Higher Plasma Viral Load Research Articles

Serum Amylase Activity in Children Living with HIV-1 at the Charles de Gaulle Pediatric University Hospital in Ouagadougou

Biological monitoring is an essential part of the management of HIV infection. The aim of this study was to assess serum amylase activity during follow-up of children living with HIV-1 (CLHIV-1) at the Charles de Gaulle Pediatric University Hospital (CHUP-CDG). This was a descriptive and analytical cross-sectional study, with retrospective data collection from January 1, 2020 to December 31, 2022. Patients under 15 years of age who were being monitored for HIV-1 at CHUP-CDG and who had undergone a serum amylase assay during the study period were included. A total of 746 patients have been included, with a M/F sex ratio of 0.91 and a mean age of 8.52±4.08 years. Among CLHIV-1, 88.05% had a TCD4 lymphocyte count > 500/mm<sup>3</sup> and 60.32% an undetectable plasma viral load (PVL). The incidence of hyperamylasemia in the study population was 57.64%. Hyperamylasemia was significantly more frequent in children aged 0-2 years (<i>p<0.00001</i>), in patients with a high PVL (<i>p=0.0016</i>) and in those on the protocol combining two nucleoside reverse transcriptase inhibitors with a protease inhibitor. Several abnormalities in serum amylase activity were detected in CLHIV-1 during the course of the study. Clinical correlation and adequate follow-up of these abnormalities are essential to reduce the morbidity and mortality associated with pancreatic damage in people living with HIV.

Viral and immunologic evaluation of smokers with severe COVID-19

Smoking negatively affects B cell function and immunoglobulin levels, but it is unclear if this immune dysfunction contributes to the risk of severe COVID-19 in smokers. We evaluated binding IgM, IgA and IgG antibodies to spike and receptor binding domain antigens, and used a pseudovirus assay to quantify neutralization titers in a set of 27 patients with severe COVID-19. We found no significant differences between binding and neutralization antibody responses for people with a smoking history and people who never smoked. High plasma viral load, but not antibody titers, was linked to an increased risk of death. Humoral immune dysfunction was not a major driver of severe COVID-19 in smokers.

Natural Killer Repertoire Restoration in TB/HIV Co-Infected Individuals Experienced an Immune Reconstitution Syndrome (CAMELIA Trial, ANRS 12153).

IRIS is a common complication in HIV-infected patients treated for tuberculosis (TB) and cART. Our aim was to evaluate NK cell reconstitution in HIV-infected patients with TB-IRIS compared to those without IRIS. 147 HIV-infected patients with TB from the CAMELIA trial were enrolled. HIV+TB+ patients were followed for 32 weeks. The NK cell repertoire was assessed in whole blood at different time points. As CAMELIA has two arms (early and late cART initiation), we analysed them separately. At enrolment, individuals had low CD4 cell counts (27 cells/mm3) and high plasma viral loads (5.76 and 5.50 log/mL for IRIS and non-IRIS individuals, respectively). Thirty-seven people developed IRIS (in the early and late arms). In the early and late arms, we observed similar proportions of total NK and NK cell subsets in TB-IRIS and non-IRIS individuals during follow-up, except for the CD56dimCD16pos (both arms) and CD56dimCD16neg (late arm only) subsets, which were higher in TB-IRIS and non-IRIS individuals, respectively, after cART. Regarding the repertoire and markers of NK cells, significant differences (lower expression of NKp30, NKG2A (CD159a), NKG2D (CD314) were observed in TB-IRIS compared to non-IRIS individuals after the start of cART. In the late arm, some changes (increased expression of CD69, NKG2C, CD158i) were observed in TB-IRIS compared to non-IRIS individuals, but only before cART initiation (during TB treatment). KIR expression by NK cells (CD158a and CD158i) was similar in both groups. CD69 expression by NK cells decreased in all groups. Expression of the NCR repertoire (NKp30, NKp44, NKp46) has similar kinetics in TB-IRIS subjects compared to non-IRIS subjects regardless of the arm analysed. NK cell reconstitution appeared to be better in TB-IRIS subjects. Although NK cell reconstitution is impaired in HIV infection after cART, as previously reported, it does not appear to be affected by the development of IRIS in HIV and TB-infected individuals.

