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With more than 7000 new HIV infections each day, there is a tremendous need for a prophylactic HIV vaccine. In this study involving more than 16,000 largely heterosexual subjects in Thailand, a vaccine regimen against HIV showed some efficacy against HIV acquisition but did not have an effect on the subsequent viral load or CD4+ count in those who became infected. A vaccine regimen against HIV showed some efficacy against HIV acquisition but did not have an effect on the subsequent viral load or CD4+ count in those who became infected. In the late 1980s in Thailand, there was a dramatic increase in the prevalence of infection with the human immunodeficiency virus type 1 (HIV-1) in sentinel surveillance cohorts. 1 – 3 Initially, these groups consisted of injection-drug users and commercial sex workers; they were subsequently expanded to include persons in the general population. By 1995, the overall seroprevalence of HIV-1 reached a peak of 3.7% among conscripts in the Royal Thai Army and of 12.5% among conscripts from Northern Thailand. 2 , 4 , 5 The Thai Ministry of Public Health responded with an effective HIV-prevention campaign, and the number of new HIV-1 infections per . . .

Loss of immune control over opportunistic infections can occur at different stages of HIV-1 (HIV) disease, among which mucosal candidiasis caused by the fungal pathogen Candida albicans (C. albicans) is one of the early and common manifestations in HIV-infected human subjects. The underlying immunological basis is not well defined. We have previously shown that compared to cytomegalovirus (CMV)-specific CD4 cells, C. albicans-specific CD4 T cells are highly permissive to HIV in vitro. Here, based on an antiretroviral treatment (ART) naïve HIV infection cohort (RV21), we investigated longitudinally the impact of HIV on C. albicans- and CMV-specific CD4 T-cell immunity in vivo. We found a sequential dysfunction and preferential depletion for C. albicans-specific CD4 T cell response during progressive HIV infection. Compared to Th1 (IFN-γ, MIP-1β) functional subsets, the Th17 functional subsets (IL-17, IL-22) of C. albicans-specific CD4 T cells were more permissive to HIV in vitro and impaired earlier in HIV-infected subjects. Infection history analysis showed that C. albicans-specific CD4 T cells were more susceptible to HIV in vivo, harboring modestly but significantly higher levels of HIV DNA, than CMV-specific CD4 T cells. Longitudinal analysis of HIV-infected individuals with ongoing CD4 depletion demonstrated that C. albicans-specific CD4 T-cell response was preferentially and progressively depleted. Taken together, these data suggest a potential mechanism for earlier loss of immune control over mucosal candidiasis in HIV-infected patients and provide new insights into pathogen-specific immune failure in AIDS pathogenesis.

The conduct of Phase I/II HIV vaccine trials internationally necessitates the development of region-specific clinical reference ranges for trial enrollment and participant monitoring. A population based cohort of adults in Kericho, Kenya, a potential vaccine trial site, allowed development of clinical laboratory reference ranges. Lymphocyte immunophenotyping was performed on 1293 HIV seronegative study participants. Hematology and clinical chemistry were performed on up to 1541 cohort enrollees. The ratio of males to females was 1.9:1. Means, medians and 95% reference ranges were calculated and compared with those from other nations. The median CD4+ T cell count for the group was 810 cells/microl. There were significant gender differences for both red and white blood cell parameters. Kenyan subjects had lower median hemoglobin concentrations (9.5 g/dL; range 6.7-11.1) and neutrophil counts (1850 cells/microl; range 914-4715) compared to North Americans. Kenyan clinical chemistry reference ranges were comparable to those from the USA, with the exception of the upper limits for bilirubin and blood urea nitrogen, which were 2.3-fold higher and 1.5-fold lower, respectively. This study is the first to assess clinical reference ranges for a highland community in Kenya and highlights the need to define clinical laboratory ranges from the national community not only for clinical research but also care and treatment.

