Objective: HIV viral load (VL) monitoring is generally conducted 6–12 monthly in
low- and middle-income countries, risking relatively prolonged periods of poor viral
control. We explored the effects of different levels of loss of viral control on immune
reconstitution and activation.
Design: Two hundred and eight participants starting protease inhibitor (PI)-based
second-line therapy in the EARNEST trial (ISRCTN37737787) in Uganda and Zimbabwe
were enrolled and CD38þ/HLA-DRþ immunophenotyping performed (CD8-FITC/
CD38-PE/CD3-PerCP/HLA-DR-APC; centrally gated) in real-time at 0, 12, 48, 96
and 144 weeks from randomization.
Methods: VL was assayed retrospectively on samples collected every 12–16 weeks and
classified as continuous suppression (<40 copies/ml throughout); suppression with
transient blips; low-level rebound (two or more consecutive VL >40, <5000 copies/
ml); high-level rebound/nonresponse (two or more consecutive VL >5000 copies/ml).
Results: Immunophenotype reconstitution varied between that defined by numbers of
cells and that defined by cell percentages. Furthermore, VL dynamics were associated
with substantial differences in expression of CD4þ and CD8þ cell activation markers, with
only individuals with high-level rebound/nonresponse (>5000 copies/ml) experiencing
significantly greater activation and impaired reconstitution. There was little difference
between participants who suppressed consistently and who exhibited transient blips or
even low-level rebound by 144 weeks (P > 0.2 vs. suppressed consistently).
Conclusion: Detectable viral load below the threshold at which WHO guidelines
recommend that treatment can be maintained without switching (1000 copies/ml)
appear to have at most, small effects on reconstitution and activation, for patients
taking a PI-based second-line regime