ABSTRACT
This study described the care status of People Living with HIV (PLWH) including antiretroviral therapy (ART) and viral suppression from 2018 to 2020. We recognized that immediate ART was associated with improved viral suppression. Therefore, we also aimed to explore the factors affecting the early initiation of ART. We initiated a retrospective cohort study to evaluate the care status of people living with HIV in Shandong Province. From 2018 to 2020, patients infected by homosexual transmission in particular had a higher ART rate (78.82%, 79.69%, and 87.72%, respectively). Of PLWH who received ART, 79.57%, 77.63%, and 67.71% achieved viral suppression, respectively. However, COVID-19 may affect the rate of ART and viral suppression, which we need to explore in our research. From 2018 to 2020, the proportion of immediate antiretroviral therapy within 30 days of diagnosis increased from 48.12% to 65.42%. Multivariate logistic regression demonstrated that patients with junior college degree or above (OR, 1.39 [95%CI, 1.12–1.73]) and key population or medical institutions (OR, 3.62 [95%CI, 2.18–6.16]; OR, 3.88 [95%CI, 2.33–6.59]) were substantially likely to receive ART immediately, while patients outside the province (OR, 0.60 [95%CI, 0.50–0.73]) were less likely to receive ART immediately.
Acquired Immune Deficiency Syndrome (AIDS) is an infectious disease caused by Human Immunodeficiency Virus (HIV), which endangers human life. AIDS primarily attacks the human immune system, which weakens it and leads to infection with other diseases, such as tuberculosis and other malignant tumors (Dybul et al., Citation2021; Ghosn et al., Citation2018). By 2020, there had been 37.7 million People Living With HIV (PLWH) around the world. Given the increasing burden of new HIV infections, the health community must accelerate the development of HIV care to meet the requirements.
The “90-90-90 targets” have been launched by the Joint United Nations Program on HIV/AIDS (UNAIDS) since 2014. That is, 90% of PLWH will be diagnosed, 90% of those will be on antiviral therapy(ART), and 90% of people on treatment will achieve viral suppression (Guaraldi et al., Citation2021b; Kirby, Citation2018). In 2021, UNAIDS proposed a new target to end the AIDS epidemic and achieve 95-95-95 goals. These goals are based on a global test and treatment model, as supported by mathematical modeling of the effect of universal voluntary HIV testing plus immediate combined ART on the elimination of HIV transmission (Hulgan et al., Citation2018; Luis et al., Citation2020). Historically, there has been consensus that PLWH should initiate ART as soon as they have an HIV-defining disease. This research took Shandong Province as the research site. COVID-19 lockdowns and other restrictions disrupted HIV testing and led to a sharp decline in diagnoses and referrals to HIV treatment in many countries. In the current HIV-COVID-19 epidemic, public health workers are not only involved in HIV care, but also in COVID-19 care. As a result, patients’ follow-up and therapy may be prolonged due to the impact of COVID-19 (Gareta et al., Citation2021). Therefore, it is of great importance to study the current impact of COVID-19 on PLWH, including the short-term and long-term impact of the current crisis on HIV treatment (Zhang et al., Citation2016). At the same time, studies have shown that the more immediate ART, the better the subsequent treatment effect (Zhao et al., Citation2018). Rapid-start ART is an important strategy to achieve “90-90-90” targets and improve the life quality of PLWH (Boyd et al., Citation2019). HIV infection is associated with a high risk of infection-related diseases. Due to the increased risk and longer lives for PLWH, cancer has become a major reason of morbidity for PLWH. The study had found that immediate ART initiation can reduce the incidence of cancer (Borges et al., Citation2016). Therefore, in this research, we aimed to evaluate the care status of PLWH, and explore the influencing factors of immediate ART.
Data and methods
Study population
We conducted a retrospective cohort study on newly diagnosed PLWH in Shandong province, China. The eligibility criteria for participants were patients currently living in Shandong province and older than 18 months.
Database
We obtained cases from Shandong Provincial HIV/AIDS Comprehensive Response Information Management System (CRIMS). CRIMS is an integrated web-based system that facilitates timely monitoring of all aspects of the HIV epidemic in China. It provided scientific evidence for policy decisions at the national level and even down to individual counties, towns, and villages (Wu et al., Citation2020). Since CRIMS is designed to provide evidence for decision-making and evaluation of large-scale prevention and intervention, the quality of the data contained is required to be maintained at a high level.
