Am. J. Chin. Med. 2014.42:1333-1344. Downloaded from www.worldscientific.com by UNIVERSITY OF CALIFORNIA @ SAN DIEGO on 01/05/15. For personal use only.
The American Journal of Chinese Medicine, Vol. 42, No. 6, 1333–1344 © 2014 World Scientific Publishing Company Institute for Advanced Research in Asian Science and Medicine DOI: 10.1142/S0192415X14500839
Traditional Chinese Medicine Could Increase the Survival of People Living with HIV in Rural Central China: A Retrospective Cohort Study, 2004–2012 Yantao Jin,*,† Huijun Guo,†,‡ Xin Wang,§ Xiumin Chen,† Ziqiang Jiang,† Guanpeng Hu,† Jianghong Hou,¶ Shiqing Jiang,|| Xiaoping Yang,** Ying Liu,†† Liran Xu†,‡ and Ning Wang* *National Center for AIDS/STD Control and Prevention Chinese Center for Disease Control and Prevention, Beijing 102206, P. R. China † Department of AIDS Treatment and Research Center The First Affiliated Hospital of Henan University of Traditional Chinese Medicine Zhengzhou 45000, P. R. China ‡
Key Laboratory of Viral Diseases Prevention and Treatment of Traditional Chinese Medicine of Henan Province, Zhengzhou 450000, P. R. China §School
of International Education Zhengzhou Railway Vocational and Technical College Zhengzhou 450000, P. R. China ¶
Department of Pediatrics The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine Zhengzhou 45000, P. R. China ||Digestive Department The Third Affiliated Hospital of Henan University of Traditional Chinese Medicine Zhengzhou 45000, P. R. China **Digestive Department, Henan Province Chinese Medicine Research Institute, Zhengzhou 450000, P. R. China ††
Traditional Chinese Medicine Center for Acquired Immune Deficiency Syndrome Prevention and Treatment China Academy of Traditional Chinese Medicine Beijing 100700, P. R. China Published 5 December 2014
Correspondence to: Prof. Liran Xu, Department of AIDS Treatment and Research Center, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 45000, P. R. China. Tel: (þ86) 3716626-4733, E-mail:
[email protected] and Prof. Ning Wang, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, P. R. China. Tel: (þ86) 10-58900955, E-mail:
[email protected] 1333
Am. J. Chin. Med. 2014.42:1333-1344. Downloaded from www.worldscientific.com by UNIVERSITY OF CALIFORNIA @ SAN DIEGO on 01/05/15. For personal use only.
1334
Y. JIN et al.
Abstract: A retrospective cohort study was conducted to explore the effectiveness of Traditional Chinese Medicine (TCM) in treating people living with HIV (PLHIV) by comparing the survival of PLHIV treated with TCM and without TCM. To identify prognostic factors that affect the survival of PLHIV, patients who enrolled in the national TCM HIV treatment trial program (NTCMTP) in October 2004 and PLHIV in the same region who did not enroll in the NTCMTP were compared. Participants were followed up to October 2012. Survival time was estimated through the Kaplan–Meier method, and hazard ratios to identify prognostic factors were computed through Cox proportional hazard models. A total of 3,229 PLHIV (1,442 in the TCM therapy group and 1,787 in the non-TCM therapy group) were followed up for 21,876 person-years. In this time period, 751 (23.3%) died and 209 (6.5%) were lost to follow-up, for an overall mortality rate of 3.43/100 person-years. In the TCM therapy group, 287 (19.0%) died and 139 (9.7%) were lost to follow-up, and in the nonTCM therapy group, 464 (26.0%) PLHIV died and 70 (3.9%) were lost to follow-up. The mortality rate in the TCM therapy group was 2.97/100 person-years, which was lower than the rate of 3.79/100 person-years in the non-TCM therapy group. The 8-year cumulative survival in the TCM therapy group was 78.5%, lower than the 74.0% survival in the nonTCM therapy group. After adjusting for other factors, risk factors of death included male gender, older age, less education, taking combined antiretroviral therapy (cART) at enrollment, not taking cART at follow-up, and lower CD4þ T cell counts. Our retrospective cohort study indicates that TCM increased the survival and lengthened the lifetime of PLHIV in Henan Province of China. However, the limitations of a retrospective cohort could have biased the study, so prospective studies should be carried out to confirm our primary results. Keywords: Retrospective Cohort Study; Human Immunodeficiency Virus; Acquired Immune Deficiency Syndrome; Survival; Traditional Chinese Medicine.
