Study On The Relationship Between Antiretroviral Therapy And Antituberculosis Treatment In Patients With AIDS Complicated With Pulmonary Tuberculosis

Objectives To study the interactive relationships between antiretroviral therapy(ART)and antituberculosis therapy(ATT),we analysis the trend of erythron,liver and kidney function,bacteriology,immunology and virology in HIV/TB co-infection patients who receiving ART in combination with ATT.These results may optimize clinical treatment of HIV/TB coinfected patient.Methods Ambispective cohort study was used to assess the HIV/TB coinfected patients who were enrolled from January 2014 to December 2017 in Yunnan Provincial Hospital of Infectious Diseases.These patients were divided into three groups based on the timing of receiving ART.The three groups were group A(ATT treatment on basis of ART),group B(starting ART in 8 weeks of ATT)and group C(starting ART after 8 weeks of ATT).Erythron,liver and kidney function were monitored at baseline,1,2,4 and 8week during these two months of intensive therapy.At the same time,M.tuberculosis smear wasused to examine negative conversion ratio of mycobacterium tuberculosis in sputum during intensive period.CD4+T lymphocytes and HIV-RNA viral load were also measured at 24 and 48 weeks.Results According to the inclusion criteria,268 HIV/TB coinfected patients were enrolled in the study,including 140 patients in group A,87 patients in group B and 41 patients in group C,respectively.240 patients had achieved follow-up during the intensive period,including 112 patients in group A,87 patients in group B,and 41 patients in group C,respectively.There were 28 patients whose monitoring data incomplete in intensive period and 6 patients were died.In the completed follow-up during the consolidation period of 262 patients,220 patients showed intact CD4+T lymphocytes countsat 24 week,and CD4+T lymphocytes counts of 201 patients at 48 week were examined.The HIV-1 viral load results of 197 patients were obtained after 24 weeks.1.Erythron: A total of 119 patients had mild anemia before treatment with ATT.After treatment,75 patients had anemia symptoms at the end of the intensive period.The recovery rate of anemia was 36.97%(44/119).The prevalence of anemia showed statistically significantdifference before and after ATT.The proportion of normal cell uniform anemia reduced,and the proportion of large cell heterogeneous anemia increased.(1)According to the time of receiving ART treatment,we found that there was no significant difference in the baseline level of RBC count among three groups.The group of Starting ART in 8 weeks of ATThad an increase of HGB after treatment with 4 weeks.With or without ART,MCV and RDW were increased after ATT treatment.(2)Analyzing different ART regimens combined with ATT,the results exhibited no significant difference in RBC countswhen compared baseline with after different ART with ATT.But the increase in RBC count was greater in TDF/3TC/EFV than AZT/3TC/EFV at 8 week.When TDF/3TC/EFV was combined with ATT for 8weeks,the HGB was higher than the baseline,and the increase in HGB was greater than that of AZT/3TC/EFV.2.Liver function:A total of 47 patients had mild liver function damage before ATT.After ATT treatment,21 patients had mild liver function damage at the end of the intensive period,and the recovery rate of liver function injury was 55.32%(26/47).There was no significant difference in liver function damage before and after ATT.(1)According to the time of receiving ART treatment,we found that T-Bil decreased in group B(starting ART in 8 weeks of ATT),and there was no significant difference between group A(ATT treatment on basis of ART)and C(starting ART after 8 weeks of ATT).ALT levels in three groups all decreased after 8 weeks of treatment compared with the baseline,but ALT in group B was decreasing fast.AST also decreased in group B,and no significant difference was found between group A and C.The levels of ALB group A and B both were higher than the baseline,and there was no significant difference when comparing with group C.