-8.2) of ART-suppression. RV sequences were identical to pre-ART plasma viruses (5%), infectious viruses induced in QVOA (4%) and rebound viruses (5%) (total n = 21/154 (14%) across the 3 participants). RV sequences identical to ART-interruption "rebound" sequences were detected 0.1-7.4 years prior to ART-interruption. RV variant prevalence and persistence were not associated with detection of the variant among rebound sequences. Shortly after ART-re-suppression, variants that had been replicating during ART-interruptions were detected as RV (n = 5). These studies show a dynamic, virion-producing HIV reservoir that contributes to rekindling infection upon ART-interruption. The persistence of identical RV variants over years suggests that a subpopulation of HIV-infected clones frequently or continuously produce virions that may resist immune clearance; this suggests that cure strategies should target this active as well as latent reservoirs.

Astroviruses cause diarrhea, but it is not known whether they circulate in human plasma. Astrovirus MLB2 was recently discovered in diarrhea samples from children. We detected MLB2 in the plasma of a febrile child, which suggests that MLB2 has broader tropism than expected and disease potential beyond the gastrointestinal tract.

Hepatitis C virus remained a public health problem with approximately half of the patients untreated and undiagnosed. Chronic HCV is a leading cause of cirrhosis, fibrosis, hepatocellular carcinoma and other hepatic morbidities. Active HCV has a prevalence rate of about 1% (71 million). By July, 2019, 10 million population of Pakistan was declared to have active HCV infection. According to World Health Organization, 23,720 people died of hepatitis-related complexities in Pakistan in 2016. Individuals with certain types of ABO blood groups were more susceptible to diverse kinds of infections. For instance, blood types A and AB predisposed individuals to severe malaria, while type O conferred resistance to the many of the protozoan agent. This study was designed to explore the association of hepatitis C viremia to blood groups, Rh factors, age and gender distribution among Pakistani population. Total 246 participants were screened for HCV in Taqwa diagnostics laboratory, Multan and 200 were found positive. They were divided into 4 groups on the basis of their age. First group included patients ranging from 17 to 25 (52), second, third and fourth group included patients from 26 to 34 (92), 35 to 43 (42) and 44 to above (14) respectively. Confirmed Hepatitis C patients were subjected to analysis of blood group, Rh factor and viral load. Results demonstrated that patients having 'O' blood group (60.37%) were reported for high viral load than any of the other blood groups in the patients of Southern Punjab, Pakistan. Furthermore, Rh-negative factor (26.42) was associated with high viral load than that of the Rh-positive factor (73.58). Disclosure practiced that age group (26-34) was reported for the high viral load than that of the any other group of this study. Females were more aggressively affected by HCV Viremia than male because the mean viral load among the females was higher than that of the males. Greater social awareness and gender-sensitive healthcare is necessary to improve the experiences of patients with HCV.

Antigenemia is commonly detected in rotavirus-infected children. Although rotavirus RNA has been detected in serum, definitive proof of rotavirus viremia has not been shown. We aimed to analyze a defined patient population to determine if infectious virus could be detected in sera from children with rotavirus antigenemia.

Infections during pregnancy have been suggested to be involved in childhood leukemias. We used high-throughput sequencing to describe the viruses most readily detectable in serum samples of pregnant women. Serum DNA of 112 mothers to leukemic children was amplified using whole genome amplification. Sequencing identified one TT virus (TTV) isolate belonging to a known type and two putatively new TTVs. For 22 mothers, we also performed TTV amplification by general primer PCR before sequencing. This detected 39 TTVs, two of which were identical to the TTVs found after whole genome amplification. Altogether, we found 40 TTV isolates, 29 of which were putatively new types (similarities ranging from 89% to 69%). In conclusion, high throughput sequencing is useful to describe the known or unknown viruses that are present in serum samples of pregnant women.

Arboviruses are public health threats that cause explosive outbreaks. Major determinants of arbovirus transmission, geographic spread, and pathogenesis are the magnitude and duration of viremia in vertebrate hosts. Previously, we determined that multiple alphaviruses are cleared efficiently from murine circulation by the scavenger receptor MARCO (Macrophage receptor with collagenous structure). Here, we define biochemical features on chikungunya (CHIKV), o'nyong 'nyong (ONNV), and Ross River (RRV) viruses required for MARCO-dependent clearance in vivo. In vitro, MARCO expression promotes binding and internalization of CHIKV, ONNV, and RRV via the scavenger receptor cysteine-rich (SRCR) domain. Furthermore, we observe species-specific effects of the MARCO SRCR domain on CHIKV internalization, where those from known amplification hosts fail to promote CHIKV internalization. Consistent with this observation, CHIKV is inefficiently cleared from the circulation of rhesus macaques in contrast with mice. These findings suggest a role for MARCO in determining whether a vertebrate serves as an amplification or dead-end host following CHIKV infection.

