Search

BACKGROUND: HVTN 120 is a phase 1/2a randomized double-blind placebo-controlled human immunodeficiency virus (HIV) vaccine trial that evaluated the safety and immunogenicity of ALVAC-HIV (vCP2438) and MF59- or AS01B-adjuvanted bivalent subtype C gp120 Env protein at 2 dose levels in healthy HIV-uninfected adults. METHODS: Participants received ALVAC-HIV (vCP2438) alone or placebo at months 0 and 1. At months 3 and 6, participants received either placebo, ALVAC-HIV (vCP2438) with 200 μg of bivalent subtype C gp120 adjuvanted with MF59 or AS01B, or ALVAC-HIV (vCP2438) with 40 μg of bivalent subtype C gp120 adjuvanted with AS01B. Primary outcomes were safety and immune responses. RESULTS: We enrolled 160 participants, 55% women, 18-40 years old (median age 24 years) of whom 150 received vaccine and 10 placebo. Vaccines were generally safe and well tolerated. At months 6.5 and 12, CD4+ T-cell response rates and magnitudes were higher in the AS01B-adjuvanted groups than in the MF59-adjuvanted group. At month 12, HIV-specific Env-gp120 binding antibody response magnitudes in the 40 μg gp120/AS01B group were higher than in either of the 200 μg gp120 groups. CONCLUSIONS: The 40 μg dose gp120/AS01B regimen elicited the highest CD4+ T-cell and binding antibody responses. Clinical Trials Registration . NCT03122223.

BACKGROUNDEarly antiretroviral therapy initiation (ARTi) in HIV-1 restricts reservoir size and diversity while preserving immune function, potentially improving opportunities for immunotherapeutic cure strategies. For antibody-based cure approaches, the development of autologous neutralizing antibodies (anAbs) after acute/early ARTi is relevant but is poorly understood.METHODSWe characterized antibody responses in a cohort of 23 participants following ARTi in acute HIV (

CD4 T follicular helper cells (Tfh) are essential for establishing serological memory and have distinct helper attributes that impact both the quantity and quality of the antibody response. Insights into Tfh subsets that promote antibody persistence and functional capacity can critically inform vaccine design. Based on the Tfh profiles evoked by the live attenuated measles virus vaccine, renowned for its ability to establish durable humoral immunity, we investigated the potential of a Tfh1/17 recall response during the boost phase to enhance persistence of HIV-1 Envelope (Env) antibodies in rhesus macaques. Using a DNA-prime encoding gp160 antigen and Tfh polarizing cytokines (interferon protein-10 (IP-10) and interleukin-6 (IL-6)), followed by a gp140 protein boost formulated in a cationic liposome-based adjuvant (CAF01), we successfully generated germinal center (GC) Tfh1/17 cells. In contrast, a similar DNA-prime (including IP-10) followed by gp140 formulated with monophosphoryl lipid A (MPLA) +QS-21 adjuvant predominantly induced GC Tfh1 cells. While the generation of GC Tfh1/17 cells with CAF01 and GC Tfh1 cells with MPLA +QS-21 induced comparable peak Env antibodies, the latter group demonstrated significantly greater antibody concentrations at week 8 after final immunization which persisted up to 30 weeks (gp140 IgG ng/ml- MPLA; 5500; CAF01, 2155; p

Background: Transgender women (hereafter "trans women") face social marginalization, stigma, and discrimination and experience a high burden of HIV. More recently, trans women have been identified as having a high risk for hepatitis C (HCV) infection. The interaction between these two diseases and the risks for HIV/HCV co-infection among trans women are understudied. Objective: To characterize epidemiological, behavioral, and socio-structural interactions between HIV and HCV infections among trans women. Methods: This cross-sectional study examined data from a community-based survey of trans women in San Francisco recruited through respondent-driven sampling (RDS) in 2019/2020. Face-to-face interviews collected data on demographics, medical history, drug injection practices, sexual behavior, and socio-structural factors (e.g., poverty, housing insecurity, incarceration, social support). HIV and HCV antibodies were detected using oral fluid rapid tests and prior diagnosis and treatment were collected by self-report. Blood specimens were collected to confirm antibodies using ELISA. Multinomial logistic regression analysis characterized factors associated with HIV infection alone, HCV infection alone, and HIV/HCV co-infection compared to neither infection. Results: Among 201 trans women recruited, HIV prevalence was 42.3%; HCV infection by history or current seroprevalence was 28.9%; evidence for both HIV and HCV infection was present for 18.9%. Two-thirds of trans women (67.2%) had been incarcerated; 30.8% had ever injected drugs. History of injection drug use and receiving emotional support from family were factors found in common for HIV infection, HCV infection, and HIV/HCV co-infection compared to no infection. Having a sexual partner who injects drugs was associated with HIV infection alone. Not lacking care due to cost and older age were associated with co-infection. Older age was also associated with HCV infection. Of trans women with HIV infection, 91.8% had accessed HIV care, whereas only 62% with HCV had accessed some form of care. Conclusions: Our study found high levels of HIV, HCV, and HIV/HCV co-infection among trans women in San Francisco. We found common associations between HIV and HCV through injection practices and emotional support, but having a sexual partner who injects drugs was not associated with HCV infection alone or co-infection. We note a substantial gap in the treatment of HCV for trans women, including those in HIV care, that needs to be urgently addressed. [ABSTRACT FROM AUTHOR]

Background: High HIV viral loads (VL) are associated with increased morbidity, mortality, and on-going transmission. HIV controllers maintain low VLs in the absence of antiretroviral therapy (ART). We previously used a massively multiplexed antibody profiling assay (VirScan) to compare antibody profiles in HIV controllers and persons living with HIV (PWH) who were virally suppressed on ART. In this report, we used VirScan to evaluate whether antibody reactivity to specific HIV targets and broad reactivity across the HIV genome was associated with VL and controller status 1–2 years after infection. Methods: Samples were obtained from participants who acquired HIV infection in a community-randomized trial in Africa that evaluated an integrated strategy for HIV prevention (HPTN 071 PopART). Controller status was determined using VL and antiretroviral (ARV) drug data obtained at the seroconversion visit and 1 year later. Viremic controllers had VLs <2,000 copies/mL at both visits; non-controllers had VLs >2,000 copies/mL at both visits. Both groups had no ARV drugs detected at either visit. VirScan testing was performed at the second HIV-positive visit (1–2 years after HIV infection). Results: The study cohort included 13 viremic controllers and 64 non-controllers. We identified ten clusters of homologous peptides that had high levels of antibody reactivity (three in gag, three in env, two in integrase, one in protease, and one in vpu). Reactivity to 43 peptides (eight unique epitopes) in six of these clusters was associated with lower VL; reactivity to six of the eight epitopes was associated with HIV controller status. Higher aggregate antibody reactivity across the eight epitopes (more epitopes targeted, higher mean reactivity across all epitopes) and across the HIV genome was also associated with lower VL and controller status. Conclusions: We identified HIV antibody targets associated with lower VL and HIV controller status 1–2 years after infection. Robust aggregate responses to these targets and broad antibody reactivity across the HIV genome were also associated with lower VL and controller status. These findings provide novel insights into the relationship between humoral immunity and viral containment that could help inform the design of antibody-based approaches for reducing HIV VL. [ABSTRACT FROM AUTHOR]

