Mortality Risk Factors Among People Living with HIV Receiving Second--line Antiretroviral Therapy in Rural China.

BACKGROUND: Second-line antiretroviral therapy (ART) was introduced in Henan Province in 2009. The number of people living with human immunodeficiency virus (HIV) starting this therapy is increasing. OBJECTIVE: This study aimed to investigate the survival and factors affecting mortality among this group. METHODS: We conducted a retrospective cohort study of people living with HIV (PLHIV) who switched to second-line ART between May 1, 2010, and May 1, 2016., using the Kaplan-Meier method and Cox proportional hazards models. RESULTS: We followed 3,331 PLHIV for 26,988 person-years, of whom 508 (15.3%) died. The mortality rate was 1.88/100 person-years. After adjusting for confounding factors, we found being a woman (hazard ratio [HR], 0.66; 95% confidence interval [CI] 0.55-0.79), > 50 years old (HR, 2.69; 95%CI, 2.03-3.56), single/windowed (HR, 1.26; 95%CI, 1.04-1.52), having > 6 years of education (HR, 0.78; 95%CI, 0.65-0.94), Chinese medicine (HR, 0.75; 95%CI, 0.52-0.96), liver injury (HR, 1.58; 95%CI, 1.19-2.10), and CD4+ T cell count <200 cells/µl (HR, 1.94; 95%CI, 1.47-2.55), or 200-350 cells/µl (HR, 1.37; 95%CI, 1.03-1.82) were associated with mortality risk. CONCLUSIONS: We found lower mortality among PLHIV who switched to second-line ART than most previous studies. The limitations of a retrospective cohort may, therefore, have biased the data, and prospective studies are needed to confirm the results. Moreover, Chinese medicine combined with second-line ART shows potential as a treatment for HIV.

Effectors of Hyperlipidemia among HIV/AIDS patients with second-line antiretroviral therapy based on register data.

OBJECTIVE: In this study, we aimed to determine the prevalence and effectors of hyperlipidemia among people living with HIV/AIDS (PLWHA) and taking second-line antiretroviral therapy (ART) using registry data in central China. METHODS: We conducted a cross-sectional study and collected information of PLWHA on second-line ART during 2018 from two medical registries. Hyperlipidemia was defined according to the 2016 Chinese guidelines for the management of dyslipidemia in adults. Univariate and multivariate logistic regression analyses were performed to explore the influencing factors of hyperlipidemia. We calculated odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: A total of 2886 PLWHA taking second-line ART were included in this study, and 978 (33.9%) had hyperlipidemia. Female patients, those with hyperglycemia, and patients with CD4+ cell counts >500 cells/µL had a higher prevalence of hyperlipidemia with 37.0%, 49.0%, and 41.3%, respectively. Multivariate analysis showed that CD4+ cell count 350-500 cells/µL (OR=1.72, 95% CI: 1.26-2.38), CD4+ cell count >500 cells/µL (OR=2.49, 95% CI: 1.85-3.38), and FPG >6.2 mmol/L (OR=2.08, 95% CI:1.64-2.65) were risk factors for hyperlipidemia. Male sex (OR=0.72, 95% CI: 0.61-0.85) and Hb <110 g/L (OR=0.59, 95% CI: 0.45-0.76) were protective factors against hyperlipidemia. CONCLUSIONS: PLWHA on second-line ART had a higher prevalence of hyperlipidemia. Gender, CD4+ cell count, FPG, and hemoglobin were influencing factors of hyperlipidemia.

Suboptimal immune recovery and associated factors among people living with HIV/AIDS on second-line antiretroviral therapy in central China: A retrospective cohort study.