Susceptibility to Zika virus in a Collaborative Cross mouse strain is induced by Irf3 deficiency in vitro but requires other variants in vivo.

Zika virus (ZIKV) is a Flavivirus responsible for recent epidemics in Pacific Islands and in the Americas. In humans, the consequences of ZIKV infection range from asymptomatic infection to severe neurological disease such as Guillain-Barré syndrome or fetal neurodevelopmental defects, suggesting, among other factors, the influence of host genetic variants. We previously reported similar diverse outcomes of ZIKV infection in mice of the Collaborative Cross (CC), a collection of inbred strains with large genetic diversity. CC071/TauUnc (CC071) was the most susceptible CC strain with severe symptoms and lethality. Notably, CC071 has been recently reported to be also susceptible to other flaviviruses including dengue virus, Powassan virus, West Nile virus, and to Rift Valley fever virus. To identify the genetic origin of this broad susceptibility, we investigated ZIKV replication in mouse embryonic fibroblasts (MEFs) from CC071 and two resistant strains. CC071 showed uncontrolled ZIKV replication associated with delayed induction of type-I interferons (IFN-I). Genetic analysis identified a mutation in the Irf3 gene specific to the CC071 strain which prevents the protein phosphorylation required to activate interferon beta transcription. We demonstrated that this mutation induces the same defective IFN-I response and uncontrolled viral replication in MEFs as an Irf3 knock-out allele. By contrast, we also showed that Irf3 deficiency did not induce the high plasma viral load and clinical severity observed in CC071 mice and that susceptibility alleles at other genes, not associated with the IFN-I response, are required. Our results provide new insight into the in vitro and in vivo roles of Irf3, and into the genetic complexity of host responses to flaviviruses.

Mpox infection protects against re-challenge in rhesus macaques

The mpox outbreak of 2022-2023 involved rapid global spread in men who have sex with men. We infected 18 rhesus macaques with mpox by the intravenous, intradermal, and intrarectal routes and observed robust antibody and Tcell responses following all three routes of infection. Numerous skin lesions and high plasma viral loads were observed following intravenous and intradermal infection. Skin lesions peaked on day 10 and resolved by day 28 following infection. On day 28, we re-challenged all convalescent and 3 naive animals with mpox. All convalescent animals were protected against re-challenge. Transcriptomic studies showed upregulation of innate and inflammatory responses and downregulation of collagen formation and extracellular matrix organization following challenge, as well as rapid activation of Tcell and plasma cell responses following re-challenge. These data suggest key mechanistic insights into mpox pathogenesis and immunity. This macaque model should prove useful for evaluating mpox vaccines and therapeutics.

Impact of Hepatitis E Virus Screening in the UK Deceased Organ Donor Population.

Universal Hepatitis E Virus (HEV) screening of deceased organ donors was implemented by the UK national organ procurement organisation in October 2017. Donor testing for HEV infection is done post-transplant; detection of HEV ribonucleic acid (RNA) in donor plasma is therefore not a contra-indication for organ donation, with the result being used to inform recipient management. Immediate post-transplant detection of donor HEV viraemia triggers notification to transplant centres. Follow up of liver and kidney recipients has shown that transmission through solid organs is very efficient, particularly through liver grafts, as expected; no other organ types were transplanted in this cohort. Although donors with higher plasma viral load (VL > 103IU/mL) were invariably associated with recipient infection, transmission was also documented at lower VL levels. Knowledge of donor HEV status has led to identification of transmission of infection via solid organ grafts followed by close patient monitoring and informed clinical management decisions. The purpose of this strategy is to allow early detection of infection and recurrence and treatment to circumvent the risk of accelerated liver damage from chronic HEV infection due to undiagnosed, inadvertent donor-derived transmission of infection.

