Background
Life-long antiretroviral therapy (ART) that requires consistent access to medications and supportive services is a challenge in conflict-affected settings. By the end of 2013, 172 million people were affected by violent conflict worldwide, while 51.2 million people were forcibly displaced as a result of conflict, persecution, generalized violence, and human rights violations [
1,
2]. Of these, 16.7 million were classified as refugees who had crossed an international border to escape a well-founded fear of persecution in the absence of protection in their home country. International humanitarian and refugee law suggest that refugees should receive an equivalent standard of medical care to host nationals in countries where they have sought protection [
3]. In many settings, refugees and host nationals receive HIV services from the same facilities. An equivalent standard of HIV care should result in similar treatment outcomes. Few studies, however, have sought to rigorously compare HIV treatment outcomes between refugee and host national groups. Previous work has shown high levels of adherence to ART, increases in CD4 counts, and increases in survival among confict-affected populations [
4,
5]. In a study comparing urban refugees situated in Kuala Lumpur with Malaysian host nationals, we found comparable levels of viral suppression [
6]. Refugees, however, live in a variety of settings (e.g., camps, cities, etc.), and it is not known how these different environments might influence their HIV treatment outcomes [
7]. Better data will help governments and humanitarian agencies improve ART delivery, while retaining more people along the HIV cascade of care [
8]. We report on a repeated cross-sectional study of adherence and viral suppression among refugees and host nationals accessing ART in Kakuma Refugee Camp, Kenya, pre- and post- a remedial intervention that responded to poor baseline levels of viral suppression. Our aim was to compare viral suppression and adherence to ART among refugees and host nationals and to identify factors associated with viral suppression.
Discussion
In this study, the first of its kind to compare adherence to ART and viral suppression among refugees and host nationals who accessed ART from a refugee camp clinic, we found unacceptably low proportions of viral suppression within both groups. Among those on treatment for ≥25 weeks in the Round One survey, only 50% had a viral load of <5000 copies/mL. There was weak evidence that refugees had attained a better viral response when compared with host nationals in the Round One survey (p = 0.10); however, in the final multivariable model refugee status was not associated with viral suppression. Proportions suppressed within each group were also similar in Round Two.
Although improved in
Round Two, proportions virologically suppressed continued to be unacceptably low in relation to other resource-limited settings [
18‐
20]. Although virologic data from conflict-affected populations are sparse, a South African study found that foreigners had improved chances of viral suppression when compared with locals [
21]. In Kuala Lumpur, Malaysia, high proportions of refugees and host nationals were virologically suppressed (81% v. 84%,
p = 0.54) [
6]. Strong outcomes among refugees as measured by survival, CD4 counts and adherence were found in other conflict-affected settings [
22‐
24]. In the present study, the overall proportion suppressed was lower in comparison to findings from a meta-analysis of 89 studies of sub-Saharan African HIV treatment programs that reported 67% viral suppression after 12 months of ART [
25].
In the present study, with the exception of host national self-reports over the past month, mean adherence in Round One using any measurement was >85%. When assessing these findings in relation to viral response and leaving the possibility of drug resistance aside, it is advisable that more sensitive measures of adherence be used for monitoring purposes, especially where laboratory monitoring is intermittent or unavailable. Notably, self-reported dosing, which was defined as an incorrect self-report of dosing schedule when compared with routine dosing schedules, was associated with lack of viral suppression. As ART tablets were distributed in small bags with non-standardized, handwritten dosing instructions, prescribed changes in the dosing or regimen may not have been understood. Improvements in Round Two outcomes suggested that basic program infrastructure, including supportive services, may have been lacking.
The effect of longer duration between HIV diagnosis and ART start on viral suppression (AOR: 3.98, 95% CI 1.44, 11.01;
p-trend = 0.006) could have been related to effective patient monitoring that enabled better preparedness for ART when initiated in the home country or in the refugee camp setting. A shorter duration between diagnosis and initiation may signal a lack of engagement with health services. In other settings, delayed ART initiation was shown to be a barrier to retention in care [
26,
27].
In drug resistance testing, 64% of successful amplifications exhibited resistance mutations. Assuming conservatively that the six unsuccessful amplifications tested negative, 45% of samples would still have exhibited major resistance mutations. This suggests that drug resistance may be a serious problem within this population. In 2011, eight years after ART roll-out in East Africa, the estimated prevalence of drug resistance among ART-naive individuals was 7.4% and was increasing by 29% per year [
28]. In two contrasting Kenyan studies, the prevalence of transmitted resistance between 2008 and 2010 was 1.1% in a rural setting and 13.2% in an urban setting [
29,
30]. Higher levels of drug resistance in our study population could have been linked to a history of treatment interruptions before, during, or after displacement, but prior to the self-reported recall period used to assess adherence in our survey. This could help to explain the discordance we detected between adherence and viral suppression, whereby proportions suppressed were much lower than what adherence levels would suggest. Early-warning indicators for drug resistance in African settings depend on prescribing practices, patient retention, continuity of drug supply, and viral suppression; therefore, effective patient monitoring is critical when drug resistance testing is not routinely available [
31,
32].
