Is Forced Migration a Barrier to Treatment Success? Similar HIV Treatment Outcomes Among Refugees and a Surrounding Host Community in Kuala Lumpur, Malaysia

In this study, the first we are aware of that investigated adherence and treatment outcomes by comparing refugees with a host community in an asylum setting, a minority of both refugee (19 %) and host community clients (16 %) on HAART for ≥25 weeks did not achieve viral suppression. Only minor differences were found on self-reported and pharmacy-based adherence measures. Adherence and virological outcomes were comparable to results from other Asian HIV clinics. In a multicentre prospective cohort carried out in 17 Asian settings, Oyomopito and colleagues found that 17 % were not virologically suppressed after 12 months on HAART [16]. We are aware of only one other report of virological outcomes among forcibly displaced or conflict-affected groups situated in low and middle-income settings [17]. In a South African study, 24 % of “foreigners”, many of whom had emigrated from Zimbabwe but who were not explicitly identified as refugees, exhibited a study-specific measure of viral failure that included individuals with a viral load of ≥1000 copies/mL. Previous adherence data collected among other groups in low and middle-income settings have shown results that are consistent with other stable cohorts. In conflict-affected northern Uganda, Kiboneka and colleagues [18] found adherence levels of <95 % in 8 % of internally-displaced persons (IDP), as measured by a composite adherence score. In a Ugandan cross-sectional study of IDPs, mean self-reported adherence was 99.5 % [19]. In the western Equatorial province of Sudan, 12 % of refugees and IDPs on HAART for ≥6 months self-reported <95 % adherence [20]. During active conflict in the Democratic Republic of the Congo, sub-optimal adherence (measured by pill counts) was found in only 1 % of clients while CD4 gain at six months was similar to other stable cohorts [21].

Given the potential for cross-border displacement to increase the vulnerability of refugees to inferior outcomes, it was reassuring that a high proportion of refugees were virologically suppressed in the present study. In multivariable analyses, no independent association was found between refugee status and unsuppressed viral load after adjusting for age, sex, time on HAART, time from diagnosis to HAART start, temporary migration in the past year and time to clinic. Consistent with evidence from a Canadian setting showing an adverse impact of temporary migration [22], travel outside of current residence for ≥1 month in the past year (reported by 18 % of refugees and 14 % of Malaysians) led to a fourfold increase in the odds of unsuppressed viral load, a possible consequence of difficulties locating or refilling medications when personal stocks were depleted in the absence of contingency plans while away. Consistent with other settings, longer travel times to clinic (≥1 h) were linked to an increase in the odds of unsuppressed viral load [23‐25]. By contrast, many of the obstacles thought to adversely affect treatment outcomes among refugees such as language barriers, unemployment and instability were either not associated with the outcome or were not unique to refugees. Specifically, there was no evidence for an adverse effect of employment status or language group. Language barriers may have been overcome by the effective use of interpreters and support counsellors recruited directly from refugee communities. We did not study onwards displacement to other countries directly; however, the average length of stay for an HIV-positive refugee (3.7 years) was generally indicative of stability. The finding that temporary migration (for ≥1 continuous month in the past year) was a risk factor after adjusting for refugee status suggested that this was common to the full study group. Longer times between diagnosis and HAART start were protective, even though starting HAART at a higher CD4 counts is known to reduce mortality [26]. Longer lead-in times to routine treatment may have facilitated treatment readiness while the negative impact of delaying treatment may have been confounded by delays between seroconversion and diagnosis. Specifically, clients may have started HAART during acute illness when they were motivated to get well by adhering to treatment.

The finding that women were more likely to have achieved viral suppression could have been due to gender differences in proportions disclosing their status to partners (49 % of males vs 66 % of females, p = 0.05) and in proportions with children (40 % of males vs 61 % of females, p = 0.004). Non-disclosure of HIV status has previously been shown to affect adherence [27], while having children may provide earlier pathways to care through antenatal screening [28]. The better outcomes observed among women were consistent with results from a Chinese study [29] and a South African study that showed a tendency for men to present for treatment later and with more advanced disease [30].

Sub-optimal pharmacy refill adherence was strongly associated with lack of viral suppression, supporting the usefulness of this measure for routine monitoring especially where viral load measurement is unavailable [31, 32]. The slightly higher proportion of Malaysians not adhering optimally to the pharmacy claim schedule may have been an artefact of a system that facilitated occasional or supplementary medication collection from external pharmacies (refugees did not have similar opportunities). One-sixth of host community clients reported collecting drugs in this manner within the assessed pharmacy refill period. Multiple routine adherence indicators could help to facilitate accurate monitoring of adherence patterns over time [33].

