Introduction

In the Asia-Pacific region, the overall number of new HIV infections declined by 31% between 2000 and 2014, reaching an estimated 340,000 new infections over this 15-year period. Some countries in the region have been particularly successful in reducing the incidence rate, such as Nepal, where new infections declined by 87%, and Thailand, where a 63% decline has been achieved since 2001[1]. However, other Asian countries have experienced opposite scenarios, such as Pakistan, with an 8-fold increase, Indonesia with a 2.6-fold increase, and the Philippines, where new infections have more than doubled since 2001[1]. The AIDS response in many Asian countries is heavily dependent on donor funding and therefore highly vulnerable given the size of the population at risk. The level of dependency varies from 58% of HIV care being financed by external sources in Indonesia to more than 90% in Nepal (84% in Bangladesh, 93% in Lao Peoples’ Democratic Republic (Lao PDR), 64% in Pakistan, 60% in Philippines and 68% in Vietnam) [2].

All 7 countries included in this study: Lao PDR, Bangladesh, Indonesia, Nepal, Pakistan, Philippines and Vietnam, are experiencing concentrated epidemics, defined as having an HIV prevalence below 1% in the general population but above 5% among key populations in local areas, such as men who have sex with men (MSM), transgender (TG), sex workers, and people who inject drugs. However, some local areas, such as the remote province of Papua in Indonesia, is experiencing a generalized epidemic (HIV prevalence >1% among pregnant women attending antenatal clinics)[3]. In fact, among certain Asian key populations, e.g., 53% of people who inject drugs in Faisalabad and 15% of transgender people in the Larkana areas of Pakistan, are infected with HIV. Likewise, HIV prevalence estimates are very high in Indonesia; 56% of people who inject drugs in Jakarta and 25% of female sex workers in the Jayawijaya area are living with HIV[2].

Antiretroviral therapy (ART) services have been rapidly scaled up in the Asia-Pacific region, in turn benefiting both survival and secondary prevention. The number of people who are living with HIV (PLHIV) who receive ART increased to >4-fold in last ten years, to a regional estimate of 1.8 million in 2014. Nevertheless, treatment coverage is still low. Around 50% of PLHIV in the region who are eligible for ART receive treatment overall [1, 4], but only 6–8% of PLHIV in Indonesia and Pakistan have access to ART. Consequently, AIDS-related mortality increased rapidly in these countries over the last decade (2005–2013), with a 4-fold increase in Indonesia and a 3.5 fold increase in Pakistan [5].

Recent findings from the strategic timing of antiretroviral treatment (START) study[6] conducted at 215 sites in 35 countries, revealed that starting ART immediately rather than later (CD4 counts <350 cells/μl or at AIDS-defining illness) resulted in a 53% reduction in risk of developing serious AIDS-related events (e.g., AIDS-related cancer) or non-AIDS related events (major cardiovascular, renal and liver disease, non-AIDS cancer) and death. Earlier HIV diagnosis and linkage to care also reduced all-cause mortality by 32% among PLHIV in a study from England and Wales [7]. In a population-based study from the United States, 20% of PLHIV delayed enrollment in HIV care for more than 3 months following their HIV diagnosis [7]. The majority of PLHIV in the Asia-Pacific region are not yet tested and aware of their HIV status [5], and therefore are not only facing unnecessary and preventable HIV/AIDS-related illness, but they are also at higher risk of infecting their partners [8, 9]. Those linked to care but with poor ART adherence may also develop viral drug resistance, ultimately affect both individual and population-wide treatment outcomes[10].

The need for efficient engagement in HIV care is more evident than ever because of the expansion of earlier ART initiation and the shift towards ‘Test and Treat’[11]. In 2014, UNAIDS proposed the 90-90-90 targets, i.e., that by 2020, 90% of PLHIV will know their HIV status, 90% of PLHIV who know their HIV status will receive HIV treatment, and 90% of PLHIV on ART should be virally suppressed [11, 12]. It is estimated that three million new HIV infections and three million AIDS-related deaths could be averted if these targets are achieved [11]. To reach these targets and to optimize treatment and prevention benefits of ART, early identification of all PLHIV, optimal linkage to and retention in HIV care, and sufficient use and optimal adherence to ART to achieve viral suppression are key[13, 14].