The introduction and scale-up of antiretroviral therapy (ART) have contributed to significantly improved patients with acquired immune deficiency syndrome (AIDS) quality of life and prolongs their survival. This has occurred by suppressing viral replication and recovering the CD4 cell count. However, some patients do not normalize their CD4 cell count, despite suppression of the viral load (VL). Patients with suboptimal immune recovery (SIR), as defined by a VL < 400 copies/ml with a CD4 cell count of<200 cells/µl, after ART initiation, exhibit severe immune dysfunction and have a higher risk of AIDS and non-AIDS events. In recent years, People living with HIV/AIDS (PLWHA) with first-line ART failure began to gradually switch to second-line ART. This study aimed to examine the prevalence and factors affecting SIR among PLWHA who switch to second-line ART in rural China. A 1-year retrospective cohort study was conducted among PLWHA who switched to second-line ART between January 2009 and December 2018. All patients with a VL < 400 copies/ml after 1 year of second-line ART were included. SIR was defined as a CD4 cell count <200 cells/µl and a VL < 400 copies/ml after 1 year of second-line ART. The data collected from medical records were analyzed by univariate and multivariate analyses. A total of 5294 PLWHA met the inclusion criteria, 24 died, and 1152 were lost to follow-up after 1 year of second-line ART. Among 4118 PLWHA who were followed up, 3039 with a VL < 400 copies/ml had their data analyzed, and the prevalence of SIR was 13.1%. The patients' mean age at recruitment was 47.6 ± 8.1 years and 45.3% were men. A total of 30.7% of patients were HIV-positive for >8 years and 88.2% were receiving ART before starting second-line ART for >3 years. The mean CD4 cell count was 354.8 ± 238.2 cells/µl. A multivariable analysis showed that male sex, single status (unmarried or divorced), and a low CD4 cell count were risk factors for SIR among PLWHA with second-line ART. The prevalence of SIR among PLWHA who switched to second-line ART in this retrospective cohort study is lower than that in most other studies. Several factors associated with SIR include male sex, marital status, and CD4 cell count levels in PLWHA.

Effects of Chinese Medicine on the Survival of AIDS Patients Administered Second-Line ART in Rural Areas of China: A Retrospective Cohort Study Based on Real-World Data.

OBJECTIVES: Chinese medicine (CM) improves the symptoms of patients with acquired immune deficiency syndrome (AIDS) and prolongs their survival. This real-world study aimed to evaluate the effects of CM on the survival of AIDS patients administered second-line antiretroviral therapy (ART). METHODS: We conducted a retrospective cohort study of the medical records of patients with AIDS who switched to second-line ART between January 2009 and December 2014. Patients were divided into ART and CM + ART groups. Propensity score matching (PSM) was performed to correct for biases between groups. Kaplan-Meier analysis and the log-rank test were used to compare survival rates, and Cox regression models were employed to identify factors significantly associated with survival. RESULTS: The study population (n = 4180) was comprised of the CM + ART group (n = 855) and the ART group (n = 3325). After 1 : 2 PSM, 855 patients in the CM + ART group and 1699 in the ART group were selected for analysis. Patients in the CM + ART group were followed for 4246.8 person-years, and the mortality rate was 2.12/100 person-years. Patients in the ART group were followed for 8381.2 person-years, and the mortality rate was 2.91/100 person-years. Cox regression model analysis revealed that patients in the CM + ART group survived significantly longer than those in the ART group (hazard ratio: 0.73 and 95% confidence interval: 0.57-0.93). Gender, age, symptoms, CD4 cell counts, and viral loads were independently associated with the survival of AIDS patients treated with second-line ART. CONCLUSIONS: CM significantly improved the survival rate of AIDS patients treated with second-line ART.

Effect of Traditional Chinese Medicine Therapy on the Trend in CD4+ T-Cell Counts among Patients with HIV/AIDS Treated with Antiretroviral Therapy: A Retrospective Cohort Study.

