Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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: : 208 participants starting Protease Inhibitor (PI)-based second-line therapy in the EARNEST trial (ISRCTN37737787) in Uganda and Zimbabwe were enrolled and CD38+/HLA-DR+ 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 randomisation. METHODS: Viral Load (Viral load (VL) was assayed retrospectively on samples collected every 12-16 weeks and classified as (1) continuous suppression (<40 copies/ml throughout); (2) suppression with transient blips; (3) low-level rebound (two or more consecutive VL >40, <5000 copies/ml); (4) high-level rebound/non-response (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 CD4+ and CD8+ cell activation markers, with only individuals with high-level rebound/non-response (>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 regimen.

Original publication

DOI

10.1097/QAD.0000000000003488

Type

Journal article

Journal

AIDS

Publication Date

23/01/2023