Definition of variables
By using a western blot, researchers can identify specific proteins from a complex mixture of proteins extracted from cells. Therefore, Western blot was used as a confirmatory test for PLWH in this study. Receiving ART was defined as documentation of 1 or more prescription refills. New diagnosed patients were infected patients diagnosed with infection in the current year and previously infected patients diagnosed with previous infectious in the current year. The ART rate was used to describe the ART coverage in HIV/AIDS patients. The numerator of ART rate was defined as the number of HIV/AIDS patients receiving ART within one year after diagnosis, and the denominator was the number of newly diagnosed HIV infections in that year. Viral load detection was defined as receiving viral load testing within 1 year of receiving ART. The proportion of viral load detection was calculated using the number of patients receiving viral load detection divided by the number of receiving ART within 1 year after diagnosis. Viral suppression was defined as the viral load of less than 50 copies/ml in the first viral load test at 1 year after receiving ART. The numerator of the viral suppression rate was the number of patients who achieved viral suppression, and the denominator was the number of patients who had received viral load tests. Immediate ART was defined as receiving ART within 30 days after diagnosis. The proportion of immediate initiation on ART was calculated by dividing the number of patients receiving ART immediately by the total number of newly diagnosed patients receiving ART from 2018 to 2020.
Statistical analysis
ART rate and viral suppression rate of PLWH were calculated by gender and transmission routes. The Cochran–Armitage test was performed to test the time trend, and the Z test was used to infer whether the difference was statistically significant with an assumed α of.05. When studying the influencing factors of immediate treatment of PLWH, Univariate logistic regression and multivariate logistic regression were performed to explore the influencing factors such as gender, baseline age at diagnosis, household registration, transmission route, marriage, nation, sample source, and education. The response variable was prompt treatment and non-prompt treatment. R software, version 4.1.2 was used for all statistical analyses.
Results
Status of HIV/AIDS treatment and viral suppression in Shandong Province
presents the therapy status of newly diagnosed PLWH in Shandong province from 2018 to 2020. There were 2853, 3108, and 2825 confirmed cases, respectively. Most infections occurred in men (2609 [91.45%], 2850 [91.70%], and 2571 [91.01%], respectively) and were transmitted through homosexual transmission (1950 [68.35%], 2142 [68.92], and 1963 [69.49%], respectively). Cases of transmission through injection drug use and mother-to-child transmission were decreasing. The ART rates were 75.99%, 77.67%, and 85.84%, respectively, showing a gradual increasing trend (X2 = 233.30, P < 0.001). The ART rate among men increased from 76.12% to 85.65% (Z = 157.72, P < 0.001). The number of people receiving treatment for homosexual transmission increased from 1537 to 1722, and the ART rate increased from 78.82% to 87.72% (Z = 120.34, P < 0.001); the number of people receiving treatment for heterosexual transmission increased from 613 to 701, and the ART rate increased from 70.22% to 82.08% (Z = 44.68, P < 0.001). Patients transmitted by homosexual transmission were more likely to receive ART compared to other transmission routes.
Table 1. Status of diagnosis and treatment among newly diagnosed PLWH.
The test rate of viral load detection rate was 59.78%, 53.89%, and 60.29%, respectively. Patients transmitted by homosexual transmission had a higher viral detection rate compared to other transmission routes. The number of viral suppression for PLWH decreased from 1090 to 988, and the viral suppression rate declined from 84.10% to 67.57%. From 2018 to 2020, more patients achieved viral suppression from homosexual transmission achieved viral suppression than from other transmission routes.
Factors affecting the timeliness of PLWH antiviral therapy
From 2018 to 2020, a total of 8786 PLWH were newly diagnosed, of which 4950 (56.34%) received immediate ART within 30 days after diagnosis and were included in the immediate ART group. And the proportions of immediate treatment in each year were 48.12% (1373/2853), 55.63% (1729/3108), and 65.42% (1848/2825), respectively. The time trend difference in the proportion of immediate ART between different years was statistically significant (X2trend = 172.45, P < 0.001). Compared with patients who did not receive immediate ART, patients who received immediate ART had a higher viral suppression rate (46.34% [2295/4950] vs. 34.80% [729/2095], P < 0.001).
shows the factors influencing the timely ART of PLWH from 2018 to 2020. A large proportion of PLWH receiving immediate ART was found to be transmitted through homosexual transmission (72.44%). Univariate logistic regression indicated that the census register, transmission route, marriage, education, ethnicity, sample source, and age of diagnosis were related to the immediate initiation of ART. Multivariate logistic regression indicated that census register, sample source and education were related to immediate ART. Patients outside the province (OR, 0.60 [95%CI, 0.50–0.73]) were less likely to start ART in time than those within the province. Patients in medical establishment and in key groups (OR, 3.88 [95%CI, 2.33–6.59]; OR, 3.62 [95%CI, 2.18–6.16]) were more likely to start ART in time than those in detention. Patients with the education level of junior college or above (OR, 1.39 [95%CI, 1.12–1.73]) were more likely to start ART in time than those with illiteracy or primary school.
