Association of Age with Mortality and Virological and Immunological Response to Antiretroviral Therapy in Rural South African Adults

Abstract

ObjectiveTo assess whether treatment outcomes vary with age for adults receiving antiretroviral therapy (ART) in a large rural HIV treatment cohort.DesignRetrospective cohort analysis using data from a public HIV Treatment & Care Programme.MethodsAdults initiating ART 1st August 2004 - 31st October 2009 were stratified by age at initiation: young adults (16–24 years) mid-age adults (25–49 years) and older (≥50 years) adults. Kaplan-Meier survival analysis was used to estimate mortality rates and age and person-time stratified Cox regression to determine factors associated with mortality. Changes in CD4 cell counts were quantified using a piecewise linear model based on follow-up CD4 cell counts measured at six-monthly time points.Results8846 adults were included, 808 (9.1%) young adults; 7119 (80.5%) mid-age adults and 919 (10.4%) older adults, with 997 deaths over 14,778 person-years of follow-up. Adjusting for baseline characteristics, older adults had 32% excess mortality (p = 0.004) compared to those aged 25–49 years. Overall mortality rates (MR) per 100 person-years were 6.18 (95% CI 4.90–7.78); 6.55 (95% CI 6.11–7.02) and 8.69 (95% CI 7.34–10.28) for young, mid-age and older adults respectively. In the first year on ART, for older compared to both young and mid-aged adults, MR per 100 person-years were significantly higher; 0–3 months (MR: 27.1 vs 17.17 and 21.36) and 3–12 months (MR: 9.5 vs 4.02 and 6.02) respectively. CD4 count reconstitution was lower, despite better virological response in the older adults. There were no significant differences in MR after 1year of ART. Baseline markers of advanced disease were independently associated with very early mortality (0–3 months) whilst immunological and virological responses were associated with mortality after 12months.ConclusionsEarly ART initiation and improving clinical care of older adults are required to reduce high early mortality and enhance immunologic recovery, particularly in the initial phases of ART.

Initial suboptimal CD4 reconstitution with antiretroviral therapy despite full viral suppression in a cohort of HIV-infected patients in Senegal

“…Some authors reported, as in our study, that older patients presented with slower immune reconstitution in the short term, six months after ARVT initiation [3,5,[10][11][12]. This may be explained by a lower thymic output of CD4 cells in the elderly [2,13].…”

Younger Age Predicts Failure to Achieve Viral Suppression and Virologic Rebound Among HIV-1-Infected Persons in Serodiscordant Partnerships

“…21 A study of *9,000 adults on ART in South Africa found lower rates of virologic suppression in younger adults (16-24 years) compared with those aged 25-49 years. 22 These data suggest that younger age predicts failure to achieve viral suppression and that this risk decreases with age. Younger age is associated with poor ART adherence.…”

Outcomes of antiretroviral therapy among younger versus older adolescents and adults in an urban clinic, Zimbabwe

“…7 Most studies on ART retention have reported on adults, with adolescents included within the adult age group, making it difficult to extract information specific to adolescents. [8][9][10][11] Emerging evidence suggests that adolescents are falling behind in HIV care compared to adults as a result of not receiving specialised attention and services. 12,13 A study performed in seven African countries, excluding Zimbabwe, showed that adolescents and young adults combined (age 15-24 years) had higher rates of loss to follow-up (LTFU) and higher mortality compared with older adults (age 50 years).…”

“…A systematic search for publications on ART outcome studies in PubMed, Cochrane Database, Google Scholar and ClinicalTrial.gov, comparing younger vs. older adolescents and younger vs. older adults, showed that with respect to ART retention, adolescents (age 10-19 years) were often misclassified as adults aged 15 years, 8,9 16 years 11 or 18 years. 10 No studies reported attrition rates within the adolescent age group or between younger and older adults.…”