Antiretroviral Therapy Ameliorates Simian Immunodeficiency Virus-Associated Myocardial Inflammation by Dampening Interferon Signaling and Pathogen Response in the Heart.

People with human immunodeficiency virus have an increased risk of developing cardiovascular disease. RNA-Seq was performed on hearts from simian immunodeficiency virus (SIV)-infected rhesus macaques with or without antiretroviral therapy (ART). SIV infection led to high plasma viral load with very little myocardial viral RNA. SIV infection promoted an inflammatory environment in the heart through interferon and pathogen signaling, in the absence of myocardial viral RNA. While ART dampened interferon and cytokine response in the heart, SIV-infected animals receiving ART had deficits in the expression of genes directly involved in fatty acid metabolism relative to SIV-uninfected animals.

CCR5∆32 and SDF1 3'A: Gene Variants, Expression and Influence on Biological Markers for the Clinical Progression to AIDS among HIV-1 Virus Controllers in a Mixed Population of the Amazon Region of Brazil.

CCR5Δ32 and SDF1-3'A polymorphisms were investigated in a cohort of viremia controllers, without the use of therapy, along with their influence on CD4+ T lymphocytes (TLs), CD8+ TLs, and plasma viral load (VL). The samples were analyzed from 32 HIV-1-infected individuals classified as viremia controllers 1 and 2 and viremia non-controllers, from both sexes, mostly heterosexuals, paired with 300 individuals from a control group. CCR5∆32 polymorphism was identified by PCR amplification of a fragment of 189 bp for the wild-type allele and 157 bp for the allele with the ∆32 deletion. SDF1-3'A polymorphism was identified by PCR, followed by enzymatic digestion (restriction fragment length polymorphism) with the Msp I enzyme. The relative quantification of gene expression was performed by real-time PCR. The distribution of allele and genotype frequencies did not show significant differences between the groups. The gene expression of CCR5 and SDF1 was not different between the profiles of AIDS progression. There was no significant correlation between the progression markers (CD4+ TL/CD8+ TL and VL) and the CCR5∆32 polymorphism carrier status. The 3'A allele variant was associated with a marked loss of CD4+ TLs and a higher plasma VL. Neither CCR5∆32 nor SDF1-3'A was associated with viremia control or the controlling phenotype.

Does testosterone intake affect diagnosing primary HIV infection?

Diagnosis of primary HIV infection may be disrupted by many factors, one of which are drugs such as exogenous steroids. We report a rare case of a 37-year-old male patient, undergoing testosterone treatment in the course of Klinefelter syndrome. He presented with the general symptoms of fever, weakness and diarrhea lasting for 2 weeks. He also had incorrect results of laboratory studies. The fourth generation ELISA HIV test indicated negative outcomes. The HIV real time polymerase chain reaction test was performed and showed very high plasma viral load, over 107 copies/ml. We discuss the connection between androgen replacement therapy used in Klinefelter syndrome and the diagnosis of PHI. This case report illustrates the importance of obtaining a detailed medical history, especially of chronic diseases and medications, and applying appropriate diagnostic tests.

Association of Plasma Eicosanoid Levels With Immune, Viral, and Cognitive Outcomes in People With HIV.

Background and ObjectivesTo determine whether plasma eicosanoid levels are associated with immune, viral, and cognitive outcomes in people with HIV (PWH).MethodsWe measured 42 eicosanoids in a longitudinal study of 95 PWH and 25 demographically comparable uninfected participants. Routine clinical chemistry, virologic, immune markers, and a neuropsychological test battery assessing 7 cognitive domains were administered to all participants at 2 study visits over an average of 6.5 months.ResultsPlasma eicosanoid concentrations were elevated in PWH (n = 95) compared with seronegative controls (n = 25) (100% prediction power at 5% false discovery rate [FDR], α = 0.0531) and were negatively associated with lower current and nadir CD4 lymphocyte counts. Higher levels of eicosanoids were associated with impairments in working memory, verbal fluency, and executive function. Higher plasma viral load was associated with elevated proinflammatory eicosanoids (24% prediction power at 5% FDR and 42.4% prediction power at 10% FDR, α = 0.10). Longitudinal analyses showed that eicosanoid levels were correlated with viral load and with plasma creatinine. Despite associations of eicosanoids with viral loads, elevated plasma eicosanoids were similar in virally suppressed and not fully suppressed PWH.DiscussionThese data show that HIV infection is associated with a robust production of eicosanoids that are not substantially reduced by antiretroviral therapy (ART). The sustained elevation of these oxylipins in PWH despite ART may contribute to an accelerated aging phenotype that includes earlier than expected brain and peripheral organ damage.

