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Rapid antiretroviral therapy in primary HIV-1 infection enhances immune recovery: each day that ART was delayed was associated with a lower likelihood of achieving a CD4>900 cells and CD4/CD8 >1.0
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Dec 2023
"We demonstrate that rapid initiation of ART (within a maximum of 3 months after confirmed HIV diagnosis) in this cohort of treated PHI is associated with significant improvement in immune recovery and that the sooner ART is started after PHI diagnosis, the greater the chance of immune recovery; each day that ART is delayed in PHI confers a reduced chance of normalisation of markers of immune function. This is a key message to support rapid or immediate ART start amongst all new HIV-1 diagnoses, but especially in PHI[20]."
"each day that ART was delayed was associated with a lower likelihood of achieving a CD4>900 cells/mm3 [HR 0.99 (95%CI 0.98, 0.99), P = 0.02) and CD4/CD8>1.0 (HR 0.98 (95%CI 0.97, 0.99)."
"Lower baseline CD4 T-cell counts (P<0.001), lower CD4/CD8 ratio (P=0.01), and lower CD8 T-cell count (P<0.01) were associated with a longer time to CD4 T-cell count >900 cells/mm3", see Table 2
For each day after PHI diagnosis that ART was delayed, there was a lower likelihood of achieving a CD4 T-cell count >900 cells/mm3 [HR 0.99 (95% CI 0.98, 0.99), P=0.02).......Non-MSM transmission (P<0.001), higher CD4 T-cell counts (P<0.001) and the clinically modifiable variable of a shorter time to ART initiation [HR 0.98 (95%CI 0.97, 0.99), P<0.01], were all associated with faster time to CD4 T-cell count >900 cells/mm3 in this model"
When immune recovery was defined as time to CD4/CD8 >1.0, the factors significantly associated with a shorter time to immune recovery in both the unadjusted and adjusted model included a shorter time between HIV-1 diagnosis to ART initiation (HR 0.98 (95%CI 0.97, 0.99), P<0.01), lower baseline CD8 count (HR 2.21 (95%CI 1.54, 3.17), P<0.001) and higher CD4 T-cell count (P=0.02), Table 3. In addition, there was a trend towards a shorter time for CD4/CD8 recovery with integrase inhibitor use (P=0.08). Those diagnosed between 2009 and 2015 were less likely to achieve CD4/CD8 >1.0 compared to those diagnosed in 2015-2020; however, this was not significant in the multivariable model.
Abstract
Objective:
We present findings from a large cohort of individuals treated during Primary HIV Infection (PHI) and examine the impact of time from HIV-1 acquisition to antiretroviral therapy (ART) initiation on clinical outcomes. We also examine the temporal changes in the demographics of individuals presenting with PHI to inform HIV-1 prevention strategies.
Methods:
Individuals who fulfilled the criteria of PHI and started ART within three months of confirmed HIV-1 diagnosis were enrolled between 2009 and 2020. Baseline demographics of those diagnosed between 2009–2015 (before preexposure prophylaxis (PrEP) and universal ART availability) and 2015–2020 (post-PrEP and universal ART availability) were compared. We examined the factors associated with immune recovery and time to viral suppression.
Results:
204 individuals enrolled, 144 from 2009–2015 and 90 from 2015–2020; median follow-up was 33 months. At PHI, the median age was 33 years; 4% were women, 39% were UK-born, and 84% were MSM. The proportion of UK-born individuals was 47% in 2009–2015, compared with 29% in 2015–2020. There was an association between earlier ART initiation after PHI diagnosis and increased immune recovery; each day that ART was delayed was associated with a lower likelihood of achieving a CD4>900 cells/mm3 [HR 0.99 (95%CI 0.98, 0.99), P = 0.02) and CD4/CD8>1.0 (HR 0.98 (95%CI 0.97, 0.99).
Conclusion:
Early initiation of ART at PHI diagnosis is associated with enhanced immune recovery, providing further evidence to support immediate ART in the context of PHI. Non-UK-born MSM accounts for an increasing proportion of those with primary infection; UK HIV-1 prevention strategies should better target this group.
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