This retrospective cohort study was conducted to explore the effect of traditional Chinese medicine (TCM) therapy on the long-term trends in CD4+ T-cell count among patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) who were treated with combined antiretroviral therapy (cART) over a 14-year period. A total of 721 individuals were treated with cART alone (cART group), and 307 individuals were treated with both cART and TCM (TCM + cART group). Among all enrolled patients with HIV/AIDS, 99.5% were farmers, 71.1% had more than 6 years of education, and 96.8% were infected with HIV via a paid blood donation. For those patients with HIV/AIDS who had a baseline CD4+ T-cell count of <350 cells/mL, the CD4+ T-cell count tended to increase to approximately 350 cells/mL more rapidly in the TCM + cART group than in the cART group, but when the baseline CD4+ T-cell count was ≥350 cells/mL, there was no difference between the cART and TCM + cART groups. For other patients with HIV/AIDS who had a baseline CD4+ T-cell count of 350-500 cells/mL, the CD4+ T-cell counts tended to increase slightly, but there was no difference between the two groups. For patients with HIV/AIDS who had a baseline CD4+ T-cell count of ≥500 cells/mL, the CD4+ T-cell counts tended to be maintained at a particular level, with no difference between the two groups. The results show that the effect of TCM on the CD4+ T-cell counts of patients with HIV/AIDS is related to the CD4+ T-cell level at the time of initial treatment. TCM can increase the CD4+ T-cell count among patients with HIV/AIDS who have a baseline CD4+ T-cell count of <350 cells/mL. Sex and age have a slight influence on the therapeutic effect of TCM.

Prevalence trend and risk factors for anemia among patients with human immunodeficiency virus infection receiving antiretroviral therapy in rural China.

OBJECTIVE: To estimate the prevalence trend and risk factors for anemia in patients with human immunodeficiency virus (HIV) infection receiving antiretroviral therapy (ART) in rural China. METHODS: We conducted cross-sectional studies among the same population in 2010, 2012, and 2014, based on data from standard medical record registers. Factors associated with anemia were evaluated using a logistic regression model. RESULTS: The number of patients with HIV infection included in each cross-sectional study was 1456 in 2010, 1531 in 2012, and 1567 in 2014, and the prevalence of anemia was 44.3%, 34.7%, and 27.6%, respectively. The prevalence of anemia was lower in female patients in 2010 [odds ratio (OR) 0.68; 95% confidence interval (CI) 0.55-0.85]; however, there was no difference by sex in 2012 (OR 0.90; 95% CI 0.72-1.11) and 2014 (OR 1.05; 95% CI 0.84-1.32). Patients with a higher level of education had a lower risk of anemia in 2014 (OR 0.72; 95% CI 0.56-0.92), but there was no difference in 2010 (OR 1.00; 95% CI 0.79-1.25) and 2012 (OR 0.99; 95% CI 0.79-1.24). Patients who had received a longer duration of ART had a higher risk of anemia in 2014 (OR 1.74; 95% CI 1.15-2.64), but there was no difference in 2010 and 2012 (P > 0.05). Patients receiving Traditional Chinese Medicine (TCM) therapy had a lower risk of anemia. CONCLUSION: The prevalence of anemia among patients with HIV infection receiving ART decreased between 2010 and 2014 in Henan Province but was still higher than the prevalence in the general population of China. TCM therapy can potentially decrease the risk of anemia among patients with HIV infection.

Prevalence of liver injury among patients with acquired immunodeficiency syndrome treated with highly active antiretroviral therapy in China.