Polyomavirus BK Genome Comparison Shows High Genetic Diversity in Kidney Transplant Recipients Three Months after Transplantation.

BK polyomavirus (BKPyV) is a human DNA virus generally divided into twelve subgroups based on the genetic diversity of Viral Protein 1 (VP1). BKPyV can cause polyomavirus-associated nephropathy (PVAN) after kidney transplantation. Detection of BKPyV DNA in blood (viremia) is a source of concern and increase in plasma viral load is associated with a higher risk of developing PVAN. In this work, we looked for possible associations of specific BKPyV genetic features with higher plasma viral load in kidney transplant patients. We analyzed BKPyV complete genome in three-month samples from kidney recipients who developed viremia during their follow-up period. BKPyV sequences were obtained by next-generation sequencing and were de novo assembled using the new BKAnaLite pipeline. Based on the data from 72 patients, we identified 24 viral groups with unique amino acid sequences: three in the VP1 subgroup IVc2, six in Ib1, ten in Ib2, one in Ia, and four in II. In none of the groups did the mean plasma viral load reach a statistically significant difference from the overall mean observed at three months after transplantation. Further investigation is needed to better understand the link between the newly described BKPyV genetic variants and pathogenicity in kidney transplant recipients.

MO979: Influence of BK Virus Plasma Viral Load in Kidney Transplant Outcomes

Abstract BACKGROUND AND AIMS BK virus infection (BKi) is an important cause of kidney transplant (KT) loss. Besides to reducing immunosuppression, the rest of the therapies have not shown a clear benefit. Our purpose is to analyze the risk factors for BKi and the influence of BK plasma viral load on KT outcomes. METHOD Prospective cohort study of KT with BKi, defined by the presence of BK viremia in ≥3 consecutive determinations, from 01 January 2010 to 31 December 2020. BK viremia was determined every 10 days during the first 3 months, at 6th month, 12th month and in case of impaired renal function. In patients with positive viremia, immunosuppressive therapy was changed (reduction/discontinuation of mycophenolate and/or switching to everolimus). Patients with high-level viremia (≥10 000 copies/mL) and low-level viremia (<10 000 copies/mL) were compared. To identify risk factors for BKi, for each KT with BKi, we selected two matched controls and performed a logistic regression analysis. Graft survival was analyzed according to BK viremia (high-level, low-level and negative) using Kaplan–Meier and Cox regression analysis was performed to determine risk factors for graft survival. RESULTS 849 KT were performed, of which 67 (7.9%) presented BKi. Six KT were excluded due to incomplete data. Finally, 61 KT BKi (n = 27, high-level viremia; n = 34 low-level viremia) and 122 controls were analyzed. The median post-KT time to BKi was 2 months. In the multivariable analysis, male recipient, older age and re-KT were risk factors for BKi. Proven BK-associated nephropathy was diagnosed in five KT recipients and nine patients had persistent BK viremia, all of them from the high plasma viral loads group. Only one patient lost the graft due to BK-associated nephropathy. Patients with low-level viremia had worse renal function one month after KT than controls but without differences at the first year. Patients with high-level viremia had worse renal function one year after KT and worse graft survival than recipients with low-level viremia and controls (P = 0.037). In the multivariable analysis, when we analyzed exclusively patients with BKi, high-level viremia was a risk factor for kidney graft survival (HR: 16.31; P = 0.034). CONCLUSION BKi is not an uncommon complication after KT. Only high BK viral load was associated with BK-associated nephropathy, persistent viremia, and poorer graft survival. BK viremia <10 000 copies/mL did not affect KT outcomes. Therefore, monitoring BK plasma viral loads and changes in immunosuppression to reduce viremia are effective strategies to minimize the impact of BK virus on graft survival.