Introduction Human immunodeficiency virus (HIV) is a worldwide public health problem, especially in developing countries (Merson, 2006; Greene, 2007). At the end of 2012, UNAIDS estimated that there were 35.3 million people living with HIV (PLHIV) worldwide (UNAIDS, 2013). Since the 1980s researchers have searched for methods of treatment or prevention of the disease, and for many years did not find curable or prevention strategies. Fortunately, ever since combined antiretroviral therapy (cART) was introduced in 1996, the death rate from AIDS-related causes has declined significantly (Palella et al., 1998; Hogg et al., 1998), and the acceptance and worldwide spread of cART ushered in a new era for the treatment of HIV/AIDS. Since the first Chinese HIV/AIDS case was reported in 1985, by the end of 2011 there were approximately 780,000 HIV-1 positive cases, including about 154,000 AIDS patients and 48,000 new infections in 2011 (Ministry of Health of the People’s Republic of China, 2012) Henan is the most populous province in China, and is also a major agricultural province. Most HIV-infected people in Henan were infected through paid blood supply and illegal blood plasma collecting in the 1990s (Na and Detels, 2005). By the end of October
Am. J. Chin. Med. 2014.42:1333-1344. Downloaded from www.worldscientific.com by UNIVERSITY OF CALIFORNIA @ SAN DIEGO on 01/05/15. For personal use only.
TRADITIONAL CHINESE MEDICINE AND HIV CARE
1335
2012, there were 37,826 PLHIV in Henan, 30,660 of whom had progressed to AIDS (Liu et al., 2013a). In Henan, most PLHIV live in resource limited regions. In 2004, the State Administration of Traditional Chinese Medicine (TCM) of China initiated a national TCM HIV treatment trial program (NTCMTP) to treat AIDS patients with TCM and antiretroviral drugs. By the end of November 2011, the NTCMTP had treated over 10,000 HIV/AIDS patients in 19 provinces, including Henan Province (Ministry of Health of the People’s Republic of China, 2012). By the end of 2012, there were 5,000 patients who were treated by cART with or without TCM in Henan Province. In the last decade, Henan province has made significant strides in treating HIV/AIDS with TCM (Xu, 2005; Li et al., 2010; Xu et al., 2010). Henan Province carried out a strategy entitled ‘Three uniformities and three combinations principles’ to manage the NTCMTP. This included three uniformities (unified organization, unified therapy, and unified index) and three combinations (clinical treatment combined with scientific research, fixed prescription combined with dialectical treatment, and TCM therapy combined with cART). In Henan, all PLHIV voluntarily joined the program and were permitted to receive TCM therapy at any time. In the last 30 years, many effects of TCM on HIV/AIDS have been shown, such as reducing plasma HIV viral load, increasing CD4þ T cell counts, promoting immune reconstitution, ameliorating signs and symptoms, improving the health related quality of life, and counteracting the side effects of antiretroviral drugs (Liu et al., 2013b; Liang and Wang, 2013). However, to our knowledge there was no report on the survival of PLHIV influenced by TCM. To address this gap, we used databases, including the NTCMTP and epidemiological database of all HIV-infected patients reported to the Chinese Center for Disease Control and Prevention (Chinese CDC), to retrospectively estimate the influence of NTCMTP on the mortality of PLHIV. Methods Study Patients The data for this study were collected from three national databases, the first of which was the NTCMTP database. The second was an epidemiological database of all HIV-infected patients reported to the Chinese CDC through the national surveillance system. The third was the treatment database of the Chinese CDC, which includes all individuals receiving free national treatment based on the national HIV treatment criteria. All individuals in the TCM therapy group were enrolled in NTCMTP in October of 2004 in Henan Province of China, and all individuals in the non-TCM therapy group were HIV-infected, lived in this region, and were not enrolled in NTCMTP. All individuals were identified as HIV-infected by western blot before 30 October 2004, were older than 18 years of age in 30 October 2004, and were still living as of 30 October 2004. Information in this study included demographics, method of HIV diagnosis, route of infection, TCM therapy, antiretroviral drug status, reason for lost to follow-up, cause of death, and CD4þ cell count in 2004. Most of the information was collected from the
1336
Y. JIN et al.
epidemiological database except data of TCM therapy and reason for lost to follow-up in the TCM group (collected from the NTCMTP database) and antiretroviral drug status and lost to follow-up in the non-TCM therapy group (collected from the treatment database of the Chinese CDC).
Am. J. Chin. Med. 2014.42:1333-1344. Downloaded from www.worldscientific.com by UNIVERSITY OF CALIFORNIA @ SAN DIEGO on 01/05/15. For personal use only.