ABSTRACT HCV RNA test determines current active infection and is a requirement prior to initiating HCV treatment. We investigated trends and factors associated with post‐diagnosis HCV RNA testing rates prior to HCV treatment, and risk factors for first positive HCV RNA among people living with HIV (PLHIV) with HCV in the Asia‐Pacific region. PLHIV with positive HCV antibody and in follow‐up after 2010 were included. Patients were considered HCV‐antibody positive if they ever tested positive for HCV antibody (HCVAb). Repeated measures Poisson regression model was used to analyse factors associated with post‐diagnosis HCV RNA testing rates from positive HCVAb test. Factors associated with time to first positive HCV RNA from positive HCVAb test were analysed using Cox regression model. There were 767 HCVAb positive participants included (87% from LMICs) of whom 11% had HCV RNA tests. With 163 HCV RNA tests post positive HCVAb test, the overall testing rate was 5.05 per 100 person‐years. Factors associated with increased testing rates included later calendar years of follow‐up, HIV viral load ≥1000 copies/mL and higher income countries. Later calendar years of follow‐up, ALT >5 times its upper limit of normal, and higher income countries were associated with shorter time to first positive HCV RNA test. Testing patterns indicated that uptake was predominantly in high income countries possibly due to different strategies used to determine testing in LMICs. Expanding access to HCV RNA, such as through lower‐cost point of care assays, will be required to achieve elimination of HCV as a public health issue. [ABSTRACT FROM AUTHOR]

Treponema pallidum (T. pallidum) transmits syphilis through sexual contact or perinatal transmission. T. pallidum is widely known for being invasive and immune-evasive; its clinical symptoms are commonly mistaken for those of other diseases due to localized inflammatory responses to multiplying spirochetes. Complement fixation and precipitation/flocculation assays were developed in the early 20th century, and they were frequently combined to boost sensitivity and specificity because many cases were challenging. Despite a lifetime of negative anti-lipoidal serology, syphilis sequelae often develop. Treponemal tests (TPI, introduced in 1949) substantially improved sensitivity and reduced the number of false positives, but they were insensitive for primary syphilis. The teaching hospitals in Vienna have long confirmed that the TPHA discovers almost twice as many instances that aren't found as the VDRL. Numerous active cases without VDRL reactions were discovered using the avidity/affinity index (Boltzmann Institute for Serodiagnosis, Vienna) as a substitute for the IgM antibody. Despite these improvements, Ontario's Public Health Laboratory has discovered that gay men who are HIV antibody (+) selectively lose their treponemal antibody, making it hard to detect the incidence of syphilis. [ABSTRACT FROM AUTHOR]

Background HIV Vaccine Trials Network (HVTN) 704/085, a placebo-controlled clinical trial assessing the efficacy of VRC01 broadly neutralizing antibody infusion for HIV prevention, offered oral preexposure prophylaxis (PrEP) as the standard of prevention at no cost to participants. Methods We characterized features of- identified factors associated with- PrEP initiation and discontinuation, and the effects of PrEP initiation on HIV incidence. Results Of 2221 participants, 31.8% initiated oral PrEP during study follow-up, with the highest proportion of PrEP initiations in Brazil (83.2%) and the United States (US) (54.2%). Prior PrEP use was associated with PrEP initiation (hazard ratio [HR], 2.22 [95% confidence interval {CI}, 1.25–3.95]). Participants from Switzerland (HR, 0.5 [95% CI,.3–1.0]) and Peru (HR, 0.08 [95% CI,.06–.1]) had lower likelihood of PrEP initiation compared to the US, while participants from Brazil had higher likelihood (HR, 2.6 [95% CI, 2.0–3.3]). In the US, PrEP initiation was lower in areas with higher unmet need for PrEP (HR, 0.9 per 5 units [95% CI, 0.8–1.0]). PrEP initiators had 58% less risk of acquiring HIV than PrEP noninitiators. Among PrEP initiators, 34.4% discontinued PrEP during study follow-up. Brazil had 63% less likelihood of PrEP discontinuation than the US (HR, 0.37 [95% CI,.22–.60]). Conclusions When included as standard of prevention in HVTN 704/085, oral PrEP utilization patterns mirrored those observed in real-life settings. Variable effects of oral PrEP on HIV outcomes in clinical trials may be expected based on regional differences in oral PrEP use. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Modern Laboratory Medicine is the property of Journal of Modern Laboratory Medicine Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This article presents a case study of a 59-year-old white male patient who initially presented with symptoms that were thought to be related to a type of vasculitis called granulomatosis with polyangiitis (GPA). However, further investigation revealed that the patient had a rare and aggressive subtype of non-Hodgkin lymphoma called extranodal natural killer/T cell lymphoma (ENKTL). The patient's symptoms included nasal obstruction, epistaxis, dysphagia, and odynophagia. The article emphasizes the importance of considering alternative diagnoses in cases of ANCA-negative vasculitis and the challenges in diagnosing ENKTL. Unfortunately, the patient's condition worsened despite treatment, and he ultimately passed away from respiratory complications. [Extracted from the article]

Background. Blood safety levels have been significantly improved since the implementation of nucleic acid amplification technology (NAT) testing for blood donors. However, there remains a residual risk of transfusion transmission infections. This study aimed to evaluate the prevalence of HIV and its residual risk transmission among volunteer blood donors of Zhejiang Province, China, for five years after NAT implementation. Materials and Methods. All specimens and information were collected from voluntary unpaid donors at all blood services in Zhejiang Province, China, from January 2018 to December 2022. The HIV antibody or antigen and HIV RNA were detected using enzyme-linked immunosorbent assay and NAT, respectively. The HIV residual risk transmission was calculated using the incidence or window period model. Results. A total of 3,375,678 voluntary blood donors were detected, revealing an HIV prevalence of 9.92/100000. The HIV prevalence of blood donors in 12 blood services in Zhejiang Province was 6.11, 6.98, 7.45, 8.21, 8.36, 8.94, 9.04, 9.66, 9.73, 10.22, 11.80, and 12.47 per 100000 donors, without statistically significant difference observed among the services (p > 0.05). The HIV prevalence of males (15.49/100000) was significantly higher compared to females (1.95/100000; p < 0.05). There was an insignificant difference in HIV prevalence among blood donors of all different age groups (p > 0.05), but the HIV prevalence in the 26–35 age group and 18–25 age group was significantly higher compared to the 36–45 age group (p < 0.05). The difference in HIV prevalence between first-time blood donors (13.65/100,000) and repeat blood donors (6.78/100,000) was statistically significant (p < 0.05). From 2018 to 2022, the HIV residual risk in blood transfusion transmission was 0.266/100000. Conclusion. The prevalence of HIV among blood donors in Zhejiang Province, China, is associated with age, gender, and times of blood donation. The HIV residual risk in blood transfusion transmission remains low in the province, and increasing the rate of repeat blood donors is beneficial to improve blood safety. [ABSTRACT FROM AUTHOR]

