Main Article Content
CD4, HIV monitoring, safe HIV Management
CD4 lymphocyte cell count represents the main immunological marker used to monitor HIV infection. However, frequent monitoring may be unnecessary, could cause anxiety to the patient as well as burdening healthcare with extra expenses.
Objectives and methods
To analyse the probability of maintaining a safe number of CD4 in HIV-positive subjects under treatment with ?350 cells/µl at baseline during a three-year follow up. We conducted a retrospective study performing three analyses with Kaplan-Meyer method considering: 1) all patients independently from their viral load (VL); 2) patients with 500 > CD4 ? 350 cells/µl versus (vs) CD4 ? 500 cells/µl at baseline; 3) patients with VL < 20 copies/ml vs VL > 20 copies/ml.
253 subjects were enrolled. The median CD4 count was 623 (489-805) cells/µl. Subjects maintaining ? 350 cells/µl in the first, second and third year were respectively 238 (94.1%), 229 (90.5%) and 226 (89.3%), independently from VL. Within subjects with ? 350 CD4/µl vs ? 500 CD4/µl at baseline, those who maintained ? 350 cells/µl until the third year were respectively 241 (95.3%) and 158 (98.1%).
The probability of maintaining these values in the third year was 89.3% for those who had CD4 ? 350/µl at baseline and 98.1% for those who had CD4 ? 500/µl. This probability was around 90% vs 99% for subjects with HIV-RNA above or below 20 copies/ml. Secondly, we tried to estimate the costs of CD4 determinations in a three-year period (from April 1, 2013 to March 31, 2016). We analysed respectively 343 subjects in the first period, 364 in the second and 383 in the third, with a median value of 500 CD4/µl during the research time taken into account. We found a mean value of about two determinations patient/year (2.41 in 2013/2014; 2.32 in 2014/2015; 2.18 in 2015/2016), with a significant decrease between the first and the last period (p<0.001). The mean cost patient/year was €101.51 in the first year, €97.61 in the second, €92.00 in the third (p<0,001). Assuming to extend these procedures to all our patients with stable CD4 cells/µl and monitoring CD4 cell count once in a year, it could be possible to obtain an overall saving of €19,152/year.
A very high percentage of subjects maintained a high and safe number of CD4 cells (>350 cells/µl) during a three-year follow up. It could be possible to save up to 66% of the costs by reducing the number of CD4 count determinations in a year, to have other favourable consequences as well, releasing new resources for patient’s management.
2. Antinori, A. et al. Italian guidelines for the use of antiretroviral agents and the diagnostic-clinical management of HIV-1 infected persons. Update 2016. New Microbiol. (2017).
3. Venanzi Rullo, E. et al. “Genetic evidence that Naïve T cells can contribute significantly to the HIV intact reservoir: time to re-evaluate their role”. Clin. Infect. Dis. (2019). doi:10.1093/cid/ciz378
4. Marino, A. et al. Rapid emergence of cryptococcal fungemia, Mycobacterium chelonae vertebral osteomyelitis and gastro intestinal stromal tumor in a young HIV late presenter: A case report. BMC Infect. Dis. (2018). doi:10.1186/s12879-018-3573-z
5. EACS. European AIDS Clinical Society Guidelines Version 9.0 October 2017. European AIDS Clinical Society (EACS) (2017). doi:10.1002/oby.21371.