OBJECTIVE: To estimate the prevalence of liver injury among patients with acquired immunodeficiency syndrome (AIDS) who received highly active antiretroviral therapy (HAART) in rural Henan Province in China, and to explore whether Traditional Chinese Medicine (TCM) treatment based on HAART would increase this risk. METHODS: This was a retrospective cross-sectional study. We collected medical information on patients with AIDS from two treatment databases in 2014. Criteria established by the AIDS Clinical Trials Group in 1996 were used for grading liver injury, classified based on the limit of normal (ULN) for alanine transaminase and aspartate aminotransferase: grade 1 (1.25-2.5 × ULN); grade 2 (2.6-5 × ULN); grade 3 (5.1-10 × ULN); and grade 4 (> 10 × ULN). Factors associated with liver injury were evaluated using a logistic regression model. RESULTS: A total 6953 patients with AIDS (3324 male and 3629 female patients) were enrolled into this study. The prevalence of liver injury was 22.0% (18.0% grade 1, 3.1% grade 2, 0.9% grade 3). In multivariate analysis, patients aged 34-45 years were more likely to have liver injury than patients in other age groups [adjusted odds ratio (AOR), 1.39; 95% CI, 1.01-1.91)]. Other factors associated with liver injury included male sex (AOR, 1.64; 95% CI, 1.46-1.85), HIV infection via blood (AOR, 1.47; 95% CI, 1.19-1.82), hepatitis B virus antibody positive (AOR, 1.07; 95% CI, 0.85-1.36), and hepatitis C virus (HCV) antibody positive (AOR, 2.76; 95% CI, 2.28-3.34). CONCLUSION: The prevalence of liver injury was relatively high among HAART-experienced patients. Several factors associated with liver injury included male sex, age 35-45 years old, HIV infection through blood, and concurrent HCV infection. TCM had no relationship with liver injury in patients receiving HAART.

Advantages of Chinese Medicine for Patients with Acquired Immunodeficiency Syndrome in Rural Central China.

OBJECTIVE: To analyze the effect of Chinese medicine (CM) on mortality and quality of life (QOL) of acquired immunodefificiency syndrome (AIDS) patients treated with combined antiretroviral therapy (cART). METHODS: A random sample of AIDS patients enrolled in the National Chinese Medicine Treatment Trial Program (NCMTP) that met the inclusion criteria was included in this study. NCMTP patients were included as the CM+cART group, and those not in the NCMTP were included as the cART group. Survival from September 2004 to September 2012 was analyzed by retrospective cohort study. QOL was analyzed by cross-sectional study. RESULTS: The retrospective cohort study included 528 AIDS patients, 322 in the CM+cART group and 206 in the cART group. After 8 years, the mortality in the CM+cART group was 3.3/100 person-years, which was lower than the cART group of 5.3/100 person-years (P<0.05). The hazard ratio (HR) for mortality in the cART group was 1.6 times that of the CM+cART group by Cox proportional hazard model analysis. After controlling for gender, age, marital status, education, and CD4+ T-cell count, the HR was 1.9 times higher in the cART group compared with the CM+cART group (P<0.05). The cross-sectional study investigated 275 AIDS patients. The mean scores of all QOL domains except spirituality/personal beliefs were higher in the CM+cART group than in the cART group (P<0.05). CONCLUSIONS: For AIDS patients, CM could help to prolong life, decrease mortality, and improve QOL. However, there were limitations in the study, so prospective studies should be carried out to confifirm our primary results.

Prevalence of anaemia among HIV patients in rural China during the HAART era.

The prevalence of anaemia among HIV patients receiving highly active antiretroviral therapy (HAART) in China has not been extensively studied. The purpose of this study was to estimate the prevalence of anaemia among HIV patients receiving HAART in China. This cross-sectional study was conducted based on data in routine record registers. Factors associated with anaemia were evaluated by logistic regression model. Among the 8632 HIV patients in this analysis, the overall prevalence of anaemia was 39.2%, and the prevalence of mild, moderate, and severe anaemia were 27.2%, 10.8%, and 1.2%, respectively. Anaemia was more prevalence among male, older, little time taken HAART and lower CD4 cell count. Patients taken TCM had lower prevalence of anaemia. The prevalence of anaemia among the HIV patients receiving HAART was high in this study. HIV patients with anaemia who are older and have CD4 cells count lower than 200 cells/mL require more attention. Traditional Chinese medicine may be a potential method to lower the frequency of anaemia.

Gene Expression Profiles of HIV/AIDS Patients with Qi-Yin Deficiency and Dampness-Heat Retention.