We sought to assess factors affecting retention in HIV care at the most crucial steps in the care cascade–HIV testing, linkage to HIV care, engagement in HIV care, initiation of ART, and ART adherence—for PLHIV in 7 countries in the Asia-Pacific region that each have concentrated epidemics but varying trends and health system approaches to implement HIV prevention and treatment. We also assessed the specific health system and behavioral obstacles that need to be overcome for at least some of these countries to reach the UNAIDS 90-90-90 target, given strong and sustained national commitment combined with strengthened donor support.

Methods

Variables

The outcome variables were HIV testing, linkage to care, engagement in care, initiation of ART and ART adherence. We did not analyze the ultimate goal of HIV treatment (i.e. viral suppression) because more than 80% of our study participants from five studied countries never received a viral load test (Bangladesh 99.5%, Indonesia 81.9%, Nepal 87.8%, Philippines 92.0% and Vietnam 89.6%). HIV testing was assessed as a late presentation for HIV care (yes vs. no), which was defined as PLHIV presenting with CD4 cell count <200 cells/μl at the time of the first diagnosis of their HIV infection. Linkage to care was dichotomized as ‘timely meeting with health workers for HIV care’ (attending an appointment within 30 days of an HIV diagnosis) and timely CD4 testing (having had one or more documented CD4 tests within three months of an HIV diagnosis). Engaged in care was assessed as PLHIV who had at least one HIV medical care visit in the last 12 months. Initiation of ART was assessed as PLHIV who were eligible to take ART and also actually did receive ART. ART adherence over the past month was assessed by visual analog scale (VAS): “We would like to get your best guess about how much of your anti-HIV medication you have managed to take in the last month?” and asking the interviewee to estimate their adherence proportion (visual analog scale from 0% to 100% in 10% intervals; 0% meaning that the respondent has not taken any medication, and 100% meaning that s/he has taken every single dose) of their prescribed ART in the last month. ART adherence was later dichotomized into ≤90%: poor vs. >90%: good adherence. The VAS scale is a validated tool to measure the proportion of ART dosages taken over the last month[17]. Studies that validated VAS found that self-reported adherence to ART was consistent with electronic data and virological treatment outcome[17].

We analyzed different population and health-system level factors as independent variables (Table 1), following the theoretical framework of access to health care developed by Andersons[18] that influences the outcome variables.

Download:

• PPT
  PowerPoint slide
• PNG
  larger image
• TIFF
  original image

Table 1. Independent variables.

https://doi.org/10.1371/journal.pone.0176914.t001

Results

Fig 1 presents the study sites and the total sample sizes in each of the seven Asia-Pacific countries. In total, 7843 PLHIV were enrolled—with a mean age of 34 (6.9 SD) years of age—of which 80% identified themselves as male, 38% as female and 2.4% as transgender. The median duration on ART treatment was 3 years. Other characteristics of PLHIV are presented in Table 2.

Download:

• PPT
  PowerPoint slide
• PNG
  larger image
• TIFF
  original image

Fig 1. Study sites and sample sizes for seven countries in the Asia-Pacific region.

https://doi.org/10.1371/journal.pone.0176914.g001

Download:

• PPT
  PowerPoint slide
• PNG
  larger image
• TIFF
  original image

Table 2. Characteristics of study participants (N = 7843).

https://doi.org/10.1371/journal.pone.0176914.t002

As shown in Fig 2, four out of every 10 PLHIV presented late for HIV care. Of those diagnosed with HIV, 73% made an appointment with a health worker within 30 days of their diagnosis, but only 49% had a CD4 test done within 3 months of diagnosis. Among PLHIV, engagement in HIV care (87%; 6846/7836) and ART initiation (96%; 5946/6192) was high. Good ART adherence was reported by an average of 78% (4639/5927) across the seven countries. The outcomes of interest varied considerably in the seven countries studied especially late presentation for HIV care, timely appointment with a health worker for HIV care, having had a timely CD4 test, and ART adherence) but variation in the proportion of PLHIV engaged in HIV care and ART initiation was not significant (Table 3).

