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Viral infections
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Sarah Elizabeth Blutt, Mary K. Estes, Satya Dandekar, Phillip D. Smith
In contrast to the relentless progression of disease in the majority of subjects with HIV-1 infection, a small subset of HIV-1-infected people called “long-term nonprogressors” remain clinically asymptomatic for many years in the absence of therapy. Their plasma viral loads are usually undetectable or very low, and CD4+ T-cell numbers in peripheral blood are in the normal range. Long-term nonprogressors retain normal levels of CD4+ T cells and high levels of virus-specific cellular responses in the gastrointestinal mucosa, consistent with the critical role of mucosal immunity in limiting HIV-1 disease. In SIV-infected sooty mangabeys and African green monkeys, important nonhuman primate models of HIV-1 infection, maintenance of the integrity of the gut mucosal immune system correlates with nonpathogenic SIV infection. Thus, maintenance of the integrity of the gut mucosal immune system may become an important measure of the efficacy of HIV-1 vaccines and therapeutic agents.
Pathogenesis of HIV-1 Infection
Published in Thomas R. O’Brien, Chemokine Receptors and AIDS, 2019
G. Paolo Rizzardi, Giuseppe Pantaleo
This pattern of disease progression identifies most (60 to 70%) subjects with HIV-1 infection, so-called “typical progressors”. However, some 10 to 20% of subjects develop AIDS in less than 5 years (“rapid progressors”), whereas 5 to 15% of subjects progress to AIDS more slowly (slow progressors). Less than 1% of subjects show no disease progression for at least 8–10 years, while maintaining high CD4+ T cell counts (>500 cells/μl) and (usually) low (500–5,000 copies/ml) to very low (below 50 copies/ml) levels of HIV-1 RNA in the plasma. These subjects, so-called “long-term nonprogressors” (LTNP), represent the natural example of long-term control of HIV-1 infection.
HIV
Published in Meera Chand, John Holton, Case Studies in Infection Control, 2018
The study of two groups of patients, long-term nonprogressors (patients who maintain a good CD4 count for many years in the face of active viral replication) and elite controllers (patients who naturally reduce viral replication to undetectable levels without cART), has been used to inform our understanding of host factors affecting disease progression. These studies have suggested various immune factors including human leukocyte antigen (HLA) subtype, HIV specificity of CD4 and CD8 T-cells, humoral responses and antibody dependent cellular cytotoxicity, mutations in co-receptors, and improved natural killer (NK) cell function, may all play a role in this process.
Second-line treatment options for hepatocellular carcinoma: current state and challenges for the future
Published in Expert Opinion on Investigational Drugs, 2022
Le Li, Hao-Tian Liu, Yu-Xian Teng, Zhu-Jian Deng, Guan-Lan Zhang, Jia-Yong Su, Liang Ma, Jian-Hong Zhong
Elevated HBV DNA level is significantly associated with poor overall and recurrence-free survival [105,106]. PD-1 inhibition may increase the risk of HBV reactivation, arguing for prophylactic treatment with nucleos(t)ide analogs (NUCs). For example, a long-term nonprogressor infected with human immunodeficiency virus (HIV) and negative for HBV DNA experienced HBV reactivation after nivolumab treatment [107]. Another study reported that 6 of 114 patients (5.3%) developed HBV reactivation after PD-1 inhibition treatment, even though all of them had been negative for HBV DNA at baseline. Among the six patients, only one had prophylactic antiviral therapy, and lack of prophylactic antiviral therapy was the only significant risk factor for HBV reactivation [108]. A third study reported that none of 56 patients on antiviral therapy experienced HBV reactivation, compared to one of the six who did not receive antiviral therapy. When combined with NUCs, PD-1 inhibition can be safely used as a treatment for HCC even in patients with HBV load higher than 100 IU/mL [109]. Guidelines suggest considering HCC patients for immunotherapy, regardless of whether they have viral hepatitis [9].
Cross-reactive influenza-specific antibody-dependent cellular cytotoxicity-mediating antibodies in HIV-infected Indian individuals
Published in Infectious Diseases, 2018
Sanketkumar Nehul, Archana Kulkarni, Shailesh Pawar, Sheela Godbole, Manisha Ghate, Madhuri Thakar
We tested plasma samples from 50 HIV-infected and 20 HIV-negative healthy Indian individuals for the presence of influenza-specific ADCC and hemagglutination inhibiting (HI) antibodies. Influenza vaccination is not practiced in India and no study participants had ever been vaccinated against influenza. Of the 50 HIV-positive individuals, 25 (8 males, 17 females) were part of an ongoing cohort study of Long-Term Nonprogressors [LTNPs) with documented HIV infection, with stable CD4 counts above 500 cells/mm3 for at least seven years with no anti-retroviral therapy (ART) who were asymptomatic during the follow-up period. The remaining 25 (6 males, 19 females) had progressive HIV infection (ART-naive HIV-infected patients with CD4 counts <500 cells/μl) were selected from individuals attending the outpatient clinics of the institute and considered as progressors. The CD4 count (median: 731 cells/mm3, range: 500–1478) was significantly higher in LTNPs than in progressors (median: 389 cells/mm3, range: 263–477) (p < .0001). The median time of seropositivity was 10.4 years (range: 8–14 years) in LTNPs. Twenty (7 males, 13 females) healthy HIV-uninfected adults were included in the study. All study participants were between 23 to 48 years of age with no significant difference in age. Plasma samples collected and stored from February to August 2015 were used for analysis. The study was approved by the institutional research ethical committee and participants were enrolled after written informed consent.