Background: The continued rise of antimicrobial resistance (AMR) and reduction of pharmacological options has created an urgent need for new countermeasures to prevent the spread of multidrug-resistant organisms (MDROs) (1). Infections caused by the MDRO Candida auris (C. auris) have been proliferating since its discovery in 2009 and are associated with high mortality and AMR (2). Attention must be given to pathogen reservoirs, including surfaces of floors, which have an underappreciated potential to transfer pathogens to hands from objects in contact with the floor (3). Methods: An experimental study to explore the impact of advanced photohydrolysis (AP) technology on colony forming units (CFUs) of aerobic bacteria, fungi, and C. auris inside a hospital unit with active C. auris infections was performed from September 2023 to January 2024. Baseline pre-activation samples were compared to post-activation samples, which occurred every four weeks on Tuesday mornings prior to daily environmental services (EVS) cleaning. Patient outcomes of C. auris colonization and HAI rates were compared 8 months before and after AP technology installation. C. auris point-prevalence testing was performed during the 16-month observation period according to health department protocols and HAIs were evaluated by the same infection preventionist and defined by NHSN standards for catheter associated urinary tract infections (CAUTIs), central line associated bloodstream infections (CLABSIs), Clostridioides difficile (CDIFF), and methicillin resistant Staphylococcus aureus (MRSA) (4). Results: Pairwise comparisons with a Bonferroni correction found median floor fungal CFUs achieved a statistically significant reduction of 99% (p=0.11) from Baseline to Post-Activation #4 (Figure 1). Aerobic bacteria decreased 98% (Figure 2); C. auris by 66% (Figure 3) but did not achieve statistical significance. The rate of patient C. auris colonization after admission decreased 67% (Figure 4) and aggregate HAI rates decreased 75% (Figure 5). Additional Findings: High-touch surface samples showed reductions in mean CFUs of aerobic bacteria by 82% (6,456 to 1,161) and fungi by 99% (2,089 to 15). C. auris was reduced by 100% from Baseline to Post-Activation #3 (41 to 0) but increased in Post-Activation #4 due to two positive samples in a patient room with an active C. auris infection. Both samples tested under 500 CFU/cm2, which is associated with lower infection risk from environmental bioburden (5). Conclusion: These findings of significant reductions in microbial bioburden and abated pathogen acquisition demonstrate the positive impact that AP continuous disinfection technology can have on the environment and patient outcomes, without additional skilled labor or increases in cleaning and disinfection practices.

The human T-lymphotropic viruses (HTLVs) types 1 and 2 originated independently and are related to distinct lineages of simian T-lymphotropic viruses (STLV-1 and STLV-2, respectively). These facts, along with the finding that HTLV-1 diversity appears to have resulted from multiple cross-species transmissions of STLV-1, suggest that contact between humans and infected nonhuman primates (NHPs) may result in HTLV emergence. We investigated the diversity of HTLV among central Africans reporting contact with NHP blood and body fluids through hunting, butchering, and keeping primate pets. We show that this population is infected with a wide variety of HTLVs, including two previously unknown retroviruses: HTLV-4 is a member of a phylogenetic lineage that is distinct from all known HTLVs and STLVs; HTLV-3 falls within the phylogenetic diversity of STLV-3, a group not previously seen in humans. We also document human infection with multiple STLV-1-like viruses. These results demonstrate greater HTLV diversity than previously recognized and suggest that NHP exposure contributes to HTLV emergence. Our discovery of unique and divergent HTLVs has implications for HTLV diagnosis, blood screening, and potential disease development in infected persons. The findings also indicate that cross-species transmission is not the rate-limiting step in pandemic retrovirus emergence and suggest that it may be possible to predict and prevent disease emergence by surveillance of populations exposed to animal reservoirs and interventions to decrease risk factors, such as primate hunting.

