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Characteristics and outcomes of adult patients lost to follow-up at an antiretroviral treatment clinic in Johannesburg, South Africa
Global Health Sciences Literature Digest
Published March 17, 2008
Journal Article

Dalal RP, MacPhail C, Mqhayi M, Wing J, Feldman C, Chersich MF, et al. Characteristics and outcomes of adult patients lost to follow-up at an antiretroviral treatment clinic in Johannesburg, South Africa. J Acquir Immune Defic Syndr 2008 Jan 1;47(1):101-7.


To characterize the populations discontinuing follow-up at an urban antiretroviral therapy (ART) clinic in a resource-constrained setting; and to determine causes of loss to follow-up, with the goal of informing future service delivery to improve outcomes.

Study Design

Retrospective cohort study.


An urban public health clinic in Johannesburg, South Africa that began providing ART in April 2004 as part of the South African plan for Comprehensive Care for HIV/AIDS in the Public Health Sector. It serves a diverse patient population, including patients from the inner city and the surrounding townships.


A total of 1,631 adult patients (age ≥18 years) receiving ART at an urban public clinic in Johannesburg between April 2004 and June 2005 were included in the analysis. The study population was 66% female and 93.1% black African and had a mean age at enrollment of 36.4 years (standard deviation = 9.1 years). Men were significantly older than women (mean age 38.9 vs. 35.2 years; p<0.0001).


Adults were considered eligible for ART based on the World Health Organization's 2002 ART recommendations, which include a prior AIDS diagnosis (WHO stage 4 disease) or a CD4 cell count <200 cells/mL. During the pre-treatment phase, patients attended a series of counseling visits that stressed the importance of adherence to ART medications. First-line therapy for treatment-naive patients consisted of two nucleoside reverse transcriptase inhibitors (NRTIs; stavudine and lamivudine) along with a non-nucleoside reverse transcriptase inhibitor (NNRTI; efavirenz or nevirapine). Patients who had prior ART exposure with good response were continued on their prior regimens when possible. Provision was made for switching to a second-line protease inhibitor-based regimen in the event of virologic failure. Individual drugs were substituted in the event of severe toxicity. An access fee based on documented income levels was charged per visit, regardless of medication, clinical, or laboratory resource use. Unemployed patients were eligible to apply for a fee waiver, although the process involved significant administrative steps. A state disability grant and pensions for people older than 60 years of age also were available. Patients were generally scheduled for a follow-up visit every 30 days; they received a 30-day supply of medications at each follow-up visit.

Primary Outcomes

Demographic and clinical characteristics, including ART regimens, baseline blood CD4 cell count, and HIV RNA load, were extracted from patient charts and electronic health records by trained data abstractors and were verified for accuracy by the authors. Loss to follow-up was arbitrarily defined as missing scheduled follow-up appointments for at least 6 weeks. Tracing was conducted by telephone contact with patients or their families using information collected at clinic enrollment and at home visits. On contact, health status (e.g., living, deceased) and reasons for loss to follow-up were determined.


Of the 1,631 adult patients studied, 267 (16.4%) discontinued follow-up during the study period. Gender, ethnicity, and age were not predictive of loss to follow-up. Men discontinuing follow-up were significantly more likely to be married or cohabitating than were women (33.3% vs.16.0% p=0.0012). Although nearly 2/3 of patients not returning to the clinic reported being unemployed, only 1 in 5 had received a fee waiver to collect ART free of charge. Approximately 2 in 5 patients not returning for follow-up had a prior history of tuberculosis (TB), and 18% reported prior exposure to ART (other than single-dose nevirapine for prevention of mother-to-child transmission). The median time on ART before discontinuation of follow-up was 84 days (interquartile range [IQR] =43 to 168 days), compared with 205 days (IQR=108 to 332 days) for those in active care. The median initial CD4 count was 76 cells/mL (IQR=20 to 146 cells/mL), and the median plasma viral load was 5.14 log10 copies/mL (IQR=4.45 to 5.65 log10 copies/mL). Most participants (92.5%) were on either of two first-line NRTI/NNRTI regimens at the time of treatment default, with 89 of 230 patients (38.7%) reporting at least one side effect; 16 of 267 patients (6%) changed regimens during treatment.

Of those discontinuing follow-up, 173 (64.8%) were successfully traced, with death accounting for 48% (n=83). Overall, the known mortality rate for the cohort was 5.1% (83 of 1,631 patients). Of the patients with a known date of death (n=59), 83% (n=49) had died within 30 days of active ART. Cause of death was attributed to AIDS-defining events in 14 patients (16.9%), non-AIDS-defining events in 11 patients (13.3%), and unknown in 58 patients (69.9%). The remaining 10 of 59 patients had discontinued ART for a median of 163 days (IQR=108 to 244 days) before death. Physical relocation and clinic transfers accounted for 25.4% of those discontinuing ART, with >2/3 of these patients reporting continuation of ART at a different clinic, of whom 7 (23.3%) of 30 were obtaining ART from private physicians. Seven patients (4.0%) cited cost as a reason for discontinuing follow-up. Hospitalizations or illness not resulting in death accounted for another 10.8% of those traced, with 1/3 attributable to TB infection. Eight patients (4.6%) voluntarily discontinued follow-up because of feeling well. ART toxicity or side effects were cited by 5 (3.0%) of 173 patients traced.

