Superantigenic activity of toxic shock syndrome toxin-1 is resistant to heating and digestive enzymes.

AIMS: To elucidate the stability of superantigenic activity and pathogenesis of toxic shock syndrome toxin 1 (TSST-1) and staphylococcal enterotoxin A (SEA) against heating and digestive enzymes. METHODS AND RESULTS: Purified TSST-1 and SEA were treated with heating, pepsin and trypsin that are related to food cooking, stomach and intestine conditions. The integrity, superantigenic activity and toxicity of treated TSST-1 and SEA were analysed by Western blotting, spleen cell culture, cytokine assay and toxic shock models. Both TSST-1 and SEA showed strong resistance to heating, pepsin and trypsin digestion. Furthermore, the treated TSST-1 showed significant higher induction of interferon-γ and toxic shock compared with that of SEA. Pepsin- or trypsin-digested TSST-1 fragments still showed significant superantigenic and lethal shock toxicities. CONCLUSIONS: The superantigenic activity of TSST-1 was stable to heating and digestive enzymes. Pepsin- and trypsin-digested TSST-1 fragments still showed superantigenic and lethal shock activities, indicating that digested TSST-1 could cross epithelial cells and induce systemic toxicity. SIGNIFICANCE AND IMPACT OF THE STUDY: This study found, for the first time, that pepsin- or trypsin-digested smaller TSST-1 retained significant superantigenic and lethal shock activities. The different resistance of TSST-1 and SEA participates in the different pathogenic activities during food poisoning and toxic shock syndrome.

Incidences and factors associated with viral suppression or rebound among HIV patients on combination antiretroviral therapy from three counties in Kenya.

BACKGROUND: Limited data are available on the incidence and factors associated with viral rebound following viral suppression among HIV-infected individuals taking antiretroviral therapy (ART) in Kenya. Furthermore, the durability of viral suppression among HIV individuals taking ART is unknown. Information on incidence rates and factors associated with HIV viral load rebound and the durability of viral suppression (undetectable HIV copies in plasma) among HIV-infected individuals taking ART, will help improve the long-term management of HIV-infected individuals and explore approaches to long-term HIV remission or complete cure. OBJECTIVES: The objectives of this study were to investigate the incidence rates of viral rebound following viral suppression, factors associated with viral rebound, and the durability of viral suppression among HIV-infected individuals on ART from Kilifi, Meru, and Nakuru counties in Kenya. METHODS: This was a retrospective study involving 600 HIV-infected individuals taking combination ART (cART) and enrolled in comprehensive care centers (CCCs) at Malindi Sub-county Hospital, Nakuru Level 5 Hospital, and Meru Level 5 Hospital in Kenya. The medical files were inspected and medical history records abstracted for the selected participants. Participant laboratory data including HIV viral loads, types and history of ART, and treatment history of any opportunistic infections were abstracted using an abstraction checklist. Participants were grouped into those who achieved HIV viral suppression, with viral loads lower than the detection limit (LDL) (viral suppression), and those who experienced one or more detectable viral load measurements >40 copies/ml following the initial LDL (viral rebound). Durable viral suppression was defined as all viral load values at LDL over the 2-year period (2017-2019). Univariate and multivariate Poisson regression analyses were performed to assess the rates of viral rebound, as well as to investigate factors associated with it. RESULTS: Out of 549 HIV-positive patients, 324/549 (59%) achieved HIV viral suppression (Meru 159/194 (82%), Nakuru 21/178 (12%), and Malindi 144/177 (81%)). The overall viral rebound rate was 41%, with site-specific viral rebound of 88.2%, 18.6%, and 18.0% in Nakuru, Malindi, and Meru, respectively. There was an overall rate of first viral rebound of 3.9 (95% confidence interval (CI) 6.9-14.4), 0.7 (95% CI 0.5-1.0), and 0.89 (95% CI 0.64-1.24) per 100 person-months in Nakuru, Malindi, and Meru, respectively. Good ART adherence (p = 0.0002), widow status (p = 0.0062), and World Health Organization (WHO) stage I (p = 0.0002) were associated with viral suppression, while poor ART adherence (p < 0.0001), WHO stage II (p = 0.0024), and duration on ART of 36 months (p = 0.0350) were associated with viral rebound. CONCLUSIONS: The rate of viral suppression in patients on cART in the CCCs fell short of the WHO target. However, the study provides proof of evidence of undetectable viral load levels for more than 2 years, a sign that the United Nation's 2030 objective of controlling the risk of HIV transmission could be achieved.

CD4+ T cell counts in initiation of antiretroviral therapy in HIV infected asymptomatic individuals; controversies and inconsistencies.

The primary goal when devising strategies to define the start of therapy in HIV infected individuals is to avoid HIV disease progression and toxicity from antiretroviral therapy (ART). Intermediate goals includes, avoiding resistance by suppressing HIV replication, reducing transmission, limiting spread and diversity of HIV within the body and protecting the immune system from harm. The question of how early or late to start ART and achieve both primary and intermediate goals has dominated HIV research. The distinction between early and late treatment of HIV infection is currently a matter of CD4+ T cells count, a marker of immune status, rather than on viral load, a marker of virus replication. Discussions about respective benefits of early or delayed therapy, as well as the best CD4+ T cell threshold during the course of HIV infection at which ART is initiated remains inconclusive. Guidelines issued by various agencies, provide different initiation recommendations. This can be confusing for clinicians and policy-makers when determining the best time to initiate therapy. Optimizing ART initiation strategies are clearly complex and must be balanced between individual and broader public health needs. This review assesses available data that contributes to the debate on optimal time to initiate therapy in HIV-infected asymptomatic individuals. We also review reports on CD4+ T cell threshold to guide initiation of ART and finally discuss arguments for and against early or late initiation of ART.