The vaccine elicitation of HIV tier-2-neutralization antibodies has been a challenge. Here, we report the isolation and characterization of a CD4-binding site (CD4bs) specific monoclonal antibody, HmAb64, from a human volunteer immunized with a polyvalent DNA prime-protein boost HIV vaccine. HmAb64 is derived from heavy chain variable germline gene IGHV1-18 and light chain germline gene IGKV1-39. It has a third heavy chain complementarity-determining region (CDR H3) of 15 amino acids. On a cross-clade panel of 208 HIV-1 pseudo-virus strains, HmAb64 neutralized 20 (10%), including tier-2 strains from clades B, BC, C, and G. The cryo-EM structure of the antigen-binding fragment of HmAb64 in complex with a CNE40 SOSIP trimer revealed details of its recognition; HmAb64 uses both heavy and light CDR3s to recognize the CD4-binding loop, a critical component of the CD4bs. This study demonstrates that a gp120-based vaccine can elicit antibodies capable of tier 2-HIV neutralization. Here the authors isolate monoclonal antibody HmAb64 from a healthy volunteer who received an experimental polyvalent DNA prime-protein boost HIV vaccine, and show that it's specific for the CD4 binding site and neutralizes cross-subtype HIV isolates including several tier-2 viruses. [ABSTRACT FROM AUTHOR]

Objective lo explore the application value ot a recombinant antigen-based capture enzyme immunoassay (KAg-CEIA) in detection of recent human immunodeficiency virus type 1 (HIV-1) infection in the sentinel surveillance population. Methods Among the HIV/AIDS sentinel surveillance population in Yunnan province in 2015, the confirmed HIV-1 antibodies positive plasma specimens matching the detection criteria for recent HIV-1 infection were tested by HIV-1 RAg-CEIA. The recent HIV-1 infection specimens were classified by the normalized optical density (ODn) values, and then the HIV-1 incidence in population were estimated. The detection and analysis data were compared with those by BED capture enzyme immunoassay (BED-CEIA) and limiting antigen avidity enzyme immunoassay (LAg-Avidity EIA), respectively. Results A total of 51 313 plasma specimens were tested for HIV antibodies, in which 1 255 specimens were HIV-1 antibodies positive. 253 out of 373 specimens matching the detection criteria for recent HIV-1 infection were tested by the 3 assays, respectively. By RAg-CEIA, BED-CEIA and LAg-Avidity EIA, 88, 78 and 54 specimens were classified as recent HIV-1 infections, and the HIV-1 incidence in the sentinel surveillance population was 0.33% (95% CI: 0.26%~0.39%), 0.31% (95% CI: 0.24%-0.38%) and 0.31% (95% CI: 0.22%-0.39%), respectively. The differences between the HIV-1 incidence by the 3 assays were not statistically significant (P = 0.927). Among the sub-populations, the HIV-1 incidence in men who have sex with men (MSM) were 3.50% (95% CI: 2.48%-4.52%), 3.92% (95% CI: 2.76%-5.08%) and 4.17% (95% CI: 2.79%-5.55%), respectively. The differences between the HIV-1 incidence by the 3 assays were not statistically significant (P = 0.763). The ODn values by RAg-CEIA were linear correlation with those by BED-CEIA (Spearman's rank correlation coefficient was 0.911), and those by LAg-Avidity EIA (Spearman' s rank correlation coefficient was 0.755), respectively. Conclusion HIV-1 RAg-CEIA can be effectively used in classification of recent HIV-1 infections and estimation of HIV-1 incidence, indicating that this approach has a good application prospect in detection of recent HIV-1 infection. [ABSTRACT FROM AUTHOR]

Monoclonal antibodies are commonly engineered with an introduction of Met428Leu and Asn434Ser, known as the LS mutation, in the fragment crystallizable region to improve pharmacokinetic profiles. The LS mutation delays antibody clearance by enhancing binding affinity to the neonatal fragment crystallizable receptor found on endothelial cells. To characterize the LS mutation for monoclonal antibodies targeting HIV, we compared pharmacokinetic parameters between parental versus LS variants for five pairs of anti-HIV immunoglobin G1 monoclonal antibodies (VRC01/LS/VRC07-523LS, 3BNC117/LS, PGDM1400/LS PGT121/LS, 10-1074/LS), analyzing data from 16 clinical trials of 583 participants without HIV. We described serum concentrations of these monoclonal antibodies following intravenous or subcutaneous administration by an open two-compartment disposition, with first-order elimination from the central compartment using non-linear mixed effects pharmacokinetic models. We compared estimated pharmacokinetic parameters using the targeted maximum likelihood estimation method, accounting for participant differences. We observed lower clearance rate, central volume, and peripheral volume of distribution for all LS variants compared to parental monoclonal antibodies. LS monoclonal antibodies showed several improvements in pharmacokinetic parameters, including increases in the elimination half-life by 2.7- to 4.1-fold, the dose-normalized area-under-the-curve by 4.1- to 9.5-fold, and the predicted concentration at 4 weeks post-administration by 3.4- to 7.6-fold. Results suggest a favorable pharmacokinetic profile of LS variants regardless of HIV epitope specificity. Insights support lower dosages and/or less frequent dosing of LS variants to achieve similar levels of antibody exposure in future clinical applications. [ABSTRACT FROM AUTHOR]

BackgroundThe phase 2b proof-of-concept Antibody Mediated Prevention (AMP) trials showed that VRC01, an anti-HIV-1 broadly neutralising antibody (bnAb), prevented acquisition of HIV-1 sensitive to VRC01. To inform future study design and dosing regimen selection of candidate bnAbs, we investigated the association of VRC01 serum concentration with HIV-1 acquisition using AMP trial data.MethodsThe case-control sample included 107 VRC01 recipients who acquired HIV-1 and 82 VRC01 recipients who remained without HIV-1 during the study. We measured VRC01 serum concentrations with a qualified pharmacokinetic (PK) Binding Antibody Multiplex Assay. We employed nonlinear mixed effects PK modelling to estimate daily-grid VRC01 concentrations. Cox regression models were used to assess the association of VRC01 concentration at exposure and baseline body weight, with the hazard of HIV-1 acquisition and prevention efficacy as a function of VRC01 concentration. We also compared fixed dosing vs. body weight-based dosing via simulations.FindingsEstimated VRC01 concentrations in VRC01 recipients without HIV-1 were higher than those in VRC01 recipients who acquired HIV-1. Body weight was inversely associated with HIV-1 acquisition among both placebo and VRC01 recipients but did not modify the prevention efficacy of VRC01. VRC01 concentration was inversely correlated with HIV-1 acquisition, and positively correlated with prevention efficacy of VRC01. Simulation studies suggest that fixed dosing may be comparable to weight-based dosing in overall predicted prevention efficacy.InterpretationThese findings suggest that bnAb serum concentration may be a useful marker for dosing regimen selection, and operationally efficient fixed dosing regimens could be considered for future trials of HIV-1 bnAbs.FundingWas provided by the National Institutes of Health, National Institute of Allergy and Infectious Diseases (NIAID) (UM1 AI068614, to the HIV Vaccine Trials Network [HVTN]; UM1 AI068635, to the HVTN Statistical Data and Management Center [SDMC], Fred Hutchinson Cancer Center [FHCC]; 2R37 054165 to the FHCC; UM1 AI068618, to HVTN Laboratory Center, FHCC; UM1 AI068619, to the HPTN Leadership and Operations Center; UM1 AI068613, to the HIV Prevention Trials Network [HPTN] Laboratory Center; UM1 AI068617, to the HPTN SDMC; and P30 AI027757, to the Center for AIDS Research, Duke University (AI P30 AI064518) and University of Washington (P30 AI027757) Centers for AIDS Research; R37AI054165 from NIAID to the FHCC; and OPP1032144 CA-VIMC Bill & Melinda Gates Foundation.