Table 2. Factors influencing the timeliness of PLWH antiviral therapy.
Discussion
Our research showed a low number of newly reported HIV cases in 2020. During this period, due to the outbreak of COVID-19, most countries had to close their borders or restricted international traffic to contain the spread of the pandemic. We inferred that the decline in HIV diagnoses was related to the outbreak of COVID-19. Any HIV physicians and HIV clinics were directly involved in the work related to COVID-19. A shift in resource allocation in the health system and large-scale lockdowns had substantially affected the delivery of HIV services by health providers and the access of patients to therapy (Chenneville et al., Citation2020; Shi et al., Citation2021; Zhou et al., Citation2020). This had increased the difficulty for AIDS patients to access medical services. Although researches had indicated that PLWH may not have a high chance of contracting COVID-19, which has been hypothesized to be a function of ART, PLWH who do not receive ART may be at increased risk due to compromised immune system (Chenneville et al., Citation2020). Still, PLWH went to the hospital to buy medicine, which increased the likelihood of infection in the hospital. As a result, most patients chose not to go to the hospital for fear of infection, which reduced the number of diagnoses. In addition to the increased risk of complications from COVID-19, PLWH was also affected in a myriad of other ways. For instance, PLWH may experience ART interruptions due to restrictions on medical appointments related to physical distance requirements (Qiao et al., Citation2021). In addition, the reduction in the number of diagnoses was also related to discrimination against AIDS. Despite tremendous medical advances to make this infection more preventable, stigma was still a major barrier to the control of the epidemic (Hartog et al., Citation2020; Smith et al., Citation2020). Due to discrimination, their treatment situation was not optimistic, which aggravated the low diagnosis and treatment rate of patients (Crockett et al., Citation2019). Researches disclosed that a psychosocial mechanism by which anticipated stigma contributed to non-adherence (Camacho et al., Citation2020). PLWH were more likely to feel discriminated due to many psychological and environmental factors (Lee et al., Citation2022). Mother-to-child transmission of PLWH in Shandong province had been slowly brought under control due to the effects of the health department. The elimination of mother-to-child transmission of HIV has benefited from a series of strategies, such as ART services for women living with HIV, immediate HIV detection, and services for infants at the highest risk of HIV infection (Chi et al., Citation2020). For injection drug user, it is very important to explore needle exchange intervention models for the prevention of HIV transmission. The decline of patients transmitted through injection drug use may attribute to higher usage of clean needles or sustained methadone maintenance therapy (Furukawa et al., Citation2021; Mir et al., Citation2018).
In Shandong province, the ART rate and immediate ART rate showed an increasing trend from 2018 to 2020. This indicated that although COVID-19 had prominent impacts, the public health department (i.e., CDC) had assisted to overcome the impact to protect their populations and prevent the spread of health threats (O'Byrne et al., Citation2021). Designated AIDS hospitals in China increased their drug supplies to last at least three months, and each patient can get one month’s supply each time. Generally, the institution where the patient takes the medicine is the place where he receives the treatment, and the patients must go to the designated medical institution to obtain the corresponding medicine-taking service. During COVID-19, patients were therefore confined out of the province due to transportation restrictions, but patients could pick up medicines at designated local hospitals by borrowing medicine letters. It can also be organized by home delivery service or peer-to-peer contacts (Lesko & Bengtson, Citation2021). Before 2005, heterosexual transmission remained the dominant mode of transmission accounting for about 85% of all infections (Simon & Karim, Citation2006). With the popularization of some MSM-apps and the discovery of some genetic factors in the formation of MSM, homosexual transmission has become a major transmission route (Marano et al., Citation2017). The majority of PLWH through homosexual transmission are well-educated and they are more likely to receive therapy or take a confirmatory test (Kusejko et al., Citation2022; McNeil et al., Citation2022).
