Can HIV-positive people attain normal CD4 cell counts?

With effective antiretroviral therapy, many patients can achieve overall CD4 cell counts approaching those of healthy HIV-negative individuals. These vary from person to person, but are usually between 500 and 1500 cells/mm3.

A recent analysis of nearly 2000 participants in the EuroSIDA cohort, for example, found that CD4 cell counts increased by an average of 100 cells/mm3 during the first year of therapy in patients whose viral load was suppressed below 50 copies/ml. Smaller increases of about 50 cells/mm3 continued for five or more years, until patients attained levels above 500 cells/mm3. The researchers suggested that normalisation of CD4 counts might be possible for most or all HIV-positive individuals if viral suppression with highly active antiretroviral therapy (HAART) can be maintained for a sufficiently long period.1

But other studies have found that people with low pre-treatment CD4 cell counts may not be able to reach normal levels, even with continued therapy. Looking at more than 5000 treatment-naive participants in the Netherlands ATHENA Cohort, researchers found that about 75% of those who started HAART with baseline CD4 cell counts above 350 cells/mm3 eventually attained 800 cells/mm3 or more, but the rate was about 50% for those who started treatment with 200 to 350 cells/mm3, and only about 25% for those who started with fewer than 200 cells/mm3.2

In an analysis of French patients who maintained a viral load below 500 copies/ml on HAART for five years, 83% of those who started treatment with CD4 cell counts of 200 cells/mm3 or higher – but only 45% of those with lower baseline levels – went on to achieve CD4 counts above 500 cells/mm3.3 Similarly, in the ACTG 384 trial, patients who began treatment with more than 350 CD4 cells/mm3 usually attained normal levels, but those who started with lower counts did not catch up during the 144-week follow-up period.4

The DART trial is, thus far, the largest and longest randomised study of antiretroviral treatment to take place in a resource-limited setting. In DART, 3316 participants began first-line treatment with non-protease-inhibitor based combinations. After one year (48 weeks) on first-line treatment, 10% still had a CD4 cell count ranging from 0 to 99, 38% were in the range 100 to 199, 39% in the range 200 to 349, 10% in the range 350 to 499 and only 2% had reached a CD4 count of 500 cells/mm3 or more. CD4 responses did improve over time; over a five-year period, 19% reached a CD4 count of 500 cells/mm³ or greater and 69% reached 250 cells/mm³ or more while still on their first-line regimen.5

Another research team found that while treatment-naive individuals who started HAART with CD4 cell counts below 50 cells/mm3 continued to experience immune recovery for up to seven years, their CD4 cell counts did not reach those of patients who started therapy with higher pre-treatment levels.6

Studies also show that treated patients can recover both naive CD4 T-cells and a diverse set of memory CD4 T-cells that respond to a wide variety of antigens. But patients who start treatment with very low ‘nadir’ (lowest-ever) CD4 cell levels may not experience complete restoration of a full range of memory responses to previously encountered pathogens.7 8 Taken together, these studies suggest that starting treatment early – before advanced immune suppression occurs – can improve long-term outcomes. This issue is discussed in Starting HIV treatment.

References

  1. Mocroft A et al. Normalisation of CD4 counts in patients with HIV-1 infection and maximum virological suppression who are taking combination antiretroviral therapy: an observational cohort study. Lancet 370: 407-413, 2007
  2. Gras L et al. CD4 cell counts of 800 cells/mm3 or greater after 7 years of highly active antiretroviral therapy are feasible in most patients starting with 350 cells/mm3 or greater. J Acquir Immune Defic Syndr 45(2): 183-192, 2007
  3. Le Moing V et al. Long-term evolution of CD4 count in patients with a plasma HIV RNA persistently < 500 copies/mL during treatment with antiretroviral drugs. HIV Medicine 8: 156-163, 2007
  4. Robbins G et al. Effect of baseline CD4 cell count on immune reconstitution during combination antiretroviral therapy in ACTG 384. Fourth International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, Sydney, abstract WEPEB080, 2007
  5. Munderi P et al. Immune restoration over 5 years on ART among patients initiating treatment with advanced immune deficiency in the DART trial in Uganda and Zimbabwe. Seventeenth Conference on Retroviruses and Opportunistic Infections, San Francisco, abstract 110, 2010
  6. King M et al. When does the CD4 cell count plateau? Evidence from subjects treated with a lopinavir/ritonavir-based regimen for up to 7 years. 46th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, abstract H-1401, 2006
  7. Lange CG et al. CD4+ T-lymphocyte nadir and the effect of highly active antiretroviral therapy on phenotypic and functional immune restoration in HIV-1 infection Clin Immunol 102: 154-161, 2002
  8. Jansen CA et al. Long-term highly active antiretroviral therapy in chronic HIV-1 infection: evidence for reconstitution of antiviral immunity. Antivir Ther. 11: 105-116, 2006

Can HIV-positive people attain normal CD4 cell counts?

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This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends checking whether this is the most current information when making decisions that may affect your health.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member of your healthcare team for advice tailored to your situation.