CD4 and viral load dynamics in antiretroviral-naïve HIV-infected adults from Soweto, South Africa: a prospective cohort.

Neil A Martinson,Reginah Msandiwa,Grace L Barnes,Chris Hoffmann,Richard E Chaisson,Nikhil Gupte,Malathi Ram,Glenda Gray,Lawrence H Moulton,Marie-Louise Newell

doi:10.1371/journal.pone.0096369

Abstract

BackgroundCD4 count is a proxy for the extent of immune deficiency and declines in CD4 count are a measure of disease progression. Decline in CD4 count is an important component: for estimating benefits of ARV treatment; for individual level counselling on the rapidity of untreated disease progression and prognosis; and can be used in planning demand for health services. Our objective is to report CD4 decline and changes in viral load (VL) in a group of HIV-infected adults enrolled in a randomized trial of preventive treatment for TB in South Africa where clade C infection predominates.MethodsHIV-infected, tuberculin skin test positive adults who were not eligible for antiretroviral (ARV) treatment were randomized to a trial of preventive treatment from 2003–2005. VL and CD4 count were assessed at enrollment and CD4 counts repeated at least annually. During follow-up, individuals whose CD4 counts decreased to <200 cells/mm3 were referred for antiretroviral therapy (ART) and were analytically censored.Results1106 ARV naïve adults were enrolled. Their median age was 30 years and male to female ratio was 1∶5. Median baseline CD4 count was 490 cells/mm3 (IQR 351–675). The overall mean decline in CD4 count was 61 cells/mm3 per annum. Adjusting for age, gender, baseline hemoglobin, smoking and alcohol use had little impact on the estimate of CD4 decline. However, VL at baseline had a major impact on CD4 decline. The percent decline in CD4 count was 13.3% (95% CI 12.0%, 14.7%), 10.6% (95% CI 8.8%, 12.4%), and 13.8% (95% CI 12.1%, 15.5%) per annum for baseline VLs of <10,000 (N = 314), 10,001–100,000 (N = 338), >100,000 (N = 122) copies/ml.ConclusionsOur data suggests that six and a half years will elapse for an individual's CD4 count to decline from 750 to 350 cells/mm3 in the absence of ART.

Highlights

Since Mellor’s et al landmark papers on the relative prognostic value of viral load on CD4 count decline [1,2], there have been few reports describing CD4 cell decline and the influence of HIV RNA on CD4 decline – from developing settings where the HIV subtypes, host factors, and route of HIV acquisition differ to those in North America
Estimates of CD4 count decline, are important to predict the time to CD4 count based antiretroviral therapy (ART) initiation thresholds
The overall aim was to describe CD4 and viral load dynamics in a closely monitored group of HIV-infected antiretroviral therapy naıve adults, in South Africa, who entered the study with CD4 counts either above or close to 500 cells/mm3 and were followedup at semi-annual scheduled visits for almost four years

Summary

Introduction

Since Mellor’s et al landmark papers on the relative prognostic value of viral load on CD4 count decline [1,2], there have been few reports describing CD4 cell decline and the influence of HIV RNA on CD4 decline – from developing settings where the HIV subtypes, host factors, and route of HIV acquisition differ to those in North America. Reports of CD4 decline from South Africa, where HIV-1 subtype C is the predominant infecting strain, have described CD4 decline in ART naıve patients but lack contemporaneous HIV viral load data [6,7,8]. The overall aim was to describe CD4 and viral load dynamics in a closely monitored group of HIV-infected antiretroviral therapy naıve adults, in South Africa, who entered the study with CD4 counts either above or close to 500 cells/mm and were followedup at semi-annual scheduled visits for almost four years. Our objective is to report CD4 decline and changes in viral load (VL) in a group of HIV-infected adults enrolled in a randomized trial of preventive treatment for TB in South Africa where clade C infection predominates

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