Measuring and explaining inequality of continuous care for people living with HIV receiving antiretroviral therapy in Kunming, China.

BACKGROUND: In the context of scaling up free antiretroviral therapy (ART), healthcare equality is essential for people living with HIV. We aimed to assess socioeconomic-related inequalities in uptake of continuous care for people living with HIV receiving ART, including retention in care in the last six months, routine toxicity monitoring, adequate immunological and virological monitoring, and uptake of mental health assessment in the last 12 months. We also determined the contributions of socioeconomic factors to the degree of inequalities.
METHODS: A hospital-based cross-sectional survey was conducted among consecutive clients visiting an HIV treatment center in Kunming, China in 2019. Participants were 702 people living with HIV aged ≥18 years (median age: 41.0 years, 69.4% male) who had been on ART for 1-5 years. Socioeconomic-related inequality and its contributing factors were assessed by a normalized concentration index (CIn) with a decomposition approach.
RESULTS: The uptake of mental health assessment was low (15%) but significantly higher among the rich (CIn 0.1337, 95% CI: 0.0140, 0.2534). Retention in care, toxicity, and immunological monitoring were over 80% but non-significant in favor of the rich (CIn: 0.0117, 0.0315, 0.0736, respectively). The uptake of adequate virological monitoring was 15% and higher among the poor (CIn = -0.0308). Socioeconomic status positively contributed to inequalities of all care indicators, with the highest contribution for mental health assessment (124.9%) and lowest for virological monitoring (2.7%).
CONCLUSIONS: These findings suggest virological monitoring and mental health assessment be given more attention in long-term HIV care. Policies allocating need-oriented resources geared toward improving equality of continuous care should be developed.

Introduction

The HIV epidemic, especially in developing countries, is still a challenge worldwide. With remarkable success and scaling up of antiretroviral therapy (ART) coverage, life expectancy and survival times of people living with HIV have significantly increased [1, 2]. The healthcare systems are challenged to maintain a growing number of those people [3, 4] who demand not only access to ART but also practical, comprehensive and continuous care aligned with life-long ART [5]. Regular monitoring of responses to HIV treatment, including monitoring of long-term drug toxicity, is recommended by current international guidelines [6-8]. Additionally, people living with HIV are more likely to suffer mental health disorders than the general population [9]. Routine assessment and management for mental health conditions, especially depression, are recommended to be integrated into the package of HIV care services for this group in non-psychiatric healthcare settings [7, 10].

Although there exists a vital role of ART and HIV continuous care, inequalities in accessing and utilizing HIV care are on a large scale. For example, previous studies reported a high rate of late presentation for HIV care in some Asian countries [11], a low rate of retention in care after the first initiation of ART in the United States [12], and low uptake of regular monitoring of virological and immunological outcomes as well as monitoring the toxicity of ART in resource-limited settings [13-15]. A systematic review revealed that only a few studies reported the rate of receiving routine ART toxicity monitoring at scheduled visits in follow-up settings [16]. Overall, contemporary data on access to and utilization of comprehensive HIV care after receiving ART, especially monitoring ART response and client-perceived uptake to HIV mental health care, are sparse.

As one of the developing countries in the Asia-Pacific region, China is also facing challenges in healthcare and managing a growing number of people living with HIV, of which there were 1.2 million in 2018 [17, 18]. In particular, China is one of only a few low- and middle-income countries in which the government is the major source of spending for care and treatment of people living with HIV (98.4%) [19]. China started the National Free Antiretroviral Treatment Program (NFATP) with national standardized follow-up medical records in 2003 and since then has expanded ART coverage to meet the WHO recommendation of “Treat-all” [3]. Under this program, China’s free-ART manual was developed, in which routine blood tests accompanied by follow-up visits four times a year and at least one viral load test and CD4 count per year are free of charge for people who are stable on ART [20].

However, one free viral load test per annum is not enough. According to the Chinese guidelines, people who are stable on ART should have their viral load tested every six months to assess virological outcomes and identify virological failure to prevent drug resistance [21, 22]. Furthermore, CD4 remains the gold standard for identifying individuals with advanced disease [23]. A free CD4 test once a year is thus not adequate for people whose CD4 count is less than 300 cells/mm3 [20, 21].

A systematic review showed that the median prevalence of symptoms of depression was greater than 60% among people living with HIV in China and highlighted the need for mental healthcare for people living with HIV [24]. The Chinese national guidelines recommend that mental healthcare should be integrated into ART services when conditions permit [20, 21]. Still, there are no specific operating guidelines and rare reports of routine mental healthcare in Chinese ART cohorts.

Previous studies have indicated that socioeconomic status (SES), younger or older age, employment, education, area of residence, and health insurance were associated with HIV epidemics, HIV testing, maternal care, delays in HIV treatment, access to ART, attrition of ART, and even poorer treatment outcomes [11, 14, 25–28]. However, there is a paucity of studies measuring the socioeconomic-related inequality in care for people living with HIV who are stable on ART, especially in the Asia-Pacific region. Several Chinese studies suggested that there were disparities in HIV testing, access to HIV care or attrition of care, and viral suppression among women and key populations such as men who have sex with men [26, 29]. Nevertheless, those disparity measures did not consider socioeconomic and demographic factors, which may be social determinants that can influence health or healthcare as a whole [30]. Moreover, under the context of free ART to “Treat all” in China, no study has reported whether people living with HIV who have received ART are retained in the HIV care continuum and receive an equal amount of comprehensive care to maintain both their physical and mental health regardless of their socioeconomic status. Therefore, it is crucial to quantify the relationship between SES and comprehensive HIV care for people living with HIV who have received ART.

The relative concentration index and its decomposition have been widely used in studying socioeconomic-related inequalities in healthcare services [31-33]. Based on Wagstaff’s suggestion, the decomposition of the concentration index can explain the source of healthcare inequality by the contribution of determinants [34]. Possible determinants can be categorized into “need” and “non-need” factors. Need factors are sources of variation in healthcare that are not considered to be “unfair”. They are related to an individual’s characteristics that are direct causes of medical services, usually, age and sex [35]. Non-need factors are sources of variation in health care that are “unfair” or “unjust”, such as SES, education, and ethnicity [36].

The objectives of this study are two-fold. First, to determine whether there are socioeconomic-related inequalities in the uptake of comprehensive continuous care for people living with HIV in terms of maintaining physical and mental health, including services for retention in care, routine monitoring of ART toxicities, monitoring treatment outcomes, and routine assessment of mental health. Second, to decompose these inequalities by evaluating the contribution of socio-demographic factors.

Materials and methods

Study setting and participants

A hospital-based cross-sectional survey was conducted from April-November 2019 among people living with HIV attending a leading HIV treatment center in Kunming, the capital city of Yunnan province, southwestern China. Yunnan province has the highest number of PLWH in China [17]. At the end of 2018, there were about 15,000 people living with HIV in Kunming [37].

Individuals were eligible to be included in the study if they: 1) were aged 18 years or older, 2) had initiated ART and were currently receiving ART for more than one year but not more than five years, 3) were able to communicate in Chinese, and 4) were able to present themselves on the day of the interview and were sufficiently physically and mentally stable to provide verbal consent to participate in the study. The criterion for including only those on ART between 12 months and five years was set to ensure that the individuals had reached a requirement of 12 months as the average time of retention in care for viral suppression as detailed elsewhere [12]. Furthermore, this criterion also can avoid some of the longer-term complications after five years, which need more intensive care, such as first-line regimen failure and drug resistance, resulting in a switch to a second-line regimen, with intensive viral load, CD4 count and medication adherence monitoring [38, 39].

All eligible people living with HIV who visited the HIV treatment center during the study period were invited to participate in this study.

Sample size

The sample size was calculated using the finite population formula [40]. As no previous data on comprehensive care access among people living with HIV was available in China, it was conservatively estimated that comprehensive care access was 50%. There were nearly 8,000 people receiving ART in the HIV treatment center. Considering a margin of error of 4%, a confidence interval of 95%, and a 20% refusal rate or missing data, the minimum required sample size for the study was 664.

Data collection

A structured questionnaire was developed in English and then translated into Chinese. Back-translation into English was also performed to validate the translation. Twenty persons living with HIV were interviewed in a pilot study to test the comprehensibility of the questionnaire. Five medical students were employed as research assistants and received a two-day training on the study protocol, interviewing skills, and data confidentiality by a field supervisor. A staff member of the HIV treatment center invited eligible participants into the study. The research assistant informed the study goals, benefits and risks of participation, and research procedures. The participants were told that they would be asked to anonymously respond to a structured questionnaire, which included socio-demographic characteristics. They were also informed that they could withdraw at any time and all information would be kept confidential. To ensure participant confidentiality, only verbal consent to participate in the study, including both questionnaire interviews and medical record reviews, was obtained. Each consenting participant provided their NFATP unique personal identification number in order to link their questionnaire data to their medical records.

