Literature Review: Addressing the Challenge of ART Attrition in South Africa: Understanding and Mitigating Loss-to-Follow-Up

INTRODUCTION

The introduction of UNAIDS' 90-90-90 targets marked a significant milestone in global efforts to combat HIV/AIDS, aiming for 90% of HIV-positive individuals to be aware of their status, 90% of those diagnosed to be on antiretroviral therapy (ART), and 90% of those on ART to achieve viral suppression. Building upon these targets, South Africa has demonstrated substantial progress, leading to the revision of these objectives to 95-95-95 (WHO, 2016). By 2018, 90% of HIV-positive individuals were aware of their status, of which 68% were receiving ART, and 87% achieved viral suppression (UNAIDS Data 2020).

The decision to implement a Universal Test and Treat (UTT) strategy in South Africa was influenced by various factors, including the WHO’s recommendation that all patients diagnosed with HIV should be initiated onto ART regardless of their CD4 cell count; findings from the HPTN052 study showing that early ART leads to a 96% reduction of sexual transmission of HIV in serodiscordant couples; and a cohort study in rural KwaZulu-Natal indicating that individual HIV risk acquisition declined substantially as ART coverage increased in the surrounding community (Takuva et al., 2017). This strategy resulted in enhanced accessibility and decentralization of HIV treatment across the country, marking a pivotal step in improving HIV care (Wilkinson et al., 2015).

However, despite these advancements, the effectiveness of ART scale-up initiatives is threatened by LTFU. The WHO has emphasized the crucial role of retaining patients on ART to realize the anticipated benefits of treatment scale-up (Fox et al., 2018). There is a universal acknowledgement that this requires the timely identification of HIV-positive individuals, their prompt initiation into ART and sustained retention in HIV care and treatment services (Carlucci et al., 2019). Thus, high rates of ART attrition threaten to diminish the positive results that the scale-up of ART could have on the population's health.

ATTRITION AND LTFU THREATEN THE EFFECTIVNESS OF ART

Research on the attrition and retention of patients on ART presents conflicting perspectives about the extent of the of these measurements. While Fox and Rosen (2015) reported that the retention rate among paediatric patients from LMIC was reflective of global rates at 85%, 81%, and 81% at 12, 24, and 36 months after ART initiation respectively, Fox et al., (2018) plausibly argue that traditional clinical cohort estimations may be underestimating retention rates (Fox & Rosen, 2015b). Yet even in their study, using the South African National Health Laboratory Service (NHLS) to account for patients moving between HIV treatment sites, they estimated a 63% retention rate across the country. This continues to contribute to a suboptimal retention rate that inhibits ART’s “treatment as prevention” (TasP) and its goals for preventing HIV-related morbidity/mortality, HIV drug resistance, and onward transmission (Makurumidze et al., 2023; Xie et al., 2022; Zürcher et al., 2017).

In a cohort study to examine the outcomes of PLHIV who were LTFU in ART programmes in Southern Africa Ballif et al., (2022) observed a higher mortality rate among PLHIV who had been on ART for less than a year and those who were LTFU for more than year. In systematic review and meta-analysis of attrition of children from low-to-middle-income countries (LMIC), attrition mostly occurred in the first six months of follow-up (Carlucci et al., 2019).  This observation corresponds with earlier systematic reviews from Fox and Rosen (2015) and Abuogi et al., (2016) in the same population and setting. Furthermore, attrition and mortality increased among older children (Abuogi, Smith, & McFarland, 2016; Fox & Rosen, 2015b). Retention rates are strikingly similar in a systematic review of adults in LMIC that saw overall adult retention rates of 83%, 74%, 68%, 64%, and 60% after 12, 24, 36, 48, and 60 months on ART, respectively (Fox & Rosen, 2015a). This emphasizes the need for strategies that rapidly trace and re-engage PLHIV who have disengaged from care.

FACTORS CONTRIBUTING TO LOSS-TO-FOLLOW-UP

Studies have identified various sociodemographic, clinical, and behavioural determinants independently associated with LTFU. While some factors, such as WHO clinical stages, comorbidities like tuberculosis (TB), and adherence to ART, are consistently implicated, there are notable differences in contributory factors between low-to-middle-income countries (LMICs) and developed nations like China (Xie et al., 2022). A review study consolidated the most frequently occurring determinants which included WHO clinical stages, comorbidities such as TB, adherence to ART and nondisclosure among other determinants (Frijters et al., 2020).

Though several scholars have suggested that long distances to clinics, costs of travel, long waiting times, stigma and discrimination can deter patients from attending appointments, there has not been a substantial exploration of LTFU factors in the context of South Africa’s healthcare system (Ballif et al., 2022). Some of these factors include undocumented local migration, the lack or slow uptake of electronic medical records, limited data exchange between public health facilities and the resultant ‘silent transfers’, which all contribute to LTFU (Ballif et al., 2022).