Study Definitions This analysis spanned 30 October 2004 through 30 October 2012 and death was the endpoint. Surviving individuals were censored on their date of last contact recorded in the databases or on 30 October 2012. Patients who died because of non-AIDS-defining illness such as suicide and accidents were also considered censored. When only a month was provided without a specific day, the 1st of the month was used. Statistical Analysis The demographic characteristics of patients in the TCM therapy group were compared with those in the non-TCM therapy group via a chi-square test. Cumulative probabilities of survival were estimated by Kaplan–Meier curves, and comparison between curves was tested for statistical significance with the log rank test. Crude and adjusted relative hazard ratios were calculated with a Cox proportional hazards model. All analyses were performed using the SPSS 19.0 software package (SPSS Inc., Chicago, IL, USA), and a two-sided p-Value less than 0.05 was considered statistically significant. Ethics Statement This study was approved by the institutional review board of the First Hospital Affiliated with Henan University of Traditional Chinese Medicine. Individual informed consent was not achieved because this analysis used currently existing data collected during the course of routine treatment, and the data were reported in aggregate without the use of individual identifying information. Patient records/information was made anonymous and de-identified prior to analysis.
Results Patients By 30 October 2004, 4,690 PLHIV in Henan Province of China were reported in the epidemiological database of the Chinese CDC. A total of 3,229 subjects met the inclusion criteria included in this study; of these, 1,442 (44.7%) received TCM therapy and 1,787 (55.3%) did not receive TCM therapy (Table 1). A total of 1,603 (49.6%) were men and 1,626 (50.5%) were women. The majority of individuals were married (74.9%), educated to primary school (63.6%), farmers (99.3%), were infected while acting as a plasma donor
TRADITIONAL CHINESE MEDICINE AND HIV CARE
1337
Am. J. Chin. Med. 2014.42:1333-1344. Downloaded from www.worldscientific.com by UNIVERSITY OF CALIFORNIA @ SAN DIEGO on 01/05/15. For personal use only.
(96.3%), were identified as HIV-infected between January 2003 and October 2004 (93.7%), and were taking antiretroviral drugs during the study period (88.6%). Mean age at enrollment was 41:07 7:98 years and 1,157 (35.8%) individuals had a CD4þ cell count result in 2004; the median count was 267 cells/L (interquartile range: 162–416 cells/L). A comparison of demographics between the TCM therapy group and the non-TCM therapy group is shown in Table 1.
Table 1. Characteristics of Patients at Study Initiation (%) Variables
p-Value
Total Sample
TCM Therapy Group
Non-TCM Therapy Group
3229
1442
1787
Sex Men Women
1603 (49.6) 1626 (50.4)
724 (50.2) 718 (49.8)
879 (49.2) 908 (50.8)
0.565
Age (years) < 30 30–40 41–50 > 50
233 (7.2) 1453 (45.0) 1107 (34.3) 436 (13.5)
90 630 518 204
(6.2) (43.7) (35.9) (14.1)
143 (8.0) 823 (46.0) 589 (33.0) 232 (13.0)
0.064
Marital status Single Married Widow(er)
85 (2.6) 2417 (74.9) 727 (22.5)
36 (2.5) 1093 (75.8) 313 (21.7)
49 (2.7) 1324 (74.1) 414 (23.2)
0.535
Education level 6 years > 6 years Unknown
2054 (63.6) 1161 (36.0) 14 (0.4)
908 (63.0) 529 (36.7) 5 (0.3)
1146 (64.1) 632 (35.4) 9 (0.5)
0.604
Year of HIV diagnosis Before 2002.12 204 (6.3) 2003.1–2004.10 3025 (93.7)
91 (6.3) 1351 (93.7)
113 (6.3) 1674 (93.7)
0.988
Treatment with cART at initiation No 1738 (53.8) Yes 1491 (46.2)
634 (44.0) 808 (56.0)
1104 (61.8) 683 (38.2)
0.001
Treatment with cART at follow-up No 368 (11.4) Yes 2861 (88.6)
95 (6.6) 1347 (93.4)
273 (15.3) 1514 (84.7)
0.001
313.39 207.66 207 (14.4) 201 (13.9) 136 (9.4) 105 (7.3) 793 (55.0)
301.03 214.07 190 (10.6) 147 (8.2) 85 (4.8) 86 (4.8) 1279 (71.6)
0.334 0.001
Sample size
CD4 cell count (cells/L) Mean (SD) 309.29 210.58 < 200 397 (12.3) 200–350 348 (10.8) 351–500 221 (6.8) > 500 191 (5.9) Unknown 2072 (64.2)
Notes: TCM, traditional Chinese medicine; cART, combined antiretroviral therapy; SD, standard deviation.