Background. Human immunodeficiency virus (HIV) vaccine development remains a global priority. We describe the safety and immunogenicity of a multiclade DNA vaccine prime with a replication-defective recombinant adenovirus serotype 5 (rAd5) boost. Methods. The vaccine is a 6-plasmid mixture encoding HIV envelope (env) subtypes A, B, and C and subtype B gag, pol, and nef, and an rAd5 expressing identical genes, with the exception of nef. Three hundred and twentyfour participants were randomized to receive placebo (n = 138), a single dose of rAd5 at 1010 (n = 24) or 1011 particle units (n = 24), or DNA at 0, 1, and 2 months, followed by rAd5 at either 1010 (n = 114) or 1011 particle units (n = 24) boosting at 6 months. Participants were followed up for 24 weeks after the final vaccination. Results. The vaccine was safe and well tolerated. HIV-specific T cell responses were detected in 63% of vaccinees. Titers of preexisting Ad5 neutralizing antibody did not affect the frequency and magnitude of T cell responses in prime-boost recipients but did affect the response rates in participants that received rAd5 alone (P = .037). Conclusion. The DNA/rAd5 vaccination regimen was safe and induced HIV type 1 multi-clade T cell responses, which were not significantly affected by titers of preexisting rAd5 neutralizing antibody. Trial Registration. ClinicalTrials.gov identifier: NCT00123968.

Background: COVID19 remains deadly to Americans over 75 years old despite vaccination and additional infection control practices in long term care (LTC). The evolution of more transmissible COVID19 variants and continued viral aerosols result in persistent COVID19 outbreaks in LTC during high community levels of COVID19. Despite the end of pandemic Federal support and the continued vulnerability of elderly to the virus, LTC facilities remain dedicated to protecting this vulnerable population. The study hypothesized that utilization of continuous, facility-wide, advanced photocatalysis (AP) disinfection technology will reduce microbial burden in air and on surfaces, demonstrating a decrease in infectious aerosols and subsequent COVID19 cases among residents and workers. Methods: A prospective facility controlled experimental study was performed in skilled nursing facilities in Pennsylvania and New Jersey from January 2023 to April 2023 to surveil aerobic bacterial and fungal colony forming units (CFUs) in air, and Methicillin-resistant Staphylococcus aureus (MRSA) and fungal CFUs on surfaces and floors prior to and post AP technology installation. Impacts on resident COVID19 cases were recorded and compared to the same extended observation period (February-July 2023) one year prior (2022) with similar year over year community COVID19 rates. In addition, two matched control centers in regional proximity to the intervention facility were also prospectively studied. A one-way analysis of variance (ANOVA) was used to analyze mean microbial burdens after each post activation period (significance p <.05). Results: From baseline to final testing, the intervention facility surface testing showed a 93% reduction in mean aerobic bacterial CFUs (p=.002); 96% reduction in mean fungal CFUs (p<.001); 97% reduction in mean MRSA CFUs (p<.001). Floor testing also showed reductions in mean CFUs for aerobic bacteria by 92% (p<.001); 96% for fungi (p<.001); 99% for MRSA (p<.001). Air testing showed reductions in mean CFUs for aerobic bacteria by 87% (p=.005); 36% for fungal (p=.005). The intervention facility observed a 94% reduction in resident COVID19 cases compared to the matched control facilities that increased 46% during the 2023 time period (Figure 1). Conclusion: This study is on the pioneering edge of demonstrating that continuous and persistent disinfection technology reduces contaminant reservoirs on surfaces, floors, and air and clearly decreases infectious aerosols and improves resident outcomes by dramatically reducing COVID19 transmission in LTC facilities.