After completing the interview, the field supervisor reviewed the participants’ medical records in the database of NFATP to collect information on the number of HIV clinic visits in the last six months. The number of routine tests for toxicity monitoring, CD4 test, and viral load assay in the previous 12 months were also obtained.

Variables

Dependent variables

The outcome variable of this study is the uptake of HIV comprehensive care. Based on Chinese and international guidelines [6–8, 21], comprehensive care in this study includes five binary variables, representing retention in care, treatment response monitoring, and mental healthcare, namely:

Retention in care was defined as having at least two HIV clinic visits in the last six months. Based on the NFATP free-ART manual, after initiating ART for more than one year, subsequent follow-up visits are scheduled every three months [20]. The dispensing of free-ART is three-monthly in the HIV treatment center to ensure enough antiretrovirals (ARVs) stocks for both newly initiated and continuously treated people. Therefore, retention in care in this study means that people living with HIV had adequate follow-up visits and ARVs in the last six months. This variable was collected from the medical records of NFATP and the outpatient system of the HIV treatment center.

Routine monitoring of ART toxicities includes tests for renal function, liver function, and complete blood cell count performed at least four times per year. This indicator was based on a technical brief of the WHO on surveillance of antiretroviral toxicity [41] and the NFATP manual, which provides four free routine tests per year [20]. If a participant has at least four test records in the outpatient system, it means that the participant has received adequate ART toxicities monitoring.

Monitoring of immunological outcomes was defined as having adequate CD4 tests depending on the test results: a) for counts between 300 and 500 cells/mm3, receiving at least one test in the last 12 months, and b) for counts less than 200 cells/mm3, receiving at least two tests in the last 12 months [7, 21]. The NFATP provides free CD4 testing only once a year, and the extra tests must be paid for by the participants themselves or their health insurance, which are voluntary based on the clients’ ability to pay. CD4 testing records were collected from the outpatient system and database of NFATP.

Monitoring of virologic outcomes was defined as having a plasma HIV viral load assay at least twice in the last 12 months. As with CD4 testing, the NFATP only provides free viral load testing once a year [20], so the additional viral load test was voluntary based on the client’s ability to pay, and test costs can be beyond the client’s affordability. Viral load testing records were collected from the outpatient system and NFATP database.

Self-reported mental health assessment was measured as perceived access to mental healthcare by the question “Have you received a mental health assessment from a health provider in the last 12 months?”. Because there are no specific operating guidelines or records in the outpatient system or database of NFATP, we employed this indicator as perceived mental healthcare uptake. During the clinic visit, the mental health state can be assessed by medical staff free of charge.

Socio-demographic characteristics

Several socio-demographic factors associated with disparities in access to care may also be associated with inequalities in the HIV care continuum [11, 14, 16, 25–28, 30]. We investigated biological sex, age (at the time of the survey), ethnicity (Han and other), religious beliefs, marital status, education level (primary school or below, secondary school, high school, and university or above), employment status (employed and unemployed), and type of medical insurance (none, New Rural Cooperative Medical Insurance (NRCMI), Urban Employees Basic Medical Insurance (UEBMI), and Urban Residents Basic Medical Insurance (URBMI)). Possible determinants of healthcare uptake can be categorized into “need” and “non-need” factors. As mentioned earlier, “need” factors include age and sex [35] and other socio-demographic factors are “non-need” factors.

Measuring socioeconomic status

The wealth index per equivalent adult used to measure individual socioeconomic status was generated from self-reported household assets and housing conditions using principal component analyses, including ownership of a house, house size, number of bedrooms, type of floor, availability of drinking water, presence of a toilet, cooking fuel source, ownership of private vehicles, household furniture (i.e., table, chair, sofa, bed, wardrobe, and cupboard) and household appliances (i.e., television, refrigerator, washing machine, computer, microwave, mobile phone, and Internet broadband) [42]. Considering the household’s size and demographic composition, we adjusted the wealth index by the number of equivalent adults in the household. The adult equivalents, AE, in the household is derived from Eq (1) below [35]: where A represents the number of adults in the household, K refers to the number of children aged 14 years and younger, and θ is the degree of economies scale [43]. We used a weight of 1.0 for adults and 0.5 for those aged 14 years and younger, and the proposed value of 0.75 for θ to represent the degree of economies scale based on an empirical study in China [44].

For decomposition analysis, the wealth index was categorized by tercile (low, middle, and high).

Measuring socioeconomic related inequality

This study used a concentration index (CI) to measure socioeconomic-related inequality. It can be computed conveniently using the covariance between a healthcare outcome variable and the fractional rank in the socioeconomic position as Eq (2) [31]: where y, μ, and R are the outcome variables of the ith individual, the mean or proportion of the outcome variable, and the fractional rank of the ith individual in the socioeconomic distribution, respectively.

The index typically ranges from -1 to +1, where a positive value emerges when uptake of healthcare is concentrated among the groups with higher SES, and a negative value means people in the lower SES group are more likely to receive healthcare than the rich. In practice, a value between 0.2 and 0.3 is regarded as a high degree of inequality [35]. Because of bounds dependence on the mean of the binary outcome, a normalized index, CI was proposed by Wagstaff to correctly solve quantifying the degree of inequality within -1 to +1 [45] and can be written as follows: where μ refers to the mean of the outcome variable and CI is the unnormalized concentration index.

Decomposition of the concentration index

To quantify the contribution of socio-demographic factors to observed healthcare inequalities of people living with HIV in Kunming, decomposition of the normalized concentration index (CI) was employed. We only focused on how socio-demographic explanatory variables influenced healthcare inequalities, so we did not include other health variables and clinical factors.

The decomposition method was first introduced for a linear, additive model for continuous outcome variables by Wagstaff et al. [34] as: where β is the coefficient of the explanatory variable x, and ɛ is an error term.

The concentration index can be decomposed to the contribution to concentration index (CC), in which each contribution equals the product of the elasticity of socio-demographic factor to y (β ®x /μ) and concentration index of x (C), i.e. (β ®x /μ) C [34], so the concentration index can be formulated as: where μ is the mean or proportion of y, ®x is the mean of x and GC is the generalized concentration index for the error term (ε). Eq (5) demonstrates that CI is equal to a weighted sum of k explanatory factors’ concentration indices, i.e., C. C reflects the distribution of SES by k explanatory factors. For example, a positive C of males means that males are concentrated among the rich. The residual term (GC /μ) implies the inequality in healthcare that is not explained by the systematic variation of explanatory factors, and it should be close to zero for a well-specified model [35].

However, because health sector outcome variables are intrinsically nonlinear, the decomposition approach is possible only if some linear approximation to the nonlinear model is performed. One common choice yielding probabilities in the range (0, 1) is the probit model, which is the standard additively normally distributed model. For binary outcome variables, one possibility is to use estimates of the marginal effects evaluated at the means [36]. That is, a nonlinear approximation for a binary outcome y to Eq (6) with need variables and non-need variables is given by: where x and z refer to need variables and non-need variables, and; i refers to an individual; the β and γ are the marginal effects from the probit model of each variable treated as fixed parameters evaluated at the means, and ε is the error term. Decomposition of the concentration index of a binary outcome based on the additive approximation regression of Eq (6) can be used [34], such that the normalized concentration index for y can be yielded as: where the first term refers to the partial contribution of need variables, the second term is the contribution of non-need variables and SES, and the C and C are normalized concentration indices of need and non-need variables, respectively. A positive contribution percentage to the concentration index suggests that the combined marginal effect of explanatory factors and its distribution with respect to SES increases the size of inequality. If an explanatory factor makes a negative contribution percentage to the concentration index, the level of the pro-rich inequality in healthcare would be higher should that explanatory factor be removed.

