CD4 cell count and the risk of AIDS or death in HIV-Infected adults on combination antiretroviral therapy with a suppressed viral load: a longitudinal cohort study from COHERE.

John Bartlett

doi:10.1371/journal.pmed.1001194

Abstract

Most adults infected with HIV achieve viral suppression within a year of starting combination antiretroviral therapy (cART). It is important to understand the risk of AIDS events or death for patients with a suppressed viral load. Using data from the Collaboration of Observational HIV Epidemiological Research Europe (2010 merger), we assessed the risk of a new AIDS-defining event or death in successfully treated patients. We accumulated episodes of viral suppression for each patient while on cART, each episode beginning with the second of two consecutive plasma viral load measurements <50 copies/µl and ending with either a measurement >500 copies/µl, the first of two consecutive measurements between 50-500 copies/µl, cART interruption or administrative censoring. We used stratified multivariate Cox models to estimate the association between time updated CD4 cell count and a new AIDS event or death or death alone. 75,336 patients contributed 104,265 suppression episodes and were suppressed while on cART for a median 2.7 years. The mortality rate was 4.8 per 1,000 years of viral suppression. A higher CD4 cell count was always associated with a reduced risk of a new AIDS event or death; with a hazard ratio per 100 cells/µl (95% CI) of: 0.35 (0.30-0.40) for counts <200 cells/µl, 0.81 (0.71-0.92) for counts 200 to <350 cells/µl, 0.74 (0.66-0.83) for counts 350 to <500 cells/µl, and 0.96 (0.92-0.99) for counts ≥500 cells/µl. A higher CD4 cell count became even more beneficial over time for patients with CD4 cell counts <200 cells/µl. Despite the low mortality rate, the risk of a new AIDS event or death follows a CD4 cell count gradient in patients with viral suppression. A higher CD4 cell count was associated with the greatest benefit for patients with a CD4 cell count <200 cells/µl but still some slight benefit for those with a CD4 cell count ≥500 cells/µl.

Highlights

More than 90% of those infected with HIV achieve viral suppression within a year of starting a combination antiretroviral therapy [1,2]
This study considers the prognostic value of a CD4 cell count, not when starting combination antiretroviral therapy (cART), but while a patient is being successfully treated, that is, while a patient is on cART with a suppressed viral load
We selected patients from the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) database, accumulated episodes of viral suppression for each patient while on cART, and used these episodes to estimate the association between a time updated CD4 cell count and progression to a new AIDS-defining event or death, or death alone

Summary

Introduction

More than 90% of those infected with HIV achieve viral suppression within a year of starting a combination antiretroviral therapy (cART) [1,2]. The immune system can no longer fight off infections by other disease-causing organisms and HIV-positive people develop one or more AIDS-defining condition(s), including severe but unusual infections, Kaposi sarcoma (a skin cancer), and non-Hodgkin lymphoma (a cancer of the lymph nodes). Many of these AIDS-defining conditions are life-threatening and, in the past, HIV-positive people died on average within 10 years of infection. There is still no cure for HIV infection, combination antiretroviral therapy (cART; a cocktail of powerful antiretroviral drugs) has turned HIV/AIDS into a chronic, treatable condition, at least in developed countries

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