Bone marrow stromal antigen 2 (BST-2) genetic variants influence expression levels and disease outcome in HIV-1 chronically infected patients

BackgroundBone marrow stromal antigen 2 (BST-2) also known as Tetherin (CD317/HM1.24), is a host restriction factor that blocks the release of HIV-1 virions from infected cells. Previous studies reported that BST-2 genetic variants or single nucleotide polymorphims (SNPs) have a preventative role during HIV-1 infection. However, the influence of BST-2 SNPs on expression levels remains unknown. In this study, we investigated the influence of BST-2 SNPs on expression levels and disease outcome in HIV-1 subtype C chronically infected antiretroviral therapy naïve individuals.ResultsWe quantified BST-2 mRNA levels in peripheral blood mononuclear cells (PBMCs), determined BST-2 protein expression on the surface of CD4+ T cells using flow cytometry and genotyped two intronic single nucleotide polymorphisms (SNPs) rs919267 and rs919266 together with one SNP rs9576 located in the 3’ untranslated region (UTR) of bst-2 gene using TaqMan assays from HIV-1 uninfected and infected participants. Subsequently, we determined the ability of plasma antibody levels to mediate antibody-dependent cellular phagocytosis (ADCP) using gp120 consensus C and p24 subtype B/C protein. Fc receptor-mediated NK cell degranulation was evaluated as a surrogate for ADCC activity using plasma from HIV-1 positive participants. BST-2 mRNA expression levels in PBMCs and protein levels on CD4+ T cells were lower in HIV-1 infected compared to uninfected participants (p = 0.075 and p < 0.001, respectively). rs919267CT (p = 0.042) and rs919267TT (p = 0.045) were associated with lower BST-2 mRNA expression levels compared to rs919267CC in HIV-1 uninfected participants. In HIV-1 infected participants, rs919267CT associated with lower CD4 counts, (p = 0.003), gp120-IgG1 (p = 0.040), gp120-IgG3 (p = 0.016) levels but higher viral loads (p = 0.001) while rs919267TT was associated with lower BST-2 mRNA levels (p = 0.046), CD4 counts (p = 0.001), gp120-IgG1 levels (p = 0.033) but higher plasma viral loads (p = 0.007). Conversely, rs9576CA was associated with higher BST-2 mRNA expression levels (p = 0.027), CD4 counts (p = 0.079), gp120-IgG1 (p = 0.009), gp120-IgG3 (p = 0.039) levels but with lower viral loads (p = 0.037).ConclusionOur findings show that bst-2 SNPs mediate BST-2 expression and disease outcome, correlate with gp120-IgG1, gp120-IgG3 levels but not p24-IgG levels, ADCC and ADCP activity.Graphical

Profiling Hepatitis B Viral Load: Treatment and Epidemiological Implications in a West African Hospital