(2)According to different ART schemes combined with ATT,the results showed thatthe levels of T-Bil and AST were lower,and ALB were higher thanbaseline after ART with AZT/3TC/EFV and TDF/3TC/EFV.The levels of ALT decreased after treated with TDF/3TC/EFV,and in AZT/3TC/EFV regimen did not change.At 8 weeks of treatment with TDF /3TC/LPV/r,the levels of T-Bil,ALT,and AST all decreased comparing with baseline,but ALB increased from baseline.No changes were found in AZT/3TC/LPV/r regimen.3.Renal function: There were no renal dysfunction in 240 patients in baseline.After ATT treatment,3 patients exhibited renal dysfunction(recompensation of renal insufficiency)at the end of the intensive phase,and the incidence of renal dysfunction was 1.25%(3/240).There was no significant difference before and after treatment.(1)According to the time of receiving ART treatment,we found no significant difference in levels of UREA among three groups before and after ATT.The CREA level of group A and B decreased after treatment,but there was no change in group C.The UA level in all three groups increased after 1 week of treatment.(2)According to different ART schemes combined with ATT,after treated with AZT/3TC/EFV and TDF/3TC/EFV,CREA level decreased,UA level increased,and UREA did not change.The levels of UREA and UA increased when treated with AZT/3TC/LPV/r and TDF/3TC/LPV/r.CREA level decreased after treated with TDF/3TC/LPV/r,and with AZT/3TC/LPV/r there was no change.4.Bacterological:The positive rate of sputum M.tuberculosis smear in HIV/TB patients was 25.00%(60/240)before ATT.After received ATT,the positive rate of sputum smear was 7.08%(17/240),and the positive rate reduced 71.67%(43/60).There was a statistically significant difference in the positive rate of sputum smear among three groups before and after ART and ATT.No differences were found after treatment in the three groups,that is,the three groups were consistent in efficacy.In AZT or TDF/3TC/EFV combined with HRfp ZE/HRfp(EFV+RFP group)and AZT or TDF/3TC/LPV/r combined with HRfb ZE/HRfb(LPV/r+RFB group),sputum conversion rate in EFV+RFP group was 71.05%,and in LPV/r+RFB group was 87.50%.There was no significant difference in the sputum conversion rate between the two groups.5.Immunology: The differences of CD4+T lymphocyte counts at 24 and 48 weeksin three groups were significant comparing with baseline.After receiving ART and ATT,CD4+T lymphocyte counts was significantly higher than the baseline,and the CD4+T lymphocytes count increased with prolongingof treatment time.There was no significant difference in the degrees of change in CD4+T lymphocyte counts among three groups at 24 and 48 weeks,that is,the three groups were consistent in efficacy.6.Virology:47 of 197 patients showeddetectable HIV-1 viral load(>20 copies/m L)after 24 weeks of combination therapy,and the positive rate was 23.86%(47/197).The failure rate of ART was 11.17%(22/197).A total of 21 patients with antiviral therapy failure(>1000 copies/m L)were tested for HIV-1 genotype resistance,15 patients were amplified positively,and9 patientsexhibited drug-resistant mutations.The resistance rate was 60.00%(9/15).The NRTIs mutation was M184V(26.67%),and NNRTIs mutations were V179D(26.67%)and V106M(20.00%),and major PIs mutations were not found.Analyzing factors of affecting HIV-1 replication found that ALB,sputum smear,CD4+T,CD8+T,CD4+T / CD8+T,ATT and ART didn’t affect HIV-1 replication,and starting ART in 8 weeks of ATT can inhibit replication of HIV-1.Conclusion1.Combination antiretroviral therapy could not affect the effectiveness of antituberculosis treatment.The earlier antiretroviral therapy is started,the better to improve anemia and liver and kidney function in HIV/TB patients.2.Anti-tuberculosis therapy combined with antiretroviral therapy in different periods can improve the immune function of HIV/TB patients,and CD4+T lymphocyte counts increased significantly with the extension of the combined therapy.3.ART combined with ATT therapy did not accelerate the emergence of HIV-1genotype resistant mutations in HIV/TB coinfection.Early initiation of antiretroviral therapy was more beneficial to inhibiting HIV-1 viral load in patients with HIV/TB.