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Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents

Laboratory Testing

CD4 T-Cell Count

(Last updated:February 12, 2013; last reviewed:February 12, 2013)

The CD4 T-cell count (CD4 count) serves as the major laboratory indicator of immune function in patients who have HIV infection. It is one of the key factors in determining both the urgency of antiretroviral therapy (ART) initiation and the need for prophylaxis for opportunistic infections. It is also the strongest predictor of subsequent disease progression and survival according to findings from clinical trials and cohort studies.1,2 CD4 counts are highly variable; a significant change (2 standard deviations) between 2 tests is approximately a 30% change in the absolute count, or an increase or decrease in CD4 percentage by 3 percentage points.

  • Use of CD4 Count for Initial Assessment. The CD4 count is one of the most important factors in determining the urgency of ART initiation and the need for prophylaxis for opportunistic infections. All patients at entry into care should have a baseline CD4 count (AI). Recommendations for initiation of ART can be found in the Initiating Antiretroviral Therapy in Antiretroviral-Naive Patients section of these guidelines.
  • Use of CD4 Count for Monitoring Therapeutic Response. An adequate CD4 response for most patients on therapy is defined as an increase in CD4 count in the range of 50 to 150 cells/mm3 per year, generally with an accelerated response in the first 3 months of treatment. Subsequent increases in patients with good virologic control average approximately 50 to 100 cells/mm3 per year until a steady state level is reached.3 Patients who initiate therapy with a low CD4 count4 or at an older age5 may have a blunted increase in their counts despite virologic suppression.

Frequency of CD4 Count Monitoring. ART now is recommended for all HIV-infected patients. In untreated patients, CD4 counts should be monitored every 3 to 6 months to determine the urgency of ART initiation. In patients on ART, the CD4 count is used to assess the immunologic response to ART and the need for initiation or discontinuation of prophylaxis for opportunistic infections (AI).

The CD4 count response to ART varies widely, but a poor CD4 response is rarely an indication for modifying a virologically suppressive antiretroviral (ARV) regimen. In patients with consistently suppressed viral loads who have already experienced ART-related immune reconstitution, the CD4 cell count provides limited information, and frequent testing may cause unnecessary anxiety in patients with clinically inconsequential fluctuations. Thus, for the patient on a suppressive regimen whose CD4 cell count has increased well above the threshold for opportunistic infection risk, the CD4 count can be measured less frequently than the viral load. In such patients, CD4 count may be monitored every 6 to 12 months, unless there are changes in the patient’s clinical status, such as new HIV-associated clinical symptoms or initiation of treatment with interferon, corticosteroids, or anti-neoplastic agents (CIII).

Factors that affect absolute CD4 count. The absolute CD4 count is a calculated value based on the total white blood cell (WBC) count and the percentages of total and CD4+ T lymphocytes. This absolute number may fluctuate in individuals or may be influenced by factors that may affect the total WBC count and lymphocyte percentages, such as use of bone marrow-suppressive medications or the presence of acute infections. Splenectomy6,7 or co-infection with human T-lymphotropic virus type I (HTLV-1)8 may cause misleadingly elevated absolute CD4 counts. Alpha-interferon, on the other hand, may reduce the absolute CD4 count without changing the CD4 percentage.9 In all these cases, CD4 percentage remains stable and may be a more appropriate parameter to assess the patient’s immune function.

References

  1. Mellors JW, Munoz A, Giorgi JV, et al. Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection. Ann Intern Med. Jun 15 1997;126(12):946-954. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9182471.
  2. Egger M, May M, Chene G, et al. Prognosis of HIV-1-infected patients starting highly active antiretroviral therapy: A collaborative analysis of prospective studies. Lancet. Jul 13 2002;360(9327):119-129. Available at http://www.ncbi.nlm.nih.gov/pubmed/12126821.
  3. Kaufmann GR, Perrin L, Pantaleo G, 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. Oct 13 2003;163(18):2187-2195. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14557216.
  4. Moore RD, Keruly JC. CD4+ cell count 6 years after commencement of highly active antiretroviral therapy in persons with sustained virologic suppression. Clin Infect Dis. Feb 1 2007;44(3):441-446. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17205456.
  5. Althoff KN, Justice AC, Gange SJ, et al. Virologic and immunologic response to HAART, by age and regimen class. AIDS. Oct 23 2010;24(16):2469-2479. Available at http://www.ncbi.nlm.nih.gov/pubmed/20829678.
  6. Zurlo JJ, Wood L, Gaglione MM, Polis MA. Effect of splenectomy on T lymphocyte subsets in patients infected with the human immunodeficiency virus. Clin Infect Dis. Apr 1995;20(4):768-771. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7795071.
  7. Bernard NF, Chernoff DN, Tsoukas CM. Effect of splenectomy on T-cell subsets and plasma HIV viral titers in HIV-infected patients. J Hum Virol. Jul-Aug 1998;1(5):338-345. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10195261.
  8. Casseb J, Posada-Vergara MP, Montanheiro P, et al. T CD4+ cells count among patients co-infected with human immunodeficiency virus type 1 (HIV-1) and human T-cell leukemia virus type 1 (HTLV-1): High prevalence of tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM). Rev Inst Med Trop Sao Paulo. Jul-Aug 2007;49(4):231-233. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17823752.
  9. Berglund O, Engman K, Ehrnst A, et al. Combined treatment of symptomatic human immunodeficiency virus type 1 infection with native interferon-alpha and zidovudine. J Infect Dis. Apr 1991;163(4):710-715. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1672701

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