Some important factors were not assessed in this study. These included the effects of very high viral loads at ART start, reduced potency of medications resulting from hot storage conditions, and acute malnutrition. Very high viral loads (≥100,000 copies/mL) are associated with a lower likelihood of ever achieving viral suppression [
33]. Since viral load testing had not previously been implemented among this population, it was not possible to evaluate this possibility. In
Round One, however, 15% (24/159) had a viral load in excess of 100,000 copies/mL. Although we did not measure acute malnutrition quantitatively, in accompanying qualitative work many clients reported that they were food insecure and believed that ART was toxic when taken without sufficient food [
34]. Associations between food insecurity, viral load and mortality have been reported in other populations [
35,
36] and are thought to be mediated by drug absorption and adherence [
37‐
40]. Future studies conducted in refugee settings should use a sensitive measure of food insecurity to assess its true impact. Finally, we did not test the potency of medications, therefore any impact of storage conditions on potency could not be determined. The average annual temperature in Kakuma is 28 °C and can reach 40 °C or more in the dry season. The medications were stored in an indoor room that was not air conditioned.
This study had several limitations. Adherence self-reports may have suffered from recall and/or social desirability biases. As the host national community were primarily Turkana, a highly mobile group, findings may not be generalizable to other Kenyan host nationals. Bias may have been introduced to our comparisons of refugees and host nationals if a local clinic at Kakuma Mission Hospital had served healthier HIV-positive Kenyans. We could not assess this bias as we did not study this clinic. Risk factors were not assessed in
Round Two due to a lack of resources to implement a follow-up survey questionnaire. Differences in mobility between refugees and host nationals may have introduced bias if one group had been less likely to participate in
Round Two [
41,
42]. If this had resulted in a lower likelihood of refilling prescriptions, for example, viral suppression could have been overestimated in one group compared with the other. The fact that few clients in
Round Two had travelled for at least one consecutive month in the year prior to the study when compared with those who participated only in
Round One, suggested that the
Round Two cohort was more stable. Interestingly, the
Round Two cohort included a greater proportion of host nationals who had travelled outside of the camp for one month or more in the year prior to the study, yet fewer were virologically suppressed in comparison to the refugee group. Although the overall
n was small, a notable strength of the study was its relative completeness as 85% of all eligible clients were initially recruited. Strong efforts were made to mitigate recall and social desirability biases by conducting face-to-face interviews with well-trained local researchers. As Kakuma was founded in 1992, this setting was relatively stable and, arguably not generalizable to other acute humanitarian settings; however, recent but periodic influxes of refugees due to the intensification of conflicts in South Sudan and Somalia suggest that this stability was unreliable. Given that refugee settings around the world are often protracted, these findings might inform other, relatively stable refugee camp settings.
Conclusions
In summary, unacceptably low proportions of refugees and host nationals were virologically suppressed in cross-sectional surveys conducted at two time-points. A remedial intervention that strengthened clinic procedures and adherence support between the surveys may have helped to improve outcomes; however, this finding was tentative given attrition between survey rounds. The proportions suppressed at <5000 copies/mL in
Round Two were still unacceptably low, and drug resistance mutations were found in a high proportion of those who were not suppressed. Overall, there were only minor differences between refugees and host nationals across outcome measures, suggesting that socio-structural factors operating at the clinic level, not refugee status, were the best explanation for observed levels of viral suppression. Future work should evaluate interventions to improve adherence counseling, monitoring, and viral suppression across the range of settings where refugees and host nationals share HIV services, including acute and longer-term humanitarian settings and settings located outside of formal encampments. Within the framework of a public health approach to ART focused on increasing levels of viral suppression by retaining patients across the HIV cascade of care, these results have highlighted the importance of laboratory and counseling services for vulnerable populations who access services in remote settings. Given that early detection of treatment failures can prevent drug resistance [
43] and consistent viral suppression limits onward HIV transmission [
44], routine viral load testing using dried blood spots and/or point of care devices should be adopted in view of the potential long-term benefits. This study serves as a clear reminder that programs operating in remote settings should monitor performance carefully in an effort to maintain consistently high levels of viral suppression.
Acknowledgements
The authors wish to thank the study participants, the research team, the local and refugee home-based care teams, the HIV Comprehensive Care Clinic staff, and the International Rescue Committee for their tremendous support. We acknowledge Neal Alexander who provided statistical advice and Nadine Cornier who provided assistance with study implementation. Thanks to Clayton Anyongo and Frank Angira for comments on a previous draft. The authors acknowledge the National Council for Science and Technology of Kenya and the Kenya Medical Research Institute for granting permissions to conduct this work.