To assess inequity in healthcare distribution, standardization of concentration index for differences in need variables is also important. The indirect standardization approach has demonstrated that one simply needs to deduct the contributions of the standardizing variables (including in the regression along with others) from the total concentration index, the index of horizontal inequity (i.e., indirectly standardized concentration index), obtained by deducting the contributions of need variables in Eq (7). The indirect standardized concentration index (CI) can be explained as follows [35]:

Statistical analysis

Data were entered using Epidata 3.1 and analyzed using R software version 4.0.1 and STATA/MP version 14.2 (Stata Corp. Lp, College Station, USA). Categorical variables were described as frequencies and percentages, while continuous variables were described as means and standard deviation (SD) or median value with interquartile range (IQR). The probabilities of dependent variables in different age groups, education levels, and SES groups were calculated and compared using the chi-square test for trend and Bonferroni’s adjustment for multiple comparisons. We used a user-written Stata command “conindex” [46], which enables users to estimate the Wagstaff normalized concentration index and p-value for testing that the index is equal to zero. We employed the “probit” model with all socio-demographic explanatory variables to obtain the marginal effect for the calculation of contributions to the concentration index.

Ethical approval

The protocol of this study was approved by the Human Research Ethics Committee of Prince of Songkla University, Hat Yai, Songkhla, Thailand (REC: 61-340-18-1) and the Medical Ethics Committee, the Third People’s Hospital of Kunming, Yunnan, China (REC: 2019012901). All researchers and data collectors were re-trained on the ethical issues prior to data collection. Before data collection, the aims of the study were presented to all participants. Confidentiality and anonymity of eligible participants were assured. Verbal consent was obtained from all subjects before the interviews. Participation in the study was voluntary, and participants could refuse to respond to any questions or discontinue their participation at any time. Unique codes were used to maintain the participants’ confidentiality, and no personal identifiers were recorded. Because we conducted the study when participants were attending the routine visits, there was no compensation given to them.

Results

Socio-demographic characteristics of the respondents

Table 1 presents respondents’ socio-demographic characteristics with their corresponding normalized concentration indices (C). A total of 702 adults living with HIV in Kunming participated in the study. The participants ranged in age from 18 to 77 years, with a median age of 41.0 years (IQR, 32.0 to 48.0 years). Most were under the age of 50 years (80.9%), male (69.4%), Han ethnicity (83.9%), and non-religious (83.9%). The percentages of married and single participants were 44.3% and 35.3%, respectively. About half were employed, over one-third achieved a secondary school level of education, and 22.7% had completed university. Basic medical insurance covered 92.7% of participants, including 44.3% using rural medical insurance with NRCMI and 30.5% urban residents with URBMI. Based on this medical insurance type, there was an approximately equal distribution of study participants in urban (48.3%) and rural (44.3%) sites.

Table 1

Distribution and concentration indices of socio-demographic characteristics.

	N (%)	Ck	p- value
Total	702 (100.0)
Biological sex
Male	487 (69.4)	0.0744	0.116
Female	215 (30.6)	-0.0744	0.116
Age (years)
18–34	244 (34.8)	0.1070	0.019
35–49	324 (46.2)	-0.0163	0.710
≥50	134 (19.1)	-0.1316	0.018
Ethnicity
Han	589 (83.9))	-0.0138	0.817
Other	113 (16.1)	0.0138	0.817
Religious belief
Yes	589 (83.9)	0.0673	0.257
No	113 (16.1)	-0.0673	0.257
Marital status
Married	311 (44.3)	0.1949	<0.001
Single	248 (35.3)	-0.2660	<0.001
Divorced	110 (15.7)	-0.0454	0.320
Widowed	33 (4.7)	-0.0572	0.579
Education level
< = Primary school	174 (24.8)	-0.0657	0.194
Secondary school	245 (34.9)	-0.0901	0.049
High school	124 (17.7)	0.0137	0.811
> = University	159 (22.7)	0.1754	0.001
Employed status
Employed	387 (55.1)	0.0217	0.621
Unemployed	315 (44.9)	-0.0217	0.621
Medical insurance
None	51 (7.3)	-0.3401	<0.001
NRCMI	311 (44.3)	0.0994	0.024
UEBMI	126 (18.0)	0.1011	0.075
URBMI	214 (30.5)	-0.0778	0.101

SES, socioeconomic status; C, concentration index of socio-demographic factors; NRCMI, New Rural Cooperative Medical Insurance; UEBMI, Urban Employees Basic Medical Insurance; URBMI, Urban Residents Basic Medical Insurance. P-value is for concentration index.

There were significantly positive concentration indices among persons aged 18 to 34 years, married, with university or higher education level, and NRCMI insurance indicating that these factors were intensely concentrated among the rich. Conversely, participants who were aged more than 50 years, single, had achieved only secondary school education, and possessed no medical insurance were significantly more concentrated among the socioeconomically disadvantaged group.

Uptake of HIV continuous care

Table 2 illustrates the distribution of complete uptake of HIV continuous care by socio-demographic characteristics. More than 80% of respondents reached the targets of retention in care in the past six months, monitoring of toxicities, and monitoring of immunological outcomes in the past 12 months, regardless of their SES. However, the proportions of those receiving adequate plasma viral load assay (15.8%) and mental health assessment services (15.0%) were low in the past 12 months.

Table 2

Distribution of complete uptake of HIV continuous care by socio-demographic characteristics.

Variable	RIC (%)	RMT (%)	MIO (%)	MVO (%)	AMH (%)
Total	82.9	81.9	80.6	15.8	15.0
SES group	p = 0.713	p = 0.904	p = 0.349	p = 0.899	p = 0.044
Low	80.8	81.2	77.4	15.0	10.3
Middle	86.8	82.1	82.5	17.5	17.9
High	81.3	82.5	82.1	15.0	16.7
Biological sex	p = 0.957	p = 0.194	p = 0.242	p = 0.116	p = 0.036
Male	83.0	83.2	79.5	17.2	16.8
Female	82.8	79.1	83.3	12.6	10.7
Age (years)	p = 0.557	p = 0.167	p < 0.001	p < 0.001	p = 0.200
18–34	81.1	81.6	88.5	23.4	19.3
35–49	84.3	79.3	78.4	13.0	13.3
50+	82.8	88.8	71.6	9.0	11.2
Ethnicity	p = 0.527	p = 0.343	p = 0.817	p = 0.084	p = 0.600
Han	82.5	82.5	80.5	14.8	15.3
Minority	85.0	78.8	81.4	21.2	13.3
Religions belief	p = 0.147	p = 0.515	p = 0.817	p = 0.420	p = 0.004
Yes	87.6	84.1	81.4	13.3	23.9
No	82.0	81.5	80.5	16.3	13.2
Marital status	p = 0.252	p = 0.962	p = 0.119	p = 0.047	p = 0.100
Married	81.4	81.4	78.1	13.5	12.5
Single	86.7	81.9	85.5	20.6	18.2
Divorced	80.0	83.6	77.3	14.6	17.7
Widowed	78.8	81.8	78.8	6.1	6.1
Education level	p = 0.145	p = 0.500	p = 0.081	p = 0.062	p = 0.004
≤Primary school	81.6	82.2	83.9	13.8	10.9
Secondary school	80.8	79.6	73.9	13.9	13.1
High school	83.9	83.9	77.4	16.1	15.3
≥University	86.8	83.7	89.9	20.8	22.0
Employment status	p = 0.710	p = 0.429	p = 0.085	p < 0.001	p = 1.000
Employed	82.4	82.9	82.9	20.7	15.0
Unemployed	83.5	80.6	77.8	9.8	14.9
Medical insurance	p = 0.128	p = 0.270	p = 0.117	p = 0.034	p = 0.060
None	86.3	74.5	82.4	19.6	19.6
NRCMI	79.4	83.0	80.4	16.7	10.9
UEBMI	88.1	85.7	87.3	21.4	16.7
URBMI	84.1	79.9	76.6	10.3	18.7

RIC, retention in care; RMT, routine monitoring of toxicities; MIO, Monitoring of immunological outcome; MVO, Monitoring of virologic outcome; AMH, Self-reported assessment of mental health; NRCMI, New Rural Cooperative Medical Insurance; UEBMI, Urban Employees Basic Medical Insurance; URBMI, Urban Residents Basic Medical Insurance.

The tendency of respondents to receive adequate immunological and virological monitoring significantly decreased with increasing age (p <0.001). Single subjects accounted for the highest proportion (20.6%) of receiving adequate monitor of virologic outcomes (p = 0.047). Employed participants obtained more frequently adequate virological monitoring than the unemployed (p <0.001). There was also a significant difference in the proportions of those receiving monitoring for virological outcomes by type of medical insurance (p = 0.034).

Respondents in the low SES group reported the lowest percentage of uptake of mental health assessment (10.3%) followed by those in the high (16.7%) and middle SES groups (17.9%), and these differences were statistically significant (p = 0.044). A significant sex disparity was also found for the proportions of those receiving mental health assessment (p = 0.036). The proportion of people undergoing mental health assessments increased significantly with increasing education level (p = 0.004). Participants with religious beliefs reported significantly higher rates of receiving mental health assessments than those without religious beliefs (p = 0.004).