Infections have been suggested to be involved in Multiple Sclerosis (MS). We used metagenomic sequencing to detect both known and yet unknown microorganisms in 2 nested case control studies of MS. Two different cohorts were followed for MS using registry linkages. Serum samples taken before diagnosis as well as samples from matched control subjects were selected. In cohort1 with 75 cases and 75 controls, most viral reads were Anelloviridae-related and >95% detected among the cases. Among samples taken up to 2 years before MS diagnosis, Anellovirus species TTMV1, TTMV6 and TTV27 were significantly more common among cases. In cohort2, 93 cases and 93 controls were tested under the pre-specified hypothesis that the same association would be found. Although most viral reads were again related to Anelloviridae, no significant case-control differences were seen. We conclude that the Anelloviridae-MS association may be due to multiple hypothesis testing, but other explanations are possible.

HIV-infected, postpartum women on antiretroviral therapy (ART) have high rates of viremia. We examined predictors of postpartum viremia in the PROMISE study.

Previous studies have demonstrated an association between adenovirus viremia and disease severity in immunocompromised children. However, few studies have focused on this association in immunocompetent children. This study explored the association between adenovirus viremia and adenovirus pneumonia severity in immunocompetent children.

Non-suppressible HIV-1 viremia (NSV) can occur in persons with HIV despite adherence to combination antiretroviral therapy (ART) and in the absence of significant drug resistance. Here, we show that plasma NSV sequences are comprised primarily of large clones without evidence of viral evolution over time. We defined proviruses that contribute to plasma viremia as "producer", and those that did not as "non-producer". Compared to ART-suppressed individuals, NSV participants had a significantly larger producer reservoir. Producer proviruses were enriched in chromosome 19 and in proximity to the activating H3K36me3 epigenetic mark. CD4 + cells from NSV participants demonstrated upregulation of anti-apoptotic genes and downregulation of pro-apoptotic and type I/II interferon-related pathways. Furthermore, NSV participants showed no elevation in HIV-specific CD8 + cell responses and producer proviruses were enriched for HLA escape mutations. We identified critical host and viral mediators of NSV that represent potential targets to disrupt HIV persistence and promote viral silencing.

Non-suppressible HIV-1 viremia (NSV) is defined as persistent low-level viremia on antiretroviral therapy (ART) without evidence of ART non-adherence or significant drug resistance. Unraveling the mechanisms behind NSV would broaden our understanding of HIV-1 persistence. Here we analyzed plasma virus sequences in eight ART-treated individuals with NSV (88% male) and show that they are composed of large clones without evidence of viral evolution over time in those with longitudinal samples. We defined proviruses that match plasma HIV-1 RNA sequences as 'producer proviruses', and those that did not as 'non-producer proviruses'. Non-suppressible viremia arose from expanded clones of producer proviruses that were significantly larger than the genome-intact proviral reservoir of ART-suppressed individuals. Integration sites of producer proviruses were enriched in proximity to the activating H3K36me3 epigenetic mark. CD4+ T cells from participants with NSV demonstrated upregulation of anti-apoptotic genes and downregulation of pro-apoptotic and type I/II interferon-related pathways. Furthermore, participants with NSV showed significantly lower HIV-specific CD8+ T cell responses compared with untreated viremic controllers with similar viral loads. We identified potential critical host and viral mediators of NSV that may represent targets to disrupt HIV-1 persistence.

Variants in the Apolipoprotein L1 (APOL1) gene (G1-rs60910145, rs73885319, G2-rs71785313) are common in Africans and in individuals of recent African ancestry and are associated with an increased risk of non-diabetic chronic kidney disease (CKD) and in particular of HIV associated nephropathy (HIVAN). In light of the significantly increased risk of HIVAN in carriers of two APOL1 risk alleles, a role in HIV infectivity has been postulated in the mechanism of APOL1 associated kidney disease. Herein, we aim to explore the association between HIV viremia and APOL1 genotype. In addition, we investigated interaction between BK and JC viruria, CKD and HIV viremia. A total of 199 persons living with HIV/AIDS (comprising 82 CKD cases and 117 controls) from among the participants in the ongoing Human Heredity and Health in Africa (H3Africa) Kidney Disease Research Network case control study have been recruited. The two APOL1 renal risk alleles (RRA) genotypes were associated with a higher risk of CKD (OR 12.6, 95% CI 3.89-40.8, p < 0.0001). Even a single APOL1 RRA was associated with CKD risk (OR 4.42, 95% CI 1.49-13.15, p = 0.007). The 2 APOL1 RRA genotypes were associated with an increased probability of having HIV viremia (OR 2.37 95% CI 1.0-5.63, p = 0.05). HIV viremia was associated with increased CKD risk (OR 7.45, 95% CI 1.66-33.35, P = 0.009) and with a significant reduction of JC virus urine shedding (OR 0.35, 95% CI 0.12-0.98, p = 0.046). In contrast to prior studies, JC viruria was not associated with CKD but was restricted in patients with HIV viremia, regardless of CKD status. These findings suggest a role of APOL1 variants in HIV infectivity and emphasize that JC viruria can serve as biomarker for innate immune system activation.

