Key points

 

• • The role of CD4+ count testing is to establish whether CTX prophylaxis, sCrAg testing and urine LAM testing is required, and to identify patients with advanced HIV disease who may need closer follow-up to monitor for opportunistic infections and other HIV-related complications. See the Southern African HIV Clinicians Guidelines for hospitalised adults with Advanced HIV Disease here.
• Monitoring ART efficacy is best established using VL, not CD4+ count.
• Once the CD4+ count is > 200 cells/μL, repeat CD4 count testing is of no value unless the patient subsequently develops virologic or clinical failure.
• If CD4+ count does not rise despite viral suppression, the ART regimen does not need to be altered. This phenomenon may reflect an ‘immunological discordant response to ART’; although if the patient is unwell, then other secondary causes should be sought. Cotrimoxazole prophylaxis is indicated with immunological discordant CD4+ count of < 200 cells/ μL. ⁷⁸

A CD4+ count < 200 cells/µL indicates the need for CTX prophylaxis, principally to prevent Pneumocystis jirovecii pneumonia, although CTX is also active against other opportunistic pathogens, including Toxoplasma gondii, Cystoisospora belli and Nocardia spp. A baseline CD4+ count < 200 cells/µL is also an indication to reflexly perform sCrAg testing, and urine LAM testing should be offered at baseline if the CD4+ count is < 200 for outpatients, or < 100 for inpatients, even in the absence of TB symptoms or overt clinical illness. If the CD4+ count is > 200 cells/μL at baseline or it increases above this threshold on ART, then CD4+ testing can be stopped, since therapeutic monitoring on ART is best accomplished with VL, not CD4+ count or clinical criteria. However, if virologic or clinical failure occurs, then the CD4+ count should be repeated, as CTX prophylaxis should be commenced if the count drops to < 200 cells/μL on ART.

Common pitfall: Routinely checking CD4+ counts if the previous result was >200 cells/μL.

This is unnecessary unless virological or clinical failure subsequently occurs.

CD4⁺ counts should be performed:

• At baseline (to guide decisions about CTX prophylaxis)
• Every 6 months thereafter if the previous CD4⁺ count was < 200 cells/μL.
• If a patient experiences virological failure (to assess the need to restart CTX prophylaxis).

Common pitfall: Not checking a CD4+ count in a patient with virological failure.

In patients who start ART with an abnormally low CD4+ count, the CD4+ count typically increases rapidly in the first month of ART, by ~75–100 cells/ μL, with a more gradual rise thereafter (50–100 cells/ μL per year). ⁷⁹ Most patients achieve a CD4+ count > 500 cells/μL after several years of ART, provided that the VL remains suppressed. However, CD4+ count responses are highly variable and may fail to increase despite virological suppression in about 10–20% of patients. ^{80, 81} Such patients have a delayed or absent CD4+ count response to ART despite viral suppression, which is termed an ‘immunological discordant response to ART’, previously, ‘immune non-responders’ . Certain studies suggest that older patients are at higher risk of this response. There is no evidence that such patients benefit from a change in ART regimen; therefore, the same regimen should be continued. CTX prophylaxis should be continued if the CD4+ count remains < 200 cells/μL. There is evidence that the prognosis of such patients is worse than in those who have a CD4+ response, but better than that of patients experiencing both virological and immunological failure. ⁸¹ If patients with an immunological discordant response to ART are clinically unwell, then TB or lymphoma should be considered as the cause of persistent CD4+ lymphopenia. CD4+ counts may remain stable in the presence of incomplete viral suppression in patients receiving ART until the VL is high (approximately ≥ 10 000 copies/mL). ⁸²

Common pitfall: Confusing an ‘immunological discordant response to ART’ with treatment failure.

There is no role for changing ART if the VL is suppressed.

Figure 3 outlines the suggested approach to patients with low CD4+ counts despite a suppressed viral load on ART.

FIGURE 3: Suggested approach to patients with low CD4+ counts despite a suppressed viral load on ART (ART; antiretroviral therapy; CD4+, cluster of differentiation 4; OIs, opportunistic infections; SLE, systemic lupus erythematosus; TB, tuberculosis; VL, viral load).