Download:

• PPT
  PowerPoint slide
• PNG
  larger image
• TIFF
  original image

Fig 2. HIV testing, linkage to care, engaged in care, ART initiation and ART adherence among PLHIV in seven countries of the Asia-Pacific region.

https://doi.org/10.1371/journal.pone.0176914.g002

Download:

• PPT
  PowerPoint slide
• PNG
  larger image
• TIFF
  original image

Table 3. HIV testing, linkage to care, engaged in care, ART initiation and ART adherence among PLHIV by country.

https://doi.org/10.1371/journal.pone.0176914.t003

HIV testing: PLHIV presenting with CD4 cell count <200 cells/μl at time HIV diagnosis

As shown in Fig 3, those who identified as transgender and also were living with HIV had a significantly higher risk of presenting late for HIV care. Being a refugee/ asylum seeker/ or internally displaced and living with HIV was negatively associated with presenting late for HIV care. Young PLHIV (age ≤ 24 years) had a significantly lower risk of presenting late for HIV care. Different characteristics of PLHIV (past vs. current alcohol user, good vs. poor HIV treatment literacy, and place of HIV diagnosis (government hospital/ voluntary counselling center in public hospital vs. private hospital) was positively associated with presenting late for HIV care, whereas lacking formal education and health insurance were significantly and negatively associated. There was a marginally significant positive association between living area (rural/small town vs. urban) and late presentation for HIV care.

Download:

• PPT
  PowerPoint slide
• PNG
  larger image
• TIFF
  original image

Fig 3. Factors associated with late presentation for HIV care and linkage to care (health workers) among people living with HIV in seven countries of the Asia-Pacific region.

¥ coefficients of factors of late presentation for HIV care and linkage to care based on generalized structural equation model (GSEM) * p ≤ .05; ** p < .01; *** p < .001; ^ap = 0.083; ^b 0.073; ^cp = 0.084.

https://doi.org/10.1371/journal.pone.0176914.g003

Timely linkage to HIV care: Timely appointment with health workers for HIV care and/ or having a timely CD4 test performed

As shown in Figs 3 and 4, being a current and/or past injecting drug user was significantly and negatively associated with timely linkage to HIV care. PLHIV who perceived their own health status as poor, and those who felt uncertain about whether or not their HIV-related medical records were kept confidential at the clinic/ hospital they were visiting, had a significantly lower chance of linking up to HIV care on time. In contrast, PLHIV who reported that a doctor had referred them for HIV testing were significantly more likely to meet with health workers for HIV care in a timely manner and to have a timely CD4 assessment. PLHIV who reported marriage preparations or that they were going overseas to work as a reason for taking an HIV test, as well as those who were injecting drugs users, had a significantly lower likelihood of receiving a timely CD4 assessment.

Download:

• PPT
  PowerPoint slide
• PNG
  larger image
• TIFF
  original image

Fig 4. Factors associated with linkage to care (CD4 test) and engagement in care among people living with HIV in seven countries of the Asia-Pacific region.

¥ coefficients of factors of engagement in care, retention in care and poor ART adherence, based on generalized structural equation model (GSEM). * p ≤ .05; ** p < .01; ^ap = .075.

https://doi.org/10.1371/journal.pone.0176914.g004

ART initiation: PLHIV eligible for ART who also were started on ART

As shown in Fig 5, PLHIV with good HIV treatment literacy, as well as those diagnosed with tuberculosis after HIV infection, had a significantly higher chance to initiate ART. On the other hand, PLHIV ≤ 24 years, female sex workers and PLHIV without health insurance all had a significantly lower chance to initiate ART.

Download:

• PPT
  PowerPoint slide
• PNG
  larger image
• TIFF
  original image

Fig 5. Factors associated with ART initiation and poor ART adherence among people living with HIV in seven countries of the Asia-Pacific region.