Concentration indices of HIV continuous care outcomes and contribution of socio-demographic factors

Results of concentration indices of dependent variables and their aggregated contribution of socio-demographic factors are displayed in Table 3. A statistically significant concentration index for the uptake of mental health assessment was found (CI = 0.1337, p = 0.029), indicating a pro-rich inequality. After controlling for unequal need distribution (age and sex), the indirect standardized concentration index remained significant for uptake of mental health assessment (CI = 0.1127, p = 0.042).

Table 3

Concentration index and aggregated contribution of regressors to concentration indices for HIV care continuum.

	RIC	RMT	MIO	MVO	AMH
	AC (CC%)	AC (CC%)	AC (CC%)	AC (CC%)	AC (CC%)
CIn	0.0117	0.0315	0.0736	-0.0308	0.1337*
CIxIS	0.0157	0.0344	0.0707	-0.0501	0.1123*
Need factors
Age	-0.0031 (-26.9)	-0.0037 (-11.9)	0.0051 (7.0)	0.0171 (-55.5)	0.0149 (11.1)
Biological sex	-0.0009 (-7.5)	0.0008 (2.7)	0.0240 (-3.0)	0.0022 (-7.0)	0.0065 (4.9)
Subtotal	-0.0040 (-34.3)	-0.0029 (-9.2)	0.0291 (4.0)	0.0193 (-62.5)	0.0214 (16.0)
Non-need factors
SES	0.0046 (39.6)	0.0018 (5.8)	0.0117 (15.9)	-0.0008 (2.7)	0.1670 (124.9)
Ethnicity	0.0000 (0.3)	-0.0001 (-0.3)	-0.0001 (-0.1)	0.0006 (-2.1)	-0.0004 (-0.3)
Religious belief	0.0044 (37.3)	0.0017 (5.5)	0.0005 (0.7)	-0.0101 (32.7)	0.0365 (27.3)
Marriage status	-0.0009 (-8.3)	-0.0018 (-5.5)	-0.0009 (0.0)	-0.0074 (24.1)	-0.0157 (-11.8)
Education level	0.0017 (14.1)	0.0020 (6.3)	0.0036 (4.9)	-0.0089 (22.2)	0.0108 (8.1)
Employment status	-0.0002 (-1.4)	0.0003 (0.9)	0.0000 (0.0)	0.0046 (-15.0)	-0.0016 (-1.2)
Medical insurance	-0.0015 (-13.0)	0.0049 (15.6)	0.0002 (0.2)	0.0004 (-1.5)	-0.0319 (-23.9)
Subtotal	0.0037 (68.7)	0.0079 (28.3)	0.0150 (21.6)	-0.0216 (63.4)	0.1647 (123.0)
Residual (unexplained)	-0.0040	0.0256	0.0557	-0.0306	-0.0524

CI, normalized concentration index; CI, Indirectly standardized concentration index; RIC, retention in care; RMT, routine monitoring of toxicities; MIO, Monitoring immunological outcome; MVO, Monitoring virological outcome; AMH, Self-reported assessment of mental health; AC, absolute contribution to concentration index; CC%, percentage of contribution to concentration index;

*p-value <0.05.

Non-significant pro-rich inequalities were found for retention in care (CI = 0.1168, p = 0.840), routine monitoring of toxicities (CI = 0.0315, p = 0.579), and monitoring of immunological outcomes (CI = 0.0736, p = 0.182). However, the opposite direction was found for the uptake of adequate virological monitoring with a concentration index of -0.0308 (p-value 0.607), indicating pro-poor inequality slightly. Subtracting the contribution of need variables (i.e., age and sex), the need-adjusted concentration indices for retention in care, routine monitoring of toxicities, and monitoring immunological outcome were 0.0157, 0.0344, and 0.0707, respectively, showing the same direction of pro-rich horizontal inequality. The need-adjusted concentration index of monitoring virological outcomes was -0.0501, indicating a stronger horizontal inequality degree favoring the poor.

Table 3 also shows the contribution of socio-demographic characteristics on socioeconomic-related inequalities where a positive contribution percentage increases inequality, and a negative contribution percentage decreases inequality. The utilization of mental health assessment, a significant pro-rich inequality, is taken as an example to illustrate the decomposition of a concentration index into its determinants. Participants’ SES (124.9%), religious belief (27.3%), and age (11.1%) had the highest positive contributions to the measured inequality. In contrast, participants’ medical insurance (-23.9%) and marital status (-11.8%) had negative contributions to the pro-rich inequality of mental health assessment, that is, these factors decreased the inequality size in the utilization of mental health assessment. The residuals of the regression models (-0.0524, -39.2%) implied a large unexplained proportion of factors contributing to the concentration index of mental health assessment. SES positively contributed to inequalities of all dependent variables, with the highest contribution for assessing mental health (124.9%) and the lowest for monitoring virological outcomes (2.7%).

For the non-significant concentration index, these factors’ positive and negative contributions were canceled out. Need variables (age and sex) provided the main negative aggregated contribution to concentration indices of adequate monitoring of virological outcomes (-62.5%), retention in care (-34.3%), and routine monitoring of ART toxicities (-9.2%), but mild positive contribution for monitoring immunological outcomes (4.0%). On the other hand, having a religious belief provided high contributions to inequalities for retention in care (37.3%) and virological monitoring (32.7%). Medical insurance offered positive contributions for routine monitoring of toxicities and monitoring immunological outcomes and negative contributions to the other outcome variables. Ethnicity and employment status had tiny contributions to inequalities of all outcomes.

Discussion

Main findings and comparison with previous studies

This study expands other previous research by applying a concentration index to examine the presence of socioeconomic-related inequality in comprehensive continuous care for people living with HIV who had been on ART more than one year but less than five years the context of “national free ART” in Kunming, the epicenter of HIV in China. We also identified the contribution of some socio-demographic characteristics to the inequality by a decomposition approach.

In the present study, for the first time, the socioeconomic-related inequality in receiving mental healthcare in China was measured and explained. We found a low rate of having mental health assessment (15%), which was consistent with other studies around the world [47]. A systematic review reported that people living with HIV were at risk for mental health problems in their lifetimes, and this is true in China as this vulnerable group suffered more severe discrimination and lack of available resources than did those living in other countries [24]. Failure to be screened and treated for these psychological disorders may hamper the successful treatment of their HIV infection [10]. To integrate mental healthcare and ART services, a training course for health providers, an action guideline, and an information system with a standardized procedure for assessing and recording mental status are needed [48].

We also found that perceived uptake to mental health assessment was disproportionately concentrated among people with a higher socioeconomic status. This is consistent with inequalities in the utilization of specialty mental health services among persons living with HIV in the USA [49]. These results agree with the general global consensus around the relationship between socioeconomic inequality and pro-rich healthcare utilization under the shrinkage of financial subsidy and fund support [50]. Moreover, we found that the main positive contributor to inequality of mental health assessment was SES, which accounted for 124.9%, indicating that a higher socioeconomic position may increase the size of the pro-rich inequality compared to those in a lower socioeconomic group. Apart from receiving free mental health assessment in the HIV treatment center, the rich may also receive mental health assessment in specialized psychiatric settings, which is not free. This explains how SES plays a role in a pro-rich inequality of this type of care.

Other socioeconomic and socio-demographic factors also play a certain role in the inequality of receiving mental health assessments. Religious belief positively contributed to the pro-rich inequality of mental health assessment. Participants with religious beliefs were concentrated in the high SES group (positive C), and they tended to have more retention in care, so they increased their chance of receiving mental health assessment. Medical insurance accounted for a negative contribution to pro-rich on mental health assessment, suggesting that having medical insurance and the choice of medical insurance may affect the uptake of mental health assessment and health services utilization [51], as the cost of mental healthcare can be covered by medical insurance.

Our study indicated that under the national free ART program in China, inequalities of the utilization of all other comprehensive continuous care for people living with HIV who were stable and on ART in Kunming were not significant. Retention in care is a critical indicator of success in long-term HIV medication and the necessary component of a successful treatment-as-prevention strategy [12]. Our study showed that the majority of participants were retained in the care of the free ART program with clinic visit-based indicators in Kunming. This was consistent with recent studies in China and some other Asian countries [3, 11].