OBJECTIVES: Traditional Chinese Medicine (TCM) applied in the clinic as a complementary and alternative therapy has helped improve immunity and reduce side effects and symptomatic treatment in patients with HIV/AIDS. However, the mechanisms of TCM syndromes are not clear. Transcriptomics enables the study of such TCM syndromes. DESIGN: This study compared the messenger RNA (mRNA) expressions of healthy persons and patients with HIV/AIDS who had two common TCM syndromes, qi-yin deficiency and dampness-heat retention, to find the difference in HIV/AIDS with TCM syndromes. RESULTS: Comparison with healthy persons identified 113 mRNAs-41 enhanced and 72 decreased-in the qi-yin deficiency group. Additionally, 76 mRNAs were found in the dampness-heat retention group: 14 increased and 62 decreased. Functional genetic analysis of the mRNAs indicated that two TCM syndromes were correlated with cell apoptosis, immunoinflammatory responses, and lymphocyte activation. Differentially expressed mRNAs in the qi-yin deficiency group were obviously associated with cellular activity, communication, protein localization, cellular ion homeostasis, and regulation of cell motion, whereas mRNAs in the dampness-heat retention group were associated with sequence-specific DNA binding, cellular response to stress, and hemopoietic or lymphoid organ development. CONCLUSIONS: These results suggest that the formation of different TCM syndromes in patients with HIV/AIDS were founded on biological transcriptomics, which reveal mechanisms of the formation of these syndromes in HIV/AIDS. Differentially expressed mRNAs in two TCM syndrome groups tended to normalize after TCM intervention, which indicates that TCM might remit symptoms by changing genetic expression.

[Breakthrough Point of Chinese Medicine and Pharmacy for HIV/AIDS Prevention and Treatment in the Post-HAART Period].

HIV/AIDS is a severe infectious disease with ineffective drug or method found till now. Highly active antiretroviral therapy (HAART) is a treatment method widely internationalized. Its coverage populations are continually expanding due to its definite clinical effect. AIDS prevented and treated by Chinese medicine and pharmacy has ever been reported. Especially early intervention of Chinese medicine syndrome differentiation based treatment can delay the process of HIV-infected subjects' entry into AIDS in AIDS asymptomatic phase. However, it has great significance of clinical and basic researches in the following 4 aspects: (1) attenuating toxic/adverse reactions of HAART; (2) improving clinical effects of HAART; (3) lowering resistance rate of HAART; and (4) treating common opportunistic infections of AIDS in the post-HAART period.

Effect of treatment course of comprehensive intervention with Traditional Chinese Medicine on mortality of acquired immunodeficiency syndrome patients treated with combined antiretroviral therapy.

OBJECTIVE: To investigate the effect of a treatment course of comprehensive intervention with Traditional Chinese Medicine (TCM) on the mortality of patients with acquired immunodeficiency syndrome (AIDS) treated with combined antiretroviral therapy (cART). METHODS: AIDS patients who had taken cART in a national TCM human immunodeficiency virus treatment trial program (NTCMTP) before 2009 were enrolled in this study and followed for 36 months from November 2009. Patients enrolled in the NTCMTP in 2004 were taken as the first group, those enrolled in 2006 as the second group, and those enrolled in 2009 as the third group. Cumulative survival rates were calculated by the life table method. Survival curves for subgroups were compared by the log-rank test. Hazard ratios were calculated with a Cox proportional hazards model. RESULTS: A total of 1443 AIDS patients were followed for 3 years (4198 person-years). During this period, 91 (6.3%) patients died and 13 (0.9%) were lost to follow-up. The total mortality rate was 2.17/ 100 person-years. The mortality rate of patients enrolled in the NTCMTP in 2004 was 1.49/100 person- years, which was lower than that of patients enrolled in 2006 (2.23/100 person-years) and 2009 (3.48/100 person-years). After adjusting for other factors, a shorter time of treatment with TCM, male sex, older age, lower CD4 + T-cell counts, and long-term treatment with cART were risk factors of mortality. CONCLUSION: Long-term treatment with TCM decreased the mortality risk of AIDS patients. Factors such as being male, older age, CD4 + T-cell counts, and time of treatment with TCM and cART were correlated with mortality.