Study On Risk Factors Of Antiviral Therapy Failure And Death In HIV / AIDS Patients With Initial HAART In

Background HIV infector and AIDS patients (HIV/AIDS) appeared explosive growth suddenly and the case fatality rate of HIV/AIDS patients increased quickly year by year since2007in Liuzhou city. In order to control the trend of HIV/AIDS epidemic effectively, Liuzhou government started implementation10special projects of A IDS prevention and treatment according to Guangxi "AIDS Crucial Project". In order to evaluate the effect of "AIDS Crucial Project", it is necessary to make clinical epidemiological analysis of large sample in HIV/AIDS patients who have accepted initial HAART in Liuzhou city.Objective To master the clinical epidemiological characteristics of HIV/AIDS patients who had received initial HAART in Liuzhou city and provide theoretical basis for government to establish AIDS prevention and control strategy.Methods The history card of HIV/AIDS patients from1998to2013was downloaded from Chinese information system for the prevention and control of HIV/AIDS.The database was established by Excel2007.The clinical data of8AIDS antiviral treatment points in Liuzhou city was summarized. We employed descriptive analysis method to study the time distribution, city distribution, population distribution and clinical characteristics of HIV/AIDS patients who had accepted initial HAART in Liuzhou city.Results1. There were46cases of HIV/AIDS patients who received HAART and6death cases(13.05%) during the period from1998to2004in Liuzhou city. There were226,502,813,925,1115,1295,925,1277and993cases who began HAART during the period from2005to2013, respectively.The death numbers were54(23.89%),68(13.55%),82(10.09%),73(7.89%),110(9.87%),95(7.34%),113(7.60%),72(5.64%) and27(2.72%) during the period from2005to2013, respectively.2. All patients were distributed in8AIDS antiviral treatment points in Liuzhou city. The numbers of therapeutic management patients and death patients were5800(62%) and425cases(61%) in Guangxi Longtan Hospital,1497(16%) and159(23%) cases in LuZhai County People’s Hospital,716(8%) and48(7%) caeses in Liuzhou People’s Hospital,582(6%)and28(4%) cases in Liujiang County People’s Hospital,545(6%) and33(5%) cases in Liucheng County People’s Hospital,120(1%) and4(0.6%)cases in RongAn County People’s Hospital,112(1%) and3(0.4%) cases in RongShui County People’s Hospital, respectively. There were only7cases in SanJiang County People’s Hospital and no death patients.3. The mumber of male HIV/AIDS patients were6096(65%),while those of female HIV/AIDS patients were3283(35%).4. The median age was38(14-87) years-old and the average age was42±14years-old. There were119cases (1.27%) who were less than20years-old,5043patients (53.77%) who were between20and40years-old,3006cases (32.05%) who were between40and60years-old and1211cases (12.91%) who were more than60years-old, respectively.5. There were1752(18.68%) cases of unmarried,6224(66.36%) cases of married or cohabitation,644(6.87%) cases of divorce or separation,759(8.09%) cases in widowed, respectively.6. There were25(0.26%) cases of transfusion transmitted,1125(11.99%) cases of intravenous drug use,35(0.37%)cases of same-sex sexual transmission,8194(87.37%) cases of heterosexual sex and no mother-to-child transmission case.7. There were3395(36.20%) patients in WHO clinical stage I,1472(15.69%) patients in WHO clinical stage II,1635(17.43%) patients in WHO clinical stage III,2024(21.58%) patients in WHO clinical stage IV and853(9.09%) patients who were not staged correctly, respectively. There were50%～60%patients who reached WHO clinical stage III or IV when they began initial HAART in nearly4years.8. The median value of baseline CD4+T lymphocyte was80(1-1363) cells/mm3and the average value of baseline CD4+T lymphocyte was (128±132) cells/mm3. There were only1665(17.75%) cases of patients who had baseline viral load, which was4.945(2.30～6.96) log10(copies/ml) for the median value and (4.89±0.739) log10(copies/ml) for the average value.9. The numbers that had HBsAg testing were4335(46.22%) cases [656(15.13%) cases of HBsAg positive and3679(84.87%) cases of HBsAg negative] and that had AntiHCV testing were4271(45.54%)[379(8.87%) cases of AntiHCV positive and3892(91.13%) cases of AntiHCV negative].10. There were8955(95.48%)cases who used the first line therapeutic regimen and424(4.52%) cases who used the second line therapeutic regimen which contained LPV/r.11. There were5082cases (54%) who had one or more opportunistic infections within3months or1year before HAART. The opportunistic infections rounding out the top five were:tuberculosis (28.18%), oral candidiasis (23.77%), herpes zoster (6.46%), pneumocystis pneumonia (4.57%) and Ma Erni penicillium disease (3.64%).12. The rate of skin mucous membrane damage was as high as93.78%. The rate of patients in intermittent or repeated fever more than1month reached28%(2328/9379), while that of persistent diarrhoea more than1month was6.23%(585/9379).13. The baseline blood routine and biochemical indexes of HIV/AIDS patients were in normal range.Conclusion1."Guangxi AIDS Crucial Project" has obtained expected target in decreasing the motality rate of HIV/AIDS