The development of the human immunodeficiency virus-1 (HIV-1)/simian immunodeficiency virus (SIV) chimeric virus macaque model (SHIV) permits the in vivo evaluation of anti-HIV-1 envelope glycoprotein immune responses 1 , 2 , 3 . Using this model, others, and we have shown that passively infused antibody can protect against an intravenous challenge 4 , 5 . However, HIV-1 is most often transmitted across mucosal surfaces 6 , 7 , 8 , 9 and the intravenous challenge model may not accurately predict the role of antibody in protection against mucosal exposure. After controlling the macaque estrous cycle with progesterone 10 , anti-HIV-1 neutralizing monoclonal antibodies 2F5 and 2G12, and HIV immune globulin were tested 11 , 12 , 13 . Whereas all five control monkeys displayed high plasma viremia and rapid CD4 cell decline, 14 antibody-treated macaques were either completely protected against infection or against pathogenic manifestations of SHIV-infection. Infusion of all three antibodies together provided the greatest amount of protection, but a single monoclonal antibody, with modest virus neutralizing activity, was also protective. Compared with our previous intravenous challenge study with the same virus and antibodies 5 , the data indicated that greater protection was achieved after vaginal challenge. This study demonstrates that antibodies can affect transmission and subsequent disease course after vaginal SHIV-challenge; the data begin to define the type of antibody response that could play a role in protection against mucosal transmission of HIV-1.

Hunting and butchering of wild non-human primates infected with simian immunodeficiency virus (SIV) is thought to have sparked the HIV pandemic. Although SIV and other primate retroviruses infect laboratory workers and zoo workers, zoonotic retrovirus transmission has not been documented in natural settings. We investigated zoonotic infection in individuals living in central Africa. We obtained behavioural data, plasma samples, and peripheral blood lymphocytes from individuals living in rural villages in Cameroon. We did serological testing, PCR, and sequence analysis to obtain evidence of retrovirus infection. Zoonotic infections with simian foamy virus (SFV), a retrovirus endemic in most Old World primates, were identified in people living in central African forests who reported direct contact with blood and body fluids of wild non-human primates. Ten (1%) of 1099 individuals had antibodies to SFV. Sequence analysis from these individuals revealed three geographically-independent human SFV infections, each of which was acquired from a distinct non-human primate lineage: De Brazza's guenon (Cercopithecus neglectus), mandrill (Mandrillus sphinx), and gorilla (Gorilla gorilla), two of which (De Brazza's guenon and mandrill) are naturally infected with SIV. Our findings show that retroviruses are actively crossing into human populations, and demonstrate that people in central Africa are currently infected with SFV. Contact with non-human primates, such as happens during hunting and butchering, can play a part in the emergence of human retroviruses and the reduction of primate bushmeat hunting has the potential to decrease the frequency of disease emergence.

Characterization of HIV-1 subtype diversity in regions where vaccine trials are conducted is critical for vaccine development and testing. This study describes the molecular epidemiology of HIV-1 within a tea-plantation community cohort in Kericho, Kenya. Sixty-three incident infections were ascertained in the HIV and Malaria Cohort Study conducted in Kericho from 2003 to 2006. HIV-1 strains from 58 of those individuals were full genome characterized and compared to two previous Kenyan studies describing 41 prevalent infections from a blood bank survey (1999-2000) and 21 infections from a higher-risk cohort containing a mix of incident and prevalent infections (2006). Among the 58 strains from the community cohort, 43.1% were pure subtypes (36.2% A1, 5.2% C, and 1.7% G) and 56.9% were inter-subtype recombinants (29.3% A1D, 8.6% A1CD, 6.9% A1A2D, 5.2% A1C, 3.4% A1A2CD, and 3.4% A2D). This diversity and the resulting genetic distance between the observed strains will need to be addressed when vaccine immunogens are chosen. In consideration of current vaccine development efforts, the strains from these three studies were compared to five candidate vaccines (each of which are viral vectored, carrying inserts corresponding to parts of gag, pol, and envelope), which have been developed for possible use in sub-Saharan Africa. The sequence comparison between the observed strains and the candidate vaccines indicates that in the presence of diverse recombinants, a bivalent vaccine is more likely to provide T-cell epitope coverage than monovalent vaccines even when the inserts of the bivalent vaccine are not subtype-matched to the local epidemic.