Background: Chronic hepatitis B virus (HBV) infection is one of the largest public health problems with nearly 350 million chronic carriers and 500,000 deaths each year. These deaths are most often associated with disease progression to cirrhosis or hepatocellular carcinoma, which some studies have shown is associated with long-term viral replication in chronic carriers. Viral load quantification, a key element of disease management, is expensive and difficult to access. Viral load plays a crucial role in patient classification and treatment initiation. Four years after the implementation of viral load platform, the objective of this study was to assess viral load profile in HBs chronic carriers in a sub-Saharan Hospital and to determine the potential impact of this distribution on preventive and therapeutic strategies against hepatitis B infection. Materials and Method: The study was carried out between April 2016 and October 2020 in the laboratory of the PRINCIPAL Hospital in Dakar. All patients referred for HBV DNA viral load testing following a positive AgHBs test were included. Incomplete medical records were excluded from the study. Only the first quantification test performed on each patient is recorded. DNA extraction was performed with COBAS AmpliPrep (Roche Molecular Systems, Inc., Branchburg, NJ, USA). Amplification was performed using COBAS TaqMan48 (Roche Molecular Systems, Inc., Branchburg, NJ, USA). Data were collected from the laboratory’s computer system and entered into Microsoft Excel (2007). Statistical analyzes were performed using Epi-Info 7 software. Results: A total of 3002 patients, 76.1% (2285/3002) men and 33.9% (717/3002) women, were included in the study. Young adults were most represented among the subjects (23.2%) and (20.1%) in the age groups 25 - 30 and 30 - 35. The majority (52.7%) of patients had viral loads between 20 and 2000 IU. Patients with undetectable viral loads and patients with viral loads below 20 IU comprised 14.6% and 7.53% of the study population, respectively. Patients with viral loads between 2000 and 20,000 IU/ml and those with viral loads greater than 20,000 IU/ml represented 16.3% and 8.89% of the study population, respectively. Viral load was higher in males than females, with corresponding median and interquartile ranges of 2.7 log IU (2.2, 2.75) and 2.23 log IU (2.1, 2.4) (p < 0.001). This viral load also decreases with age. There were more patients with an undetectable viral load over 30 years than those under 30 years, with a ratio of 1.62 (IC95% = 1.29 - 2.05) (p = 0.009). Conclusion: This study shows a successful implementation of virus quantification in the context of resource-constrained countries. The second finding of this study is the high prevalence of adolescents with high plasma viral loads, indicating the need for additional investigations to initiate therapy. The large population with a low HBV replication rate points to the problem of financing follow-up care for chronically infected people. Studying this population in the context of an unknown genomic profile indicates the need to deepen virological laboratory testing through a sequencing platform. Finally, regular viral load reporting in major hospital cities could be a powerful and accessible management tool for hepatitis B programs in resource-constrained countries.

Elevated Plasma von Willebrand Factor Levels Are Associated With Subsequent Ischemic Stroke in Persons With Treated HIV Infection.

BackgroundWe assessed whether key biomarkers of endothelial activation and hemostasis/thrombosis were elevated in individuals receiving effective antiretroviral therapy (ART) in the year before ischemic stroke.MethodsWe conducted a case–control study nested in the CFAR Network of Integrated Clinical Systems cohort, comparing 42 adjudicated cases with ischemic stroke with 83 controls matched for ART regimen. Angiopoietin-1, angiopoietin-2, C-reactive protein, interleukin-6, plasminogen activation inhibitor–1, P-selectin, serum amyloid–A, soluble CD14, ICAM-1, VCAM-1, apolipoprotein A1, ADAMTS13, and von Willebrand factor (VWF) were measured in stored plasma collected before the stroke event. We used conditional logistic regression to identify associations with ischemic stroke, with and without adjustment for Atherosclerotic Cardiovascular Disease (ASCVD) and Veterans Aging Cohort Study (VACS) scores.ResultsAfter adjustment for age and sex, higher plasma viral load and higher angiopoeitin-2, soluble CD14, and VWF were associated with increased odds of ischemic stroke; higher nadir CD4 count was associated with decreased odds of ischemic stroke. VWF remained associated with subsequent ischemic stroke after adjustment for ASCVD score (adjusted odds, 1.74; 95% CI, 1.01–2.98 per log2 increment). In a separate model adjusting for VACS score, only VWF (adjusted odds, 1.80; 95% CI, 1.04–3.12 per log2 increment) was associated with subsequent ischemic stroke. In a sensitivity analysis excluding participants with viral load ≥400 copies/mL, associations between VWF and ischemic stroke were attenuated, with risk estimates ranging from 1.59 to 1.64 per log2 increment.ConclusionsEndothelial activation and related release and attachment of VWF may play an important role in ischemic stroke among persons with treated HIV infection.

Deep sequencing analysis of M184V/I mutation at the switch and at the time of virological failure of boosted protease inhibitor plus lamivudine or boosted protease inhibitor maintenance strategy (substudy of the ANRS-MOBIDIP trial).

