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Published on: October 15, 2013
Elevated CD8 T-cell counts and virological failure in HIV-infected patients after combination antiretroviral therapy
Nam Su Ku1, Awachana Jiamsakul, Oon Tek Ng
1Department of Internal Medicine and AIDS Research Institute, Yonsei University College of Medicine, Seoul, Korea The Kirby Institute, UNSW Australia, Sydney, Australia Institute of Infectious Disease and Epidemiology, Communicable Disease Centre, Tan Tock Seng Hospital, Singapore, Singapore Working Group on AIDS Faculty of Medicine, University of Indonesia/Cipto Mangunkusumo Hospital, Jakarta, Indonesia Infectious Diseases Department, Bach Mai Hospital, Hanoi, Vietnam Queen Elizabeth Hospital and Integrated Treatment Centre, Hong Kong, China Hospital Sungai Buloh, Sungai Buloh, Malaysia HIV-NAT/Thai Red Cross AIDS Research Centre, Bangkok, Thailand Taipei Veterans General Hospital, Taipei, Taiwan University Malaya Medical Centre, Kuala Lumpur, Malaysia Beijing Ditan Hospital, Capital Medical University, Beijing, China Institute of Infectious Diseases, Pune, India Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand National Center for Global Health and Medicine, Tokyo, Japan Hospital Raja Perempuan Zainab II, Kota Bharu, Malaysia Chennai Antiviral Research and Treatment Clinical Research Site (CART CRS), YRGCARE Medical Centre, VHS, Chennai, India National Hospital for Tropical Diseases, Hanoi, Vietnam Research Institute for Tropical Medicine, Manila, Philippines Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand Faculty of Medicine, Udayana University and Sanglah Hospital, Bali, Indonesia TREAT Asia, amfAR - The Foundation for AIDS Research, Bangkok, Thailand.
Insights
Elevated CD8 counts may indicate future treatment failure in HIV patients on combination antiretroviral therapy (cART). While recent high CD8 levels correlated with virological failure, earlier counts did not, suggesting CD8 response to viral load increase.
Area of Science:
- Immunology
- Virology
- Public Health
Background:
- Combination antiretroviral therapy (cART) is standard for HIV management.
- Early identification of treatment failure is crucial for patient outcomes.
- CD8+ T-cell counts are immune markers that may predict treatment responses.
Purpose of the Study:
- To investigate the association between elevated CD8 counts and virological failure (VF) in Asian HIV-infected patients initiating cART.
- To determine if CD8+ T-cell levels serve as an early warning indicator for treatment failure.
Main Methods:
- Analysis of data from the TREAT Asia HIV Observational Database (TAHOD).
- Inclusion of patients who started cART between 1996-2013 with pre- and post-initiation CD8 and viral load measurements.
- Definition of virological failure as viral load ≥400 copies/mL and elevated CD8 as ≥1200 cells/μL.
- Cox regression analysis to model time to VF.
Main Results:
- 2475 patients were analyzed; 27% experienced VF within 4 years of cART.
- The most recent elevated CD8 count was significantly associated with an increased hazard of VF (HR=1.35, P=0.001).
- Time-lagged CD8 counts (≥6 months prior to endpoint) were not significantly associated with VF (P=0.420).
Conclusions:
- Recent elevated CD8+ T-cell counts may indicate an increased risk of virological failure in HIV patients on cART.
- The association might reflect CD8 cell response to viral load increase rather than a causal role.
- CD8+ T-cell levels could be a valuable, albeit potentially reactive, indicator for monitoring treatment response in HIV management.
Abstract:
Elevated CD8 counts with combination antiretroviral therapy (cART) initiation may be an early warning indicator for future treatment failure. Thus, we investigated whether elevated CD8 counts were associated with virological failure (VF) in the first 4 years of cART in Asian HIV-infected patients in a multicenter regional cohort.We included patients from the TREAT Asia HIV Observational Database (TAHOD). Patients were included in the analysis if they started cART between 1996 and 2013 with at least one CD8 measurement within 6 months prior to cART initiation and at least one CD8 and viral load (VL) measurement beyond 6 months after starting cART. We defined VF as VL ≥400 copies/mL after 6 months on cART. Elevated CD8 was defined as CD8 ≥1200 cells/μL. Time to VF was modeled using Cox regression analysis, stratified by site.In total, 2475 patients from 19 sites were included in this analysis, of whom 665 (27%) experienced VF in the first 4 years of cART. The overall rate of VF was 12.95 per 100 person-years. In the multivariate model, the most recent elevated CD8 was significantly associated with a greater hazard of VF (HR = 1.35, 95% CI 1.14-1.61; P = 0.001). However, the sensitivity analysis showed that time-lagged CD8 measured at least 6 months prior to our virological endpoint was not statistically significant (P = 0.420).This study indicates that the relationship between the most recent CD8 count and VF was possibly due to the CD8 cells reacting to the increase in VL rather than causing the VL increase itself. However, CD8 levels may be a useful indicator for VF in HIV-infected patients after starting cART.
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