¥ coefficients of factors of engagement in care, retention in care and poor ART adherence, based on generalized structural equation model (GSEM). * p ≤ .05; ** p < .01.

https://doi.org/10.1371/journal.pone.0176914.g005

Discussion

We studied barriers and facilitators for uptake and retention in the HIV care cascade among 7843 PLHIV in seven countries in the Asia-Pacific Region. We found that lack of timely HIV diagnosis and poor linkage to care, including having a timely CD4 test assessment, are two major barriers to HIV care in this region. However, the proportions of PLHIV in other key steps of the HIV care continuum such as engagement in care and ART initiation (but not ART adherence) were above or close to the global 90-90-90 targets [11]. However, evidence suggests that progress in any single step of the HIV care cascade only has minimal impact on the overall goal, i.e., on increasing the high proportion of PLHIV with viral suppression [13]. Improved uptake and retention across all steps of the HIV care cascade are necessary; otherwise, multiple, serial barriers at each step of the cascade can hinder participation in subsequent steps[13]. Consistent with previous studies[19–27], we identified several population and health-system level barriers and facilitators of the HIV care continuum.

In our study, PLHIV who belonged to key populations (people who inject drugs, transgender, female sex workers, and prisoners), were less likely to be retained in HIV care, which is consistent with previous study findings [7, 19–22]. Different reasons have been reported for poor retention in HIV care among key populations, such as internalized stigma related to sex work and sexual orientation, discrimination, sex work environment, criminalization of risk behaviors (injecting drug use and sex work), and negative attitudes towards HIV treatment [20–22, 28, 29]. An American study found that transgender women living with HIV were less likely to be retained in HIV care because they prioritized hormone therapy and had concerns about adverse interactions between ART and hormone therapy [21]. Growing evidence suggests that the use of hormones without medical supervision is common among transgender in Asia [30] but its association with the HIV care continuum in those living with HIV is unexplored.

In the Asia-Pacific region, HIV prevalence rates vary between 10% in China and 20% in Vietnam among prisoners who inject drugs [31]. Sharing of contaminated injecting equipment and unprotected sex in prison settings makes prisoners a key population for HIV infection[28]. Poor quality HIV services and the transient nature of prisoners [32] often leads to poor ART access, adherence and retention in care. However, HIV management education in prison, as well as individual needs assessment and transportation assistance after release, are active interventions that could increase retention in HIV care among detainees[33].

Since 2005, the global scale-up of ART has contributed to a 35% reduction in overall HIV-related mortality. However, actions to reach young people have not been successful enough. AIDS mortality rates increased by 50% from 2005 to 2012 among young and adolescents worldwide [23]. Similar to previous research, our study also found that although young PLHIV (18–24 years of age) are more likely to ‘seek’ and ‘test’, they are less likely to engage in and retain HIV care [14, 19, 24, 34, 35]. ART adherence was also poorer among younger as compared to older PLHIV (aged ≥25). A recent review found individual and environmental barriers (stigma, discrimination, depression, lack of social support and lack of ‘youth-centered’ services) for adherence to and retention in care among young people and adolescents living with HIV [23].

Our findings suggest that PLHIV who were referred by a health worker for HIV testing due to suspected HIV-related symptoms were more likely to link to HIV care on time. This contrasts with previous findings from generalized epidemic suggesting that PLHIV who have self-referred for HIV testing are more likely to be linked to HIV care than are PLHIV referred by a health worker[36]. Our study also found that PLHIV who went for HIV testing in preparation for marriage or because they planned to work overseas, were less likely to be linked to HIV care. In consistent with findings of other study, those who test positive without actively wanting to be tested for HIV (and who do not have any HIV-related symptoms) are less likely to be linked to HIV care because they are less prepared for an HIV diagnosis, and less motivated [37]. In our study, self-reported poor health status was significantly and negatively associated with linkage to HIV care. PLHIV can avoid seeking care despite self-perceived poor health status because of multiple barriers and competing urgencies such as stigma, abuse from providers and risk of losing income[38].