IMPROVING TRACING AND RETENTION STRATEGIES

The results from Ballif et al., (2022) study exhibited that the success rate of tracing was hampered by the delays between LTFU and tracing, prompting for a prioritisation of more timely tracing processes. Thus, the timely identification of at-risk individuals and rapid tracing processes can prevent LTFU or facilitate re-engagement in care.

CONCLUSION

In conclusion, while significant progress has been made in scaling up ART access and uptake in South Africa, LTFU remains a formidable obstacle to achieving optimal HIV treatment outcomes. Addressing the multifaceted factors contributing to LTFU and implementing targeted interventions are essential steps in maximizing the benefits of ART.

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References

Abuogi, L. L., Smith, C., & McFarland, E. J. (2016). Retention of HIV-Infected Children in the First 12 Months of Anti-Retroviral Therapy and Predictors of Attrition in Resource Limited Settings: A Systematic Review. PloS one, 11(6), e0156506. https://doi.org/10.1371/journal.pone.0156506

Ballif, M., Christ, M. B., Anderegg, N. T., Chammartin, F. S., Muhairwe, J., Jefferys, L., Hector, J., van Dijk, J., Vinikoor, M. J., & van Lettow, M. (2022). Tracing people living with HIV who are lost to follow-up at ART programs in Southern Africa: A sampling-based cohort study in six countries. Clinical Infectious Diseases, 74(2), 171-179.

Carlucci, J. G., Liu, Y., Clouse, K., & Vermund, S. H. (2019). Attrition of HIV-positive children from HIV services in low-and middle-income countries: a systematic review and meta-analysis. AIDS (London, England), 33(15), 2375.

Fox, M. P., Bor, J., Brennan, A. T., MacLeod, W. B., Maskew, M., Stevens, W. S., & Carmona, S. (2018). Estimating retention in HIV care accounting for patient transfers: A national laboratory cohort study in South Africa. PLoS Medicine, 15.

Fox, M. P., & Rosen, S. (2015a). Retention of Adult Patients on Antiretroviral Therapy in Low- and Middle-Income Countries: Systematic Review and Meta-analysis 2008–2013. JAIDS Journal of Acquired Immune Deficiency Syndromes, 69(1), 98-108. https://doi.org/10.1097/qai.0000000000000553

Fox, M. P., & Rosen, S. (2015b). Systematic review of retention of pediatric patients on HIV treatment in low and middle-income countries 2008–2013. Aids, 29(4), 493-502. https://doi.org/10.1097/qad.0000000000000559

Frijters, E. M., Hermans, L. E., Wensing, A. M., Devillé, W. L., Tempelman, H. A., & De Wit, J. B. (2020). Risk factors for loss to follow-up from antiretroviral therapy programmes in low-income and middle-income countries. Aids, 34(9), 1261-1288.

Makurumidze, R., Decroo, T., Jacobs, B. K. M., Rusakaniko, S., Van Damme, W., Lynen, L., & Gils, T. (2023). Attrition one year after starting antiretroviral therapy before and after the programmatic implementation of HIV “Treat All” in Sub-Saharan Africa: a systematic review and meta-analysis. BMC Infectious Diseases, 23(1). https://doi.org/10.1186/s12879-023-08551-y

Takuva, S., Brown, A. E., Pillay, Y., Delpech, V., & Puren, A. J. (2017). The continuum of HIV care in South Africa: implications for achieving the second and third UNAIDS 90-90-90 targets. Aids, 31(4), 545-552. https://doi.org/10.1097/qad.0000000000001340

Wilkinson, L. S., Skordis‐Worrall, J., Ajose, O., & Ford, N. (2015). Self‐transfer and mortality amongst adults lost to follow‐up in ART programmes in low‐and middle‐income countries: systematic review and meta‐analysis. Tropical Medicine & International Health, 20(3), 365-379.

Xie, J., Gu, J., Chen, X., Liu, C., Zhong, H., Du, P., Li, Q., Lau, J. T. F., Hao, C., Li, L., Hao, Y., & Cai, W. (2022). Baseline and Process Factors of Anti-Retroviral Therapy That Predict Loss to Follow-up Among People Living with HIV/AIDS in China: A Retrospective Cohort Study. AIDS and Behavior, 26(4), 1126-1137. https://doi.org/10.1007/s10461-021-03466-8

Zürcher, K., Mooser, A., Anderegg, N., Tymejczyk, O., Couvillon, M. J., Nash, D., Egger, M., IeDEA, & consortia, M. (2017). Outcomes of HIV‐positive patients lost to follow‐up in African treatment programmes. Tropical Medicine & International Health, 22(4), 375-387.