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Failure to achieve a CD4+ cell count response on combination antiretroviral therapy despite consistent viral load
Jemma L O'Connor1, Colette J Smith, Fiona C Lampe
1aResearch Department of Infection & Population Health, UCL, London bNorth Bristol NHS Trust, Bristol cSt. George's Healthcare NHS Trust, London dSouth Tees Hospitals NHS Foundation Trust, Middlesbrough eBrighton and Sussex University Hospitals NHS Trust, Brighton fNorth Middlesex University Hospital NHS Trust gMortimer Market Centre, University College Medical School hImperial College Healthcare NHS Trust iHomerton University Hospital NHS Trust jBarts and The London NHS Trust kChelsea and Westminster Hospital NHS Foundation Trust lSouth London Healthcare NHS Trust, London mThe Lothian University Hospitals NHS Trust, Edinburgh nUniversity Hospitals of Leicester NHS Trust, Leicester oKings College Hospital NHS Foundation Trust, London, UK pRoyal Free Hampstead NHS Trust, London, UK.
Insights
For individuals with severely low CD4 counts starting antiretroviral therapy (ART), achieving viral load suppression leads to significant CD4 cell count recovery. Over 90% can reach over 200 cells/μl by 3 years on ART.
Area of Science:
- Immunology
- Virology
- Public Health
Background:
- Antiretroviral therapy (ART) is crucial for managing HIV.
- Severe immunosuppression at ART initiation poses challenges for immune recovery.
- Viral load suppression is a key indicator of treatment success.
Purpose of the Study:
- To evaluate CD4 cell count recovery in severely immunosuppressed individuals on ART.
- To determine the impact of sustained viral load suppression on immune reconstitution.
- To provide prognostic information for patients with low baseline CD4 counts.
Main Methods:
- Analysis of data from the UK Collaborative HIV Cohort Study.
- Inclusion of participants with pre-ART CD4 count < 100 cells/μl and viral load suppression by 9 months on ART.
- Assessment of CD4 cell count thresholds (100, 150, 200, 350, 500 cells/μl) at last follow-up or 5 years.
Main Results:
- Among 400 participants, failure to reach >200 cells/μl was 7% by the censoring date.
- Kaplan-Meier estimates show 90% reached >200 cells/μl by 3 years on ART.
- High rates of immune recovery were observed, with 95% reaching >150 cells/μl and 59% reaching >350 cells/μl by 3 years.
Conclusions:
- Sustained viral load suppression on ART enables significant CD4 cell count recovery.
- Individuals with pre-ART CD4 < 100 cells/μl have a >90% chance of exceeding 200 cells/μl by 3 years.
- Consistent engagement with care and viral suppression are critical for immune reconstitution in this population.
Objective:
To assess CD4 cell count recovery in people severely immunosuppressed at start of antiretroviral therapy (ART) who achieve and maintain viral load suppression.
Methods:
Eligible participants from the UK Collaborative HIV Cohort Study started ART with at least three drugs after 1 January 2000. Participants were required to have pre-ART CD4 cell count below 100 cells/μl, at least 2 years of follow-up on ART, have achieved viral load suppression (≤ 50 copies/ml) by 9 months after starting ART and to have maintained this throughout follow-up. Participants were further required to be regularly engaged with care. We calculated the proportion of people who failed to achieve a CD4 cell count of more than 100, 150, 200, 350 and 500 cells/μl by the time of the last follow-up, or 5 years from start of ART, whichever occurred first (censoring date).
Results:
Of the 400 participants [median (interquartile range) pre-ART CD4 cell count of 38 (14-65) cells/μl], 2 (0.5%), 8 (2%), 28 (7%), 131 (33%) and 259 (65%) failed to achieve a CD4 cell count of more than 100, 150, 200, 350 and 500 cells/μl, by the censoring date, respectively. Kaplan-Meier estimates of the proportion of people reaching each CD4 cell count threshold after 1 year on ART were 88, 70, 50, 14 and 3%, respectively, and after 3 years on ART, 98, 95, 90, 59 and 25%, respectively. Median (interquartile range) follow-up on ART was 3.9 (2.7-4.8) years.
Conclusion:
Given a person with pre-ART CD4 cell count below 100 cells/μl survives and maintains consistent viral load suppression on ART, there is over a 90% chance of reaching a CD4 cell count above 200 cells/μl by 3 years.
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