HIV蛋白酶抑制剂的抗白念珠菌作用

由白念珠菌引起的口咽念珠菌病是HIV感染者常见的机会感染.自从应用高效抗逆转录病毒治疗以来,HIV感染者口咽念珠菌病的发生率明显下降.HAART降低口咽念珠菌病发病率不仅是由于改善了患者的免疫力,而且还由于HAART中的蛋白酶抑制剂抑制了白念珠菌分泌型天冬氨酸蛋白酶的活性、形态转换及其生长过程而发挥其抗念珠菌的作用.本文综述了PI抗白念珠菌的机制.     

Neurological complications in AIDS patients receiving HAART: a 2-year retrospective study

The positive role of highly active anti-retroviral therapy (HAART) in reducing opportunistic infections in acquired immunodeficiency syndrome (AIDS) patients is well known. However, case reports from around the world have demonstrated that some patients seem to suffer a paradoxical deterioration of health as their immune function improves with treatment. This phenomenon has been called immune restoration inflammatory syndrome (IRIS). In northern Thailand, GPO-vir (Stavudine-D4T + Lamivudine-3TC + Nevirapine-NVP) has been promoted for the treatment of AIDS patients since April 2002, in accordance with the Government Pharmaceutical Organization's guidelines. However, the incidence rates of IRIS affecting nervous system (NIRIS) and non-NIRIS in comparison with the previous incidence of AIDS-defining disease have not been reported. We conducted a retrospective study to review the incidence of NIRIS and non-NIRIS in AIDS patients treated with GPO-vir in Chiang Mai University Hospital, Thailand, between May 2002 and April 2004. We compare these incidence rates with the incidence rates of neurological complications in the pre-HAART era. Altogether 506 AIDS patients were treated with GPO-vir during the specified period. The overall incidence of NIRIS, including progressive multifocal leukoencephalopathy (PML), cerebral toxoplasmosis and cytomegalovirus (CMV) retinitis, was lower than the previous incidence of AIDS-defining disease in the pre-HAART era. However, the incidence of ischemic stroke, hemorrhagic stroke and primary central nervous system (CNS) lymphoma had increased.     

Prevalence and factors associated with late diagnosis among older adults living with HIV in liuzhou,China: 2010−2020

This paper aimed to quantify and characterize the prevalence and associated factors for late diagnosis in older adults living with human immunodeficiency virus (HIV) in Liuzhou, China, from 2010 to 2020. The characteristics of older adults living with HIV were described separately in time, space and population. Multivariate logistic regression analysis evaluates the factors influencing late diagnosis in HIV-positive adults ≥ 50 years of age. The majority of older adults living with HIV were over 60 years old, male, and with CD4 counts < 200 cells/μl at diagnosis, with most late diagnoses being more likely to report heterosexual transmission. These two factors may potentially provide a positive influence on late diagnosis: older and CD4 counts < 500 cells/μl. In contrast, females and those with homosexual or other transmission provide a negative. These results suggest that late diagnosis of HIV-positive adults ≥ 50 years of age remains a severe and growing epidemiological issue.     

Reconstitution of CD4+ T cell responses in HIV-1 infected individuals initiating highly active antiretroviral therapy (HAART) is associated with renewed interleukin-2 production and responsiveness

Reconstitution of functional CD4(+) T cell responsiveness to in vitro stimuli is associated with continuous highly active antiretroviral therapy (HAART). Thirty-six antiretroviral naive patients received HAART over 16 weeks. Antigen-specific, mitogen and interleukin (IL)-2 induced lymphocyte proliferative responses and specific IL-2 and IL-4 production were assessed at each time-point, together with quantification of HIV-1 RNA load and lymphocyte populations. Reconstitution of recall responses was limited largely to persistent antigens such as Herpes simplex virus and Candida, rather than to HIV-1 or neo-antigens. Recall antigens, mitogens and IL-2-induced renewed responses were associated with in-vitro production of IL-2, but not IL-4. Differential responsiveness to low versus high concentration IL-2 stimulus increases in a stepwise manner, suggesting normalization of IL-2 receptor expression and improved functionality. These increases in in-vitro proliferative responses thus probably reflect short lived effector clones, driven by ongoing antigenic stimulus associated with persisting long-term organisms. In this context non-responsiveness to HIV-1 antigens suggests ongoing HIV-1 specific clonal T cell anergy.     

Proliferation and telomere length in acutely mobilized blood mononuclear cells in HIV infected patients

The aim of the study was to investigate the mobilization of T cells in response to a stressful challenge (adrenalin stimulation), and to access T cells resided in the peripheral lymphoid organs in HIV infected patients. Seventeen patients and eight HIV seronegative controls received an adrenalin infusion for 1 h. Blood was sampled before, during and 1 h after adrenalin infusion. Proliferation and mean telomere restriction fragment length (telomeres) of blood mononuclear cells (BMNC) and purified CD8+ and CD4+ cells were investigated at all time points. In patients, the proliferation to pokeweed mitogens (PWM) was lower and decreased more during adrenalin infusion. After adrenalin infusion the proliferation to PWM was restored only in the controls. In all subjects telomeres in CD4+ cells declined during adrenalin infusion. Additionally, the patients had shortened telomeres in their CD8+ cells, and particularly HAART treated patients had shortened telomeres in all cell-subtypes. The finding that patients mobilized cells with an impaired proliferation to PWM during and after adrenalin infusion has possible clinical relevance for HIV infected patients during pathological stressful conditions, such as sepsis, surgery and burns. However, this study did not find a correlation between impaired proliferation and telomeres. It is concluded that physiological stress further aggravates the HIV-induced immune deficiency.     