1338
Y. JIN et al.
Am. J. Chin. Med. 2014.42:1333-1344. Downloaded from www.worldscientific.com by UNIVERSITY OF CALIFORNIA @ SAN DIEGO on 01/05/15. For personal use only.
Mortality Density and Cumulative Survival Of the 3,229 PLHIV followed for 8 years, including 21,876 person-years of follow-up, 2,269 (70.3%) PLHIV were still under follow-up in October 2012, 751 (23.3%) PLHIV had died, and 209 (6.5%) were lost to follow-up. The total mortality rate over the study period was 3.43/100 person-years. In the TCM therapy group, 1,442 were followed for 9,659 person-years, and by the end of follow-up 287 (19.9%) had died and 139 (9.7%) were lost to follow-up. In the non-TCM therapy group, 1,787 were followed for 12,217 person-years, and by the end of follow-up 464 (26.0%) had died and 70 (3.9%) were lost to follow-up. Mortality density over the study period was 2.97/100 person-years in the TCM therapy group and 3.79/100 personyears in the non-TCM therapy group. In the TCM therapy group, 97.3% were alive after 1 year, 84.5% after 5 years, and 78.5% after 8 years, whereas the cumulative survival of the non-TCM therapy group was 96.1% after 1 year, 80.5% after 5 years, and 74.0% after 8 years. The difference in cumulative survival between the two groups was statistically significant (Fig. 1). Of the 139 PLHIV lost to follow-up in the TCM therapy group, 39 died because of a non-AIDS-defining illness such as suicide and accident, 34 PLHIV did not follow-up because they left home to work, 10 exited because of disease aggravation, and the reason was not identified for 56. This information was collected from the NTCMTP database, and according to the epidemiological database of the Chinese CDC, 23 of these people had died by October 2012. Thus, of the 139 PLHIV lost to follow-up in the TCM therapy group, the death density was 3.28/100 person-years, which is higher than that of the TCM group and lower than that of the non-TCM therapy group.
Figure 1. Comparison of cumulative survival percent of PLHIV between the TCM therapy and non-TCM therapy groups.
TRADITIONAL CHINESE MEDICINE AND HIV CARE
1339
Of the 70 PLHIV lost to follow-up in the non-TCM therapy group, 12 PLHIV died because of non-AIDS-defining illness and the reason was not identified for the others who were lost to follow-up.
Am. J. Chin. Med. 2014.42:1333-1344. Downloaded from www.worldscientific.com by UNIVERSITY OF CALIFORNIA @ SAN DIEGO on 01/05/15. For personal use only.
Factors Associated with AIDS-Related Death of PLHIV Table 2 shows the results of the Cox proportional hazards model analysis of factors associated with AIDS-related death of PLHIV. The mortality risk of PLHIV in the non-TCM therapy group was 1.28 times higher than in the TCM therapy group. After adjusting for the potential confounding factors, the mortality risk of the former was still 1.27. Multivariable analysis revealed that sex, age, education level, treatment with cART, and CD4þ T cell counts were all associated with mortality. The mortality risk of females was 0.59 [95% confidence interval (CI): 0.51–0.79] times that of males. The mortality risk increased with older age. People aged between 41 and 50 had a 1.88 (95% CI: 1.30–2.73) times higher risk of death than those under 30. Patients with more than 6 years of education had a lower risk than those with less than 6 years education. The mortality risk of patients receiving cART treatment at enrollment was 1.41 (95% CI: 1.17–1.69) times higher than the patients without cART treatment, while during the follow-up, the mortality risk of the former was 0.17 (95% CI: 0.14–0.21) compared with that of the latter. Compared with patients with CD4þ T cell counts < 200 cells/L, the mortality risk of patients with CD4þ T cell counts of 200–350 cells/L, 350–500 cells/L, and > 500 cells/L at enrollment were 0.46 times, 0.32 times, and 0.27 times lower, respectively. Discussion