The group traced to be living (n=90) was compared with the group traced to be deceased (n=83). Characteristics associated with death were older age at ART initiation (mean age =39.4 vs. 36.0 years; p=0.022), lower baseline CD4 cell count (median=33 vs. 98 cells/mL; p=0.0073), higher initial HIV RNA load (median=5.28 vs. 4.96 log10 copies/mL; p=0.024), and loss of weight on ART (median=-1.0 vs.+0.5 kg; p=0.033). Significantly fewer patients traced living were found to have current TB than were patients traced deceased or untraceable (8.6% vs. 20.0% and 20.5%, respectively). In all respects, except for current TB, the untraceable group was not significantly different from the group traced living. Assessment of fees was not associated with increased mortality.


The authors concluded that this analysis of patients receiving ART in an urban, resource-limited setting showed that a significant proportion (nearly 1 in 6) of patients were lost to follow-up during the study period. Early death was the most common outcome, suggesting that timely ART initiation rather than aggressive patient tracking would decrease mortality in this population.

Quality Rating

Considering the general limitations of retrospective cohort studies, this study was of high quality. The results of this study, however, are limited by the following: 1. data were retrieved from a clinic with limited staff and a high workload, thus limiting the quality of the primary data; 2. patients enrolled in the clinic at different times, thus contributing variable durations of follow-up, 3. the study was limited to adult patients in an urban clinic, and the results may not be generalisable to pediatric populations or rural settings; and 4. the study presented only limited characteristics of patients in active care (e.g., age, gender, ethnicity, mortality), thus limiting analysis of factors associated with loss to follow-up.

In Context

The rate of loss to follow-up observed in this study (16.4%) is consistent with a similar study of adult ART patients at a hospital in Nairobi, Kenya, which found that 12.3% of patients were lost to follow-up over a 12-month period.(1) Additionally, the median time on ART of 80 days among those who died is also consistent with other studies showing that mortality is greatest in the first few months of ART in resource-constrained settings due to advanced immunodeficiency.(2,3) Although other studies have reported that the side effects of ART can be a barrier to adherence, this study did not find that these side effects frequently resulted in actual loss to follow-up.(4,5)

Programmatic Implications

The high rate of mortality and early death of patients lost to follow-up emphasizes the importance of starting ART earlier. Notably, at the time of this study, eligibility for ART was based on WHO's 2002 recommendations; the updated WHO recommendations include stage 3 disease with a CD4 count <350 cells/mL, which may lead to lower early mortality rates if these patients present to clinic and are able to receive ART. The study had several other interesting findings. First, although only 4% of traced patients cited cost as a reason for discontinuing follow-up, >60% were unemployed. Additional data on other sources of income (e.g., spousal income, family support) are needed to fully reveal the role of cost. Second, side effects infrequently lead to loss to follow-up, indicating good tolerability of the WHO-recommended first-line regimens, which are common throughout the developing world. Third, the high prevalence of TB found among patients lost to follow-up is of concern, given that >60% of patients with TB in South Africa have HIV co-infection and that >12% of deaths in patients who have TB are attributable to HIV. Integration of TB and HIV care may improve the effectiveness of interventions aimed at both diseases. Finally, the large percentage of untraceable patients indicates that improvements are needed for accurate evaluation of ART program outcomes and for continuity of care for populations in resource-constrained settings. This study did not look at many factors that could be related to loss to follow-up, including transportation and migratory employment. Additionally, the clinic had just begun to provide ART. The role of experience in clinic operations and patient support in patient retention is not clear. Further studies that look into these and other factors will be useful for efforts to improve patient retention in care.


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  2. Braitstein P, Brinkhof MW, Dabis F, Schechter M, Boule A, Miotti 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 Mar 11;367(9513):817-24.
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  4. Weiser S, Wolfe W, Bangsberg D, Thior I, Makhema J, Kebaabetswe P, et al. Barriers to antiretroviral adherence for patients living with HIV infection and AIDS in Botswana. J Acquir Immune Defic Syndr 2003 Nov 1;34(3):281-8.
  5. Carrieri MP, Leport C, Protopopescu C, Cassuto JP, Bouvet E, Peyramond D, et al. Factors associated with nonadherence to highly active antiretroviral therapy: a 5-year follow-up analysis with correction for the bias induced by missing data in the treatment maintenance phase. J Acquir Immune Defic Syndr 2006 Apr 1;41(4):477-85.