Early initiation of antiretroviral therapy (ART) alters viral rebound kinetics after analytic treatment interruption (ATI) and may play a role in promoting HIV-1 remission. Autologous neutralizing antibodies (aNAbs) represent a key adaptive immune response in people living with HIV-1. We aimed to investigate the role of aNAbs in shaping post-ATI HIV-1 rebound variants. We performed single-genome amplification of HIV-1 env from pre-ART and post-ATI plasma samples of 12 individuals who initiated ART early after infection. aNAb activity was quantified using pseudoviruses derived from the most common plasma variant, and the serum dilution that inhibited 50% of viral infections was determined. aNAb responses matured while participants were on suppressive ART, because on-ART plasma and purified immunoglobulin G (IgG) demonstrated improved neutralizing activity against pre-ART HIV-1 strains when compared with pre-ART plasma or purified IgG. Post-ATI aNAb responses exerted selective pressure on the rebounding viruses, because the post-ATI HIV-1 strains were more resistant to post-ATI plasma neutralization compared with the pre-ART virus. Several pre-ATI features distinguished post-treatment controllers from noncontrollers, including an infecting HIV-1 sequence that was more similar to consensus HIV-1 subtype B, more restricted proviral diversity, and a stronger aNAb response. Post-treatment control was also associated with the evolution of distinct N-glycosylation profiles in the HIV-1 envelope. In summary, aNAb responses appeared to mature after early initiation of ART and applied selective pressure on rebounding viruses. The combination of aNAb activity with select HIV-1 sequence and reservoir features identified individuals with a greater chance of post-treatment control.

IntroductionInfant HIV prophylaxis with broadly neutralizing anti-HIV antibodies (bNAbs) could provide long-acting protection against vertical transmission. We sought to estimate the potential clinical impact and cost-effectiveness of hypothetical bNAb prophylaxis programmes for children known to be HIV exposed at birth in three sub-Saharan African settings.MethodsWe conducted a cost-effectiveness analysis using the CEPAC-Pediatric model, simulating cohorts of infants from birth through death in Côte d'Ivoire, South Africa and Zimbabwe. These settings were selected to reflect a broad range of HIV care cascade characteristics, antenatal HIV prevalence and budgetary constraints. We modelled strategies targeting bNAbs to only WHO-designated "high-risk" HIV-exposed infants (HR-HIVE) or to all HIV-exposed infants (HIVE). We compared four prophylaxis approaches within each target population: standard of care oral antiretroviral prophylaxis (SOC), and SOC plus bNAbs at birth (1-dose), at birth and 3 months (2-doses), or every 3 months throughout breastfeeding (Extended). Base-case model inputs included bNAb efficacy (60%/dose), effect duration (3 months/dose) and costs ($60/dose), based on published literature. Outcomes included paediatric HIV incidence and incremental cost-effectiveness ratios (ICERs) calculated from discounted life expectancy and lifetime HIV-related costs.ResultsThe model projects that bNAbs would reduce absolute infant HIV incidence by 0.3-2.2% (9.6-34.9% relative reduction), varying by country, prophylaxis approach and target population. In all three settings, HR-HIVE-1-dose would be cost-saving compared to SOC. Using a 50% GDP per capita ICER threshold, HIVE-Extended would be cost-effective in all three settings with ICERs of $497/YLS in Côte d'Ivoire, $464/YLS in South Africa and $455/YLS in Zimbabwe. In all three settings, bNAb strategies would remain cost-effective at costs up to $200/dose if efficacy is ≥30%. If the bNAb effect duration were reduced to 1 month, the cost-effective strategy would become HR-HIVE-1-dose in Côte d'Ivoire and Zimbabwe and HR-HIVE-2-doses in South Africa. Findings regarding the cost-effectiveness of bNAb implementation strategies remained robust in sensitivity analyses regarding breastfeeding duration, maternal engagement in postpartum care, early infant diagnosis uptake and antiretroviral treatment costs.ConclusionsAt current efficacy and cost estimates, bNAb prophylaxis for HIV-exposed children in sub-Saharan African settings would be a cost-effective intervention to reduce vertical HIV transmission.

Vaccination strategies aimed at maturing broadly neutralizing antibodies (bnAbs) from naïve precursors are hindered by unusual features that characterize these Abs, including insertions and deletions (indels). Longitudinal studies of natural HIV infection cases shed light on the complex processes underlying bnAb development and have suggested a role for superinfection as a potential enhancer of neutralization breadth. Here we describe the development of a potent bnAb lineage that was elicited by two founder viruses to inform vaccine design. The V3-glycan targeting bnAb lineage (PC39-1) was isolated from subtype C-infected IAVI Protocol C elite neutralizer, donor PC39, and is defined by the presence of multiple independent insertions in CDRH1 that range from 1-11 amino acids in length. Memory B cell members of this lineage are predominantly atypical in phenotype yet also span the class-switched and antibody-secreting cell compartments. Development of neutralization breadth occurred concomitantly with extensive recombination between founder viruses before each virus separated into two distinct population "arms" that evolved independently to escape the PC39-1 lineage. Ab crystal structures show an extended CDRH1 that can help stabilize the CDRH3. Overall, these findings suggest that early exposure of the humoral system to multiple related Env molecules could promote the induction of bnAbs by focusing Ab responses to conserved epitopes.

Background: Blood transfusion is associated with exposure to blood Transfusion Transmissible Infection (TTIs). The threat posed by the blood-borne pathogens is disproportionately distributed in different healthcare facilities in Cameroon. Thus, there is a need for continuous surveillance of TTIs in the country. This study aimed to assess the screening procedure for blood transfusion and determine the trend in immunological markers of TTIs among blood donors at the Mamfe District Hospital. Methods: A prospective descriptive, cross-sectional and analytical study was conducted at Mamfe District Hospital from March to May 2022. A total of 165 blood donors were recruited by the consecutive sampling method. Donors were screened using both Rapid diagnostic tests,T. pallidum haemagglutination test and indirect enzyme-linked immunosorbent assay (ELISA) for the detection of TTIs. Data generated was entered into an Excel spreadsheet and analysed using the statistical software R, version 4.2.0. Statistical analysis included descriptive statistics of percentages, means ± standard deviation, and student t-test was used to compare both diagnostic techniques, and was considered significant when p < 0.05. Results: A hundred and sixty-five donors were enrolled in the study with a male preponderance giving a male-female sex ratio of 22.5 and a mean age of 32.23 ± 8.60 years. The majority (75.2%) of the donors were of the O-positive blood type, repeat donors (69.1%) and were mainly family replacement and paid donors as against the voluntary blood donors (39.4% and 37.0% vs. 23.6% respectively). overall TTIs prevalence was 18.78% (31/165) (), with HBsAg being the most predominant marker at 12.12% (20/165) followed by Treponema pallidum, HCV and HIV antibodies at 4.85 (8/165), 1.21%(2/165), 0.60% (1/165) respectively. Except for the HBV, The prevalence of TTIs was higher when using a single RDT than the ELISA test, and the difference was significant (p < 0.05). Conclusion: Bloodborne pathogens remain a major menace to safe blood transfusion practice in Mamfe district hospital and their detection could be easily missed if the RDT method alone is used for donor screening. Therefore, the donor screening protocol in Mamfe District Hospital should systematically incorporate a confirmation diagnostic test such as ELISA. [ABSTRACT FROM AUTHOR]

