CD4 Count Slope and Mortality in HIV-Infected Patients on Antiretroviral Therapy: Multicohort Analysis From South Africa

Hoffmann, Christopher J. MD, MPH*,†; Schomaker, Michael PhD; Fox, Matthew P. DSc§,‖; Mutevedzi, Portia MBBch; Giddy, Janet MBBch#; Prozesky, Hans MBBch**; Wood, Robin MBBch††; Garone, Daniela B. MBBch‡‡; Egger, Matthias MD§§; Boulle, Andrew MBBch, PhD; for the IeDEA Southern Africa Collaboration

JAIDS Journal of Acquired Immune Deficiency Syndromes: 1 May 2013 - Volume 63 - Issue 1 - p 34–41
doi: 10.1097/QAI.0b013e318287c1fe
Clinical Science

Background: In many resource-limited settings monitoring of combination antiretroviral therapy (cART) is based on the current CD4 count, with limited access to HIV RNA tests or laboratory diagnostics. We examined whether the CD4 count slope over 6 months could provide additional prognostic information.

Methods: We analyzed data from a large multicohort study in South Africa, where HIV RNA is routinely monitored. Adult HIV-positive patients initiating cART between 2003 and 2010 were included. Mortality was analyzed in Cox models; CD4 count slope by HIV RNA level was assessed using linear mixed models.

Results: About 44,829 patients (median age: 35 years, 58% female, median CD4 count at cART initiation: 116 cells/mm3) were followed up for a median of 1.9 years, with 3706 deaths. Mean CD4 count slopes per week ranged from 1.4 [95% confidence interval (CI): 1.2 to 1.6] cells per cubic millimeter when HIV RNA was <400 copies per milliliter to −0.32 (95% CI: −0.47 to −0.18) cells per cubic millimeter with >100,000 copies per milliliter. The association of CD4 slope with mortality depended on current CD4 count: the adjusted hazard ratio (aHRs) comparing a >25% increase over 6 months with a >25% decrease was 0.68 (95% CI: 0.58 to 0.79) at <100 cells per cubic millimeter but 1.11 (95% CI: 0.78 to 1.58) at 201–350 cells per cubic millimeter. In contrast, the aHR for current CD4 count, comparing >350 with <100 cells per cubic millimeter, was 0.10 (95% CI: 0.05 to 0.20).

Conclusions: Absolute CD4 count remains a strong risk for mortality with a stable effect size over the first 4 years of cART. However, CD4 count slope and HIV RNA provide independently added to the model.

*Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD;

Aurum Institute, Johannesburg, South Africa;

Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa;

§Department of Medicine, Faculty of Health Sciences, Health Economics and Epidemiology Research Office, University of the Witwatersrand, Johannesburg, South Africa;

Center for Global Health and Development, Boston University, Boston, MA;

Africa Centre for Health and Population Studies, Somkhele, Mtubatuba, South Africa;

#McCord Hospital, Durban, South Africa;

**Division of Infectious Diseases, Department of Medicine, University of Stellenbosch and Tygerberg Academic Hospital, Cape Town, South Africa;

††The Desmond Tutu HIV Centre, Institute for Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa;

‡‡Khayelitsha ART Programme and Médecins sans Frontières, Cape Town, South Africa; and

§§Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.

Correspondence to: Christopher J. Hoffmann, MD, MPH, Johns Hopkins University School of Medicine, 1550 Orleans St, CRB II Rm 1M-07, Baltimore, MD 21231 (e-mail:

Supported by National Institute of Allergy and Infectious Diseases (NIAID), grant 2U01-AI069924. C.J.H. was supported by NIAID AI083099. M.P.F. was supported by NIAID K01AI083097.

The content is solely the responsibility of the authors and does not necessarily represent the official views of NIAID or the National Institutes of Health.

The authors have no conflicts of interest to disclose.

Received August 14, 2012

Accepted January 14, 2013

© 2013 Lippincott Williams & Wilkins, Inc.