The ANRS12286/MOBIDIP trial showed that boosted protease inhibitor (bPI) plus lamivudine dual therapy was superior to bPI monotherapy as maintenance treatment in subjects with a history of M184V mutation. We aimed to deep analyse the detection of M184V/I variants at time of switch and at the time of virological failure (VF). Ultra-deep sequencing (UDS) was performed on proviral HIV-DNA at inclusion among 265 patients enrolled in the ANRS 12026/MOBIDIP trial, and on plasma from 31 patients experiencing VF. The proportion of M184V/I variants was described and the association between the M184V/I mutation at 1% of threshold and VF was explored with logistic regression models. M184V and I mutations were detected in HIV-DNA for 173/252 (69%) and 31/252 (12%) of participants, respectively. Longer duration of first-line treatment, higher plasma viral load at first-line treatment failure and higher baseline HIV-DNA load were associated with the archived M184V. M184I mutation was always associated with a STOP codon, suggesting defective virus. The 48 week estimated probability of remaining free from VF was comparable with or without the M184V/I mutation for dual therapy. At failure, M184V and major PI mutations were detected in 1/17 and 5/15 patients in the bPI arm and in 2/2 and 0/3 in the bPI+lamivudine arm, respectively. Using UDS evidenced that archiving of M184V in HIV-DNA is heterogeneous despite past historical M184V in 96% of cases. The antiviral efficacy of lamivudine-based dual therapy regimens is mainly due to the residual lamivudine activity.

HLA-C: Plasma viral load and antibiotic susceptibility pattern of microbial infection in HIV-1 among serodiscordant couples in Nigeria

Background: The role Human Leucocyte Antigen-C class I play in microbial infections and antibiotic susceptibility among heterosexual HIV-1 serodiscordant couples is not known in Nigeria. Therefore, this study evaluated the association between HLA-C Class I, microbial infection, antibiotic susceptibility in HIV-1 transmission amongst heterosexual serodiscordant couples in Nigeria. Methods and materials: A total of 271 serodiscordant who signed informed consent document were enrolled into this study. Extracted genomic DNA was sequenced on exons 2 and 3 DNA for both high and low resolutions of HLA-C class 1 genotyping using allele-specific primers. Baseline and follow-up HIV-1 RNA (plasma viral load), CD4+ count analysis was done for HIV positive individuals. One hundred and twenty-six (126) High vaginal/endocervical swabs, 11 urethral swabs and 137 early morning urine samples passed through: microscopy, culture, Antibiotics susceptibility test and other identification methods. Results: Participants age ranged from 20 to >50 years with median age of 38 years. Two hundred and eight (208) etiologic agents were isolated and Candida spp. 56 (26.9%), Staphylococcus aureus and Escherichia coli 46 (22.1%) respectively were the most prevalent. Staphylococcus aureus showed more sensitivity to Augmentin (95.4%) and Gentamycin (90.4%) and more resistance to Ceftazidime and Gentamycin (81.4%/72.3%). HLA-C*040101 72 (34.5%)/C*0701 57 (24.2%) and C*040101 106 (39.0%)/C*0701 86 (31.6%) were the most prevalent alleles associated with high plasma viral load at baseline and after 6 months on ARV (p<0.000, p<0.003). Sexually transmitted infections (STIs) and Reproductive tract infections (RTIs) were associated with increased plasma viral load (p < 0.057/p > 0.071). HLA-C*070201 22 (9.0%) was independently associated with HIV-1 susceptibility (p < 0.006) among Serodiscordant Couples. Conclusion: High plasma viral load was significantly associated with STIs and RTIs which was independently associated with resistance to Ceftazidime and Gentamycin. The HLA-C alleles which has increased chances of HIV-1 transmission from HIV positive Index to the recipient Partner is also significantly associated with high plasma viral load. Seriologic HLA-C*070201, was the allele associated with HIV-1 susceptibility based on polymorphism in HLA-C class 1 genetic markers in serodiscordant couples in Nigeria.

