University of California, San Francisco Logo

University of California, San Francisco | About UCSF | Search UCSF | UCSF Medical Center

Changes in programmatic outcomes during 7 years of scale-up at a community-based antiretroviral treatment service in South Africa
Global Health Sciences Literature Digest
Published February 28, 2011
Journal Article

Nglazi MD, Lawn SD, Kaplan R, Kranzer K, Orrell C, Wood R, et al. Changes in programmatic outcomes during 7 years of scale-up at a community-based antiretroviral treatment service in South Africa. J Acquir Immune Defic Syndr. 2010; 56(1):e1-8.


To determine early and long-term trends in outcomes of patients treated in a community-based antiretroviral therapy (ART) program in Africa


Poor peri-urban area in Cape Town, South Africa

Study Design

Observational cohort


ART-naïve patients aged ≥15 years enrolled in cohort and started on ART

Main Outcome Measures

Loss-to-follow up (LTFU) defined as not attending the clinic for ≥12 weeks and not dead or transferred; deaths due to all cause mortality; transferring to another clinic for ART care; retention-in-care defined as alive and receiving ART; virological failure defined as 2 viral loads of >1000 copies/mL; viral load suppression (<400 copies/mL) after 16 wks of ART; CD4 count ≤200 cells/µl after 48 wks of ART.


Data from patients enrolled from Sept 2002 through September 2008, with data censored at Sept 2009, were analyzed. Patients were started on 2 nucleoside reverse transcriptase inhibitor (NRTI) and 1 non-nucleoside reverse transcriptase inhibitor (NNRTI) per national and WHO guidelines, with eligibility based on WHO stage 4 disease or a CD4 cell count <200 cells/µl. Patients were monitored regularly (every 16 weeks) for CD4 cell count and viral load. Community based peer counselors provided patient and adherence support and counseling. Survival analyses, Kaplan-Meier estimates, Cox proportional hazard modeling and multivariable logistic regression were used to analyze the data.


Overall, 3162 patients were enrolled; two-thirds were female and median age was 34 yrs. The following changes in patient profile were observed in cohorts enrolled during 2002-4 compared to those enrolled from 2007-8: proportion of women (75.5% vs. 65.9%), the median CD4 cell count at ART initiation (87 vs 121 cells/µl), the number on AZT rather than D4T (9.6% vs 20.2%). There was no difference in viral load at initiation over time. Peer counselor-to-patient ratios decreased (1:22 to 1:98) as well as doctor-to-patient ratios (1:202 to 1:395), as greater numbers of patients were enrolled during each period (404 patients from 2002-4 vs. 659 patients from 2007-8). Overall, 334 patients (10.6%) died, 592 (18.7%) were LTFU, 326 (10.3%) transferred to another ART facility. The probability of being lost to care through death or LTFU was 37.4% (95% CI [34.9-40.0]) at 6 yrs; including transfers, the probability of leaving the program for any reason was 52.5% (95% CI [49.5-55.6]). The probability of death was greatest in the first 1 year of ART (7.9% 95% CI [7.0-8.9%]), and this decreased slightly over time (8.4% in the first enrolment period, and 6.9% in the last). The proportion of patients LFTU or transferring out increased significantly between successive calendar periods. At 6 years, the overall probability of virological failure was 23.1% and increased with each calendar period; however, early outcome (suppression to <400 copies/mL after 16 weeks of treatment) was >93% for each calendar period. The proportion of patients with CD4 count ≤200 cells/µl decreased from 90% at baseline to 20.8-31.1% after 48 wks of ART. Risk of death did not change with calendar period. Factors independently associated with mortality risk were: being male, baseline CD4≤50cells/µl, WHO stage III or IV; factors associated with being LTFU were being male, younger age and WHO stage III or IV, and later calendar periods of enrollment. Transferring to another facility was not associated with baseline characteristics but was associated with cohort year of enrollment. Factors associated with viral failure at any point included young age, lower baseline CD4 cell count, higher baseline viral load and later calendar period of enrolment. Viral failure at 16 weeks was associated with age ≤25 years and baseline viral load ≥5 log10copies/mL but not cohort year of enrolment; factors associated with CD4 count of ≤200 cells/µl at 48 weeks were being male, age ≥41 years, lower baseline CD4 and viral load, but not cohort year of enrolment.