With the need for life-long ART and long-term toxicities of ART, our study found that more than 80% of participants received routine regular laboratory monitoring of toxicities of ART, which meant that NFATP in Kunming put surveillance of antiretroviral toxicity as a national priority indicator of the health sector response to HIV and agreed with the technical brief given by the WHO [41]. Toxicities appeared to be a relative reason for disengagement from care [3]. A study in Thailand demonstrated that simple and inexpensive monitoring of key biomarkers was feasible at some time points [15].

Different directions were shown for monitoring treatment outcomes in our study. Most participants received adequate immunological response monitoring, whereas 84.2% lacked adequate routine virological monitoring [21], which was lower than in a previous study in sub-setting in sub-Saharan Africa [52]. Interestingly, virological response monitoring was non-significant in favor of the poor in our research, and SES contributed minimally to the uptake of intensive viral load testing in Kunming. As an additional viral load test has to be paid out of pocket or by medical insurance based on the client’s ability to pay, test costs can be beyond the client’s affordability, neither the rich nor the poor might be willing to pay this fee. This explained the low uptake rate of adequate viral load test. The policies for HIV response, services, and core indicators in China for viral load testing should be adjusted practically to close the gap in viral load testing [53, 54].

Age provided a main negative aggregated contribution to reduce pro-rich inequalities of adequate virological monitoring (-62.5%), retention in care (-34.3%), and routine monitoring of toxicities (-9.2%). As the prolongation of life expectancy of people aging with HIV, this population is also facing an aging problem, similar to the general population. We found that age was the main contributor between the need variables, suggesting that need-oriented utilization of health care can reduce the degree of inequality to meet the needs of HIV care in Kunming.

Strengths and limitations

This study used comprehensive indicators to cover physical and mental aspects of long-term care for people living with HIV on ART rather than a single specific indicator to measure healthcare utilization. To our knowledge, this is the first study to measure and explain the inequality of a series of comprehensive HIV continuous care by socio-demographic factors. We provide an informative picture of thorough care for the HIV care continuum among different socioeconomic groups in China.

There were several limitations in this study. First, the household assets and conditions were self-reported, which might result in both under- or over-reporting of participants’ SES. Second, this study’s findings are only valid for the population of Kunming city using hospital facilities. The inclusion of healthcare users outside the hospital setting would provide a clearer picture of the real inequality gap among the whole healthcare system for people living with HIV who had been on ART in Kunming. National multicenter studies on all-integrated healthcare for people living with HIV would provide such information. Third, the lack of qualitative data, such as pro-rich inequality in mental health assessment and pro-poor inequality in virological monitoring, limited our ability to explain inequality in another dimension. The nature of a cross-sectional study limited its ability to make causal inferences. Finally, a sizeable unexplained proportion of contribution suggested that other mechanisms that we were unable to measure played a substantial role in inequality in the utilization of comprehensive continuous care. Further studies are needed to illuminate the impact of the scope from individual factors such as clinical characteristics or medication adherence, healthcare providers’ role, the performance of the healthcare system, and other unmeasured variables.

Implications from the study

Considering the low coverage of intensive virological monitoring and mental health assessment found in this study, there is an urgent need for (i) increasing the awareness of viral load monitoring and mental health assessment for people living with HIV among clinicians, (ii) improving the attention on the importance of performing viral load testing and mental health assessment among people living with HIV during their long-term treatment period, (iii) reliable return of results, point-of-care viral load testing in healthcare facilities, (iv) well-trained professional mental health service personnel and facilities for people living with HIV, and (v) reducing the cost of viral load testing. To diminish the degree of inequality of HIV care utilization under a free ART context, implications include (i) strengthening governmental policies, welfare, and social support to reduce the gap between the rich and poor, including vulnerable people living with HIV, (ii) response by the civil affairs department to improve the assistance system for people living with HIV, (iii) a lower user-pay amount from medical insurance companies and an expansion in the scope of medical insurance reimbursement to support access to ancillary long-term HIV care such as mental health services, (iv) the allocation of medical care resources based on the needs of people living with HIV which can reduce the degree of the socioeconomic-related inequality, and (v) addressing staffing and resource limitations around HIV comprehensive care.

Conclusions

In Kunming City of China, there is a higher prevalence of retention in care, monitoring of toxicities, and immunological outcomes, but lower rates of completing adequate virological monitoring and self-reported mental health assessment receipt among people living with HIV receiving ART. We found that under the national free ART program in Kunming, pro-rich inequality of the utilization of mental health assessment was significant, but no significant inequalities of other comprehensive continuous care for people living with HIV were found in Kunming. We also found that socioeconomic status positively contributed to inequalities in mental health assessment. Between the two need variables (age and sex), age contributed more to the inequalities in the utilization of all HIV continuous care. This implies that the degree of such inequalities can be reduced should comprehensive care be provided proportionately to people living with HIV of all age groups. These findings can provide evidence for policymakers to develop policies that allocate need-oriented healthcare utilization geared toward more equality in comprehensive continuous care for people living with HIV.

Study questionnaire (English and Chinese version).

(DOCX)

Click here for additional data file.

Minimal dataset.

(CSV)

Click here for additional data file.

STROBE statement—Checklist of items that should be included in reports of observational studies.

(DOCX)

Click here for additional data file.

9 Feb 2021

PONE-D-20-28608

Measuring and Explaining Inequality of Continuous Care for People Living With HIV/AIDS on Antiretroviral Therapy in Kunming , China

PLOS ONE

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Additional Editor Comments:

We apologize for the delay in receiving comments from reviewers. Only one reviewer submitted his/her comments and suggested rejection. However, I would like to give the authors another chance to revise and resubmit the paper.

Overall, the quality of writing left the reviewers in difficulty judging the study. Please follow standard scientific report writing rules (e.g., use of tenses and terminologies, spelling out numbers smaller than 10, use of tenses and punctuations). I have spotted several easy grammatical errors, typos, and complex sentences across the manuscript. Many statements also require supporting references and clarification. In the text, please minimize the use of uncommon and unnecessary abbreviations (IRC, RTM, MIO, MVO, AMH, etc.) that reduce the manuscript’s readability. The manuscript is not publishable in its current form and will benefit from thorough proofreading by a native or more experienced academic writer. Below are some suggestions, which may not be exhaustive. We will decide whether to continue reviewing the paper based on the improvement made in the next submission.

Title and keywords:

Please revise the title according to PLOS’ styles and guidelines (e.g., do not start each word with a capital).

Please remove ‘AIDS’ from ‘people living with HIV.’ UNAIDS recommended that ‘HIV/AIDS’ should not be used since 2015. Also, ‘people living with HIV’ should not be abbreviated or addressed as patients. This is applied across the paper, including keywords. See: https://www.unaids.org/sites/default/files/media_asset/2015_terminology_guidelines_en.pdf

To increase the visibility of your paper, please avoid keywords that are overlapping with those in the title. This may help: https://falconediting.com/en/blog/6-tips-for-choosing-keywords-for-your-scientific-manuscript

For PLOS journals, keywords should be included in the submission system, not in the text.

Abstract:

A structured abstract is recommended (background, methods, results, conclusions).

In Methods, please provide the study period and summarize the sampling methods.

Results should provide the sample size and essential characteristics (age, sex).

Introduction:

The Introduction contains long and complex sentences that are difficult to read and need to be re-structured.

Materials and Methods:

Inclusion criteria should be revised to improve the quality of writing and understanding and avoid redundancy. For example, the first sentence under the ‘Study setting and participants’ stated that this study included people living with HIV who had initiated ART for at least one year, but not more than five years. This information was repeated in inclusion criteria 3, and it was not entirely consistent.

Was sample size calculation performed?

Please provide a reason for excluding people living with HIV aged 18 and those who had received ART more than five years.

Inclusion criteria 3 is difficult to read, and criteria 5 is not understandable. What does ‘physical and psychological ability’ mean? What happened if someone could not complete the questionnaire in 30 minutes?

Please provide references to support variable measurements. I am not quite sure if the criteria remained applicable in China in 2019. For example, are people living with HIV are still required to visit an ART clinic two times or more in 90 days? Is mental health a component in the treatment and care service package?

Please be sensitive in using the term ‘gender’ and ‘sex.’ Please double-check if ‘gender’ is the correct term for this study context.

Line 163: What does ‘need or non-need factor’ mean?

Data analysis needs further details and should be aligned with the result presentation. For example, I am not sure if I understand why the authors compare socio-demographic characteristics in SES groups (Table 1), which is quite predictable. In the data analyses, the authors mentioned about the comparison of dependent variables in different groups. It was also not clear whether the analyses were controlled for confounding factors. If so, how were the models built, or how were the covariates selected?  Only Bonferroni's adjustment was mentioned.

