Background
The morbidity and mortality of HIV infection have been sharply decreasing all over the world due to the global implementation of antiretroviral therapy (ART), and now HIV infection is recognized as a chronic disease instead of a deadly one. Ever since China began to establish national HIV prevention and treatment programs in 2003, the morbidity and mortality of AIDS have been reduced significantly [
1]. Since the domestic financial resources being allocated to HIV/AIDS were increasing, the ART eligible criteria in China kept changing accordingly. Initially, it was recommended that ART should be initiated when CD4 < 200 cells/mm
3, and the criteria changed to <350 cells/mm
3 in 2008 [
1]. In 2013, the recommendation to initiate ART at CD4 counts <500/mm
3 was documented [
2] while in this year, ART should be started immediately with the informed consent if HIV infection was determined. At the same time, despite the nationwide scale-up of HIV programs in China over the past decade, the proportion of ART-eligible HIV-positive patients who receive treatment remains low [
3,
4]. What even worse is that many HIV-positive people receive late HIV diagnoses [
5‐
7]. Both of these factors weaken the effect of ART among HIV-positive populations [
8,
9]. Therefore, the vital steps to maximize the efficacy of ART for HIV infected patients would be expanding screening of HIV antibody and initiating ART as soon as possible when the patients meet the criteria [
10]. With the recommendation of expanding ART to all HIV-positive people [
11‐
13], a delay in diagnosis and referral could definitely weaken the effect of expanding the ART program. However, considering the imbalance in the development of the regional economy, the resources for HIV prevention and treatment in Shanghai are more readily available than in the smaller counties in China. Once patients in Shanghai received an HIV screening test and the test was confirmed by Western Blot test, the local CDC would contact the infected patients. Then, the CDC followed up with the HIV-positive patients and performed routine CD4 tests to monitor their immunological status. If the HIV patients met the criteria for ART initiation, the patients were transferred to our clinic and given adherence education, and other preparations were made for the patients to receive ART. The eligible patients started ART within a few days in our clinic. Therefore, the time to initiation in Shanghai was rapid, and patients with more advanced HIV diagnoses received much quicker referral to our clinic. However, we still could receive HIV patients in the late stage of AIDS in our hospital. What factors driving them come to our clinic so late? How to facilitate the screening, diagnosing and ART initiating? There was little data can be found about late ART in China. As we all know that, targeting the HIV-positive population who are most likely to be at risk for being diagnosed or receiving ART late would facilitate the control of the HIV epidemic. Therefore, identifying the factors underlying the current delay of HIV treatment and the risk factors for the late initiation of ART will be helpful to policymakers.
In this study, we conducted a cross-sectional survey of clinical data from the Shanghai Public Health Clinical Center. The trends in the median CD4 cell counts among different patient groups over time and the risk factors for the late initiation of ART were analyzed.
Discussion
To our knowledge, this study is the first survey of the trends in CD4 cell counts and the first analysis of the predictors for late ART initiation of HIV-positive patients in Shanghai. In this study, we observed that the median CD4 cell counts at the initiation of ART among overall HIV patients and in the late initiation group increased steadily from 2008 to 2014 in Shanghai. At the same time, the overall number of patients who received ART increased sharply, while the number of patients initiating ART late grew slowly and the proportion of patients with late ART initiation fell rapidly.
The above observation reflects the great improvement on HIV prevention and treatment that has been made in Shanghai China for the last few years. Since 2004, China has compiled three editions of its HIV prevention and treatment guidelines, and people meeting the criteria for HIV treatment can obtain free ART medications [
3,
4,
14]. Furthermore, routine CD4 cell count measurements and HIV-RNA tests are performed for free. Thus, the number of HIV-positive patients was found to be growing quickly in recently years, especially in 2013, when the guidelines expanded the treatment initiation criteria from CD4 counts <350/mm
3 to CD4 counts <500/mm
3 [
2]. Accompanied by these changes, public education on the AIDS epidemic was expanded throughout the country, and HIV screening was also vigorously expanded [
15]. Consequently, an increasing number of at-risk populations for HIV have the chance to receive an HIV diagnosis earlier than before [
16]. Therefore, the CD4 cell counts of HIV patients at ART initiation have increased each year. However, the rate of late ART initiation in the first half of 2014 was still high (45%), and thus, much more effort is still needed for future prevention and treatment.
We found that male gender, older age, and heterosexual transmission were all risk factors for delayed ART. Similar to the study from sub-Saharan Africa [
17] and the meta-analysis [
18], compared with females, in our study the male patients were more likely to receive delayed treatment initiation. Female patients have more chances to be diagnosed early because of family planning, gynecological follow-up and prenatal screening [
19]. In this study, patients older than 30 years were closer to the point of progression to advanced HIV disease when they initiated ART. This is consistent with the research data from Canada [
20], Asian multicenter study [
21] and Mozambique study [
22]. At the same time, like the findings of Cescon A, et al. [
20] and Boettiger D, et al. [
21], patients who were infected via heterosexual transmission were more at risk for the delayed initiation of HIV treatment. We assumed that compared with younger patients less than 30 years old, the older patients often did not have sufficient information from the internet or the AIDS related education which is often launched in school or other semi-closed surroundings, and thus, their knowledge of HIV was limited before they progressed to AIDS. Furthermore, since the risk of acquiring of HIV among heterosexuals is lower as compared to homosexual men, most of the HIV education did not attach importance to this group, while the homosexual patients received more attention from HIV prevention agencies or NGOs (non-government organizations) and had more opportunities to obtain knowledge of HIV transmission and screening tests [
6]. Thus, in contrast to the homosexual patients, the heterosexual group was more likely to initiate ART late. Therefore, both of these populations should be given more opportunity to obtain knowledge of the HIV epidemic and AIDS. Previous studies [
21,
23] have shown that the people who inject drugs (PWID) are more likely to initiate ART late; however, in our study, this trend was not significant by a multivariate logistic regression test. It is possible that the number of PWID (99 patients) in our analysis was not large enough.
In comparing the late initiation group and the non-late group, one of the results should be noted: the time to initiation was significantly different between the two groups. Patients with late ART initiation had a much shorter time interval from testing positive to commencing ART. This result is reasonable, and to some extent, it implies that the late ART initiation is mainly due to the patients receiving delayed HIV diagnoses. This finding is consistent with that of previous studies [
23,
24].
There are still some limitations to be considered. First, the patients’ information was collected from the clinic, and the information regarding HBV and HCV infection status, educational level, and career background was unavailable. Undoubtedly, this might skew the analysis of risk factors for delayed ART initiation. Second, we did not analyze the impact of late ART initiation on the outcome of HIV-positive patients because of the unavailability of follow-up data. However, many other studies [
1,
8,
9] have demonstrated that the late initiation of ART significantly weakens its effect. Thirdly, those patients with missing CD4 cell count were excluded out of this study and it might result in selection bias.
Acknowledgments
We extend our heartfelt thanks to the colleagues of HIV health care clinic and the staff in the Department of Infectious Disease of Shanghai Public Health Clinical Center.