Caution must be used when generalising these findings to other refugee populations given that only one setting was studied and HAART delivery systems are so often setting-specific. The HIV-positive caseload among refugees was considerably higher in Malaysia in comparison to other major programs in the region (ten cases each in Bangkok and New Delhi). Moreover, there are differences between refugee settings (e.g. urban, rural, dispersed, and camp) in relation to service-provision challenges [34]. Socioeconomic differences between different refugee settings may be partially mitigated by individual financial assistance (distributed by UNHCR and assessed at the country-level). As with other studies that have compared different clinical settings within one national program [35], the clinic setting itself may be the primary consideration. In the present setting, the access that refugees had to HIV services from a leading reference hospital was unusual in comparison to rural, dispersed or camp-based refugee groups. As laboratory monitoring for refugees is implemented according to national protocols, any differences in access to these services among refugees ought to have been similar to routine differences between countries.

Factors identified from these data will help to locate those who might benefit from targeted interventions. To this end, additional counselling for men on HAART, support for those HAART clients who spend lengthy periods in transit to access treatment and care, and those who do not consistently refill their HAART prescriptions as monitored by the pharmacy, could prove to be beneficial. Risk assessments for clients who may travel for extended periods could be implemented to ensure that consistent medication supply is available and contingency plans are in place. Use of mobile phones, either through training in using personal alarms, or more actively through a text-message intervention, may help to address some of these challenges [36, 37]. Given the importance of the pharmacy-based adherence assessment, this measure should be formalised as a routine adherence indicator, linked to medical records, and monitored. When the reported result is poor, this should alert providers and trigger more advanced and expensive testing (e.g. viral loads).

This study had important limitations. Selection bias in the host community group may have affected our findings as response rates were high in both groups, but slightly lower in the host community. Moreover, the recruited host community sample represented 6 % of the target population. As non-participants may have possessed characteristics leading to bias, we compared routine socio-demographic indicators of the study sample with a simple random sample of 150 host community clients drawn from the clinic database. The random sample was statistically similar to the study sample on all socio-demographic indicators with the exception that ethnic Chinese clients were over-represented in the study sample. This could have introduced bias as ethnic Chinese Malaysians tend to have higher household incomes than other ethnic groups in Malaysia [38]. Given that refugees only had routine access to the clinic one day per week, we accounted for the possibility that routine appointments may not have occurred during the study period by making additional efforts (by telephone and/or community representative) to contact refugees who had not been seen in the clinic two weeks prior to the close of recruitment. This procedure facilitated a near-complete sample, while potentially introducing bias linked to these more intensive recruitment efforts that were not similarly implemented among the host community. The cross-sectional design of the study limited our ability to draw any firm causal conclusions, and to accurately measure and classify longer-term viral suppression and adherence [39]. Lastly, as only a single study viral load sample was collected, outcomes may have been subject to sporadic viral escape, or “viral blips” leading to misclassification of the outcome [40‐42]. Using ≥500 copies/mL as indicator of viral rebound [43], we compared results in the 40–499 copies/mL range among clients for whom the previous routine viral load was suppressed with those for whom it was not, and found no evidence for differences between groups (Table 2).

This study excluded asylum-seekers who began HAART in their country of origin and who may have been vulnerable to inferior outcomes given the possibility that their HAART was exhausted prior to gaining refugee status and becoming eligible for the national treatment program. These cases were routinely expedited and programs should continue to facilitate and improve pathways to treatment for asylum-seekers. Strengths of the study included detailed adherence assessment using self-report and pharmacy claim measures in accordance with best-practices [33], collection of blood samples using routine phlebotomy, analysis of samples conducted in an independent laboratory on a reliable platform, effective quality control, and the use of well-trained local research staff.

In summary, the high proportion of refugee and host community clients attending this public sector clinic who achieved viral suppression supports the notion that providing HAART to these groups on an equitable basis in this urban setting is both feasible and beneficial. Given the current global reduction of funding for HIV, the future sustainability of HAART for refugees needs to be critically assessed. The Malaysian national program fully subsidises first-line treatments for refugees; however, second-line treatments and virological monitoring are paid for by UNHCR. The concern is that national treatment programs that currently include refugees may opt to exclude them in the future if funding continues to decline. If the goal of universal access to treatment is to be reached and the public health benefits of antiretroviral therapy are to be realised, refugees and other conflict-affected persons must be fully included in country and regional proposals and planning for HIV and AIDS.