Over the last five decades, the oil business and infrastructure development in the Gulf Cooperation Council countries has led to massive migration movements of unskilled workers (mainly male) from the Asia-Pacific region [39]. Migrant workers undergo mandatory HIV screening annually to renew their work permit [40] and get deported if they test HIV-positive without being linked to HIV care in most of these Gulf countries. Implementation of such discriminatory policies is a missed opportunity to catch and link migrant labourers to HIV care, but migrating for work is also an important barrier for linkage and retention in HIV care in the home countries [25].

Participants in our study who were diagnosed with HIV at government hospitals or public voluntary counseling and testing centers were more likely to present late for HIV care than those diagnosed at a private hospital. This supports findings from a multi-country analysis showing that individuals with higher household income were more likely to seek private sector HIV testing and care[41]. People with low socioeconomic status usually seek health service from the public sector because it costs significantly less than a private hospital. They are also less likely to seek health services and to present late for care because they cannot pay.

In our study, PLHIV not enrolled in any health insurance program were more likely to seek HIV testing but less likely to engage in HIV care and initiate ART. Enrollment in any health insurance program was lower in Indonesia (39%) and Vietnam (40%) than in the Philippines (85%) (data not shown). Insurance that covers health care among PLHIV does not exist in Nepal and Bangladesh. In Pakistan, PLHIV can enroll in a health insurance program, but detailed data is not available about coverage or impact on accessing health care among PLHIV.

None of our study participants from Lao PDR had enrolled in the available health insurance program. Four countries (Indonesia, Vietnam, Philippines and Lao PDR) provide antiretroviral drugs and CD4 cell count tests free of charge, and have social protection programs (Asuransi Kesehatan untuk Keluarga Miskin–Askeskin in Indonesia; Community-Based Health Insurance in Lao PDR; PhilHealth in Philippines; and Vietnamese Social Security Social Health Insurance Program). These programs prioritize health care and other services (monthly cash allowance for daily necessities and common drug provision) among PLHIV. However, studies conducted in Indonesia, Lao PDR and Vietnam found that PLHIV experiences a catastrophic financial burden while seeking HIV/AIDS-related health services which are not covered by social protection programs, such as viral load tests, hospital admission fees or diagnosis and treatment of comorbid diseases[3, 42, 43]. Serious loopholes also exist in available social protection programs, for example, Indonesian PLHIV who not yet are eligible for ART, need to pay for HIV care[3]. The coverage of social protection programs is also limited because of barriers such as lengthy administrative processes (to obtain an identification card and certificate of poverty), unclear procedures, and lack awareness about available social protection services among PLHIV[43–45].

Consistent with previous literature[26], our study found that PLHIV living in rural/small town were more likely to present late for HIV care than their urban counterparts. The most frequently reported barriers to HIV care were long distances to the health center, a shortage of health workers, a lack of access to transportation and community stigma toward PLHIV in the community [26].

PLHIV in our study who reported fear of confidentiality breach by health workers in relation to their HIV-related medical records were less likely to make timely appointments for HIV care. Nine percent of the PLHIV in our study reported that health workers disclosed their HIV status to others without their consent (widely differ between study countries). A study from Bangladesh found that 80% of the nurses and 90% of the physicians behaved discriminatory towards PLHIV[46]. Despite the adoption of guidelines to protect the human rights of PLHIV by different Asian countries, fear of a confidentiality breach is still frequently reported as a barrier for seeking HIV care [27, 47].

PLHIV with no formal education in our study were more likely to seek HIV testing and care, findings consistent with those in a previous study in which low literacy level was associated with acceptability of HIV testing in a health care setting[48]. Factors like trust and dependence on health workers may influence the association we observed between literacy level and acceptability of HIV testing. PLHIV with good HIV treatment literacy in our study were more likely to initiate HIV care than those with poor literacy. Knowledge of ART and what taking it would mean may encourage PLHIV to retain HIV care despite presenting late for it initially.

Prevalence of TB/HIV co-infection is slowly emerging in the Asia-Pacific region; estimated prevalence is 17.2%[49]. Five of the countries we studied (Bangladesh, Indonesia, Pakistan, Philippines and Vietnam) are on the list of 22 ‘high TB burden’ countries that accounted for 82% of all estimated cases in the world [49]. An encouraging finding of our study was that PLHIV who had co-infection with TB were more likely to initiate ART. Studies suggest that TB-related deaths among PLHIV have declined significantly in the Asia-Pacific region since 2004, in some countries, mortality rates have more than halved[49]. Despite this progress, access to HIV testing among TB patients in Asia ranges from 1–2% in Bangladesh and Indonesia to 100% in Bhutan and Brunei[49].