Our findings showed that there was no difference in the test rate of viral load from 2018 to 2020. However, there was a declined trend in viral suppression rate, which could be consistent with the low ART effect. Compliance of PLWH after treatment also influences the outcome of treatment. Patients faced multiple barriers in adherence to treatment, including lack of access to treatment, failure of ART, side effects, and stigma. In 2020, health workers were busy responding to COVID-19, lacking follow-up, compliance education, and effectiveness evaluation of AIDS patients. Although patients have the opportunity to free test once or twice a year for free, the immediate testing of PLWH had been interrupted due to the influence of COVID-19, which represented more risk factors for virus progression (Byrd et al., Citation2019; Guaraldi et al., Citation2021a). During the outbreak, changes in the allocation of health resources affected the delivery of HIV services and patients’ access to viral load testing (Kowalska et al., Citation2020).
According to our study, immediate treatment of PLWH can improve the viral suppression effect, so immediate ART should be strengthened immediate ART. The immediate treatment rate in Shandong province increased by 35.95% from 2018 to 2020. ART can effectively reduce the mortality of PLWH and prolong the survival time of patients. There has been a consensus that PLWH should initiate ART immediately. One study showed that PLWH initiating ART within 30 days after diagnosis had a reduction in mortality (Zhao et al., Citation2018). However, the immediate treatment also encountered many difficulties. The current path from screening to the start of ART in China includes many hospital visits and complex programs which result in a huge loss of immediate follow-up and medical services. Feeling healthy was one of the reasons why they stopped taking ART (Chan et al., Citation2022). The rate of immediate ART in Shandong province gradually increased, as the local public health authorities formulated policies to cope with these risks.
To further improve the timeliness of ART, we need to pay more attention to the factors influencing the immediate treatment of PLWH. In this study, we found that PLWH registered in Shandong province had a high probability of receiving immediate treatment. And PLWH outside the province did not belong to the province in terms of registered residence, so the procedures for taking drugs would be different from patients in the province, including the attention of the government policies and medical security of the corresponding department. This suggested that we should pay more attention to other provinces’ PLWH, which can help to improve the treatment rate of out-of-province patients and reduce the mortality rate. Patients from medical institutions and key populations were more likely to receive immediate antiviral treatment. In contrast, it is more difficult for detained people to obtain immediate ART. Most of those in custody were undergoing drug rehabilitation management, so their normal follow-up treatment may be affected. Patients with higher levels of education may be more concerned about their health (Wang et al., Citation2021). This was consistent with our research that PLWH with higher education level (junior college or above) had a higher proportion of immediate ART in Shandong province.
This study also had some limitations. First, we did not evaluate the impact of national HIV care policies on AIDS care and without a control group, we cannot explain the uniqueness of COVID-19’s effects. Relevant national policies may have an impact on the treatment effect of AIDS, while we only describe the status of diagnosis and treatment in Shandong province from 2018 to 2020. Second, we did not calculate the estimated number of PLWH in Shandong province, so we cannot evaluate the impact of COVID-19 on the diagnostic detection rate. Third, since the follow-up time of this study is only one year, and virus detection after antiviral treatment is generally carried out within half a year, we chose to use the results of the first virus detection after treatment to evaluate the effect of antiviral treatment. Therefore, we did not analyze the effect of long-term treatment in the context of the COVID-19 epidemic.
Conclusions
In Shandong province, the rate of ART gradually increased, but the rate of viral load suppression showed a decreased trend from 2018 to 2020, suggesting that COVID-19 had an impact on HIV treatment, so follow-up services and compliance education for PLW during the epidemic should be strengthened to improve the viral suppression rate of PLWH. From 2018 to 2020, the immediate treatment rate in Shandong province gradually increased which played an important role in improving the outcome of patient treatment. Furthermore, strengthening immediate ART for the population outside the province, with low education level and detained people can further improve the immediate ART of PLWH.
Disclaimer
The content of this publication does not necessarily reflect the policies of the Department of Health and Human Services. The opinions expressed in this article are personal and do not represent the official position of Shandong Provincial Center for Disease Control and Prevention.
Acknowledgements
Na Zhang conceptualized the study and contributed to the data collection and validation. Jiongjiong Wang conducted the statistical analysis. All authors reviewed the final version of the manuscript.
Disclosure statement
No potential conflict of interest was reported by the authors.
Additional information
Funding
References
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