Whether prolonged maternal viremia after Zika virus infection represents a risk factor for maternal-fetal transmission and subsequent adverse outcomes remains unclear. In this prospective cohort study in French Guiana, we enrolled Zika virus-infected pregnant women with a positive PCR result at inclusion and noninfected pregnant women; both groups underwent serologic testing in each trimester and at delivery during January-July 2016. Prolonged viremia was defined as ongoing virus detection >30 days postinfection. Adverse outcomes (fetal loss or neurologic anomalies) were more common in fetuses and neonates from mothers with prolonged viremia (40.0%) compared with those from infected mothers without prolonged viremia (5.3%, adjusted relative risk [aRR] 7.2 [95% CI 0.9-57.6]) or those from noninfected mothers (6.6%, aRR 6.7 [95% CI 3.0-15.1]). Congenital infections were confirmed more often in fetuses and neonates from mothers with prolonged viremia compared with the other 2 groups (60.0% vs. 26.3% vs. 0.0%, aRR 2.3 [95% CI 0.9-5.5]).

Infections with polyomavirus BK virus (BKV) are a common cause of renal dysfunction after renal transplantation and may also be harmful in surgical patients with shock. The aim of the present study was to determine the frequency of BKV viremia in critically ill surgical patients with septic or hemorrhagic shock, and, if viremia is detectable, whether viremia may be associated with renal dysfunction.

There are currently no approved drugs to treat Zika virus (ZIKV) infection during pregnancy. Hyperimmune globulin products such as VARIZIG and WinRho are FDA-approved to treat conditions during pregnancy such as Varicella Zoster virus infection and Rh-incompatibility. We administered ZIKV-specific human immune globulin as a treatment in pregnant rhesus macaques one day after subcutaneous ZIKV infection. All animals controlled ZIKV viremia following the treatment and generated robust levels of anti-Zika virus antibodies in their blood. No adverse fetal or infant outcomes were identified in the treated animals, yet the placebo control treated animals also did not have signs related to congenital Zika syndrome (CZS). Human immune globulin may be a viable prophylaxis and treatment option for ZIKV infection during pregnancy, however, more studies are required to fully assess the impact of this treatment to prevent CZS.

Serial samples from the same individuals may be required for certain virological studies, however, some small animals cannot easily be blood-sampled. Therefore, we evaluated the use of Culex quinquefasciatus Say and Aedes albopictus Skuse mosquitoes as "biological syringes" to draw blood for virus titer determinations in small vertebrates. Groups of chicks (Gallus gallus), hamsters (Mesocricetus auratus), and house sparrows (Passer domesticus) were experimentally infected with West Nile virus (WNV) or Highlands J virus (HJV). In general, good correlation was seen between mosquito- and syringe-derived blood samples at titers ≥5.0 log10 pfu/mL serum as compared with titers <5.0 log10 pfu/mL serum for chicks, hamsters, and sparrows. Ninety-two percent (24/26) of sparrows with virus titers >105 pfu/mL serum had mosquito- and syringe-derived titers within one log of each other. Sparrow viremia profiles generated from single mosquito blood meals and syringe were not significantly different (p>0.05). This technique is valuable for assessing the roles of small vertebrates in the ecologies of arboviruses, and could be used in applications beyond virology and infectious diseases, when <10 µL of whole blood is required.

Despite the combined antiretroviral therapy has improved the length and quality of life of HIV infected patients, the survival of these patients is always decreased compared with the general population. This is the consequence of non-infectious illnesses including cardio vascular diseases. In fact large studies have indicated an increased risk of coronary atherosclerotic disease, myocardial infarction even in HIV patients on cART. In HIV infected patients several factors may contribute to the pathogenesis of cardiovascular problems: life-style, metabolic parameters, genetic predisposition, viral factors, immune activation, chronic inflammation and side effects of antiretroviral therapy. The same factors may also contribute to complicate the clinical management of these patients. Therefore, treatment of these non-infectious illnesses in HIV infected population is an emerging challenge for physicians. The purpose of this review is to focus on the new insights in non AIDS-related cardiovascular diseases in patients with suppressed HIV viremia.