Ageing and long‐term CD4 cell count trends in HIV‐positive patients with 5 years or more combination antiretroviral therapy experience

Abstract

Background The aim of this analysis is to describe the long-term changes in CD4 cell counts beyond 5 years of combination antiretroviral therapy (cART). If natural ageing leads to a long-term decline in the immune system via low-grade chronic immune activation/inflammation, then one might expect to see a greater or earlier decline in CD4 counts in older HIV-positive patients with increasing duration of cART. Methods Retrospective and prospective data were examined from long-term virologically stable HIV-positive adults from the Australian HIV Observational Database. We estimated mean CD4 cell counts changes following the completion of 5 years of cART using linear mixed models. Results A total of 37,916 CD4 measurements were observed for 892 patients over a combined total of 9,753 patient years. Older patients (>50 years) at cART initiation had estimated mean(95% confidence interval) change in CD4 counts by Year-5 CD4 count strata (<500, 501–750 and >750 cells/μL) of 14(7 to 21), 3(−5 to 11) and −6(−17 to 4) cells/μL/year. Of the CD4 cell count rates of change estimated, none were indicative of long-term declines in CD4 cell counts. Conclusions Our results suggest that duration of cART and increasing age does not result in decreasing mean changes in CD4 cell counts for long-term virologically suppressed patients. Indicating that level of immune recovery achieved during the first 5 years of treatment are sustained through long-term cART.

Association of Viral Suppression With Lower AIDS-Defining and Non–AIDS-Defining Cancer Incidence in HIV-Infected Veterans

“…An independent inverse association between CD4 count and ADC risk is well-established (12). In addition, evidence suggests weaker, subtler inverse associations between CD4 count and specific NADC types, especially those caused by viruses (12, 18) Furthermore, since CD4 count is correlated with long-term HIV RNA levels (41, 42), CD4 count might confound and likely mediates the association between viral suppression status and cancer risk. When we stratified by CD4 count, decreasing viral suppression IR trends persisted for all cancer and ADC within each CD4 stratum, but did not persist for virus-NADC.…”

CD4+/CD8+ ratio, age, and risk of serious noncommunicable diseases in HIV-infected adults on antiretroviral therapy

“…We used the CD4/CD8 ratio after one year of virologic suppression as our primary predictor of interest rather than time-updated values in order to limit the effect of episodic HIV viremia [24]. The immune response following the first few years of ART has been shown in other studies to be a reliable reflection of changes over time during ART and has been associated with NCD outcomes [4, 49]. However, we are unable to draw conclusions about the role of time-varying changes in CD4/CD8 ratio and risk of future NCDs based upon results of our study.…”

CD4 Response Up to 5 Years After Combination Antiretroviral Therapy in Human Immunodeficiency Virus-Infected Patients in Latin America and the Caribbean

“…To date, several studies have reported that the strongest predictor of long-term CD4 response is baseline CD4, even among patients with long-term HIV RNA suppression [ 8 , 11 ]. In addition, studies have found that women [ 12 ] and patients initiating treatment at younger ages [ 13 ] show better CD4 response, whereas specific cART regimens have not been shown to significantly impact long-term immune response [ 14 ]. Our results corroborate these findings.…”