Ethics: Describe the measures taken to protect participants’ privacy and confidentiality. Also, did the participants receive any compensation?

Results

The wording and terminologies used in the description of the results need improvement.

Descriptive results can be summarized as they are mostly repeating the information in tables.

Table 2: Exact p values should be presented rather than showing *p-value <0.05, ** p-value <0.01, and ***p-value <0.001 in the footnote.

Discussion

Please refine the discussion according to the earlier comments and reviewer’s comments, focusing on this study's significant findings. It is also important to discuss the socio-economic burden of HIV care continuum on people living with HIV, particularly in the study setting context (e.g., free vs. charged services, other costs).

References

The reference list needs to be revised to be aligned with PLOS’s styles and requirements.

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Reviewer #1: Partly

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Reviewer #1: Yes

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Reviewer #1: No

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Reviewer #1: 1) Many concentration indices were with non-significant p-values, but the authors still interpreted as if there were effect, which is inappropriate. The results of the manuscript should be summarized in a succinct manner with the significant and important results stressed.

2) Table 3, it is unclear to me for the same variable why the absolute contribution and percentage of contribution to concentration index can have different signs?

3) Please ask for professional editing help with English language.

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18 Mar 2021

Responses to Editor and Reviewer

PLOS One Manuscript number: PONE-D-20-28608

Measuring and explaining inequality of continuous care for people living with

HIV on antiretroviral therapy in Kunming, China

Additional Editor Comments:

1.Overall, the quality of writing left the reviewers in difficulty judging the study. Please follow standard scientific report writing rules (e.g., use of tenses and terminologies, spelling out numbers smaller than 10, use of tenses and punctuations). I have spotted several easy grammatical errors, typos, and complex sentences across the manuscript. Many statements also require supporting references and clarification. In the text, please minimize the use of uncommon and unnecessary abbreviations (IRC, RTM, MIO, MVO, AMH, etc.) that reduce the manuscript’s readability. The manuscript is not publishable in its current form and will benefit from thorough proofreading by a native or more experienced academic writer. Below are some suggestions, which may not be exhaustive. We will decide whether to continue reviewing the paper based on the improvement made in the next submission.

Response: Thank you for your valuable comments. We have checked and made revisions accordingly. We have also asked a native English academic to edit the final manuscript.

2.Title and keywords:

• Please revise the title according to PLOS’ styles and guidelines (e.g., do not start each word with a capital).

Response: Checked and revised accordingly.

• Please remove ‘AIDS’ from ‘people living with HIV.’ UNAIDS recommended that ‘HIV/AIDS’ should not be used since 2015. Also, ‘people living with HIV’ should not be abbreviated or addressed as patients. This is applied across the paper, including keywords. See: https://www.unaids.org/sites/default/files/media_asset/2015_terminology_guidelines_en.pdf

Response: Thank you for your advice. We have checked and made revisions accordingly.

• To increase the visibility of your paper, please avoid keywords that are overlapping with those in the title. This may help: https://falconediting.com/en/blog/6-tips-for-choosing-keywords-for-your-scientific-manuscript

Response: Thank you for your suggestions. We have modified the keywords as: HIV, healthcare utilization, healthcare inequality, concentration index, decomposition, China.

• For PLOS journals, keywords should be included in the submission system, not in the text.

Response: We have made revisions accordingly.

3. Abstract:

• A structured abstract is recommended (background, methods, results, conclusions).

Response: We have made revisions accordingly.

• In Methods, please provide the study period and summarize the sampling methods.

Response: We have made revisions accordingly.

• Results should provide the sample size and essential characteristics (age, sex).

Response: We have added the sample size and essential characteristics (age, sex) in the methods part.

4. Introduction:

• The Introduction contains long and complex sentences that are difficult to read and need to be restructured.

Response: We have rewritten the introduction part.

5. Materials and Methods:

• Inclusion criteria should be revised to improve the quality of writing and understanding and avoid redundancy. For example, the first sentence under the ‘Study setting and participants’ stated that this study included people living with HIV who had initiated ART for at least one year, but not more than five years. This information was repeated in inclusion criteria 3, and it was not entirely consistent.

Response: We have made revisions accordingly.

(Lines 152-156: “Individuals were eligible to be included in the study if they: 1) were aged 18 years or older; 2) had HIV infection clinically diagnosed and confirmed with serological tests; 3) had initiated ART and were currently receiving ART for more than 1 year but not more than 5 years; 4) were able and willing to provide verbal consent to participate in the study, and; 5) were able to communicate in Chinese.”)

• Was sample size calculation performed?

Response: Yes, we have added the sample size calculation in the revised manuscript.

(Lines 164-170: “The sample size was calculated using the finite population formula. As no previous data on comprehensive care access among PLWH was available in China, it is conservatively estimated that comprehensive care access was 50%, there were nearly 8,000 people receiving ART in the HIV treatment center, considering a margin of error of 4%, a confidence interval of 95% and a 20% refusal rate or missing data. Finally, the minimum required sample size for the study was 664.”)

• Please provide a reason for excluding people living with HIV aged 18 and those who had received ART more than five years.

Response: We did not exclude people living with HIV aged 18 years. We apologize for the confusing sentence in the previous version. In this version, we have rewritten the inclusion criteria to make them clearer. (Lines 152-153)

• Inclusion criteria 3 is difficult to read, and criteria 5 is not understandable. What does ‘physical and psychological ability’ mean? What happened if someone could not complete the questionnaire in 30 minutes?

Response: We have checked and made revisions accordingly. We have changed “physical and psychological ability” to “were able and willing to provide verbal consent to participate in the study and were able to communicate in Chinese”. (Lines 155-156)

• Please provide references to support variable measurements. I am not quite sure if the criteria remained applicable in China in 2019. For example, are people living with HIV are still required to visit an ART clinic two times or more in 90 days? Is mental health a component in the treatment and care service package?

Response: We have made revisions accordingly (Lines 196-224). People living with HIV were still required to visit the ART clinic every 3 months in 2019. Based on the free ART manual of China free antiretroviral treatment program (NFATP), after initiating ART for more than one-year, subsequent follow-up visits are scheduled every 3 months, and the dispensing of free ART is three-monthly in the HIV treatment center to ensure enough stocks of ART for both newly initiated and continuously treated people. Mental health is not a standard component in the ART service package. However, Chinese national guidelines recommend that mental healthcare can be integrated into ART services when conditions permit, but there are no specific operating guidelines or records in the outpatient system or database of NFATP.

• Please be sensitive in using the term ‘gender’ and ‘sex.’ Please double-check if ‘gender’ is the correct term for this study context.

Response: We have checked and made revisions accordingly. We have used “sex” or “biological sex” throughout the manuscript.

• Line 163: What does ‘need or non-need factor’ mean?

Response: As stated in the Introduction (lines 131-135) and Materials and methods (Lines 233-235), “Possible determinants (of healthcare inequality) can be categorized into “need” and “non-need” factors. Need factors are sources of variation in healthcare that are not considered to be “unfair”. They are related to characteristics of an individual that are direct causes of the use of medical services, usually age and sex. Non-need factors are sources of variation in health care that are “unfair” or “unjust”, such as SES, education, and ethnicity.” In this study, “need” factors include age and sex and other socio-demographic factors are “non-need” factors.

• Data analysis needs further details and should be aligned with the result presentation. For example, I am not sure if I understand why the authors compare socio-demographic characteristics in SES groups (Table 1), which is quite predictable. In the data analyses, the authors mentioned about the comparison of dependent variables in different groups. It was also not clear whether the analyses were controlled for confounding factors. If so, how were the models built, or how were the covariates selected? Only Bonferroni's adjustment was mentioned.

Response: We have revised Table 1 to show the distribution and concentration indices of socio-demographic characteristics and reduced comparison of SES groups; we employed the Stata command “conindex” to calculate the p-value for testing if the concentration index is equal to zero. Because our outcomes were binary, the decomposition of the concentration index involved using a probit model with marginal effects for all socio-demographic explanatory variables. We only focused on how socio-demographic explanatory variables influenced healthcare inequalities, so we did not include other health variables and clinical factors and reduced the socio-demographic variables from the model.

• Ethics: Describe the measures taken to protect participants’ privacy and confidentiality. Also, did the participants receive any compensation?

Response: We have made revisions accordingly. (Lines 174-176, 179-182 and 338-345). Because we conducted the study when participants were attending the routine visits, there was no compensation given to them.

6. Results

• The wording and terminologies used in the description of the results need improvement.

Response: We have checked and made revisions accordingly. We have rewritten several parts of the results to make them clearer and easier to read.