Background: The human immunodeficiency virus (HIV) targets the host immune system, particularly the CD4 T cells. The host resistance to opportunistic and non-opportunistic infections such as tuberculosis, fungal infections, severe bacterial infections, and several malignancies is weakened as a result of destruction of these CD4 cells by HIV. The purpose of this study was to determine the prevalence of HIV among individuals who participated in pre-employment medical screening at David Umahi Federal University Teaching Hospital Uburu, Ebonyi State, Nigeria, with the aim of connecting those who are HIV-positive to voluntary counseling and treatment programs. Methodology: This was a retrospective analysis of the medical records of 537 eligible participants who underwent pre-employment medical screening exercise, and whose blood samples were tested for presence of HIV antibodies at the University Teaching Hospital, using the Determine HIV-1/2 (T1) and Unigold HIV-1/2 (T2), and the tie breaker Statpak HIV-1/2 (T3) tests. The serological results were interpreted according to the national HIV testing algorithm, with test result declared negative for HIV antibodies if T1 was negative or if only T1 was positive but T2 and T3 were both negative. Results: Of the total record of 756 pre-employment participants for the medical screening exercise, only 537 met the inclusion criteria for the study. The mean age of the 537 participants was 34.2±6.9 and age range of 18-67 years; 325 (61.0%) were females while 212 (39.0%) were males. The seroprevalence of HIV among the study participants was 2.4% (13/537), with 1.4% (3/212) in the males and 3.1% (10/325) in the females (x²=0.879, OR=0.45; 95% CI=0.12-1.60, p=0.3485). Only participants in the age range 26--35 and 36-45 years were HIV seropositive, with prevalence of 2.9% (9/310) and 2.4% (4/169) respectively but the HIV seroprevalence was not significantly associated with age and gender of the participants (p>0.05). Conclusion: The study findings provide useful information for the hospital administration of the HIV situation of its planned workforce, which will help with decisions on HIV positive participants to enrol in antiretroviral therapy program. [ABSTRACT FROM AUTHOR]

Background: Sexually transmitted infections (STIs) such as syphilis and HIV remain to be a significant public health issue worldwide. Dual rapid point-of-care tests (POCTs) have shown promise for detecting antibodies to HIV and syphilis but have not been fully evaluated in the field. Our study supported the WHO ProSPeRo study on Sexually Transmitted Infection Point-of-Care Testing (STI POCT) by providing external quality assessment (EQA) for HIV and syphilis testing in reference laboratories and their associated clinical sites in seven countries. Methods: HIV/syphilis serum liquid and dried tube specimen (DTS) panels were prepared by CDC. Liquid panels were distributed to the reference laboratories for three rounds of testing using commercially and locally available laboratory-based serological tests. DTS panels were sent to the clinical testing sites for 8 rounds of POC testing using the Abbott SD BIOLINE HIV/Syphilis Duo test (hereafter referred to as SD BIOLINE) and the Chembio Dual Path Platform (DPP) HIV-Syphilis assay. EQA panels were tested at CDC using the Rapid Plasma Reagin (RPR) test and the Treponema pallidum Particle Agglutination assay (TP-PA) for syphilis antibodies. Genetic Systems HIV-1/HIV-2 Plus O EIA, Geenius HIV Supplemental Assay and the Oraquick Advance HIV test were used to detect HIV antibodies in the EQA panels. Results from the reference laboratories and POCT sites were compared to those obtained at the CDC and a percentage agreement was calculated. Results: Qualitative RPR and TP-PA performed at the reference laboratories demonstrated 95.4–100% agreement with CDC results while quantitative RPR and TP-PA tests demonstrated 87.7% and 89.2% agreement, respectively. A 93.8% concordance rate was observed for qualitative HIV testing in laboratories. EQA testing at clinical sites using dual tests showed 98.7% and 99.1% agreement for detection of HIV antibodies and eight out of 10 sites had > 95.8% agreement for syphilis testing. However, two clinical sites showed only 65.0–66.7% agreement for SD BIOLINE and 84.0–86.7% for DPP, respectively, for syphilis testing. Conclusions: Overall, laboratories demonstrated high EQA performance in this study. Both HIV/syphilis POCTs gave expected results in the clinic-based evaluations using DTS. However, testing errors were identified in a few testing sites suggesting the necessity for continuous training and monitoring the quality of POC testing. [ABSTRACT FROM AUTHOR]

Background: Dual point-of-care tests (POCTs) for the simultaneous detection of antibodies to HIV and syphilis have been developed. Since community-based organisations (CBO) are effective providers of HIV and syphilis testing among men who have sex with men (MSM), evaluation of the utility of these dual tests at CBO testing services is a high priority. The aim of this study is to determine the feasibility of performing dual HIV-syphilis POCT testing among both users and providers at these non-clinical sites. Methods: This evaluation assessed the utility of two lateral flow immunochromatographic antibody technologies for dual screening for HIV/syphilis among MSM seeking testing in four CBO testing services in Spain, Slovenia, Latvia, and Ukraine. The study's conceptual framework divides the concept of feasibility into two inter-related domains, acceptability, and usability and further breaks it down into six subdomains: learnability, willingness, suitability, satisfaction, efficacy, and effectiveness. The feasibility analysis was performed by calculating the median score in 3 stages (for individual questions, subdomains, and domains), using a summated scores method. Results: The final sample included 844 participants, 60 of which were found to be HIV test positive (7.1%) and 61 (7.2%) positive on testing for syphilis. There was a small difference (1.1%) when comparing the results of the two dual POCTs under evaluation to the tests routinely used at each site. The inter-rater agreement showed a high concordance between two independent readings. The analysis of the feasibility for the users of the services indicated good satisfaction, suitability, and willingness. In addition, among 18 providers the total mean score showed good acceptability and usability, good willingness, easy learnability, high suitability, and good efficacy, but lower satisfaction and effectiveness. The operational characteristics of both dual study POCTs were well evaluated by providers. Conclusions: The introduction of dual HIV and syphilis POCTs in CBO testing services for screening of MSM is feasible, with a high acceptability and usability both for users and providers. Implementation of dual POCTs for HIV and syphilis in CBO testing services is an opportunity for scaling up integrated HIV/syphilis testing for MSM. [ABSTRACT FROM AUTHOR]