This retrospective cohort is unique because most PLHIV in this cohort were former plasma donors in rural central China and infected with HIV in the early-to-mid 1990s (Na and Detels, 2005), and were identified by mass HIV screening in these regions in 2004 (Wu et al., 2006; Sun et al., 2007). Almost all PLHIV in this cohort were poor farmers with almost no injection drug use or commercial sex work in their communities. The 3,229 PLHIV in this cohort were followed for 8 years, including 1,422 PLHIV in the TCM therapy group and 1,787 PLHIV in the non-TCM therapy group. The cumulative survival rate of PLHIV was 78.5% after 8 years for those with TCM therapy, whereas the 8-year cumulative survival rate for those without TCM was 74.0%. After controlling for other confounding factors, the non-TCM group had a 1.27 times higher risk of an AIDSdefining death, which suggests that TCM could decrease the morality rate of PLHIV. Compared with a study from Yunnan in China, where the mortality rate was 8.31/100 person-years (Yang et al., 2012), and Henan in China, where the mortality rate was 5.1/100 person-years (Sun et al., 2012), the overall mortality in our study was 3.43/100 personyears. The aim of most survival analysis of PLHIV are to estimate the time to HIV-related death, and different methodological approaches have been reported. Some studies take the date of diagnosis of AIDS as the beginning of the cohort (Rapiti et al., 2000; Fordyce et al., 2002; Marins et al., 2003), while others may include HIV-infected individuals in their
1340
Y. JIN et al. Table 2. Hazard Ratios for Variables of AIDS-Related Death of PLHIV Unadjusted All
No. of Deaths
crRR (95% CI)
p-Value
adjRR (95% CI)
p-Value
Group TCM therapy Non-TCM therapy
1442 1787
287 464
1 1.28 (1.11–1.49)
0.01
1 1.27 (1.09–1.48)
0.03
Sex Men Women
1603 1626
437 314
1 0.68 (0.59–0.79)
0.001
1 0.59 (0.51–0.69)
0.001
Age (years) < 30 30–40 41–50 > 50
233 1453 1107 436
33 266 271 181
1 1.36 (0.95–1.96) 1.88 (1.31–2.69) 3.59 (2.48–5.21)
0.093 0.001 0.001
1 1.27 (0.88–1.83) 1.88 (1.30–2.73) 3.22 (2.19–4.72)
0.198 0.001 0.001
Marital status Single Married Widow(er)
85 2417 727
25 557 169
1 0.73 (0.49–1.09) 0.71 (0.47–1.08)
0.124 0.085
1 1.06 (0.70–1.59) 0.88 (0.58–1.36)
0.791 0.575
Education level < 6 years > 6 years Unknown
2054 1161 14
527 217 7
1 0.70 (0.60–0.82) 2.26 (1.07–4.76)
0.001 0.032
1 0.72 (0.61–0.84) 1.58 (0.74–3.37)
0.001 0.233
Year of HIV diagnosis Before 2002.12 204 2003.1–2004.10 3025
38 712
1 1.34 (0.96–1.85)
0.082
1 1.36 (0.98–1.89)
0.063
Treatment with cART at initiation No 1738 Yes 1491
411 340
1 0.97 (0.84–1.12)
0.662
1 1.41 (1.17–1.69)
0.001
Treatment with ARV at follow-up No 368 Yes 2961
208 543
1 0.23 (0.19–0.26)
0.001
1 0.17 (0.14–0.21)
0.001
CD4 cell count (cells/L) < 200 394 200–350 348 351–500 221 > 500 191 Unknown 2072
176 86 38 34 417
0.44 0.29 0.31 0.33
1 (0.34–0.57) (0.21–0.41) (0.21–0.44) (0.29–0.40)
0.001 0.001 0.001 0.001
0.46 0.32 0.27 0.30
1 (0.35–0.59) (0.23–0.46) (0.19–0.40) (0.25–0.36)
0.001 0.001 0.001 0.001
Categories
Am. J. Chin. Med. 2014.42:1333-1344. Downloaded from www.worldscientific.com by UNIVERSITY OF CALIFORNIA @ SAN DIEGO on 01/05/15. For personal use only.
Adjusted
Notes: TCM, traditional Chinese medicine; cART, combined antiretroviral therapy; crRR, crude relative ratio; adjRR, adjusted relative ratio; CI, confidence interval.
cohort regardless of clinical status at baseline (Ledergerber et al., 1999; Van Sighem et al., 2003; Braga et al., 2007). We took the latter approach, and as a result may have included some PLHIV not in the AIDS stage. The aim of this study was to explore the effect of TCM on the mortality of PLHIV. The mortality rate of PLHIV in the TCM therapy group was
Am. J. Chin. Med. 2014.42:1333-1344. Downloaded from www.worldscientific.com by UNIVERSITY OF CALIFORNIA @ SAN DIEGO on 01/05/15. For personal use only.
