Bakanda C, Birungi J, Mwesigwa R, Ford N, Cooper CL, Au-Yeung C, Chan K, Nachega JB, Wood E, Hogg RS, Dybul M, Mills EJ. Association of aging and survival in a large HIV-infected cohort on antiretroviral therapy in Uganda. AIDS. 2011 Mar 13;25(5):701-705.
With the increasing use of antiretroviral therapy (ART) in developing countries, the number of older HIV-infected persons is likely to increase. While numerous studies have documented the survival benefit associated with ART, there are few data available regarding survival in an older, HIV-infected population in resource-constrained areas because of inadequate monitoring systems.(1,2)
To compare survival between older and younger HIV-infected persons receiving ART.
An HIV/AIDS support organization in Uganda.
Observational prospective cohort.
Persons receiving ART through The AIDS Support Organization (TASO) in Uganda, aged 18 years and above.
Patients who initiated ART from 2004 to January 2010 were included. Patients were divided into groups based on their age. The age-specific crude mortality was calculated for those aged 18-24 years, and for five-year age groups thereafter up to persons aged 65 years and above. The fifty percent of persons lost to follow-up were considered to have died, with this assumption weighted by CD4 cell counts at initiation of ART and age. Survival from the date of initiating ART was estimated using the Kaplan-Meier method. The Cox regression model was used to measure the independent effect of age on survival. Missing CD4 count values were imputed using the Markov chain Monte Carlo method and compared to the model that excluded records with missing CD4 values.
There were a total of 22,087 patients included in the analysis, 1,481 of whom had documentation of death and 730 of whom had deaths imputed from those who were lost to follow-up. Eighty-nine percent of the patients were aged 18-49 years. A significantly greater proportion of older patients were men, had lower CD4 cell counts, and had died, compared to younger patients. WHO clinical stage at baseline, loss to follow-up, and year of starting ART did not differ between the two age groups. However, patients lost to follow-up had a lower median CD4 count than those retained in care (105 cells/mm3 vs. 144 cells/mm3, respectively; p≤ 0.001).
The pooled crude mortality among the older age group was 45.6 deaths per 1000 person-years compared to a pooled crude mortality rate of 36.5 deaths per 1000 person-years in persons aged 18-49 years. The lowest mortality rate was observed among patients age 40-44 years (31.4 deaths per 1000 person-years) and patients aged 60-64 had the highest rate (58.9 deaths per 1000 person-years). The median follow up for persons age 18-49 years was 32 months, and for the older patients was 31 months. The estimated probability of survival after three months of ART was 96.3% (95% CI 96.0-96.5) in the younger patients, and 95.7% (95% [CI 94.9%-96.5%]) among the older patients. After six months ART survival in the younger group was 94.4% (95%[CI 94.1%-94.8%]) and was 93.5% (95% [CI 92.5%-94.5%]) in the older. After 12 months of ART, survival decreased to 92.5% (95% [CI 92.1%-92.8%]) in the younger group and 91.3% (95% [CI 90.2%-92.4%]) in the older patients. After four years of follow-up, survival probability in the younger group was 89.4% (95% [CI 88.9%-89.8%]) and 86.5% (95% [CI 85.2%-88.1%]). The adjusted risk of mortality among the older group was 1.23 (95% [CI 1.08, 1.42]). Male gender, baseline CD4 counts and years on ART were also independently associated with mortality.
Age is an independent risk factor for mortality.
This was a well-designed and -conducted study. Although it is difficult to assess the representativeness of the population, it is likely that they are comparable to other groups of persons receiving ART in resource-constrained countries. The ascertainment of co-factors was from medical records, and with the exception of missing CD4 counts, was very good. A key limitation concerns the ascertainment of death which was based on estimations from persons lost to follow-up.
Clinical management of older persons with HIV is an increasingly important issue because of the large impact of ART on improved survival. Increasing evidence points to age as an important factor in survival and in the development of non-AIDS related conditions. The worse survival in older persons found in this study is consistent with other studies, though other studies have found better response to ART in older patients.(4,5) With the increased availability and use of ART in resource constrained areas, the number of older persons with HIV who are on ART will continue to increase. Increased knowledge of the clinical issues that affect older persons with HIV is urgently needed in developing countries.
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