Page 39 - HIVMED_v21_i1.indb

Page 13 of 39 Guideline

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population even in the absence of drug pressure. Transmitted Role of CD4 count monitoring
drug resistance to other drug classes is unusual; therefore, +
first-line therapy with a DTG-based regimen is unlikely to be A CD4 count < 200 cells/μL indicates the need for CTX
affected by this phenomenon. prophylaxis, principally to prevent Pneumocystis jirovecii
pneumonia, although CTX is also active against other
Interpreting a high viral load result of a patient receiving opportunistic pathogens, including Toxoplasma gondii,
dolutegravir Cystoisospora belli and Nocardia spp. A baseline CD4 count
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Dolutegravir has been proved to be a remarkably robust < 200 cells/μL is also an indication to reflexly perform
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drug in InSTI-naive patients when paired with at least one sCrAg testing. If the CD4 count is > 200 cells/μL at
active NRTI. To date, less than five cases of DTG resistance baseline or it increases above this threshold on ART, then
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have been described in this scenario. Thus, although a high CD4 testing can be stopped, as therapeutic monitoring on
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VL has traditionally been a marker of possible resistance, this ART is best accomplished with VL, not CD4 count or
paradigm no longer applies for the most part in patients clinical criteria. However, if virologic or clinical failure
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receiving a DTG-based regimen, provided that: occurs, then the CD4 count should be repeated, as CTX
prophylaxis should be commenced if the count drops to
1. The patient has not had previous exposure to InSTIs as < 200 cells/μL on ART.
part of a failing regimen.
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° Common pitfall: Routinely checking CD4 counts
2. The patient is known to have at least one fully active
NRTI as part of their regimen. (Note that patients if the previous result was > 200 cells/µL. This is
who contract HIV whilst on pre-exposure prophylaxis unnecessary unless virological or clinical failure
[PrEP] are at risk of not having a fully active NRTI subsequently occurs.
backbone). Timing of CD4 count measurements
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3. The patient was not recently exposed to a scenario
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where a drug–drug interaction would have substantially CD4 counts should be performed:
decreased DTG concentrations (e.g. RIF-based TB therapy • at baseline (to guide decisions about CTX prophylaxis)
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without increasing DTG dosing frequency to 12 hourly). • every 6 months thereafter if the previous CD4 count was
< 200 cells/μL.
Provided that none of the above conditions are met, a
detectable VL should not be assumed to reflect possible CD4 count response
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resistance. Rather, it can be assumed that the detectable In patients who start ART with an abnormally low CD4
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VL, if not fulfilling criteria for a viral blip, merely count, the CD4 count typically increases rapidly in the first
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represents poor adherence, and efforts to address this month of ART, by ~75 cells/μL – 100 cells/μL, with a more
should be undertaken. We do not recommend performing gradual rise thereafter (50 cells/μL per year – 100 cells/μL
resistance testing for patients on a DTG-based regimen within 2 per year). Most patients achieve a CD4 count > 500 cells/
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56
years of commencing the drug, provided that the above conditions μL after several years of ART, provided that the VL remains
are met.
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suppressed. However, CD4 count responses are highly
9. CD4 count variable and may fail to increase despite virological
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suppression in about 10% – 20% of patients.
Such patients
57,58
Key points have a delayed or absent CD4 count response to ART despite
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viral suppression, which is termed an ‘immunological
ÿ All HIV-positive patients should be started on ART discordant response to ART’, previously ‘immune non-
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irrespective of their CD4 counts. responders’. Some studies have suggested that older patients
ÿ CD4 counts should be used only to establish whether are at a higher risk of this response. There is no evidence that
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CTX prophylaxis and sCrAg testing are required (CD4 <
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200 cells/μL). such patients benefit from a change in ART regimen;
ÿ Monitoring ART efficacy is best established using VL, not therefore, the same regimen should be continued.
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CD4 count. Cotrimoxazole prophylaxis should be continued if the CD4
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ÿ Most patients newly initiating ART with an abnormally count remains < 200 cells/μL. There is evidence that the
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low CD4 count will see a rapid initial CD4 count increase prognosis of such patients is worse than in those who have a
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(75 cells/μL – 100 cells/μL), followed by a more gradual CD4 response, but better than that of patients experiencing
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rise thereafter (50 cells/μL – 100 cells/μL per year) until a both virological and immunological failure. If patients with
normal CD4 count > 500 cells/μL is achieved. an immunological discordant response to ART are clinically
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ÿ If CD4 count does not rise despite viral suppression, the unwell, then TB or lymphoma should be considered as the
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ART regimen does not need to be altered. This cause of persistent CD4 lymphopenia. CD4 counts may
phenomenon may reflect an ‘immunological discordant remain stable in the presence of incomplete viral suppression
response to ART’; however, if the patient is unwell, then in patients receiving ART until the VL is high (approximately
other secondary causes should be sought. ≥ 10 000 copies/mL). 59
http://www.sajhivmed.org.za 31 Open Access