BackgroundHuman immunodeficiency virus type 1 (HIV-1) sequence diversity and the presence of archived epitope muta-tions in antibody binding sites are a major obstacle for the clinical application of broadly neutralizing antibodies (bNAbs) against HIV-1. Specifically, it is unclear to what degree the viral reservoir is compartmentalized and if virus susceptibility to antibody neutralization differs across tissues.MethodsThe Last Gift cohort enrolled 7 people with HIV diagnosed with a terminal illness and collected antemortem blood and postmortem tissues across 33 anatomical compartments for near full-length env HIV genome sequencing. Using these data, we applied a Bayesian machine-learning model (Markov chain Monte Carlo-support vector machine) that uses HIV-1 envelope sequences and approximated glycan-occupancy information to quantitatively predict the half-maximal inhib-itory concentrations (IC50) of bNAbs, allowing us to map neutralization resistance pattern across tissue reservoirs.ResultsPredicted mean susceptibilities across tissues within participants were relatively homogenous, and the susceptibility pattern observed in blood often matched what was predicted for tissues. However, selected tissues, such as the brain, showed ev-idence of compartmentalized viral populations with distinct neutralization susceptibilities in some participants. Additionally, we found substantial heterogeneity in the range of neutralization susceptibilities across tissues within and between indi-viduals, and between bNAbs within individuals (standard deviation of log2(IC50) >3.4).ConclusionsBlood-based screening methods to determine viral susceptibility to bNAbs might underestimate the presence of resistant viral variants in tissues. The extent to which these resistant viruses are clinically relevant, that is, lead to bNAb therapeutic failure, needs to be further explored.

The extent to which perinatally HIV-infected children, following cART initiation, develop a low proviral reservoir burden over time, as measured by HIV DNA droplet-digital polymerase chain reaction (ddPCR) and the effect on HIV antibody is not well characterized. We measured proviral HIV DNA and plasma RNA virus load (VL) in 37 perinatally HIV-infected children at 6 months of age who initiated stable cART. At 6-11 years of age, HIV proviral DNA, HIV VL (RNA), and HIV antibody by Western Blot (WB) were assessed. CART was initiated before 6 months of age in 13 children and after 6 months in 24. At school age, the HIV DNA levels did not differ by the timing of cART, and the HIV DNA levels were lower in children with negative/indeterminate WB (p = 0.0256). Children with undetectable HIV RNA VL > 50% of the time since cART initiation had lower median DNA VL than children with undetectable VL < 50% of the time (p = 0.07). Long-term viral suppression in perinatally HIV-infected children is associated with a decrease in HIV antibodies and reduced HIV reservoirs.

Blood donations in South Africa are tested for HIV RNA using individual donation NAT (ID-NAT), allowing detection and rapid antiretroviral therapy (ART) of acute HIV infections. We enrolled a cohort of acute and recent HIV-infected blood donation candidates in South Africa in 2015-2018, measured HIV antibody, ID-NAT, and recency of infection

The article explores the potential of using broadly neutralizing antibodies (bnAbs) as a long-acting injectable immunoprophylaxis to reduce HIV acquisition in high-risk populations. It acknowledges the slow progress in meeting HIV prevention targets and highlights the ability of bnAbs to recognize and neutralize a wide range of HIV strains, making them a promising tool for prevention. Ongoing clinical trials are mentioned, focusing on the use of bnAbs in adults. The article emphasizes the importance of addressing social, economic, and structural barriers to effectively deliver HIV prevention and treatment. [Extracted from the article]

INTRODUCTION: Rapid initiation of antiretroviral therapy (ART) in early HIV infection is important to limit seeding of the viral reservoir. A number of studies have shown that if ART is commenced prior to seroconversion, the seroconversion may, or may not, occur. We aimed to assess whether seroreversion or no seroconversion occurs using samples collected during an early treatment study in South Africa. METHODS: We tested 10 longitudinal samples collected over three years from 70 blood donors who initiated ART after detection of acute or early HIV infection during donation screening on fourth- and fifth-generation HIV antibody and RNA assays, and three point of care (POC) rapid tests. Donors were allocated to three treatment groups: (1) very early, (2) early, and (3) later. Longitudinal samples were grouped into time bins post-treatment initiation. RESULTS: On all three high-throughput HIV antibody assays, no clear pattern of declining signal intensity was observed over time after ART initiation in any of the treatment initiation groups and 100% detection was obtained. The Abbott Determine POC assay showed 100% detection at all time points with no seroreversion. However, the Abbott ABON HIV1 and OraSure OraQuick POC assays showed lower proportions of detection in all time bins in the very early treated group, ranging from 50.0% (95% CI: 26.8-73.2%) to 83.1% (95% CI: 64.2-93.0%), and moderate detection rates in the early and later-treated groups. CONCLUSION: While our findings are generally reassuring for HIV detection when high-throughput serological screening assays are used, POC assays may have lower sensitivity for detection of HIV infection after early treatment. Findings are relevant for blood safety and other settings where POC assays are used.

BackgroundRecent studies have indicated that broadly neutralizing antibodies (bnAbs) in children may develop earlier after human immunodeficiency virus (HIV) infection compared to adults.MethodsWe evaluated plasma from 212 antiretroviral therapy-naive children with HIV (1-3 years old). Neutralization breadth and potency was assessed using a panel of 10 viruses and compared to adults with chronic HIV. The magnitude, epitope specificity, and immunoglobulin (Ig)G subclass distribution of Env-specific antibodies were assessed using a binding antibody multiplex assay.ResultsOne-year-old children demonstrated neutralization breadth comparable to chronically infected adults, whereas 2- and 3-year-olds exhibited significantly greater neutralization breadth (P = .014). Likewise, binding antibody responses increased with age, with levels in 2- and 3-year-old children comparable to adults. Overall, there was no significant difference in antibody specificities or IgG subclass distribution between the pediatric and adult cohorts. It is interesting to note that the neutralization activity was mapped to a single epitope (CD4 binding site, V2 or V3 glycans) in only 5 of 38 pediatric broadly neutralizing samples, which suggests that most children may develop a polyclonal neutralization response.ConclusionsThese results contribute to a growing body of evidence suggesting that initiating HIV immunization early in life may present advantages for the development of broadly neutralizing antibody responses.

