Author: Monika Müller
Position: Medical student
Institution: Institute of Social and Preventive Medicine, University of Bern, Switzerland
E-mail: mmueller@ispm.unibe.ch
Additional Authors: Andrew Boulle (Infectious Disease Epidemiology Unit, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa), Martin Brinkhof (Institute of Social & Preventive Medicine (ISPM), University of Bern, Switzerland), Matthias Egger (Institute of Social & Preventive Medicine (ISPM), University of Bern, Switzerland)
Submitted Date: November 27, 2007
Published Date: November 28, 2007
This comment was originally posted as a “Reader Response” on the publication date indicated above. All Reader Responses are now available as comments.

We read the meta-analysis by Rosen et al on patient retention in antiretroviral therapy (ART) programmes in sub-Saharan Africa with interest [1].

We are involved in the ART in Lower Income Countries (ART-LINC) collaboration [2], a network of treatment programsme, mainly from sub-Saharan Africa, many of whom were included by Rosen et al. Based on weighted averages, the authors conclude that "African ART programs are retaining about 60 per cent of their patients in the first two years" [1]. We have several concerns.

Rosen et al "accepted the varying definitions of loss to follow-up used by the respective studies" [1]. However, of the 33 studies included, 16 did not provide a definition for loss to follow-up. Among the studies that did, definitions included missing two visits, no visit for 1 month, 2 months, 3 months or 6 months as well as leaving an insurance scheme. This is important: in the Khayelitsha cohort, for example, estimated cumulative loss to follow-up at 2 years was 11.1 per cent with the 6-month compared to 13.4 per cent with the 3-month and 31.4 per cent with the 1-month definition. The linear interpolation and extrapolation of results is also problematic: loss to follow-up occurs at a considerably higher rate in the first months after ART initiation [2,3]. Also, retention rates will have been affected by the eligibility criteria for ART. The high retention in an early analysis of the Khayelitsha cohort [4] ("South Africa 3" in Rosen et al) is not surprising, considering that patients were required to nominate a person to assist with adherence and that patients were visited in their home to verify environment and disclosure. Attendance, on time, for at least three previous appointments was also required [4]. These stringent criteria are no longer in place in Khayelitsha. Finally, reliable assessments of programme retention depend on the tracing of patients not returning to the clinic to find out whether they died or transferred to another programme [2]. In Rosen et al, 10 of 33 ART programmes reported that patients lost to follow-up were actively traced and information on transfers out were available for 12 programs only [1].

Loss to programme and retention are important issues in treatment programmes in low-income settings and we commend Rosen et al for drawing attention to them. However, the heterogeneous nature of study populations, definitions and reporting means that combining results will produce misleading results [5]. Rather than calculating weighted averages that are applicable to few, if any, ART treatment programs in sub-Saharan Africa, we should identify the factors that influence patient retention both at the individual level and the level of the program – elements that can inform appropriate interventions to increase patient retention. We found that compared to free treatment, fee for service programs were associated with reduced retention and higher mortality [2, 3]. Similarly, in the Medecins Sans Frontieres program in Malawi, community support improved outcomes [6].

References

1. Rosen S et al. Patient retention in antiretroviral therapy programs in sub-Saharan Africa: a systematic review. PLoS Med, 2007. 4(10):e298.
2. Braitstein P et al. Mortality of HIV-1-infected patients in the first year of antiretroviral therapy: comparison between low-income and high-income countries. Lancet 2006;367:817-824.
3. Brinkhof MW et al. Early loss to program in HIV-infected patients starting potent antiretroviral therapy in lower-income countries. Bull World Health Organ (in press).
4. Coetzee D et al., Outcomes after two years of providing antiretroviral treatment in Khayelitsha, South Africa. AIDS 2004;18:887-95.
5. Egger M et al. Spurious precision? Meta-analysis of observational studies. BMJ 1998;316:140-4.
6. Zachariah R et al. Community support is associated with better antiretroviral treatment outcomes in a resource-limited rural district in Malawi. Trans R Soc Trop Med Hyg, 2007;101:79-84.