Efficacy And Predictive Factors Of Virologic And Immunologic Outcome Of A48-Week CART In517Chinese Treatment-naive HIV/AIDS Patients

[Objective]Since the introduction of combined antiretroviral therapy (cART),it has been proved to greatly reduce the viral load in HIV/AIDS patients, hence brought by great improvements in immunologic recovery and clinical outcome. This study aims to evaluate the virologic and immunologic efficacy of first-line cART regime based on domestic generic drugs in a prospective cohort of Chinese HIV/AIDS patients, so as to quantify the need for second-line therapy. We further assess the effect of baseline-and treatment-related factors on virologic and immunologic outcome after48weeks of cART, as would provide cautions and intervention measures to maximize the duration of cART regimes, hence improve the outcome of cART.[Method]The517patients were selected from a cohort of treatment-naive HIV/AIDS patients of the national11th-five year-plan. The including criteria were:1)18-65years old;2)Patients were found to be HIV-seropositive by standard serum enzyme-linked immunosorbent assay(ELISA)and Western blotting analysis;3) CD4+T cells≤350cells/ul;4) treatment-naive. Primay endpoints were defined as:1) the first time for patients’ plasma viral load to reach VL<40copies/ml;2) At the end of the48-week cART, virologic suppression were defined as a VL<40copies/ml, whereas a VL40≥copies/ml as incomplete virologic suppression;3) At the end of the48-week cART, complete immunologic response was defined as an increase of CD4cell count≥100cells/ul), whereas an increase<100cells/ul) as incomplete immunologic response. We processed further Cox regression and logistic regression to assese the effect of baseline-and treatment-related factors on above-mentioned endpoints.[Results]1. At the end of1year cART, the virologic suppression rate of the cohort reaches78.8%(VL<40copies/ml) or93.8%(VL<400copies/ml), while the rate of complete immunologic response is63.0%, and incomplete immunologic response rate being27.0%. The mean increase of CD4+T cell is139.8cells/ul.2. Male sex is associated with a lower possibility of reaching virologic suppression short after the starting of cART (RH0.83compared to female;95%CI:0.78-0.89, P=0.04), as well as having lower virologic suppression rate than female at the end of48weeks of cART (OR=3.14compared to female;95%CI:1.40-7.04; P=0.01).3. Higher baseline plasma VL level is associated with less possibility of reaching virologic suppression short after the starting of cART (RH0.67per Ig copies/ml;95%CI0.59-0.76; P<0.01), especially with baseline VL>10000copies/ml (RH0.37compared to VL<400copies/ml;95%0.15-0.9; P=0.03). Whether a patient can achieve complete virologic suppression at48weeks after starting cART is significantly related to the time needed for VL to drop to TND (OR=1.06per each week;95%CI:1.04-1.07; P<0.01).4. History of opportunistic infections (OR=2.91;95%CI:1.47-5.73; P<0.01) and cART drug resistance (OR=4.24;95%CI:1.55-11.61; P<0.01) are significantly correlated to the possibility to achieve complete virologic suppression after1year treatment.5. Group B which used AZT as a part of cART experienced a higher rate of incomplete immune response (OR=2.04compared to Group A;95%CI:1.07-3.89; P=0.03). Group C which switched from AZT to d4T has a lower rate of incomplete immune response (OR=1.90compared to Group A;95%CI:1.01-3.60; P=0.05).[Conclusions]This study is the first prospective research to assess the predictive factors on virologic and immunologic outcome of cART among Chinese treatment-naive HIV/AIDS patients. Given optimal adherence and adjusting the cART regime appropriately when adverse events or drug resistance occurred, most of the patients in our corhort experienced preferable virologic and immune outcome. Both virologic and immunologic responses are most obvious during the first3-6months of cART, and then become less drastic. After1year of cART treatment, female patients achieved a better virologic suppression than male patients, but no difference as in immunologic response. Possible mechanisms include different immune function, different hormone level and different cART pharmacokinetics between genders. Compared to baseline plasma VL, the time to reach TND affects the result of virologic response after1year of cART more remarkably. Previous opportunistic infections and resistance to cART drugs are the main influencing factors of virologic suppression. The cART regime containing AZT may lead to myelosuppression, thus hindering the immunologic response after1year of cART. The possibility to achieve complete immunologic response is not significantly related to being able to reach virologic suppression or not.