Poorer ART outcomes show need to prioritise older people in HIV test and treat programmes

HIV testing and treatment programmes in sub-Saharan Africa need to prioritise older individuals, according to research published in PLOS ONE. Investigators in Uganda found that after starting antiretroviral therapy (ART) people aged 50 years and older had higher mortality and poorer immune reconstitution compared to younger people.

“Older age is associated with poorer response to ART and excess mortality compared to the younger,” comment the authors. “Our data show that older persons retain a significantly higher risk for mortality and this is not modified over time.”

The prevalence of HIV among the over-50s is increasing. Almost 60% of older HIV-positive individuals live in sub-Saharan Africa. Studies conducted in richer settings have shown that older age at ART initiation is associated with poorer outcomes, such as impaired CD4 response and higher mortality risk.

Investigators in Uganda wanted to see if this was also the case in sub-Saharan Africa. They therefore designed a retrospective study involving 8500 adults who started ART between 2006 and 2012 at the HIV clinic at Mbarara Hospital. Data collected during routine follow-up were analysed to see if age was associated with mortality risk and immune reconstitution. Participants were stratified into three age groups at the time they started ART: younger (18-34 years); middle (35-49 years) and older (50 years and older). Information was also gathered on key baseline characteristics associated with outcomes after starting ART, including HIV disease stage, CD4 cell count and body mass index (BMI).

Approximately two-thirds of participants were female. Median age was 32 years. Over half (56%) were in the younger age group, 37% in middle age and 7% in the older age group.

Individuals were followed for a median of 1.5 years and contributed over 66,000 person-years of follow-up.

Older people were less likely than other age groups to have a baseline CD4 cell count above 350 cells/mm³. A significantly higher proportion of the over-50s had low BMI. 

During follow-up, 2% of people died. After adjusting for potential confounders, older age was associated with a 63% increase in mortality compared to younger people (adjusted RR = 1.63; 95% CI 1.26-2.11). Men had a higher mortality risk than women, and more advanced HIV disease at baseline was also associated with an increase in mortality risk.

“After adjustment for gender, CD4 count, education and duration of ART, age at ART initiation remained an important predictor of mortality and older patients had a poorer prognosis compared to the young age group,” comment the authors.

There was also some evidence that older age was associated with a fall in CD4 cell count after ART initiation, but this finding fell just short of significance (RR = 1.79; 95% CI 0.89-3.58).

The poorer immunological response in older people could be due to impaired thymus function, as this gland plays an important role in CD4 cell reconstitution.

The investigators believe their findings have clear implications for ART treatment programmes in sub-Saharan African settings – older people should be a priority group for eligibility to initiate ART very early. 

“Older patients showed poorer immunological response and higher risk for mortality following ART initiation compared to the young adults,” conclude the authors “Further studies should be conducted to further understanding the biological mechanisms for the poorer immunological response and the excess mortality in the older patients. Interventions such as adjuvant therapy to antiviral therapy may be necessary to improve immunological recovery.”