6. Kaufmann, G. R. et al. CD4 T-lymphocyte recovery in individuals with advanced HIV-1 infection receiving potent antiretroviral therapy for 4 years: The Swiss HIV cohort study. Arch. Intern. Med. (2003). doi:10.1001/archinte.163.18.2187
7. Mocroft, A. et al. Estimated average annual rate of change of CD4 + T-cell counts in patients on combination antiretroviral therapy. Antivir. Ther. (2010). doi:10.3851/IMP1559
8. Nozza, S. et al. Antiretroviral therapy in geriatric HIV patients: The GEPPO cohort study. J. Antimicrob. Chemother. (2017). doi:10.1093/jac/dkx169
9. Ford, N., Meintjes, G., Vitoria, M., Greene, G. & Chiller, T. The evolving role of CD4 cell counts in HIV care. Current Opinion in HIV and AIDS (2017). doi:10.1097/COH.0000000000000348
10. Hamers, R. L. et al. Cost-effectiveness of laboratory monitoring for management of HIV treatment in sub-Saharan Africa: A model-based analysis. AIDS (2012). doi:10.1097/QAD.0b013e3283560678
11. Panel on Clinical Practices for Treatment of HIV infection. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Rev. Panam. salud pu?blica = Pan Am. J. public Heal. (2011). doi:10.1037/e530922008-004
12. Ford, N. et al. CD4 changes among virologically suppressed patients on antiretroviral therapy: A systematic review and meta-analysis. Journal of the International AIDS Society (2015). doi:10.7448/IAS.18.1.20061
13. Gale, H. B. et al. Is frequent CD4+ T-lymphocyte count monitoring necessary for persons with counts ?300 cells/?L and HIV-1 suppression? Clin. Infect. Dis. (2013). doi:10.1093/cid/cit004
14. Caniglia, E. C. et al. When to monitor CD4 cell count and HIV RNA to reduce mortality and aids-defining illness in virologically suppressed hiv-positive persons on antiretroviral therapy in high-income countries: A prospective observational study. J. Acquir. Immune Defic. Syndr. (2016). doi:10.1097/QAI.0000000000000956
15. Hyle, E. P., Sax, P. E. & Walensky, R. P. Potential Savings by Reduced CD4 Monitoring in Stable Patients With HIV Receiving Antiretroviral Therapy. JAMA Intern. Med. (2013). doi:10.1001/jamainternmed.2013.9329
16. Johnson, L. F. et al. Life Expectancies of South African Adults Starting Antiretroviral Treatment: Collaborative Analysis of Cohort Studies. PLoS Med. (2013). doi:10.1371/journal.pmed.1001418
17. Katz, M. H. Directing Resources to Where They Are the Most Needed. JAMA Intern. Med. (2013). doi:10.1001/jamainternmed.2013.8590
18. Young, B., Ng, O. T., Lye, D. C. & Leo, Y. S. Derivation and validation of an accurate estimation of CD4 counts from the absolute lymphocyte count in virologically suppressed and immunologically reconstituted HIV infected adults. BMC Infect. Dis. (2015). doi:10.1186/s12879-015-1079-5
19. Mussini, C. et al. CD4/CD8 ratio normalisation and non-AIDS-related events in individuals with HIV who achieve viral load suppression with antiretroviral therapy: An observational cohort study. Lancet HIV (2015). doi:10.1016/S2352-3018(15)00006-5
20. Chereau, F. et al. Impact of CD4 and CD8 dynamics and viral rebounds on loss of virological control in HIV controllers. PLoS One (2017). doi:10.1371/journal.pone.0173893
21. Bellissimo, F., Rita Pinzone, M., Maurizio Celesia, B., Cacopardo, B. & Nunnari, G. Baseline CD4/CD8 T-Cell Ratio Predicts Prompt Immune Restoration Upon cART Initiation. Curr. HIV Res. (2016). doi:10.2174/1570162x14666160414111554
22. Ryom, L. et al. Highlights of the 2017 European AIDS Clinical Society (EACS) Guidelines for the treatment of adult HIV-positive persons version 9.0. HIV Med. (2018). doi:10.1111/hiv.12600
23. Camoni, L. et al. Estimating minimum adult HIV prevalence: a cross sectional study to assess the characteristics of people living with HIV in Italy. AIDS Res. Hum. Retroviruses (2014). doi:10.1089/AID.2014.0154
24. Ford, N. et al. The future role of CD4 cell count for monitoring antiretroviral therapy. The Lancet Infectious Diseases (2015). doi:10.1016/S1473-3099(14)70896-5