patients who have received HAART in Liuzhou city.2. There are more than two-thirds of HIV/AIDS patients who have received HAART are concentrated in the two tertiary hospital which are the key units in stable case mortality rate in Liuzhou city.3. Most of the HIV/AIDS patients are young and middle aged adults (20～60years-old). There is increasing trend in the elderly HIV/AIDS patients recently years.Male is the main population, which is2times of female.The amrried people is more than unmarried people. Sexual transmission has become the main route of transmission of AIDS in Liuzhou. The start ART time is still relatively late in most of the HIV/AIDS patients in recently4years.4. The ratio of baseline CD4+T lymphocyte which is less than50/mm3is high in HIV/AIDS patients with initial HAART, but the trend of baseline CD4+T lymphocyte is rising in recent years in Liuzhou city.5. The spectrum of opportunistic infections disease which is at the top five are tuberculosis, oral candidiasis, herpes zoster, pneumocystis pneumonia and Ma Erni penicillium disease. The skin damage is one of the most common clinical manifestations in HIV/AIDS patients.If a patient who has persistent diarrhoea and/or continuous or intermittent fever more than1month, he should be tested HIV antibody in time. Background Since HAART began to appear in1995, the treatment of HIV/AIDS has changed greatly. HAART can effectively reverse the progression of AIDS and rebuilt body’s immune function for HIV/AIDS patients. The failure of antiviral treatment may be caused by a variety of reasons with the the extension of antiviral treatment time under the pressure from the choice of antiviral drugs because HIV itself has high degree of variability. Success and failure of antiviral treatment can be measured by virology, immunology and clinical criteria.If HIV/AIDS patients appear virological and/or immunology failure after HAART, they will develop clinical treatment failure that eventually leads to their case fatality rate increasing.lt is necessary to explore clinical influence factors of virological and immunology failure in HIV/AIDS patients who have accepted HAART in order to provide theoretical basis for the establishment of ART strategies in HIV/AIDS patients.Objective To explore the clinical influence factors of virological and immunology failure in HIV/AIDS patients who have accepted HAART.Methods The baseline and follow-up clinical data were collected from HIV/AIDS patients who had received initial HAART in the People’s Hospital of Liuzhou.Those data which may be associated with virological and immunology response included gender, marital status, route of transmission, tuberculosis within1year before HAART, opportunistic infections within three months before HAART, WHO clinical stage, baseline CD4+T lymphocyte,whether combining with virus hepatitis B and/or C, baseline viral load, initial HAART scheme and age, and so on. The first step was analyzed for each factor by single factor unconditioned Logistic regression analysis.The second step was to put those variables that had statistically significant value in single factor unconditioned Logistic regression analysis into multi-factor unconditioned Logistic regression models in order to filtrate the independent risk factors of virological failure and immunology failure in HIV/AIDS patients during the course of HAART.The evaluation of the value of immunology response predicting virological response was decided by the area under the ROC curve (AUC).Results1. There were two factors including X4(with and without tuberculosis)(OR=3.17095%CI:1.568～6.411) and X11(initial HAART scheme)(OR=0.19695%CI:0.071～0.538) which had statistical significance differences (P<0.01) in the12baseline clinical factors that might be associated with virological failure by single factor and multiple factors Logistic regression analysis. But X11had no clinical value.2. There were three factors including X1(gender)(OR=3.87495%CI:1.660～9.044), X7(baseline level of CD4+T lymphocyte)(OR=0.25495%CI:0.153～0.422) and X13(virological response)(OR=11.79295%CI:4.486～30.999) which could enter into multi-factor model (P<0.01) by Logistic regression analysis in the13clinical factors that might be associated with immunology failure.3.There was certain correlation between immunological response and virological response(rs=0.340P<0.01).The AUC of immunology failure predicting virological failure reached0.725(95%CI:0.631～0.820)(P<0.01).The SN, SP,PPV, NPV and Youden index were56.10%,88.98%29.49%,96.10%and45.08%,respectively.The best diagnostic threshold of the added value of CD4+T lymphocytes at the12th month after HAART predicting virological failure was82cells/mm3, whose AUC arrived at0.724(95%CI:0.610～0.839)(P<0.01) and SN, SP,PPV, NPV and Youden index were70%,77.5%,20.57%,97%and47.5%, respectively.Conclusion1. The factor that HIV/AIDS patient has history of tuberculosis(TB) before HAART within1year is the independent factor of virological failure in the course of HAART.2. X1(gender), X7(baseline level of CD4+T lymphocyte) and X13(virological response) are the independent risk factors of immunology failure in HIV/AIDS patients during the HAART course.3. The immunological response can