• Descriptive results can be summarized as they are mostly repeating the information in tables.

Response: We have made revisions accordingly.

• Table 2: Exact p values should be presented rather than showing *p-value <0.05, ** p-value <0.01, and ***p-value <0.001 in the footnote.

Response: We have made revisions accordingly. (Table 1 and Table 2 )

7. Discussion

• Please refine the discussion according to the earlier comments and reviewer’s comments, focusing on this study's significant findings. It is also important to discuss the socio-economic burden of HIV care continuum on people living with HIV, particularly in the study setting context (e.g., free vs. charged services, other costs).

Response: Thank you for your suggestion. We have revised the discussion part and focussed on the significant findings. (Line 448-475)

8. References

• The reference list needs to be revised to be aligned with PLOS’s styles and requirements.

Response: We have revised the reference style as “Vancouver” based on PLOS’s requirements.

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

Response: We have made revisions accordingly.

2. Please include additional information regarding the survey or questionnaire used in the study and ensure that you have provided sufficient details that others could replicate the analyses. For instance, if you developed a questionnaire as part of this study and it is not under a copyright more restrictive than CC-BY, please include a copy, in both the original language and English, as Supporting Information, or include a citation if it has been published previously.

Response: We have added accordingly.

3. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information.

Response: We have added and update accordingly.

Reviewers' comments:

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: No

Response: We have made revisions accordingly.

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1:

1) Many concentration indices were with non-significant p-values, but the authors still interpreted as if there were effect, which is inappropriate. The results of the manuscript should be summarized in a succinct manner with the significant and important results stressed.

Response: Thank you for your suggestion. We have revised the discussion part and focussed on the significant findings. (Line 448-475)

2) Table 3, it is unclear to me for the same variable why the absolute contribution and percentage of contribution to concentration index can have different signs?

Response: As we described in lines 282-285 and 293-297, the percentage of contribution equals (100*(βk ®xk / μ) Ck/ CIn). If the concentration index is negative, the absolute contribution can follow the concentration index sign as a negative value, but the contribution percentage was positive, so the positive contribution percentage increases the size of the inequality, a negative contribution percentage decreases the size of the inequality.

3) Please ask for professional editing help with English language.

Response: Thank you. We have asked for professional editing help with the English.

Submitted filename: Responses to Reviewers.docx

Click here for additional data file.

7 Apr 2021

PONE-D-20-28608R1

Measuring and explaining inequality of continuous care for people living with HIV receiving antiretroviral therapy in Kunming, China

PLOS ONE

Dear Dr. Assanangkornchai,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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We look forward to receiving your revised manuscript.

Kind regards,

Siyan Yi, MD, MHSc, PhD

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments:

We thank the authors for addressing the reviewers’ comments. The revised manuscript has been greatly improved. However, it still requires further attention, particularly in the Introduction and Methods. Below are some suggestions, that may not be exhaustive. The revised manuscript requires thorough proofreading to remove several minor grammatical errors, typos, terminology use, tenses, etc. Also, please ensure that your revised manuscript is prepared according to the journal’s styles and guidelines, particularly in the reference list. Please note that PLOS usually does not provide an opportunity for the authors to proofread their paper before the publication if it is accepted.

Title page:

Please use a consistent font and font size.

Abstract:

As commented earlier ‘people living with HIV’ should not be abbreviated or addressed as patients. This is applied across the paper, including keywords. See: https://www.unaids.org/sites/default/files/media_asset/2015_terminology_guidelines_en.pdf

Please refine the objective of the study, which is too long and difficult to read. The authors may consider breaking it down into two sentences. Also, ‘impact’ is an incorrect term in this context, given the study’s cross-sectional nature.

Results:

Line 28: what does ‘uptakes of retention’ in care mean?

Is there any other ways to explain ‘non-significant pro-rich and pro-poor,’ that are easier to understand?

Please make it clear if the last results (Lines 31-33) were statically significant.

Introduction

Overall, the introduction is well written but unnecessarily too long that should be condensed. Please try to limit it to approximately 1000 words (1-2 paragraphs for problem statement, 1-2 paragraphs on literature review of previous studies on inequality in access to HIV services and its associated factors, and 1 paragraph on rationales, and 1 paragraph on study’s objectives).

Please also proofread it carefully after the revisions (e.g., on line 45, no need to write ART in full as it was already spelled out on line 43)

Materials and Methods

Line 150-151: It sounds a little bit awkward when saying, “Kunming city was chosen as the study area because it has the highest prevalence of HIV/AIDS in Yunnan.” Any rationale directly linked to Kunming? The prevalence of HIV also needs a reference to support. Please remove ‘AIDS’ from the highest prevalence of HIV/AIDS. As commented earlier, PLWH is not currently in use as recommended by UNAIDS.

Eligibility criteria:

Does HIV infection require a clinical diagnosis? Many people living with HIV do not present with any symptoms and are diagnosed only by serological tests – were they eligible for the study? Usually, getting registered to receive HIV services indicates that they live with HIV, which is clearly stated in criteria 3.

Any criteria related to physical and mental health stability to participate in the interview?

Lines 154, 157, 159: As commented earlier, numbers smaller than 10 should be spelled out in words in scientific and academic writing. This is applied to the whole document.

Line 155: Please remove ‘,’ before ‘and.’

Lines 156-161: The sentence is too long and should be broken down into 2-3 sentences.

Line 161: Please replace ‘;’ by ‘.’

Lines 165-169: The sentence is too long and should be broken down into 2 sentences.

Line 184: Please spell out NFATP if it was used for the first time in the manuscript.

Line 192: Guess ‘outcome’ should read ‘outcome variable.’

Line 197: Not sure if the word ‘free’ before ‘ART manual’ is necessary. Is the manual applied only for ‘free’ ART? I do not find it necessary to keep saying ‘free ART’ (e.g., lines 198, 201) as it brings more confusion than help. The authors may just describe in the description of the study site that the HIV center where the study was conducted provides ART and other HIV services free of charges.

Line 211: The use of ‘;’ before ‘and’ is incorrect.

The NFATP only provides free CD4 and viral load testing once a year, and people living with HIV have to pay for the remaining tests. It is important to state whether the non-free tests were voluntary based on the clients’ ability to pay or compulsory as the test costs can be beyond their affordability. This may explain the relationships between inequality and socio-demographic characteristics, leaving alone other potential financial barriers (transport costs, busy working). I would suggest this point be discussed in the discussion section. This may also explain the low rate of viral load test presented in the results.

Line 256: Please use past tense in the methods section (e.g., this study used…).

Line 329: …using the Chi-square test.

Line 352: Please present the median value with an interquartile range.

Line 496: WHO was already defined in the introduction.

Lines 497-498: the sentence “A study in Thailand suggested that simple and inexpensive monitoring of key biomarkers could be done at some time points” is not clear and should be further elaborated. What did the authors intend to tell – feasibility, efficacy, or else?

Lines 523-524: A self-reporting measure can lead to both under- or over-reporting unless this study could prove that it was under-reporting.

Line 556: Guess Kunming does not require ‘the.’

Lines 556-559: Conclusions should summarize the key findings that respond to the research questions and objectives. The comparison of this study’s findings to the literature should be discussed in the discussion section.

Lines 563-565: The sentence “Furthermore, need variables (i.e., age and sex) could not negatively contribute to all concentration indices to diminish the degree of inequalities” needs clarity as it is hard to understand.

References are still inconsistent and not entirely aligned with PLOS’s style and requirements. Please ensure that they have been corrected before re-submission.

[Note: HTML markup is below. Please do not edit.]

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21 Apr 2021

Rebuttal letter to Editor and Reviewer

PLOS One Manuscript number: PONE-D-20-28608

Measuring and explaining inequality of continuous care for people living with HIV receiving antiretroviral therapy in Kunming, China

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Response: As we condensed the introduction, we removed six references and revised the reference list.

Additional Editor Comments:

We thank the authors for addressing the reviewers’ comments. The revised manuscript has been greatly improved. However, it still requires further attention, particularly in the Introduction and Methods. Below are some suggestions, that may not be exhaustive. The revised manuscript requires thorough proofreading to remove several minor grammatical errors, typos, terminology use, tenses, etc. Also, please ensure that your revised manuscript is prepared according to the journal’s styles and guidelines, particularly in the reference list. Please note that PLOS usually does not provide an opportunity for the authors to proofread their paper before the publication if it is accepted.

Response: Thank you for your valuable comments. We have checked and made revisions accordingly, especially Introduction and Methods. We have checked and made revisions in the reference list based on the journal’s styles and guidelines.

