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HIV Med. 2018 Mar;19(3):184-194. doi: 10.1111/hiv.12567. Epub 2017 Dec 1.

Predictors of CD4 cell recovery following initiation of antiretroviral therapy among HIV-1 positive patients with well-estimated dates of seroconversion.

Author information

1
MRC Clinical Trials Unit, University College London, London, UK.
2
Research Department of Infection & Population Health, University College London, London, UK.
3
Department of Medicine, University of Calgary, Calgary, AB, Canada.
4
Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center (AMC), Amsterdam, The Netherlands.
5
Department of Infectious Diseases, Public Health Service of Amsterdam, Amsterdam, The Netherlands.
6
Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam.
7
Nuffield Department of Clinical Medicine, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.
8
Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
9
Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel and University of Basel, Basel, Switzerland.

Abstract

OBJECTIVES:

To 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.

METHODS:

We 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.

KEYWORDS:

ART ; HAART ; HIV ; CD4; antiretroviral therapy; longitudinal data; mixed effects model

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