predict virological response in a certain extent. The best diagnostic threshold of the added value of CD4+T lymphocyte at the12th month after HAART predicting virological failure is82cells/mm3. Background With the widely application of HAART in clinical, the death of AIDS-related diseases is gradually declining. However, the mortality of AIDS patients is higher than that of general population and the absolute number of AIDS-related death continues to increase in recent years.What are the factors associated with outcome of HIV/AIDS patients who have started HAART is the key by clinical doctors and government department. One of the "AIDS Crucial Project" goal is to control case mortality rate below3/100person-years in those HIV/AIDS patients who have received HAART. It is necessary to evaluate the effect of "AIDS Crucial Project" because it has implemented4years in Liuzhou city.Objective To discusse the death risk factors with HIV/AIDS patients who had accepted HAART and evaluate the effect of the "AIDS Crucial Project" in decreasing the mortality rate of HIV/AIDS patients who had accepted HAART.Methods The information was gathered from8AIDS antiviral treatment points in Liuzhou city. It included baseline data and clinical follow-up data of HIV/AIDS patients who had received initial HAART. According to the results of the first part and second part, we analyzed the social factors which included "AIDS Crucial Project", medical institution and route of transmission, demographic characteristics which included age, gender and marital status, and clinical features which included WHO clinical stage, baseline CD4+T lymphocyte,viral load, HAART regimen, opportunistic infection, virological response and immunological response. The methods of single factor analysis were the Crosstabs, One-Way ANOVA and Life Tables. The indicators which had statistical differences in the single factor analysis were put into multiple factors analysis. The independent risk factors on HIV/AIDS patients were filtrated by Cox regression model risk ratio.Results1. The mortality rate during the period of "AIDS Crucial Proj ect"(after2010) was5.73%, which was lower than that of the period before "AIDS Crucial Project"(9.78%)(X2=54.483, P<0.01). The mortality rate of the previous two years during the period of "AIDS Crucial Project" was6.96%, which was higher than that of the latter two years during the period of "AIDS Crucial Project"(4.18%)(X2=18.882, P<0.01); The cumulative survival rate of HIV/AIDS patients who had begun HAART before "AIDS Crucial Project" were0.96,0.94,0.92and0.90, respectively, in the1st to4th years after HAART. The cumulative survival rate was kept stablization at0.94in the1st to4th years during the period of "AIDS Crucial Project".2. The case mortality rate of the group of baseline CD4+T lymphocyte<50cell/mm3, the group whose baseline CD4+T lymphocyte was between51and200cells/mm3, the group whose baseline CD4+T lymphocyte was between201and350cells/mm3, the group whose baseline CD4+T lymphocyte was between351and500cells/mm3and the group whose baseline CD4+T lymphocyte was above500cells/mm3were10.93%,6.69%,3.34%,0.98%and0, respectively.There were significantly differences among the five groups(X2154.838, P<0.01).3. There was no significantly difference between tertiary hospital and secondary hospital in the case mortality rate (X=1.292, P>0.05).4. The independent death risk factors with HIV/AIDS patients were X22(age)(OR=6.86295%CI:2.317～20.324), X23(gender)(OR=1.47795%CI:1.140～1.914), X24(route of transmission)(OR=2.12995%CI:1.601～2.832), X25(WHO clinical stage)(OR=1.37095%CI:1.235～1.521), X26(baseline level of CD4+T symphocyte)(OR=0.70695%CI:0.608～0.819) and X30(virological response)(OR=13.04195%CI:4.214～40.361) in the social factors, baseline factors, clinical characteristics and follow-up indexes.5. The cumulative survival rates of the first to eighth year after HAART in all HIV/AIDS patients were0.95,0.93,0.92,0.90,0.88,0.88,0.88and0.88, respectively. Those of the first to fourth year after HAART with HIV/AIDS patients in single center were0.94,0.92,0.91and0.88, respectively.Conclusion1. The mortality rate of HIV/AIDS patients who have received HAART is decreasing greatly and the cumulative survival rate have improved obviously after the implementation of "AIDS crucial project" in Liuzhou city.We could achieve the goal of the mortality rate below3/100person-years according to the criteria that HAART should be started if the baseline CD4+T lymphocytes is eaqual or below350cells/mm3.2. The follow-up management of AIDS antiviral treatment could focus on the AIDS antiviral treatment points in secondary hospital.3. The independent risk factors of HIV/AIDS patients who have received HAART include X22(age of starting HAART), X23(gender), X24(route of transmission), X25(WHO clinical stage), X26(baseline level of CD4+T lymphocyte) and X30(virological response) in the social factors, baseline factors, clinical characteristics and follow-up indexes.4. If HIV/AIDS patients could use HAART for3to5years, their immune function will stabilize and they rarely appear new AIDS correlation disease. The main death cause after HAART3to5years may be some non-AIDS related diseases.