Methylation regulation of Antiviral host factors, Interferon Stimulated Genes (ISGs) and T-cell responses associated with natural HIV control.

GWAS, immune analyses and biomarker screenings have identified host factors associated with in vivo HIV-1 control. However, there is a gap in the knowledge about the mechanisms that regulate the expression of such host factors. Here, we aimed to assess DNA methylation impact on host genome in natural HIV-1 control. To this end, whole DNA methylome in 70 untreated HIV-1 infected individuals with either high (>50,000 HIV-1-RNA copies/ml, n = 29) or low (<10,000 HIV-1-RNA copies/ml, n = 41) plasma viral load (pVL) levels were compared and identified 2,649 differentially methylated positions (DMPs). Of these, a classification random forest model selected 55 DMPs that correlated with virologic (pVL and proviral levels) and HIV-1 specific adaptive immunity parameters (IFNg-T cell responses and neutralizing antibodies capacity). Then, cluster and functional analyses identified two DMP clusters: cluster 1 contained hypo-methylated genes involved in antiviral and interferon response (e.g. PARP9, MX1, and USP18) in individuals with high viral loads while in cluster 2, genes related to T follicular helper cell (Tfh) commitment (e.g. CXCR5 and TCF7) were hyper-methylated in the same group of individuals with uncontrolled infection. For selected genes, mRNA levels negatively correlated with DNA methylation, confirming an epigenetic regulation of gene expression. Further, these gene expression signatures were also confirmed in early and chronic stages of infection, including untreated, cART treated and elite controllers HIV-1 infected individuals (n = 37). These data provide the first evidence that host genes critically involved in immune control of the virus are under methylation regulation in HIV-1 infection. These insights may offer new opportunities to identify novel mechanisms of in vivo virus control and may prove crucial for the development of future therapeutic interventions aimed at HIV-1 cure.

HIV transmission by human bite: a case report and review of the literature\u2014implications for post-exposure prophylaxis

We report a case of a probable HIV-1 transmission by human bite. The analyzed data from ten previously reported suspected or allegedly confirmed HIV transmissions revealed a deep bleeding bite wound as the primary risk factor. A high HIV plasma viral load and bleeding oral lesions are present most of the time during HIV transmission by bite. HIV post-exposure prophylaxis (PEP) should be recommended in case of a bleeding wound resulting from a bite of an HIV-infected person. PEP was missed in this presented case.

An HIV-1 Nef genotype that diminishes immune control mediated by protective human leucocyte antigen alleles.

Certain human leucocyte antigen (HLA)-B alleles (protective alleles) associate with durable immune control of HIV-1, but with substantial heterogeneity in the level of control. It remains elusive whether viral factors including Nef-mediated immune evasion function diminish protective allele effect on viral control. The naturally occurring non-Ser variant at position 9 of HIV-1 subtype C Nef has recently exhibited an association with enhanced HLA-B downregulation function and decreased susceptibility to recognition by CD8 T cells. We therefore hypothesized this Nef genotype leads to diminished immune control mediated by protective HLA alleles. Nef sequences were isolated from HIV-1 subtype C-infected patients harboring protective alleles and several Nef functions including downregulation of HLA-A, HLA-B, CD4, and SERINC5 were examined. Association between Nef non-Ser9 and plasma viral load was examined in two independent South African and Botswanan treatment-naïve cohorts. Nef clones isolated from protective allele individuals encoding Nef non-Ser9 variant exhibited greater ability to downregulate HLA-B when compared with the Ser9 variant, while other Nef functions including HLA-A, CD4, and SERINC5 downregulation activity were unaltered. By analyzing a cohort of South African participants chronically infected with subtype C HIV-1, Nef non-Ser9 associated with higher plasma viral load in patients harboring protective alleles. Corroboratively, the Nef non-Ser9 correlated with higher plasma viral load in an independent cohort in Botswana. Taken together, our study identifies the Nef genotype, non-Ser9 that subverts host immune control in HIV-1 subtype C infection.