TRADITIONAL CHINESE MEDICINE AND HIV CARE
1341
2.97/100 person-years, which was lower than the mortality rate in the non-TCM therapy group, which was 3.79/100 person-years. The effect of gender on survival has often been the focus of researchers, but results have varied in the literature. A study conducted in Brazil reported that women had higher mortality than men, which agreed with an Italian cohort study (Braga et al., 2007). However, in Uganda men were reported more likely to die because of less access to routine testing or treatment compared with women (Kanters et al., 2013). In some developed countries, there was no significant difference in time to death between men and women (Nicastri et al., 2005; Pérez-Elías et al., 2013). In our study, women had a lower risk of death than men, which agrees with previous studies in China (Sun et al., 2000; Yang et al., 2012). Older age was also associated with higher risk of death; in particular, we report that the relative ratio (RR) of death among PLHIV older than 50 years was 3.22 times that of those under 30, in accordance with many studies (Nogueras et al., 2006). Even with the introduction of cART, age was a strong predictor for disease progression and mortality risk (Darby et al., 1996) because older PLHIV have poor immune response (Goetz et al., 2001; Kaufmann et al., 2002). Some studies have reported that older PLHIV showed the same immunological and virological behaviors as younger PLHIV; however, older PLHIV had little benefit associated with cART due to worse clinical features at their first visit (Perez and Moore, 2003; Nogueras et al., 2006). Given the characteristics of the PLHIV in this study, we are prone to agree on the former reason. More education was a protective factor in our study, which could be because PLHIV with more education are able to access more information about health, which may promote their health. In response to the tens of thousands of HIV-infected individuals identified through mass HIV screening in 2004, the Chinese government established the National Free Antiretroviral Treatment Program, which was initially started in Henan Province of China (Zhang et al., 2005; Wu et al., 2007). In this analysis, the survival rate of PLHIV taking cART at enrollment was lower than PLHIV not taking cART at enrollment. This is likely because in 2004, the criterion for taking cART were CD4 cell counts < 200 cell/mm3 or WHO stage 3 or 4. Initiating care at a lower CD4 cell count or worse clinical stage increases the risk of mortality. If PLHIV took antiretroviral drugs when CD4 cell counts were higher or when the PLHIV were at a better clinical stage, the survival rate was higher (Mills et al., 2012), which was also proved in our study. The PLHIV taking cART at follow-up had lower HR compared with those not taking cART, because the criterion for taking cART was changed in 2008 and again in 2012 (Editor Group, 2012). In other words, with higher CD4 cell counts the risk of death was lower in our study. Our study cohort had a rather long follow-up period, which has both strengths and the weakness. Long time span was an advantage of the analysis, but the epidemiological database was not perfect because the study started some time ago. Some information from the early years of this study was either not collected or there was more missing data, such as CD4 cell count and cART adherence. Adherence is a confirmed factor related to the effectiveness of cART and also influences survival. Because of the limitations of a retrospective cohort study, some factors (such as nutrition state, smoking, drinking, or comorbidities) related with death could not be investigated here. The TCM therapy group and
1342
Y. JIN et al.
the non-TCM therapy group in this cohort were not divided at random, which could lead to selection bias. Almost all of the PLHIV in our study cohort lived on a farm and were infected with HIV through plasma donation, so this cohort was simple and stable, but these factors also restrict extrapolation of our results to other populations. Thus, further research is needed to confirm this result.
Am. J. Chin. Med. 2014.42:1333-1344. Downloaded from www.worldscientific.com by UNIVERSITY OF CALIFORNIA @ SAN DIEGO on 01/05/15. For personal use only.