Consistent with previous studies [38, 50], we found that PLHIV who were satisfied with the information provided by their health worker were more likely to adhere to ART. Good communication between client and provider helps clients fully understand the CD4 level and the importance of adhering to ART, which ultimately foster adherences [38]. Alcohol consumption is associated with poor ART adherence and also negatively affects the survival of PLHIV through different pathways (e.g. alcohol-induced immunosuppression that exacerbates the HIV related immunosuppression which increased hepatotoxicity)[51]. A quarter of our study participants were current alcohol users, and this behavior was also associated with poor ART adherence in the past month.

In our study, 21% of PLHIV were not eligible for ART (based on CD4 cell count during this study period), and we did not analyze engagement in HIV care among PLHIV who were not eligible for ART. Retention in pre-ART care is poor in many settings. For example, only 49% of PLHIV in South Africa with an initial CD4 cell count above > 200 cells/μl returned for CD4 testing within the next 13 months [52]. Similarly, PLHIV not eligible for ART were 3.4-fold less likely to retain in HIV care than patients with lower CD4 counts in Western Kenya [52].

Some limitations of this study need to be considered. The cross-sectional nature of data limits our ability to estimate the number of PLHIV retained in HIV care over time after initiation of ART and its associated factors. The purposive sampling technique might overestimate some of the country-specific outcomes of interest (ART initiation) if PLHIV participated in our study differ from those PLHIV who were missed during enrollment or refused to participate in our study. For example, the outcome of interest (ART initiation) is overestimated if PLHIV who took part in our study were more aware of HIV care services because of their association with national HIV support networks than those PLHIV who were not in touch with a national network. Different studies found that the key populations (either HIV-positive or HIV-negative) experience a high burden of psychosocial health problems (depression, suicidality)[53–55] and growing evidence also suggest that suicidality associated with less likely to engage in HIV care [56]. Our study does not assess the burden of psychosocial health problems and its association with HIV care continuum.

In summary, our study to assess factors affecting participation in the HIV treatment cascade among PLHIV in the Asia-Pacific Region showed a high proportion of PLHIV presented late for HIV care and delayed linkage to care. Despite this, their participation in the other steps of the HIV care cascade (engaged in and retention in HIV care/ART adherence) was encouraging. A large study (named SEARCH) implemented in rural Kenya and Uganda has already exceeded UNAIDS targets of 90-90-90 (for example estimate is above 90%) [57]. SEARCH study provided a comprehensive package (appointment reminders, quarterly visits with patient-centered care providing reduced waiting and overall visit duration) to increase demand for testing, improve treatment initiation, linkage to care and retention in HIV care. The effectiveness of similar interventions needs to be evaluated in the Asia-Pacific region. We also identified several population (young PLHIV, HIV treatment literacy, health insurance) and health system (confidential handling of HIV-related records) facilitators and barriers that need to be addressed to improve outcomes along the HIV care cascade in the study countries.

Supporting information

Acknowledgments

We are very grateful to Pamela Derish for editing this article. Above all, we would like to thank the people living with HIV who agreed to participate in this study. We also wish to thank "CAT-S group members: Asghar Satti, Association of People Living with HIV Pakistan; Basanta Chetteri, National Association of PHILV Nepal; Jun Orena (Noel), Pinoy Plus Association Philippines; Khamla Thidavanh, Association of People Living with HIV/AIDS Lao People’s Democratic Republic; Laura Milette, Jaringan Gaya Warna Lentera (Jaringan GWL-INA), Indonesia; Mohammed Sharif, Ashar Alo Society Bangladesh; and Nguyen Hien, Vietnam Network of People Living with HIV” for making this project possible. The lead author for this group is Sushil Koirala (Email: sushil@apnmata.org).