Background & Method: The aim of the study is to study the effectiveness of Methotrexate as a steroid sparing agent in Type 2 Lepra reaction. A thorough clinical history, examination, blood counts, urine routine/microscopy, liver and renal function test, chest radiograph, abdominal-, and/or pelvic- sonography, Urine pregnancy test (if required), anti HIV antibodies (if required) were done in all the study participants. Result: In the study overall, there were 34 patients who were undergoing treatment and 18 patients had completed their treatment. In group A the number of patients undergoing treatment was greater than in group B whereas the number of patients who had completed their treatment was more in group B than group A. The mean duration of MDT treatment was greater in group B as compared to group A. The mean number of episodes was greater in group B as compared to group A. Similarly, Reaction severity scores and total duration of episodes were also more in group B participants as compared to group A. Conclusion: Methotrexate can serve as a steroid sparing agent in the treatment of T2LR where it may reduce the severity, duration and recurrences of T2LR. Methotrexate is a miraculous drug known since long with tremendous familiarity especially to dermatologists. It serves as a safe and comparatively cheaper therapeutic option. [ABSTRACT FROM AUTHOR]

The transmission of human immunodeficiency virus (HIV) through blood poses a slightly increased risk. As a result, patients requiring blood transfusions should be screened for HIV antibodies. This study examined the diagnostic effectiveness of the photostimulated chemiluminescence assay in detecting anti-HIV antibodies and determined the cut-off value for this method. The performance of the fully automated photostimulated chemiluminescence assay system was validated according to CNAS-GL038:2019 (2020) and CNAS-GL037:2019 (2019) guidelines. A retrospective study was conducted at the Department of Medical Laboratory, Nanjing Tongren Hospital, affiliated with Southeast University, from January 2020 to December 2022. A total of 77,386 cases were tested for anti-HIV antibodies using the photostimulated chemiluminescence assay, with 79 cases initially testing positive. The method's performance in detecting anti-HIV antibodies was evaluated using the Receiver Operating Characteristic (ROC) curve and the average Coefficient of Variation (CV) value of 3-year in-house quality control. The precision, detection limit, coincidence rate, and critical value of the performance verification results met the requirements. Using Western blotting (WB) as the reference method, positive cases were initially screened using the light-induced chemiluminescence method to determine the cut-off index (COI) value and draw the ROC curve. The maximum area under the ROC curve using the chemiluminescence method was 0.997, with a cutoff value of < 28.56, sensitivity of 98%, specificity of 100%, Jordan index of 0.98, and an average CV value of 3.55%. In conclusion, the photostimulated chemiluminescence assay has good diagnostic efficacy in detecting anti-HIV antibodies and is suitable for rapid screening before blood transfusion and surgery. [ABSTRACT FROM AUTHOR]

Adjuvants and antigen delivery kinetics can profoundly influence B cell responses and should be critically considered in rational vaccine design, particularly for difficult neutralizing antibody targets such as human immunodeficiency virus (HIV). Antigen kinetics can change depending on the delivery method. To promote extended immunogen bioavailability and to present antigen in a multivalent form, native-HIV Env trimers are modified with short phosphoserine peptide linkers that promote tight binding to aluminum hydroxide (pSer:alum). Here we explore the use of a combined adjuvant approach that incorporates pSer:alum-mediated antigen delivery with potent adjuvants (SMNP, 3M-052) in an extensive head-to-head comparison study with conventional alum to assess germinal center (GC) and humoral immune responses. Priming with pSer:alum plus SMNP induces additive effects that enhance the magnitude and persistence of GCs, which correlate with better GC-TFH cell help. Autologous HIV-neutralizing antibody titers are improved in SMNP-immunized animals after two immunizations. Over 9 months after priming immunization of pSer:alum with either SMNP or 3M-052, robust Env-specific bone marrow plasma cells (BM BPC) are observed. Furthermore, pSer-modification of Env trimer reduce targeting towards immunodominant non-neutralizing epitopes. The study shows that a combined adjuvant approach can augment humoral immunity by modulating immunodominance and shows promise for clinical translation. Protein antigens, such as HIV envelope protein, require adjuvants for high immunogenicity. Here the authors show that a combined adjuvant approach with slow antigen delivery and potent ISCOMs adjuvant primes robust germinal center activity and humoral immunity in non-human primates. pSer-modified antigen shifts immunodominance to allow subdominant epitope-targeting of rare B cells. [ABSTRACT FROM AUTHOR]

The low abundance of envelope spikes and the inability of IgG to aggregate virions render HIV-1 an inadequate target for antibody-mediated clearance by phagocytes. In an attempt to improve the ability of antibody to mediate the internalization of HIV-1 virions, we generated multimers of the broadly neutralizing HIV-1-specific monoclonal antibody (MAb) VRC01 using site-directed mutagenesis of the Fc segment. We then measured virion internalization using primary human monocytes and neutrophils. We found that, in the absence of complement, immune complexes consisting of HIV-1 virions and VRC01 multimers were slightly more efficiently internalized than were complexes formed with monomeric VRC01. The presence of complement, however, greatly augmented internalization of immune complexes formed with the multimeric MAb but had little impact on monomeric MAb-mediated internalization. Multimerization and the presence of complement overcome the limited ability of monomeric antibody to mediate internalization of HIV-1 virions and may thus provide a therapeutic approach to clearing virus. IMPORTANCE Antibody-mediated internalization of HIV-1 by phagocytes, a potential mechanism for clearing virus, is very inefficient. In an effort to improve viral clearance, we produced a multimeric form of the broadly neutralizing monoclonal antibody VRC01. We found that VRC01 antibody multimers (primarily hexamers) were only slightly more efficient in mediating HIV-1 internalization than was monomeric VRC01. However, the addition of complement resulted in substantially greater internalization of multimer-opsonized virus. In contrast, complement had little if any impact on internalization of monomer-opsonized virus. Therefore, antibody multimerization in combination with complement may overcome the limited ability of monomeric antibody to mediate internalization of HIV-1 virions. Our findings may provide a therapeutic approach to clearing virus.

Broadly-neutralizing antibodies (bNAbs) against HIV-1 Env can protect from infection. We characterize Ab1303 and Ab1573, heterologously-neutralizing CD4-binding site (CD4bs) antibodies, isolated from sequentially-immunized macaques. Ab1303/Ab1573 binding is observed only when Env trimers are not constrained in the closed, prefusion conformation. Fab-Env cryo-EM structures show that both antibodies recognize the CD4bs on Env trimer with an 'occluded-open' conformation between closed, as targeted by bNAbs, and fully-open, as recognized by CD4. The occluded-open Env trimer conformation includes outwardly-rotated gp120 subunits, but unlike CD4-bound Envs, does not exhibit V1V2 displacement, 4-stranded gp120 bridging sheet, or co-receptor binding site exposure. Inter-protomer distances within trimers measured by double electron-electron resonance spectroscopy suggest an equilibrium between occluded-open and closed Env conformations, consistent with Ab1303/Ab1573 binding stabilizing an existing conformation. Studies of Ab1303/Ab1573 demonstrate that CD4bs neutralizing antibodies that bind open Env trimers can be raised by immunization, thereby informing immunogen design and antibody therapeutic efforts.