Acknowledgments The authors were grateful to the medical workers who partook in the national TCM HIV treatment trial program. It was their efforts that made this program possible. This work was supported by the Research Project for Practice Development of National TCM Clinical Research Bases (No. JDZX2012035) and National Special Science and Technology Program on Major Infectious Diseases (No. 2013ZX10005001-001). References Braga, P., M.R.A. Cardoso and A.C. Segurado. Gender differences in survival in an HIV/AIDS cohort from Sao Paulo, Brazil. AIDS Patient Care STDS 21: 321–328, 2007. Darby, I., D. Ewart, I. Giangrande, R. Spooner and C. Rizza. Importance of age at infection with HIV-1 for survival and development of AIDS in UK haemophilia population. Lancet 347: 1573–1579, 1996. Editor Group. Handbook of China’s Free ART Program, 3rd edn., Ren Min Wei Sheng Chu ban She, Beijing, 2012, p. 6. Fordyce, E.J., T.P. Singh, D. Nash, B. Gallagher and S. Forlenza. Survival rates in NYC in the era of combination ART. J. Acquir. Immune. Defic. Syndr. 30: 111–118, 2002. Goetz, M.B., W.J. Boscardin, D. Wiley and S. Alkasspooles. Decreased recovery of CD4 lymphocytes in older HIV-infected patients beginning highly active antiretroviral therapy. AIDS 15: 1576–1579, 2001. Greene, W.C. A history of AIDS: Looking back to see ahead. Eur. J. Immunol. 37: S94–S102, 2007. Hogg, R.S., K.V. Heath, B. Yip, K.J. Craib, M.V. O’Shaughnessy, M.T. Schechter and J.S. Montaner. Improved survival among HIV-infected individuals following initiation of antiretroviral therapy. JAMA 279: 450–454, 1998. Kanters, S., M. Nansubuga, D. Mwehire, M. Odiit, M. Kasirye, W. Musoke, E. Druyts, S. Yaya, A. Funk and N. Ford. Increased mortality among HIV-positive men on antiretroviral therapy: Survival differences between sexes explained by late initiation in Uganda. HIV AIDS (Auckl) 5: 111–119, 2013. Kaufmann, G.R., M. Bloch, R. Finlayson, J. Zaunders, D. Smith and D.A. Cooper. The extent of HIV-1-related immunodeficiency and age predict the long-term CD4 T lymphocyte response to potent antiretroviral therapy. AIDS 16: 359–367, 2002. Ledergerber, B., M. Egger, M. Opravil, A. Telenti, B. Hirschel, M. Battegay, P. Vernazza, P. Sudre, M. Flepp and H. Furrer. Clinical progression and virological failure on highly active antiretroviral therapy in HIV-1 patients: A prospective cohort study. Lancet 353: 863–868, 1999. Li, F.Z., L.R. Xu, M.L. Zhang and J.Z. Guo. Clinical observation on 885AIDS patients treated by Yiaikang capsule combined with treatment based on syndrome differentiation. Zhong Yi Za Zhi 51: 808–810, 2010. Liang, B.Y. and J. Wang. Meta analysis of randomized controlled trials on Chinese medicine treatment for HIV/AIDS. Zhong Yi Xue Bao 28: 1095–1098, 2013.
Am. J. Chin. Med. 2014.42:1333-1344. Downloaded from www.worldscientific.com by UNIVERSITY OF CALIFORNIA @ SAN DIEGO on 01/05/15. For personal use only.
TRADITIONAL CHINESE MEDICINE AND HIV CARE
1343
Liu, Z.B., Y.T. Jin, J.P. Yang, Q. lei, L.R. Xu, Q. Li and H.J. Guo, Prevalence and related factors of anemia among human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) outpatients in resources limited region of China. 2013 IEEE International Conference on Bioinformatics and Biomedicine, 2013a, pp. 157–160. Liu, Z.B., X. Wang, H.J. Liu, Y.T. Jin, H.J. Guo, Z.Q. Jiang, Z. Li and L.R. Xu. Treatment of acquired immunodeficiency syndrome with traditional Chinese medicine in China: Opportunity, advancement and challenges. Chin. J. Integr. Med. 19: 563–567, 2013b. Marins, J.R.P., L.F. Jamal, S.Y. Chen, M.B. Barros, E.S. Hudes, A.A. Barbosa, P. Chequer, P.R. Teixeira and N. Hearst. Dramatic improvement in survival among adult Brazilian AIDS patients. AIDS 17: 1675–1682, 2003. Merson, M.H. The HIV/AIDS pandemic at 25 — The global response. N. Engl. J. Med. 354: 2414–2417, 2006. Mills, E.J., C. Bakanda, J. Birungi, S. Yaya and N. Ford. The prognostic value of baseline CD4(þ) cell count beyond 6 months of antiretroviral therapy in HIV-positive patients in a resourcelimited setting. AIDS 26: 1425–1429, 2012. Ministry of Health of the People’s Republic of China. 