Date Published: October 22, 2011
Publisher: BioMed Central
Author(s): Barbara Amuron, Jonathan Levin, Josephine Birunghi, Geoffrey Namara, Alex Coutinho, Heiner Grosskurth, Shabbar Jaffar.
There have been few reports of long-term survival of HIV-infected patients on antiretroviral therapy (ART) in Africa managed under near normal health service conditions.
Participants starting ART between February 2005 and December 2006 in The AIDS Support (TASO) clinic in Jinja, Uganda, were enrolled into a cluster-randomised trial of home versus facility-based care and followed up to January 2009. The trial was integrated into normal service delivery with patients managed by TASO staff according to national guidelines. Rates of survival, virological failure, hospital admissions and CD4 count over time were similar between the two arms. Data for the present analysis were analysed using Cox regression analyses.
1453 subjects were enrolled with baseline median count of 108 cells/μl. Over time, 119 (8%) withdrew and 34 (2%) were lost to follow-up. 197/1453 (14%) died. Mortality rates (95% CI) per 100 person-years were 11.8 (10.1, 13.8) deaths in the first year and 2.4 (1.8, 3.2) deaths thereafter. The one, two and three year survival probabilities (95% CI) were 0.89 (0.87 – 0.91), 0.86 (0.84 – 0.88) and 0.85 (0.83 – 0.87) respectively. Low baseline CD4 count, low body weight, advanced clinical condition (WHO stages III and IV), not being on cotrimoxazole prophylaxis and male gender were associated independently with increased mortality. Tuberculosis, cryptococcal meningitis and diarrhoeal disease were estimated to be major causes of death.
Practical and affordable interventions are needed to enable earlier initiation of ART and to reduce mortality risk among those who present late for treatment with advanced disease.
Antiretroviral therapy (ART) has been scaled-up rapidly. About 4 million people in Africa are now on ART . Various studies have shown that mortality during the first 6 months or so after initiating ART is much higher than in developed countries and retention of patients in programmes is poor [2,3]. However, most longitudinal studies conducted in Africa have been either short-term or have involved small numbers of participants. A recent randomised trial conducted in Uganda and Zimbabwe comparing clinical with laboratory driven monitoring found very high and similar 5-year survival rates in the two trials arms of 87% and 90% respectively . However, the participants had good access to care and were managed in research clinics by dedicated physicians. Much less is known about long-term survival on antiretroviral therapy under normal health service conditions where access to care is more difficult and the quality and level of clinical support is lower.
The study was based at The AIDS Support Organisation (TASO) clinic in Jinja, South East Uganda. TASO is a large non-governmental organisation (NGO) which provides care and support to people living with HIV/AIDS. Participants were enrolled in a cluster-randomised trial comparing home-based HIV care with facility care . All adult patients (18 years old or more) living within the TASO catchment population and initiating on ART were invited to join and enrolled consecutively. The trial was integrated into normal health service delivery [5-7]. Trial participants were managed identically to non-trial patients by TASO staff using national guidelines.
1453 subjects were enrolled. Table 1 shows the baseline characteristics. The majority (71%) were women, the median age was 38 years and the median CD4 count was 108 cells/μl. 938 (64.6%) had a baseline viral load of 100,000 copies/ml or more and 791 (54%) were at WHO clinical stage III or IV.
In this trial, which was integrated into normal health service delivery in Uganda, the mortality rate was almost 12 deaths per 100 person-years in the first year following ART initiation, five-fold higher than in subsequent years. Indeed from 12 months onwards, the mortality rate in our cohort was only slightly higher than that reported in developed countries . Other studies have reported between 8 and 26% of patients dying within the first year of starting ART . The mortality rate in the large DART was lower, with 5-year survival of 87% and 90% in the clinically driven monitoring versus laboratory and clinical monitoring arms respectively. However, participants in this study had better access to clinical care. The problem in Africa lies with the very high early mortality. We have previously shown an even higher mortality rate, around 30 deaths per 100 person-years, during the pre-treatment screening period  in this population and recent reviews show 32% loss to follow-up during this pre-treatment period despite eligibility for ART , a 20% loss to follow-up among patients within the first year of antiretroviral therapy , among whom mortality is very high . Taken together, these findings suggest that the major problem is early mortality and that mortality after 12 months in well functioning programmes will be low. We believe our findings are robust. Very few individuals refused to join the study, the loss-to-follow-up was low and the mortality rate among subjects who withdrew was similar to those who were retained in care.
The authors declare that they have no competing interests.
BA and SJ wrote the first draft of the paper and all authors contributed comments and suggestions to various draft versions. JL conducted the statistical analyses and GN managed the data. JB was responsible for patient management and JB, BA, GN were responsible for study implementation. AC, HG and SJ generated the research ideas, secured funding and co-ordinated the research programme All authors have seen and approved the final version.