The Clinical Study On Highly Active Antiretroviral Therapy And The Expression Of HMGB1 In Patients With HIV/AIDS

Acquired immune deficiency syndrome(AIDS) is a severe infectious disease caused by human immunodeficiency virus(HIV) infection. The term AIDS applies to the most advanced stages of HIV infection, defined by the occurrence of any of more than 20 opportunistic infections(OIs) or HIV-related cancers. Since 1981, the beginning of the epidemic,25 million people have died of HIV-related causes. Collectively, these deaths represent an incalculable loss of human potential. Individually, each is associated with enduring trauma in households and communities. According to estimates by WHO and UNAIDS,33 million people were living with HIV/AIDS at the end of 2008. About 700 thousands people are now living with HIV/AIDS in China and the death toll of AIDS had exceed that of hepatitis B. The incidence of it raised 45.04% last year, and the evidence showed that HIV infection has overspreaded from highrisk population to general population. The application and promotion highly active antiretroviral therapy(HAART), making antiretroviral therapy achieved good clinical results, effectively reduces HIV-associated morbidity and mortality, improved the survival and quality of the infected persons, is an important milestone in the history of treatment and prevention of AIDS.There were many papers and reports in the field of HAART efficacy, side-effection and toxicity, but lack of long-term observation data and systemic study aimed at Chinese people who living with HIV/AIDS. As we know, the time between infect of HIV and the diagnosis of AIDS can be 7-10 years, or even longer. Antiretroviral therapy (ART) can slow the disease progression by decreasing an infected person's viral load. HIV infection is chronic and that exposure to HAART is likely to be life-long, there is a need to evaluate the long-term effect of HAART in this population. In this paper, we first report the outcomes of highly active antiretroviral therapy and the expression of HMGB1 in patients with HIV/AIDS. This study includes two parts as follows: Objective To elucidate general characteristics of HIV/AIDS patients seeking care at Changsha Infectious Disease Hospital and evaluate the long-term efficacy of HAART and assess the resistance mutation of nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens in routing clinical practice.Methods From April 2003 to August 2009,388 HIV/AIDS cases were hospitalized, among them 226 cases were given two nucleoside reverse transcriptase inhibitor and one NNRTI antiretroviral therapy(ART). First, clinical characteristics of all the 388 cases were analysed; Then,226 cases who received HAART were followed up and we assessed there CD4+T cells and HIV-1 viral load; Last,6 cases who failed on first regimen were further investigated by using the genotypic resistance tests.Results Among these patients, most of them had been infected by sexual contact. The most common symptoms were fever, weight loss, cough and diarrhea, rashes and glands swollen.40.98% of cases'chest X-ray were abnormal and 83.18% of cases' CD4+T lymphocyte were less than 200 cells/ul. The most common opportunistic infections (OIs) were thrush, pulmonary infection, fungal infected diarrhea, herpes and tuberculosis. Of 226 patients who received HAART, the mortality rate was 3.54%. The most common side effects were tetter, tiredness, nausea, etc, and 22 cases occurred immune reconstitution inflammatory syndrome(IRIS). More than 70% of subjects had HIV viral load<50copies/ml at the point of 24 weeks, but 6 cases who failed on first regimen showed extensively resistance mutation on both NRTIs and NNRTIs.Conclusion The majority of cases were general population and had contracted HIV/AIDS sexually. Thrush, pulmonary infection emerged as the most frequent OIs. The most common pathogens of OIs were bacteria, fungus and virus. OIs were muti-organs effected and complicated. Antiretroviral therapy (ART) consists of two NRTIs and one NNRTIs could maximally suppress the HIV virus, increase CD4+T cell counts in a majority of subjects and stop the progression of HIV disease. Only Objective To investigate the expression and clinical significance of high mobility group box-1 protein (HMGB1) in patients with HIV infection/AIDS.Methods Seventy-four patients with HIV infection/AIDS of different pathogentic stage were recruited, while another ten healthy subjects were taken as controls. Expression of HMGB1 mRNA in PBMCs of all cases was detected by RT-PCR. And the levels of HMGB1, TNF-a and IL-2 in plasma were measured by ELISA.Results The expression of HMGB1 mRNA and levels of plasma HMGB1 in AIDS patients were significantly higher than that in cases with HIV infection or controls respectively (P<0.05). The levels of HMGB1 mRNA and plasma HMGB1 in AIDS patients with poor efficacy after HAART therapy were significantly higher than that in subjects with good efficacy (P<0.05). And both expression of HMGB1 mRNA and levels of plasma HMGB1 in those AIDS patients, whose immune function rehabilitated to normal level and got good therapy efficacy after HARRT, decreased evidently. Subjects with lower counts of CD4+T cells had higher expression of HMGB1, and there was negative correlation between CD4+T cell counts and HMGB1 levels when CD4+T cells decreased to less than 200 cells/ul.Conclusion HMGB1 probably plays an important role in the pathogenesis of HIV infection/AIDS and is closely associated with the disease course.