2012 China AIDS Response Progress Report. http://www.unaids.org/en/dataanalysis/knowyourresponse/countryprogressreports/2012countries/ce CN Narrative Report[1].pdf. Accessed on April 11, 2012. Na, H.E. and R. Detels. The HIV epidemic in China: History, response, and challenge. Cell Res. 15: 825–832, 2005. Nicastri, E., C. Angeletti, L. Palmisano, L. Sarmati, A. Chiesi, A. Geraci, M. Andreoni and S. Vella. Gender differences in clinical progression of HIV-1-infected individuals during long-term highly active antiretroviral therapy. AIDS 19: 577–583, 2005. Nogueras, M., G. Navarro, E. Antón, M. Sala, M. Cervantes, M. Amengual and F. Segura. Epidemiological and clinical features, response to HAART, and survival in HIV-infected patients diagnosed at the age of 50 or more. BMC Infect. Dis. 6: 159, 2006. Palella, F.J., K.M. Delaney, A.C. Moorman, M.O. Loveless, J. Fuhrer, G.A. Satten, D.J. Aschman, S. D. Holmberg and the HIV Outpatient Study Investigators. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N. Engl. J. Med. 338: 853–860, 1998. Perez, J.L. and R.D. Moore. Greater effect of highly active antiretroviral therapy on survival in people aged > or 50 years compared with younger people in an urban observational cohort. Clin. Infect. Dis. 36: 212–218, 2003. Pérez-Elías, M.J., A. Muriel, A. Moreno, M. Martinez-Colubi, J.A. Iribarren, M. Masiá, J.R. Blanco, R. Palcios, J. Del Romero, D.G. Pérez, V. Hernando and C.S. Group. Relevant gender differences in epidemiological profile, exposure to first antiretroviral regimen and survival in the Spanish AIDS Research Network Cohort. Antivir. Ther. 19: 375–385, 2014. Rapiti, E., D. Porta, F. Forastiere, D. Fusco and C.A. Perucci. Socioeconomic status and survival of persons with AIDS before and after the introduction of highly active antiretroviral therapy. Epidemiology 11: 496–501, 2000. Sun, X., N. Wang, D. Li, X. Zheng, S. Qu, L. Wang, F. Lu, K. Poundstone and L. Wang. The development of HIV/AIDS surveillance in China. AIDS 21: S33–S38, 2007. Sun, D.Y., Q. Wang, W.J. Yang, Q. Zhu and Z. Wang. Survival analysis on AIDS antiretroviral therapy in Henan Province during 2003–2009. Zhong Huan Liu Xing Bing Xue Za Zhi 33: 181–184, 2012. UNAIDS. Global Report: UNAIDS report on the global AIDS epidemic 2013. http://www.unaids.org/ en/media/unaids/contentassets/documents/epidemiology/2013/gr2013/unaids global report 2013 en.pdf. Accessed on December 13, 2013.
Am. J. Chin. Med. 2014.42:1333-1344. Downloaded from www.worldscientific.com by UNIVERSITY OF CALIFORNIA @ SAN DIEGO on 01/05/15. For personal use only.
1344
Y. JIN et al.
Van Sighem, A.I., M.A. van de Wiel, A.C. Ghani, M. Jambroes, P. Reiss, I.C. Gyssens, K. Brinkman, J.M.A. Lange and F. Wolf. Mortality and progression to AIDS after starting highly active antiretroviral therapy. AIDS 17: 2227–2236, 2003. Wu, Z., S.G. Sullivan, Y. Wang, M.J. Rotheram-Borus and R. Detels. Evolution of China’s response to HIV/AIDS. Lancet 369: 679–690, 2007. Wu, Z., X. Sun, S.G. Sullivan and R. Detels. Public health. HIV testing in China. Science 5779: 1475–1476, 2006. Xu, L.R. A Clinical Observation of 160 Cases of Treating HIV and AIDS with Yiaikang Capsule. He Nan Zhong Yi Xue Yuan Xue Bao 20: 4–6, 2005. Xu, L.R., F.Z. Li, Y. He, J.Z. Guo and D. Wang. Sixty-month clinical observation of HIV carriers/ AIDS patients treated with Yiaikang capsule in terms of theirs CDþ 4 T cell counts and viral load. Zhong Guo Ai Zi Bing Xing Bing 3: 231–233, 2010. Yang, Y.C., S. Duan, L.F. Xiang, R.H. Ye, Y.R. Gong, S.J. Yang, J. Gao, Z.J. Yang, W.X. Han, Z.L. Li, Y.C. Pu, J.H. Yang, D.D. Cao, W.M. Li and N. He. Study on the mortality and risk factors among HIV-infected individuals during 1989–2011 in Dehong prefecture, Yunnan Province. Zhong Huan Liu Xing Bing Xue Za Zhi 33: 1026–1030, 2012. Zhang, F.J., P. Jennifer, Y. Lan, W. Yi and Z. Yan. Current progress of China’s free ART program. Cell Res. 15: 877–882, 2005.