Over 7 years of treatment service, early outcomes (mortality, viral suppression and increased CD4 count) were sustained in sequential calendar periods; however, longer term adverse outcomes of LTFU and viral failure deteriorated over time as the service enlarged and ratios of patient to health worker staff increased. This may result in strained patient care and support systems that focus on treatment initiation and the initial few months of care.

Quality Rating

This was a high quality observational cohort study with adequate description of statistical methods used for analyses.

In Context

The combined attrition due to death and LTFU in this study was 37.4% after 6 years, which is similar to another program in Cape Town,(1) though higher than the 2 year loss of 40% reported from a meta-analysis of cohorts in sub-Saharan Africa.(2) One-year mortality in this cohort was 7.9% which is considerably lower than that reported by other ART treatment programs in sub-Saharan Africa - between 8-23%.(3) The increasing proportion of patients LTFU over sequential calendar periods of ART initiation has also been observed elsewhere.(1, 4, 5) In a previous report by these authors on this cohort,(6) many of the 23% of patients who were not virally suppressed had developed drug resistance mutations. The current study is one of the few analyses of public sector programs in which viral load monitoring was performed regularly, although a recent review described data currently available.(7) The proportion of patients transferring to another facility in this study was approximately 20% over 6 years of ART, in contrast to only 1.1% after 26 months reported in a large meta-analysis from programs in sub-Saharan Africa.(8)

Programmatic Implications

This study provides detailed information from a public sector ART program on changes in outcomes over time. The results indicate that as the patient load increased for peer support counselors and health care workers, some longer term outcomes worsened. This may be because patient care and support systems focus on treatment initiation and the initial few months of care. On the other hand, mortality was not affected by the increasing case load. Overall, at least in this setting, the health care system appears able to manage this number of patients. Some treatment outcomes may have been better than that reported from other public and community-based programs, because of the routine CD4 cell count and viral load monitoring, that is not widely available elsewhere. For almost all outcomes, men fared more poorly. Efforts need to be directed to identify the reasons for this. Good patient monitoring is important for programs to understand the impact of case load and management on the outcomes of their patient populations.


  1. Boulle A, Van Cutsem G, Hilderbrand K, et al. Seven-year experience of a primary care antiretroviral treatment programme in Khayelitsha, South Africa. AIDS. 20 2010;24:563-572.
  2. Rosen S, Fox MP, Gill CJ. Patient retention in antiretroviral therapy programs in sub-Saharan Africa: a systematic review. PLoS Med. 2007; 4:e298.
  3. SD, Harries AD, Anglaret X, et al. Early mortality among adults accessing antiretroviral treatment programmes in sub-Saharan Africa. AIDS. 2008;22:1897-1908.
  4. Boulle A, Bock P, Osler M, et al. Antiretroviral therapy and early mortality in South Africa. Bull World Health Organ. 2008;86:678-687.
  5. Brinkhof MWG, Dabis F, Myer L, et al. Early loss of HIV-infected patients on potent antiretroviral therapy programmes in lower-income countries. Bull World Health Organ. 2008;86:559-567.
  6. Orrell C, Walensky RP, Losina E, et al. HIV type-1 clade C resistance genotypes in treatment-naive patients and after first virological failure in a large community antiretroviral therapy programme. Antivir Ther. 2009;14:523-531.
  7. Barth RE, van der Loeff MF, Schuurman R, et al. Virological follow-up of adult patients in antiretroviral treatment programmes in sub-Saharan Africa: a systematic review. Lancet Infect Dis. 2010;10:155-166.
  8. Fox MP, Rosen S. Patient retention in antiretroviral therapy programs up to three years on treatment in sub-Saharan Africa, 2007-2009: systematic review. Trop Med Int Health. 2010;15(Suppl 1):1-15.