BackgroundLeronlimab, a monoclonal antibody blocker of C-C chemokine receptor type 5 originally developed to treat human immunodeficiency virus infection, was administered as an open-label compassionate-use therapeutic for coronavirus disease 2019 (COVID-19).MethodsTwenty-three hospitalized severe/critical COVID-19 patients received 700 mg leronlimab subcutaneously, repeated after 7 days in 17 of 23 patients still hospitalized. Eighteen of 23 received other experimental treatments, including convalescent plasma, hydroxychloroquine, steroids, and/or tocilizumab. Five of 23 received leronlimab after blinded, placebo-controlled trials of remdesivir, sarilumab, selinexor, or tocilizumab. Outcomes and results were extracted from medical records.ResultsMean age was 69.5 ± 14.9 years; 20 had significant comorbidities. At baseline, 22 were receiving supplemental oxygen (3 high flow, 7 mechanical ventilation). Blood showed markedly elevated inflammatory markers (ferritin, D-dimer, C-reactive protein) and an elevated neutrophil-to-lymphocyte ratio. By day 30 after initial dosing, 17 were recovered, 2 were still hospitalized, and 4 had died. Of the 7 intubated at baseline, 4 were fully recovered off oxygen, 2 were still hospitalized, and 1 had died.ConclusionsLeronlimab appeared safe and well tolerated. The high recovery rate suggested benefit, and those with lower inflammatory markers had better outcomes. Some, but not all, patients appeared to have dramatic clinical responses, indicating that unknown factors may determine responsiveness to leronlimab. Routine inflammatory and cell prognostic markers did not markedly change immediately after treatment, although interleukin-6 tended to fall. In some persons, C-reactive protein clearly dropped only after the second leronlimab dose, suggesting that a higher loading dose might be more effective. Future controlled trials will be informative.

A protective HIV-1 vaccine has been hampered by a limited understanding of how B cells acquire neutralizing activity. Our previous vaccines expressing two different HIV-1 envelopes elicited robust antigen specific serum IgG titers in 20 rhesus macaques; yet serum from only two animals neutralized the autologous virus. Here, we used high throughput immunoglobulin receptor and single cell RNA sequencing to characterize the overall expansion, recall, and maturation of antigen specific B cells longitudinally over 90 weeks. Diversification and expansion of many B cell clonotypes occurred broadly in the absence of serum neutralization. However, in one animal that developed neutralization, two neutralizing B cell clonotypes arose from the same immunoglobulin germline and were tracked longitudinally. Early antibody variants with high identity to germline neutralized the autologous virus while later variants acquired somatic hypermutation and increased neutralization potency. The early engagement of precursors capable of neutralization with little to no SHM followed by prolonged affinity maturation allowed the two neutralizing lineages to successfully persist despite many other antigen specific B cells. The findings provide new insight into B cells responding to HIV-1 envelope during heterologous prime and boost immunization in rhesus macaques and the development of selected autologous neutralizing antibody lineages. Author summary: Protection from HIV-1 infection will likely require a vaccine to elicit neutralizing antibody responses that can recognize many different viral strains. However, development of these types of antibodies requires many years of infection and is a continued challenge for vaccine design. Furthermore, most antibodies elicited against HIV-1 Env lack neutralizing activity or can only neutralize the matching viral strain. Here we conducted a high throughput longitudinal investigation of how B cells responded to heterologous prime-boost vaccines expressing different HIV-1 Env immunogens when administered to nonhuman primates. In most animals, many B cells recognized the antigen, expanded, evolved through mutation, and persisted during vaccination but without acquiring neutralizing activity. In one animal that developed neutralizing antibodies against the vaccine strain, we traced the evolution of the B cells producing those antibodies over time. We found that two neutralizing antibody-producing B cell families were elicited early in vaccination and gained neutralization strength through expansion, continued mutation, and persistence over time, while also competing with many other non-neutralizing B cells. Our results suggest that early elicitation may be one factor that favors the induction of neutralizing antibodies against HIV Env. [ABSTRACT FROM AUTHOR]

Background: High HIV viral load (VL) is associated with increased transmission risk and faster disease progression. HIV controllers achieve viral suppression without antiretroviral (ARV) treatment. We evaluated viremic control in a community-randomized trial with >48,000 participants. Methods: A massively multiplexed antibody profiling system, VirScan, was used to quantify pre- and post-infection antibody reactivity to HIV peptides in 664 samples from 429 participants (13 controllers, 135 viremic non-controllers, 64 other non-controllers, 217 uninfected persons). Controllers had VLs <2,000 copies/mL with no ARV drugs detected at the first HIV-positive visit and one year later. Viremic non-controllers had VLs 2,000 copies/mL with no ARV drugs detected at the first HIV-positive visit. Other non-controllers had either ARV drugs detected at the first HIV-positive visit (n=47) or VLs <2,000 copies/mL with no ARV drugs detected at only one HIV-positive visit (n=17). Results: We identified pre-infection HIV antibody reactivities that correlated with post-infection VL. Pre-infection reactivity to an epitope in the HR2 domain of gp41 was associated with controller status and lower VL. Pre-infection reactivity to an epitope in the C2 domain of gp120 was associated with non-controller status and higher VL. Different patterns of antibody reactivity were observed over time for these two epitopes. Conclusion: These studies suggest that pre-infection HIV antibodies are associated with controller status and modulation of HIV VL. These findings may inform research on antibody-based interventions for HIV treatment. [ABSTRACT FROM AUTHOR]

Currently there are diagnostic tests available for human immunodeficiency virus (HIV) and tuberculosis (TB); however, they are still diagnosed separately, which can delay treatment in cases of co-infection. Here we report on a multiplex microarray technology for the detection of HIV and TB antibodies using p24 as well as TB CFP10, ESAT6 and pstS1 antigens on epoxy-silane slides. To test this technology for antigen–antibody interactions, immobilized antigens were exposed to human sera spiked with physiological concentrations of primary antibodies, followed by secondary antibodies conjugated to a fluorescent reporter. HIV and TB antibodies were captured with no cross-reactivity observed. The sensitivity of the slides was compared to that of high-binding plates. We found that the slides were more sensitive, with the detection limit being 0.000954 µg/mL compared to 4.637 µg/mL for the plates. Furthermore, stability studies revealed that the immobilized antigens could be stored dry for at least 90 days and remained stable across all pH and temperatures assessed, with pH 7.4 and 25 °C being optimal. The data collectively suggested that the HIV/TB multiplex detection technology we developed has the potential for use to diagnose HIV and TB co-infection, and thus can be developed further for the purpose. [ABSTRACT FROM AUTHOR]

A 18-year-old male presented with ulcers of lips and tongue and erythema of trunk of more than a month duration. Laboratory examinations for syphilis showed that TRUST (+) 1:32, TPPA (+), and HIV antibodies were negative. Combined with his case history and signs, he was diagnosed with secondary syphilis with chancre of lips and tongue and was cured by injecting benzathine penicillin 2.4 million U into gluteal muscles on both sides once a week for three times. After a month, the erythema and chancre disappeared. Three months later, the TRUST test was positive, the titer was 1:8, and the TPPA was positive. [ABSTRACT FROM AUTHOR]

Background We aimed to investigate whether there are differences in cardiac structure and systolic and diastolic function evaluated by 2-dimensional echocardiography among men living with versus without HIV in the era of combination antiretroviral therapy. Methods and Results We performed a cross-sectional analysis of 1195 men from MACS (Multicenter AIDS Cohort Study) who completed a transthoracic echocardiogram examination between 2017 and 2019. Associations between HIV serostatus and echocardiographic indices were assessed by multivariable regression analyses, adjusting for demographics and cardiovascular risk factors. Among men who are HIV+, associations between HIV disease severity markers and echocardiographic parameters were also investigated. Average age was 57.1±11.9 years; 29% of the participants were Black, and 55% were HIV+. Most men who were HIV+ (77%) were virally suppressed; 92% received combination antiretroviral therapy. Prevalent left ventricular (LV) systolic dysfunction (ejection fraction