Immune reconstitution in human immunodeficiency virus type 1-infected children with different virological responses to anti-retroviral therapy

Immune repopulation, despite virological failure, often occurs in children under highly active anti-retroviral therapy (HAART). The aim of this study was to analyse the characteristics of immune repopulation and activation in children with and without virological response to HAART. Fourteen human immunodeficiency virus type 1 (HIV-1)-infected children with suppression of HIV-1 plasma viraemia (virological responders, VR) and 16 virological non-responders (VNR) to therapy were studied at baseline and after approximately 2 years of HAART. During therapy, CD4+ T cells increased in both groups, but were higher in the VR than in the VNR group. All CD4+ T cell subsets (naive, central memory, effector/memory and CD38+) increased significantly in VR children, while there was a significant increase only in naive cells in VNR children. Naive CD8+ T cells and T cell receptor rearrangement excision circles (TREC), an indicator of thymic output, increased in both VR and VNR children. Activated CD8+ CD38+ T cells decreased in VR but remained high in VNR children. Levels of circulating lipopolysaccharide (LPS), an indicator of microbial translocation, further increased in VNR children. In conclusion, HAART induced an increase in naive cells in all children, regardless of their virological response. However, the persistence of viraemia resulted in an impaired expansion of memory CD4+ T cells susceptible to HIV-1 infection, and together with the microbial translocation sustained the persistence of a high level of immune activation.     

Predictors and kinetics of occult hepatitis B virus infection in HIV-infected persons

It has been proposed that occult hepatitis B virus (HBV) infection, defined as detectable HBV‐DNA in serum with undetectable surface antigen (HBsAg^?), is associated with raised transaminases in HIV‐infected persons. The aim of this study was to determine the prevalence of occult HBV infection in two independent cohorts, and investigate its predictors, association with alanine‐aminotransferase (ALT) levels and response to antiretroviral therapy. Sera from HBsAg^? persons with core antibody (anti‐HBc⁺) were tested by real‐time PCR. Overall, 5.2% of patients were HBsAg⁺ and 39% HBsAg^?/anti‐HBc⁺. The prevalence of occult HBV infection was 48/343 (14.0%; 95% CI 10.7–18.1%), and 27/196 (13.8%) and 21/147 (14.3%) in the two cohorts. Median HBV‐DNA load was 342 (51–147,500) and 60 (25–33,850) copies/ml respectively. HBV‐DNA detection was associated with absence of surface antibody (anti‐HBs), but not with CD4 or ALT levels. Among 11 HBV‐DNA⁺ persons who started antiretroviral therapy containing lamivudine or lamivudine/tenofovir, HBV‐DNA was repeatedly undetectable over median 19 (3–43) months. However, HBV‐DNA detection was intermittent among drug‐naïve persons. Occult HBV infection is common in HBsAg^?/anti‐HBc⁺ HIV‐infected patients and predicted by undetectable anti‐HBs. The intermittent nature of HBV‐DNA detection poses a diagnostic challenge, but no association is observed with ALT levels. J. Med. Virol. 79:1464–1471, 2007. © Wiley‐Liss, Inc.     

Soluble human leukocyte antigen-G serum levels in patients with acquired immune deficiency syndrome affected by different disease-defining conditions before and after antiretroviral treatment

We have previously reported that the serum levels of soluble human leukocyte antigen (HLA)-A, -B, -C, and -G antigens are elevated in human immunodeficiency virus (HIV)-infected subjects and decrease after antiretroviral therapy. In this study, we measured soluble HLA-G serum levels in patients with acquired immune deficiency syndrome (AIDS) affected by different AIDS-defining conditions before and during antiretroviral therapy and correlated them with virologic and immunologic parameters of response to treatment. Soluble HLA-G levels were significantly higher in AIDS patients before treatment as compared with healthy controls and significantly decreased after 36 months of therapy. The decrease of soluble HLA-G correlated with the decrease of plasma HIV-RNA level and CD8(+) T-lymphocytes number and with the increase of CD4(+) T-lymphocytes number. Soluble HLA-G levels were significantly higher in patients with opportunistic infections and Kaposi's sarcoma compared with patients with the wasting syndrome. These data suggest that infections and neoplasms may trigger the shedding of soluble HLA-G molecules, and confirm that the level of soluble HLA-G in serum might represent a surrogate marker to monitor virologic response and immune reconstitution in HIV-positive individuals.