Abstract
ObjectivesTo investigate factors that predict speed of recovery and long‐term CD4 cell count in HIV‐1 seroconverters initiating combination antiretroviral therapy (cART), and to quantify the influence of very early treatment initiation. We make use of all pre‐treatment CD4 counts, because analyses using only a single observation at initiation may be subject to biases.MethodsWe used data from the CASCADE (Concerted Action on SeroConversion to AIDS and Death in Europe) multinational cohort collaboration of HIV‐1 seroconverters. We analysed pre‐ and post‐treatment data of patients with seroconversion dates estimated January 2003–March 2014 (n = 7600 for primary analysis) using a statistical model in which the characteristics of recovery in CD4 counts are determined by multiple predictive factors. Secondary analyses were performed incorporating uncertainty in the exact timing of seroconversion to allow more precise estimation of the benefit of very early treatment initiation.Results‘True’ CD4 count at cART initiation was the strongest predictor of CD4 count beyond 3 years on cART. Allowing for lack of complete certainty in the date of seroconversion, CD4 recovery was more rapid for patients in whom treatment was initiated within 4 months. For a given CD4 count, higher viral load (VL) at initiation was strongly associated with higher post‐treatment CD4 recovery. For other patient and drug characteristics, associations with recovery were statistically significant but small in magnitude.Conclusions CD4 count at cART initiation is the most important factor in predicting post‐treatment recovery, but VL provides substantial additional information. If cART is initiated in the first 4 months following seroconversion, recovery of CD4 counts appears to be more rapid.
Highlights
Observational studies have consistently found that, for HIV-1 positive patients initiating combination antiretroviral therapy, higher CD4 cell counts at baseline are associated with higher CD4 count levels after several years of treatment [1,2,3,4,5,6]
There is some evidence that initiation of combination antiretroviral therapy (cART) close to the date of HIV-1 infection is associated with a higher level of CD4 recovery than that expected by the baseline CD4 cell count alone
The shape of the fitted curve indicated that, on average, there is a rapid improvement in CD4 count in the 2–3 months following cART initiation with a subsequent gradual increase that continues in most cases for more than 5 years (Fig. 1)
Summary
Observational studies have consistently found that, for HIV-1 positive patients initiating combination antiretroviral therapy (cART), higher CD4 cell counts at baseline are associated with higher CD4 count levels after several years of treatment [1,2,3,4,5,6]. Le et al [13] reported that, among patients with a baseline CD4 count < 500 cells/lL, those who initiated cART within 4 months of their estimated date of infection experienced substantially higher CD4 cell levels over the first 4 years on treatment. Ding et al [14] reported a more rapid initial increase in CD4 count for patients in whom treatment was initiated within 2 months of diagnosis of a recent infection Because investigating this issue requires observation of patients with well estimated date of seroconversion, there is a need for further evidence from large seroconverter cohorts
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