Title page:

1. Please use a consistent font and font size.

Response: We have checked and made revisions accordingly.

Abstract:

2. As commented earlier ‘people living with HIV’ should not be abbreviated or addressed as patients. This is applied across the paper, including keywords. See: https://www.unaids.org/sites/default/files/media_asset/2015_terminology_guidelines_en.pdf

Response: We made revisions accordingly across the paper.

3. Please refine the objective of the study, which is too long and difficult to read. The authors may consider breaking it down into two sentences. Also, ‘impact’ is an incorrect term in this context, given the study’s cross-sectional nature.

Response: We have made revisions accordingly. (Page 2 lines 15-19: We have split the objectives into two sentences. Line 19: We changed “impact” to “contributions”.)

4. Results:

• Line 28: what does ‘uptakes of retention’ in care mean?

Response: We have modified this sentence accordingly. (Page 2 line 28: We removed “Uptakes of.”)

• Is there any other ways to explain ‘non-significant pro-rich and pro-poor,’ that are easier to understand?

Response: We have revised this as follows: (Page2 lines 29: We revised “non-significantly pro-rich” to “non-significant in favor of the rich” And lines 30-31: we revised “nonsignificant pro-poor” to “higher among the poor.”)

• Please make it clear if the last results (Lines 31-33) were statistically significant.

Response: We calculated contributions of socioeconomic status to inequalities based on equation (5), finally we did not check for statistical significance.

Introduction

5. Overall, the introduction is well written but unnecessarily too long that should be condensed. Please try to limit it to approximately 1000 words (1-2 paragraphs for problem statement, 1-2 paragraphs on literature review of previous studies on inequality in access to HIV services and its associated factors, and 1 paragraph on rationales, and 1 paragraph on study’s objectives).

Response: Thank you for your comments. We have checked revised the introduction accordingly.(Pages 3-6)

6. Please also proofread it carefully after the revisions (e.g., on line 45, no need to write ART in full as it was already spelled out on line 43)

Response: Checked and revised accordingly.

Materials and Methods

7. Line 150-151: It sounds a little bit awkward when saying, “Kunming city was chosen as the study area because it has the highest prevalence of HIV/AIDS in Yunnan.” Any rationale directly linked to Kunming? The prevalence of HIV also needs a reference to support. Please remove ‘AIDS’ from the highest prevalence of HIV/AIDS. As commented earlier, PLWH is not currently in use as recommended by UNAIDS.

Response: Revised accordingly.

Lines 116-117: As we have no rationale directly linked to Kunming, thus we have removed the sentence referring to Kunming city being chosen due to its high prevalence of HIV/AIDS and added: “Kunming is the capital city of Yunnan province.” We have also removed “AIDS” accordingly.

8. Eligibility criteria:

• Does HIV infection require a clinical diagnosis? Many people living with HIV do not present with any symptoms and are diagnosed only by serological tests – were they eligible for the study? Usually, getting registered to receive HIV services indicates that they live with HIV, which is clearly stated in criteria 3.

Response: Thank you for your suggestion. We did not require a clinical diagnosis for HIV infection. We have therefore removed this inclusion criteria.

• Any criteria related to physical and mental health stability to participate in the interview?

Response: Yes.

Page 6 line 122-124: We added the following criteria: “individuals were able to present themselves on the day of the interview and sufficiently physically and mentally stable to provide verbal consent to participate in the study” to participate in the study.

• Lines 154, 157, 159: As commented earlier, numbers smaller than 10 should be spelled out in words in scientific and academic writing. This is applied to the whole document.

Response: Revised accordingly.

• Line 155: Please remove ‘,’ before ‘and.’

Response: Done.

• Lines 156-161: The sentence is too long and should be broken down into 2-3 sentences.

Response: Done. (Pages 6-7 lines 124-130)

• Line 161: Please replace ‘;’ by. ‘’

Response: Done. (Page 7 line 130)

• Lines 165-169: The sentence is too long and should be broken down into 2 sentences.

Response: Done. (Page 7 lines 134-139)

9. Line 184: Please spell out NFATP if it was used for the first time in the manuscript.

Response: NFATP was spelled out in the Introduction section. (Page 4 line 66)

10. Line 192: Guess ‘outcome’ should read ‘outcome variable.’

Response: Yes - revised accordingly. (Page 8 line 161)

11. Line 197: Not sure if the word ‘free’ before ‘ART manual’ is necessary. Is the manual applied only for ‘free’ ART? I do not find it necessary to keep saying ‘free ART’ (e.g., lines 198, 201) as it brings more confusion than help. The authors may just describe in the description of the study site that the HIV center where the study was conducted provides ART and other HIV services free of charges.

Response: Thank you. On page 8 lines 167-171: The manual applied only for free-ART, the HIV center provides free ART, and other services are not free of charge. We have the manual to guide the free-ART services, listed in reference 20, and the Chinese national guideline to guide the national treatment and services for people living HIV, listed in reference 21.

12. Line 211: The use of ‘;’ before ‘and’ is incorrect.

Response: Thank you. Revised accordingly. (Page 9 line 181)

13. The NFATP only provides free CD4 and viral load testing once a year, and people living with HIV have to pay for the remaining tests. It is important to state whether the non-free tests were voluntary based on the clients’ ability to pay or compulsory as the test costs can be beyond their affordability. This may explain the relationships between inequality and socio-demographic characteristics, leaving alone other potential financial barriers (transport costs, busy working). I would suggest this point be discussed in the discussion section. This may also explain the low rate of viral load test presented in the results.

Response: Thank you for your valuable comments. We have made some revisions accordingly. (Page 9 lines 184, 188-189: the non-free tests were voluntary based on the client’s ability to pay, and test costs can be beyond their affordability. Page 24 lines 479-482: We added this point into the Discussion section.)

14. Line 256: Please use past tense in the methods section (e.g., this study used…).

Response: Done. (Page11 line 228)

15. Line 329: …using the Chi-square test.

Response: Thank you. (Page 14 line 303: SES groups were calculated and compared using the chi-square test.)

16. Line 352: Please present the median value with an interquartile range.

Response: Done. (Page 15 line 326: median age of 41.0 years (interquartile range, 32.0 to 48.0 years))

17. Line 496: WHO was already defined in the introduction’.

Response: Thanks and revised accordingly. (Page24 line 471)

18. Lines 497-498: the sentence “A study in Thailand suggested that simple and inexpensive monitoring of key biomarkers could be done at some time points” is not clear and should be further elaborated. What did the authors intend to tell – feasibility, efficacy, or else?

Response:We meant feasibility. (Page 24 lines 472-473: A study in Thailand demonstrated that the simple and inexpensive monitoring of key biomarkers was feasible at some time points)

Lines 523-524: A self-reporting measure can lead to both under- or over-reporting unless this study could prove that it was under-reporting.

Response: We cannot prove either way. (Page 26 lines 499-500: the household assets and conditions were self-reported, which might result in both under- or over-reporting of participants’ SES.)

20. Line 556: Guess Kunming does not require ‘the.’

Response: Yes, of course. Corrected.(Page 27 line 534)

21. Lines 556-559: Conclusions should summarize the key findings that respond to the research questions and objectives. The comparison of this study’s findings to the literature should be discussed in the discussion section.

Response: Thank you. Please see page 27 lines 534-537.

Lines 563-565: The sentence “Furthermore, need variables (i.e., age and sex) could not negatively contribute to all concentration indices to diminish the degree of inequalities” needs clarity as it is hard to understand.

Response: We have revised this as follows: (Page27 lines 541-544: Between the two need variables (age and sex), age contributed more to the inequalities in the utilization of all HIV continuous care. This implies that the degree of such inequalities can be reduced should comprehensive care be provided equally to people living with HIV of all age groups.)

23. References are still inconsistent and not entirely aligned with PLOS’s style and requirements. Please ensure that they have been corrected before re-submission.

Response: We have checked the references carefully and revised them accordingly. (Pages 29-33)

Submitted filename: Rebuttal letter.docx

Click here for additional data file.

23 Apr 2021

Measuring and explaining inequality of continuous care for people living with HIV receiving antiretroviral therapy in Kunming, China

PONE-D-20-28608R2

Dear Dr. Assanangkornchai,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Siyan Yi, MD, MHSc, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

30 Apr 2021

PONE-D-20-28608R2

Measuring and explaining inequality of continuous care for people living with HIV receiving antiretroviral therapy in Kunming, China

Dear Dr. Assanangkornchai:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Siyan Yi

Academic Editor

PLOS ONE